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Lamija Zečević

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<p><strong>Aim</strong> To determine whether demographic data, clinical features, and laboratory variables at disease onset can predict the response to methotrexate in juvenile idiopathic arthritis (JIA) patients.&nbsp;<br /><strong>Methods</strong> A cohort of 143 newly diagnosed JIA patients initially treated with methotrexate was enrolled in this study. Demographic, clinical, and laboratory parameters were analysed using univariate and multivariate logistic regression to identify predictors of response to methotrexate. The variables included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelets, IgA, IgG, the number of active joints and age at disease onset. Treatment response was assessed at six months, with patients classified as responders (those who achieved clinically inactive disease according to the American College of Rheumatology - ACR criteria) or non-responders.&nbsp;<br /><strong>Results</strong> Poor response to methotrexate was associated with the number of active joints (p=0.0001; OR=2.7), baseline levels of CRP (p=0.044; OR=1.138), IgA (p =0.004; OR=2.159), and platelet count (p=0.01; OR=1.05). IgG level (P=0.236) did not correlate with the treatment response.&nbsp;<br /><strong>Conclusion</strong> We identified widely available and clinically acceptable biomarkers that can be utilized as predictive indicators of response to methotrexate in JIA patients.</p>

Aim To determine the value of IFN (intzerferon)-α in the patients with systemic lupus erythematosus (SLE) and to correlate IFN-α with values of non-specific biochemical parameters of inflammation (C-reactive protein, leukocytes values, erythrocyte sedimentation rate, albumins and globulins). Methods Research included 55 patients with SLE diagnosis and a control group consisted of 25 healthy subjects (during period 2019-2020). IFN (Interferon)-α and non-specific biochemical parameters of inflammation were obtained using standard protocols. Results IFN-α values were independent of gender (p=0.95). The difference in serum IFN-α values in relation with the age in the SLE group was statistically significant (p=0.036). Only serum globulin was significantly higher (p=0.0023) in IFN-α positive compared to IFN-α negative SLE patients. A statistically significant correlation between the values of IFN-α and globulin was proved (r=0.315; p=0.019). No significant correlation was found between other non-specific biochemical parameters and IFN-α values. Conclusion Increased IFN-α values were observed in younger patients, and the correlation between IFN and globulin was proved.

Lamija Zečević, M. Mekić, D. Subasic, Majda Hadziabulic, Edmira Isak, Emina Subašić, K. Selmanovic

Introduction: Lately, the use of biological therapy in various autoimmune diseases is increasing. The ideal marker for monitoring the effects of modern therapy is still non-existent. Aim: To investigate early response biomarkers of SLE and RA patients under the rituximab treatment are in research phase and each new investigations offer new and original useful data. Material and Methods: Immunophenotyping of cells was carried out by a standard method of sample preparation. We investigated by flow cytometric analyses expression of NK and CD19+ cells at ten SLE and five RA patients before and after treatment with rituximab, in laboratory of Department of Clinical immunology in the Clinical Centre University of Sarajevo. Results: In both cases, SLE and RA patients, reduced number of CD16+ parameter indicates lower cytotoxic activity of NK cells. Increased number of B cells indicates higher pathological activity leading to severe autoimmune disease allegation. Conclusion: Determining the proportion of NK and B will be useful diagnostic tool in therapeutic strategy, and also in monitoring of effect of biological therapy.

Summary Background HIV infection is characterized by progressive depletion of CD4+ T cells due to their reduced synthesis and increased destruction followed by marked activation and expansion of CD8+ T lymphocytes. CD4/CD8 ratio was traditionally described as a marker of immune system ageing in the general population, but it increasingly appears as a marker of different outcomes in the HIV-infected population. The main objective of this study is to examine the power of CD4/CD8 ratio in predicting the occurrence of metabolic syndrome (MetS) in HIV-positive patients receiving cART therapy. Methods 80 HIV/AIDS subjects were included in a retrospective case-control study. Flow cytometry was used to determine the percentage of CD4+ and CD8+ cells in peripheral blood of these patients. The values of biochemical parameters (triglycerides, HDL, blood sugar, blood counts), immunological parameters (CD4/CD8, PCR), anthropometric measurements and type of cART therapy were evaluated in this study. Results After six months of cART therapy 19 (23.8%) subjects had all the elements necessary for making the diagnosis of MetS. Using multivariate analysis CD4/CD8 ratio was statistically significant (p < 0.05) and had the largest effect on development of MetS (Wald = 9.01; OR = 0.45), followed by cART (Wald = 7.87; OR = 0.10) and triglycerides (Wald = 5.27; OR = 1.7). On the other hand, body weight and waist circumference showed no statistically significant effect on the development of MetS after six months of cART, p > 0.05. Conclusions CD4/CD8 ratio proved to be a significant marker for prediction of metabolic syndrome in HIV/AIDS patients.

