BACKGROUND Left atrial stiffness index (LASI), defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to peak atrial strain, reflects reduced left atrial (LA) compliance and represents an emerging marker that can be used for noninvasive measurement of fibrosis of LA in patients with mitral regurgitation (MR). OBJECTIVE To investigate the impact of chronic MR in children and adolescents on the remodeling and function of the LA, quantified through strain parameters and diastolic function. METHODS The study included fifty patients (n= 50) diagnosed with primary and secondary chronic MR lasting at least 5 years. The echocardiographic recordings were performed by a third party, two cardiologists actively engaged in echocardiography on a daily basis. RESULTS Older participants had higher values of the LASI (r= 0.467, p= 0.001). Participants with higher LASI values had a smaller LA reservoir (r= 0.784, p= 0.0001) and smaller LA conduit values (r=-0.374, p= 0.00). Participants with higher LASI values had a larger LA diameter (r= 0.444, p-value= 0.001) and higher average E/e' ratio (r= 0.718, p= 0.0001). There was a significant difference (p= 0.04) in the LASI among participants based on the MR jet area (< 20.85 cm2/⩾ 20.85 cm2), LASI was higher in participants with an area greater than 20.85 cm2. Differences in other parameters such as LA reservoir, LA conduit, LA contractile were not statistically significant. CONCLUSION Increased LA stiffness is associated with diminished atrial compliance and reservoir capacity, and LASI has a potential to as an early marker for assessing disease severity and progression in pediatric MR.

PURPOSE When carrying out prosthetic rehabilitation of edentulous and partially edentulous patients, great attention is paid to the personal attitude of the patients, their satisfaction with oral health and psychosocial interaction due to tooth loss, as well as the treatment of the resulting disorders. This attention has led to the development of various instruments for examining the quality of life related to oral health. The aim of this study was to develop and validate a reliable instrument in the Serbian language suitable for measuring oral health-related quality of life in patients who have been rehabilitated with complete or partial dentures. Мaterials and Methods: The study was unicentric and cross-sectional, and assessed the reliability and validity of a newly developed instrument for measuring the oral health-related quality of life in denture wearers (OHRQoL-DW). It was conducted on a sample of 200 adults from Serbia, wearers of various types of dentures, with a mean age 66.9 ± 10.3 years and male/female ratio of 86/114 (43%/57%). RESULTS The definitive version of the OHRQoL-DW scale with 28 items showed very good reliability, with Cronbach's alpha = 0.938. Good temporal stability of the questionnaire was demonstrated, and satisfactory results were obtained for divergent and convergent validity tests. Exploratory factorial analysis revealed four domains of oral health-related quality of life in denture wearers: physical, psychosocial, environmental and aesthetic. CONCLUSIONS The OHRQoL-DW scale is a reliable and valid generic instrument for measuring the oral health-related quality of life in patients wearing dentures, which is one of the most important outcomes of oral health in prosthetic treatment.

Background: Lyme borreliosis is a multisystemic infection caused by the spirochete Borrelia burgdorferi. Erythema migras is the main clinical marker of the disease. Objective: This study aimed was to investigate the frequency and clinical manifestations of European borreliosis on the skin, and to determine the significance of these findings for diagnosis and therapy. Methods: A retrospective-prospective clinical study of outpatients treated and monitored in a private clinic of an infectologist was conducted over nine years from to 2013-2021. The study was clinical, descriptive and analytical in nature. Results: In the investigated period, 509 (30.8%) patients with borreliosis symptoms were treated. EM in our patients occurred under the following conditions: a) ringed redness, b) redness of target cels and d) continuous round or oval redness of different sizes of individual redness, or multiple occurrences with primary dissemination. Skin changes with multiorgan chronic symptoms of borreliosis occurred in 67.7% of cases the including: walking redness of different shapes and sizes, pink borreliosis stretch marks, white borreliosis stretch marks, borreliosis palms and soles, psoriatic changes, Acrodermatitis chronica atrophicans, Scleroderma circumscripta-morphae, Erythema nodosum, Granuloma anulare and Lichen striatus et atrophicans. Of the 509 patients treated for borreliosis, 32.3% with multi-organ symptomatology had no skin changes. Conclusion: The skin manifestations of European borreliosis are multi-layered and Erythema migrans are basic, but not the only markers of the disease. ‘Pink borreliose stretch marks, “white borreliosis striae”, “borreliosis palms or soles”, and intermittent redness accompanied by itching are unique markers for the diagnosis of chronic borreliosis, if they are manifested.

