Lviv Clinical Bulletin

15-24

Authors: Synenky O.

Introduction. Vitamin D deficiency (VDD) is a global problem of humanity. In Ukraine it is registered in 81.8 % of the adult population. In its turn, rheumatoid arthritis (RA) is the most common disease among the rheumatic diseases of the population of the Lviv region, therefore, the study of the frequency of VDD among such patients and the determination of the characteristics of the RA in case of the different levels of 25 (OH) D in serumare particularly important. Aim. To increase the efficiency of the comprehensive treatment of RA based on the study of the effect of VDD on the disease course and the ways of its corrections. Materials and methods. The study consisted of two phases: epidemiological and clinical. Patients who participated in the study, depending on their needs, underwent a general clinical examination, joint syndrome assessment, anthropometric examination, questionnaires (visual analogue scale (VAS), assessment of the disease activity by the physician and patient, DAS28 , two-photon X-ray absorptiometry, ultrasound densitometry of the heel bone, determination of total 25 (OH) D contentinserum (electrochemiluminescent and immunochemical with chemiluminescent detection methods of research), determination of the levels of rheumatoid factor (RF) and C-reactive protein (CRP) (immunoturbidimetric method), anti-CCP (flowcytometry), complete blood count, biochemical blood test with determination of activity of ionized calcium in serum, questionnaire-weight method of reproduction of a daily diet, mathematical methods for statistical processing of the obtained results. Results. It was determined that RA as the most common rheumatic disorder in Lviv region (409.7 cases per 100.000 population), has one of the highest incidence of primary morbidity (initial incidence of 19.3 per 100.000 population) and highest rate of hospitalization. Patients with RA have VDD in 54.9 % cases, vitamin D insufficiency in 37.6 %. Comparing the obtained results with epidemiological study held among the healthy population of Lviv region it was shown that the number of patients with RA and optimal serum 25(OH)D level was significantly lower (7.5 vs. 16.3 %, respectively, p = 0.04). The frequency of VDD and vitamin D in sufficiency was the same. Risk factors for VDD development in patients with RA turned out to be age, female gender, and body mass index. It is proved that serum 25(OH)D level is not an independent predictor of deterioration of structural and functional state of bone tissue. Only an age is independent factor of osteopenic syndrome (β = -0.23, (DІ 95 %: -0.50; -0.13), р < 0.001). Patients with the third degree of the disease activity have mean serum 25(OH)D level significantly lower compared with those whose disease activity is minimal (p < 0.05). VDD increases the risk of the highest activity of RA in three times (RR = 3.00; 95% CI: 1.01; 8.86, p < 0.05). Also, it is revealed that the patients with the first roentgen stage of RA have the highest serum 25(OH)D level and by 24.5 % higher level compared to the mean 25(OH)D level of the patients with II and by 39.2 % with III roentgen stage. In patients with RA and anemia the serum 25(OH)D level is significantly lower compared to those who does not have anemia (p < 0,05). Also, it was found that patients with RA and VDD had significantly lower hemoglobin level than subjects with normal 25(OH)D level (p = 0.03). It was determined the significant negative correlation between the serum 25(OH)D level and markers of RA activity (DAS28-ESR, ESR, CRP). All this associations remained statistically significant after adjustment for gender, age and body mass index. VDD can be regarded as a significant predictor of the highest activity of RA (AUROC = 0.67; 95% CI = 0.513-0.83, p = 0.05). Correction of vitamin D status by the developed individual targeted therapy of VDD in combination with basic treatment of RA reduces the markers of disease activity and significantly decreases the pain syndrome measured by visual analog scale (p < 0.05). Conclusions. Developed and implemented in health care system algorithm of correction and monitoring of vitamin D status is aimed to improve the treatment andthe life quality of the patients with RA.

30-34

Authors: Markin L., Medvyedyeva O.

Introduction. Preeclampsia (PE) continues to be a leading cause of maternal and fetal morbidity and mortality worldwide with an incidence of 3–5 %. Recently evidence suggests that PE can be subdivided into early-onset PE (EOP), requiring delivery before 34 weeks’ gestation and late-onset PE (LOP), with delivery at or after 34 weeks. They are associated with different maternal and fetal outcomes, biochemical markers, heritability, and clinical features. Although the diagnostic criteria are the same in each of these phenotypic variants of preeclampsia, they are characterized by different clinical features and are associated with different maternal and fetal outcomes. Within the context of personalized medicine, future lines for investigations dealing with the prediction and prevention of PE should be based on the identification of the PE subtypes with regard to the maternal characteristics and clinical factors. Aim. The aim of this study was to study the incidence of early-onset and late-onset preeclampsia at a tertiary care center (at obstetrical department of L’viv Regional Clinical Hospital) and to find the difference in risk factors and birth outcomes associated with early-onset and late-onset preeclampsia. Materials and methods. Clinical and anamnestic data were analyzed for 300 pregnant women aged 16-43 years old with singleton pregnancies divided into 3 groups: group I consisted of 100 patients with early-onset preeclampsia, group II – 100 patients with late-onset preeclampsia; group III (control) consisted of 100 normotensive pregnant women who delivered consecutively after preeclamptic pregnant women. Preeclampsia was defined according to the criteria of the International Society for the Study of Hypertension in Pregnancy. EOP was defined as onset of disease from 20 weeks 0 days to 33 weeks 6 days, whereas LOP was regarded as PE after 34 weeks’ gestation. Results. Our study shows that effect of risk factors such nulliparity, chronic hypertension, and diabetes vary according to the subtype of preeclampsia. For example, women who were young (younger than 20), nulliparous, had diabetes mellitus were significantly associated with increased risk of LOP, whereas women who had chronic hypertension, congenital anomalies had higher rates of EOP. Several risk factors were associated with preeclampsia, without a significant difference for early and late-onset disease. Maternal age more than 35 years, pregestational BMI more than 25, smoking during pregnancy were significantly associated with increased risk of both EOP and LOP. The rates of all adverse birth outcomes, were higher among women with EOP. For example, the rates of fetal, neonatal and perinatal death were significantly higher in the EOP group than in LOP group. The rates of NICU admission and severe neonatal morbidity were significantly higher among infants born to mothers with EOP. Conclusions. Our research revealed that EOP is a distinct and a more severe clinical entity, associated with intrauterine growth restriction, with high rates of adverse birth outcomes, with a much earlier gestational age at onset and delivery. EOP starts with a failure to transform the maternal spiral arteries, subsequently followed by alterations of the villous trophoblast, lead to severe placental lesion (early placental dysfunction), hypoxia of the placenta and fetus, the failure of compensatory mechanisms, an increase endothelial dysfunction markers. Therefore, this subtype of preeclampsia debuted early (in the midtrimester) and leads to worse perinatal outcomes. In comparison, LOP develops in the third trimester of pregnancy, rarely leads to perinatal loss.

40-53

Authors: Abrahamovych М., Abrahamovych О., Farmaha M.

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.

60-74

Authors: Abrahamovych U., Abrahamovych O., Guta S.

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.