Alopecia areata (AA) is a non-scarring inflammatory disease of the hair follicle. Although it usually presents as asymptomatic localized hair loss, it is a disese of very broad spectrum. Alopecia universalis (AU) is an uncommon form of AA that involves the loss of all haed and body hair and is estimated to account approximately 5% of all alopecia cases [1]. The cause of disease is unknown, although there is evidence to suggest that the link between lymphocytic infiltration of the follicle and the disruption of the hair follicle cycle in AA may be provided by a combination of factors, including cytokine release, cytotoxic T-cell activity, and apoptosis [2,3]. It is also considered that a disequilibrium in the production of cytokines, with a relative excess of proinflammatory and Th1 types, vs. anti-inflammatory cytokines may be involved in the persistence of AA lesions, as shown in human scalp biopsies [4]. The immune response presented in AU is associated with aberrant lesional expression of interferon-gamma (IFN-γ), interleukin-2 (IL-2) and IL-1β, and overexpression of ICAM-1 and MHC molecules on hair follicle keratinocytes and dermal papilla cells [5].

Summary Background: There is still no reliable, specific biomarker for precision diagnosis and clinical monitoring of systemic lupus erythematosus. The aim of this study was to investigate the importance of the determination of immunofenotypic profiles (T, B lymphocytes and NK cells) and serum cytokine concentrations (IL-17 and IFN-alpha) as potential biomarkers for this disease. Methods: The study included 55 patients with SLE and 25 healthy controls. The proportion of T, B, NK cells were assessed in peripheral blood using flow cytometric assays while the serum cytokine concentration (IL-17 and IFNalpha) was determined by ELISA test. Results: ROC curve analysis showed good accuracy to distinguish between patients and healthy individuals for activated T cells (AUC=0.798; p<0.001), Treg (AUC= 0.651; p=0.036), and memory B cells (AUC=0.285; p=0.002). We found statistically significant difference (p=0.036) in the levels of serum IL-17 between patients with SLE (IL-17=49.27 pg/mL) and controls (IL-17= 28.64 pg/mL). Conclusions: Significant increase in the relative number of Treg lymphocytes, and decrease in memory B cells, as well as decrease level of IL-17, in SLE patients may be implicated in the pathogenesis of the disease. These parameters, as biomarkers, could distinguish SLE patients and no-SLE patients. Monitoring subpopulations of immune cells in peripheral blood using flow cytometry provides insight into abnormal T and B cell function in SLE. Progress in understanding the immunity at SLE, results in concrete benefits for the SLE patients, which include new clinical management and therapeutic strategies.

Background: Alopecia areata (AA) is a disease characterized by focally, nonscarring hair loss on the scalp or any hair-bearing surface. The etiology is unknown, although the evidence suggests that AA is an immunologically mediated disease. In the pathogenesis of AA, Th1 immune response is predominant. A special cytokine profile is created by Th1 cells, which disturbs the natural balance of the cytokine networks and leads to inflammatory reaction and follicle damage. Objective: The aim of our study was to evaluate serum concentrations of IL-2 in patients with AA and healthy subjects. We also examined a possible association between serum levels of IL-2, disease severity, and duration of AA. Methods: Sixty patients with AA and 20 healthy controls were enrolled in the study. Serum concentrations of IL-2 were measured using enzyme-linked immunoassay techniques. Results: Comparison of mean values of IL-2 has showed that serum concentrations of this cytokine are significantly higher in serum samples of AA patients in relation to the control group (22.2 ± 1.19 vs. 21.1 ± 2.68 pg/mL, respectively; p = 0.0142). No correlations were found between clinical type, duration of the disease, and serum levels of IL-2. Conclusion: Our findings support the evidence that elevation of serum IL-2 is associated with AA. The exact role of serum IL-2 in AA should be additionally investigated in future studies.