ABSTRACT Introduction Refractory status epilepticus (RSE) is a diagnosis that can be made when tonic-clonic status epilepticus (SE) and focal SE cannot be stopped by at least two anti-seizure medications after 30 and 60 minutes, respectively, from the time of commencement. It could result in mortality, loss of functionality, neurological deficiency, and other serious short- and long-term effects. Areas covered This narrative review covers original clinical studies of any design and case series investigating long-term outcomes of RSE recorded after at least a year from the SE onset. Expert opinion The future of a patient with RSE rests mostly on the long-term effects of this severe pathological condition, which may be accompanied with systemic complications like hyperthermia, hyperkalemia, acidosis, and/or stress cardiomyopathy. Younger patients with less severe RSE of shorter duration, particularly of the convulsive kind, are reported to have better long-term outcomes. Previous studies on the factors influencing the long-term outcomes of RSE, however, did not link the outcomes to treatment options for the condition. Such circumstances currently prevent making any definitive recommendations on the treatment of RSE until future research with adequate statistical power is completed.

Abstract Alpha-mannosidosis is an inherited rare disorder of mannose-containing oligosaccharides metabolism that is currently treated by enzyme replacement therapy (ERT), bone marrow transplantation (BMT), or supportive therapy (ST). However, the relative cost-effectiveness of these treatment options is yet unknown. Our study aimed to compare the cost-effectiveness of the treatment options for mild to moderate alpha-mannosidosis. The study is based on a modeling approach using a Discrete-Event Simulation model to generate and simulate the course of the disease under the influence of each of the treatment options: ERT, BMT, and ST. The model had a lifetime horizon and was made from the perspective of the Serbian Health Insurance Fund. Currently, available causal therapy of mild to moderate alpha-mannosidosis with velmanase alpha enzyme replacement is not cost-effective compared with supportive therapy (ICER = 941,587,152 RSD) or bone marrow transplantation (ICER = −398,412,755 RSD). Bone marrow transplantation can be cost-effective compared to supportive therapy (ICER = 6,032,689 RSD), but only if the willingness-to-pay threshold is increased to 9 gross domestic products (GDP) per capita per QALY gained. According to the current threshold, velmanase-alfa is not cost-effective compared to BMT or ST. To make alfa-mannosidosis therapy widely accessible to patients, criteria for assessing the cost-effectiveness of orphan drugs must include not only the absolute value of ICER but other aspects like equity weightings of QALYs, risk-sharing, reimbursement of severe forms of a disease only, or availability of dedicated funding.

Background: Diabetes mellitus type 1 (T1D) is an autoimmune organ-specific disease with a wide range of clinical manifestations, in which the β cells of the pancreatic islets of Langerhans are destroyed by the action of autoreactive T lymphocytes and the formation of autoantibodies against β cell components. Among used serological markers of T1D, anti-glutamic acid decarboxylase antibodies (GAD65), anti-tyrosine phosphatase antibodies (IA2), islet cell antibodies (ICA), insulin autoantibodies (IAA) and anti-zinc transporter antibodies (Zn-T8) are of great significance. Objective: This study aimed to analyze presence of type 1 diabetes-related autoantibodies (GAD65, IA2, ICA, IAA and Zn-T8 and effects of age and gender on their occurrence in pediatric population. Methods: Sixty seven (N=67) T1D pediatric patients were included in the study. The levels of immunological parameters such as anti-glutamic acid decarboxylase antibodies (GAD-Ab), anti-tyrosine phosphatase antibodies (IA2-Ab), islet cell antibodies (ICA) and insulin autoantibodies (IAA) were determined by chemiluminescence immunoassay (CLIA) and anti-zinc transporter antibodies (Zn-T8-Ab) were determined by enzyme-linked immunosorbent assay (ELISA). For statistical analysis, we used SPSS statistical program. Results: Our study revealed that among 67 patients with T1D (40 male and 27 female), with an average age of 12,1±3,9 years. The average age of diabetes diagnosis was 6,15±3,29 years. 24 (35,8%) cases were positive for GAD65, 15 (22,4%) for ICA, 34 (50,7%) for IAA, 16 (23,9%) for IA2 and 36 (53,7%) for Zn-T8. The largest number of patients had single positive antibody, the most dominated among them was IAA dominated (40,9%), then Zn-T8 (31,8%). According to Spearman correlation test Zn-transporter shows a significant positive correlation with age of the participants (p=0.027) and disease duration (p=0.006). Anti IA2 shows significant negative correlation with HbA1c (p=0.043). Zn-transporter is associated with patients age and duration of T1D. Conclusion: In most cases, patients with T1D are positive for at least one of the specific autoantibodies. Zn-T8 is the most frequently detected and is an important serological marker of type 1 diabetes mellitus. Gender effects on autoantibodies seems to be insignificant, while age alongside disease duration shows important effects.

BACKGROUND Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in Bosnia and Herzegovina. Elevated LDL-cholesterol is established as a strong marker of cardiovascular risk. Some researchers believe that measuring triglyceride levels gives a good assessment of the residual risk for ASCVD besides the measurement of LDL-cholesterol. OBJECTIVE The aim of this study was to evaluate the overall prevalence of major risk factors for ASCVD, lipid profile and 10-year fatal cardiovascular risk using the HeartSCORE scoring system. Further we want to evaluate the prevalence and relationship between elevated triglyceride levels and high 10-year fatal cardiovascular risk calculated as a HeartSCORE. METHODS This is a cross-sectional study conducted on 832 volunteers aged between 40 and 65 years without a diagnosis of diabetes and without known preexisting cardiovascular disease, as a part of the preventive program conducted at the Familly Medicine office. Data were collected for ASCVD risk factors and lipid panel (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides). 10-year fatal cardiovascular risk was calculated using the HeartSCORE scoring system for countries with high CV risk. RESULTS Among 832 participants included, 565 (67.9%) were female, and 267 (32.1%) were male. We found high prevalence of hypertension (27.7%), obesity (32.2%), and smoking (36.2%). All lipid parameters, except HDL-C, were not optimal. Only 17.4% of participants had normal estimated HeartSCORE risk, while more than one-third (33.9%) had high or very high estimated HeartSCORE risk. Although we found a higher percentage of participants with elevated triglycerides in groups with higher HeartScore, there was a very weak positive correlation between values of triglycerides and the 10-year risk of a fatal cardiovascular event (r= 0.249, p= 0.000). CONCLUSION High prevalence of major known risk factors and high estimated HeartSCORE risk indicate a high overall risk for ASCVD in the sample. The proportion of participants with elevated triglycerides was increased in patients with high HeartSCORE risk what implicates importance of trygliceride measurement.

Background: Psoriasis as an immune-mediated inflammatory skin disease. The basis of the pathogenesis of psoriasis is the dysregulation of immune cell function in genetically predisposed individuals. The characteristic dysfunction of the immune system in patients with psoriasis is manifested as a variation in the cellular phenotypic profile in accordance with the disease status. Objective: The aim of this study was to evaluate the immunophenotypic profile of lymphocytes obtained by flow cytometry as an auxiliary diagnostic tool in the objectivization of the PASI score. Methods: The study group included 40 patients with psoriasis, hospitalized and treated at Dermatology Clinic of Clinical center University of Sarajevo and 30 healthy individuals as controls. After venepunction, the blood samples for determining the immune profile were prepared following standard laboratory procedures using conjugated monoclonal antibodies and BD FACSCanto II flow cytometer. T-lymphocytes (CD3, CD4, CD8), B lymphocytes (CD19), Natural killer cells (NK), and activatet T-cells (CD3HLA) were determined for all patients. Based on the PASI score, the severity and area of the disease was assessed for all psoriasis patients by dermatology specialist. Results: Our data shows no significant difference in any of the lymphocyte subpopulations between psoriasis patients and healthy controls, except CD3HLA. CD3HLA has higher values in patients with psoriasis, p=0.015. Of all the parameters, only NK cells were significantly correlated to the PASI score (rho -0.279; p=0.048). ROC curve analysis revealed a statistically significant difference for the proportion of CD3 lymphocytes (AUC 0.799; p=0.004), CD8 lymphocytes (AUC 0.733; p= 0.023), NK cells (AUC 0.722; p=0.008) and CD3HLA activated T lymphocytes (AUC 0.347; p=0.034). Conclusion: Profile of major lymphocyte subsets in patients with psoriasis is similar to that of healthy controls. The values of CD3, CD8, NK, CD3HLA were defined as biomarkers capable of distinguishing psoriasis according to the severity of the disease. Immunophenotyping of peripheral blood lymphocytes can play an important role as an auxiliary diagnostic method in differentiating the clinical stages of psoriasis and objectifying the PASI score.

Background: Lyme disease (Lyme disease-LD) is a disease of humans and animals that is transmitted by hematophagous insects, especially ticks. The causative agent is the spirochete Borrelia burgdorferi, a bacterium with a complex structure and a slow biorhythm, which has the ability to coat the host's organism with mucus - create a biofilm - or turn into a cyst, and the host does not recognize it and does not create antibodies. This is the reason why, in 10-60% of cases, Borrelia tests are negative, even though it is present. The diagnosis of LD is made clinically, and it is confirmed serologically and microbiologically by isolation and/or detection of the causative agent by the PCR method from tissue samples and body fluids. Lyme disease stage II and III is called „the great imitator“ because its symptoms resemble those of other diseases, so diagnostic errors are often made. Objective: In this article we presented a case of stubborn urticaria in a 28-year-old saleswoman. Case presentation: Mother of two children, who was ruled out by clinical examination for autoimmune diseases and allergies to available allergens. We subsequently confirmed the diagnosis of chronic borreliosis, caused by five types of borrelia, serologically, after advanced intermittent antibiotic therapy, and after acquired food intolerance was discovered. In the available literature, we did not find information that chronic generalized urticaria was caused by Borrelia in combination with food intolerance. Conclusion: The presented case of a patient with chronic urticaria indicates that similar cases with urticaria, as well as all skin changes with intermittent walking symptomatology, should: Undergo clinical treatment, rule out immunological diseases and drug allergies, then test for Borrelia (ELISA+ immunoblot with Borrelia protein sequences!). Take into account the duration of the disease, the possibility of the disappearance of antibodies created in early childhood or a false-negative finding of antibodies, and in case of a negative finding, do not give up ex-yuvantibus therapy.