Introduction: Bronchopneumonia is the most common clinical manifestation of pneumonia in pediatric population and leading infectious cause of mortality in children under 5 years. Evaluation of treatment involves diagnostic procedures, assessment of disease severity and treatment for disease with an emphasis on vulnerability of the population. Aim: To determine the most commonly used antibiotics at the Pediatric Clinic in Sarajevo and concomitant therapy in the treatment of bronchopneumonia. Patients and Methods: The study was retrospective and included a total of 104 patients, hospitalized in pulmonary department of the Pediatric Clinic in the period from July to December 2014. The treatment of bronchopneumonia at the Pediatric Clinic was empirical and it conformed to the guidelines and recommendations of British Thoracic Society. Results and Discussion: First and third generation of cephalosporins and penicillin antibiotics were the most widely used antimicrobials, with parenteral route of administration and average duration of treatment of 4.3 days. Concomitant therapy included antipyretics, corticosteroids, leukotriene antagonists, agonists of β2 adrenergic receptor. In addition to pharmacotherapy, hospitalized patients were subjected to a diet with controlled intake of sodium, which included probiotic-rich foods and adequate hydration. Recommendations for further antimicrobial treatment include oral administration of first-generation cephalosporins and penicillin antibiotics. Conclusion: Results of the drug treatment of bronchopneumonia at the Pediatric Clinic of the University Clinical Center of Sarajevo are comparable to the guidelines of the British Thoracic Society. It is necessary to establish a system for rational use of antimicrobial agents in order to reduce bacterial resistance.

Objective: Expenditures for drugs are increasingly burdening already insufficient funds for health protection. This is especially evident in less developed European countries such as Bosnia and Herzegovina. The question is whether such analyses can help save funds for financing treatment for diseases, with an emphasis on a more rational choice of drug for appropriate indication, whereby clinical complications of hypertension would be prevented and patients would have quality of their lives improved. Aim: Focus of research has been set on analysis of use of antihypertensive drugs in Bosnia and Herzegovina in the time-period January 2013–March 2015. Use of all drugs for treatment of hypertension in that time-period in the country has been shown in an unbiased manner. Methods: The study is designed as retrospective-prospective comparative research of use of antihypertensive drugs in BiH in a certain time-period. Data are collected from relevant drug utilisation database which has been established in Bosnia and Herzegovina since 2013. Results: We have calculated financial expenditure for prescribed antihypertensives in the time- period of 2013, 2014 and Q1 2015. Use of antihypertensives at the country level for this time-period is BAM 200,242,218. At the country level, physicians are most often opting for combination therapy: ACE inhibitors + diuretics (20.2%) and ACE inhibitors + Ca channel antagonists (18.0%). Conclusion: In this research, it has been shown that modern drugs are used for treatment of hypertension in Bosnia and Herzegovina. These drugs are used in the same order as they are prescribed in developed countries.

Introduction: Regulatory T cells (Treg) play a central role in the immunopathogenesis of psoriasis. Immunoregulatory T cells (Tregs) are involved in important homeostatic mechanism for maintaining tolerance and preventing autoimmunity, and autoimmune diseases. The aim of this study was to examine the role of Tregs cells in the pathogenesis of psoriasis, and determine the range value for Treg cells (CD4+ CD25+) in the peripheral blood of patients with psoriasis compared to the severity of disease. Material and methods: The study included 51 patients diagnosed with psoriasis and 25 healthy individuals. Phenotype profile of peripheral blood lymphocytes was determined by flow cytometry, and assessment of severity of disease was determined on the basis of PASI score (e.g. Psoriasis Area and Severity Index). Results: Proportion of CD4+CD25+T cells in the control group was significantly higher than in the patients with psoriasis [6,4% ±(5,4-7,6) vs. 4,1% (3,1 -5,8)–Mann–Whitney U test, p <0.001]. In the present study we did not find a statistically significant correlation between the levels of CD4+CD25+cells, in patients with psoriasis, compared to the severity of disease–PASI. (i.e. Pearson correlation, r = 0.197, p = 0.194). Conclusion: The stratification of patients, according to the severity of the clinical course was not possible on the basis of Treg cells’ level. ROC curve analysis of the optimal cutoff (PASI=10) and the CD4+CD25+, which distinguishes between patients and healthy individuals was 5% of CD4+CD25+ of the total number of CD4+ lymphocytes with specificity of 69% and sensitivity of 84%.

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