Genetic diversity of CYP3A5 and ABCB1 variants in East-Central and South European populations.

BACKGROUND: CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. AIM: The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. SUBJECTS AND METHODS: Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. RESULTS: In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively. CONCLUSION: In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely.

Serum biomarkers in normal pressure hydrocephalus.

Aim To investigate the serum value of brain derived neurotrophic factor (BDNF), proteins S-100, NSE, IL-6 in normal pressure patients (NPH) compared to control (healthy) group and also a possible correlation with radiological findings in NPH patients. Methods Study patients were included during the period of 2020- 2022. All NPH patients met the diagnostic criteria for probability of NPH. Control patients group included patients without known brain disorder, without clinical symptoms of NPH. Blood samples were taken before planned surgery for NPH. BDNF serum concentrations were assessed by a sensitive ELISA kit, and serum concentrations of S-100, NSE and IL-6 were assessed by using ECLIA technology for immunoassay detection. Results Among 15 patients who were included, seven NPH patients were compared to eight control patients. Non-significant decrease in BDNF serum concentrations, an increase of protein S-100 serum concentrations, a decrease of NSE serum concentrations, as well as an increase of IL-6 serum concentrations in NPH patients compared to healthy controls was found. Strong positive correlation between BNDF and Evans index was observed (p=0.0295). Conclusion We did not find a significant difference of BDNF, protein S-100, IL-6 and NSE between serum concentration in NPH and healthy patients. More future research is needed to find the role of BDNF in NPH patients.

Quality of Life in Multiple Sclerosis Patients: Influence of Gender, Age and Marital Status.

Background: Multiple sclerosis (MS) is a chronic disease characterised by a wide range of symptoms and a highly unpredictable prognosis, which can severely affect patient quality of life. Objective: The aim of the study was to evaluate the influence of gender, age and marital status on health-related quality of life (HRQoL) in MS patients. Methods: This study included 100 MS patients treated at the Department of Neurology, Clinical Center University of Sarajevo. Inclusion criteria were an Expanded Disability Status Scale score between 1.0 and 6.5, age between 18 and 65 years, stable disease on enrollment. HRQOL was evaluated by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Mann-Whitney and Kruskal-Wallis test were used for comparisons. Linear regression analyses were performed to evaluate prediction value of gender, age and marital status on both physical and mental HRQOL. Results: Women had significantly lower QOL scores then men in pain scale (55.00 vs. 76.67; p<0, 05). Younger patients had better physical (54.58 vs. 37.90; p<0.05) and mental health (59.55 vs. 45.90; p<0.05) composite scores. Patients with earlier age of onset scored significantly higher in health perception domain scale (45.00 vs. 32.50, p<0.05). Married patinets scored higher in physical and mental composite scores but with no significant difference except in sexual function (87,51 vs 70, 86, p<0,05) and emotional well being (66,67 vs 33,33; p<0,05) scales. Patient age retined its independent predictivity of physical health composite score (r2=0.063). Conclusion: Aging in MS proved to be important negative factor in predicting physical domains of QOL. Interventions for reducing difficulties caused by physical limitations in older patients, higher level of psychological support for patients with late onset disease and social support for those living alone are important factors in improving HRQOL in MS patients.

A Questionnaire for Rating Health-related Quality of Life.

BACKGROUND: Translations of instruments for measuring quality of life developed in certain, mostly more developed, parts of the world usually do not cover regionally specific aspects of health-related quality of life, even after transcultural validation. The aim of this study was to develop and validate a reliable questionnaire in Serbian, Croatian, Bosnian, and Montenegrin languages suitable for measuring health-related quality of life in adults. METHODS: The study was of a cross-sectional type, assessing the reliability and validity of a newly developed questionnaire for measuring health-related quality of life (HRQoL) in adults residing in western Balkan states (WB-HRQoL). It was conducted on a sample of 489 adults from Serbia, Croatia, Bosnia & Herzegovina, and Montenegro, with a mean age of 52.2±14.4 years and a male/female ratio of 195/294 (39.9%/60.1%). RESULT: The definitive version of the WB-HRQoL scale with 19 items showed very good reliability, with Cronbach's alpha 0.905. The scale was temporally stable, and satisfactory results were obtained for divergent and convergent validity tests. Exploratory factorial analysis brought to the surface four domains of health-related quality of life, namely the physical, psychical, social, and environmental. CONCLUSION: The WB-HRQoL scale is a reliable and valid generic instrument for measuring HRQoL that takes into account the cultural specifics of the western Balkan region.

Incidence and outcome of traumatic brain injury in paediatric population of Bosnia and Herzegovina: a single centre experience.

Aim To evaluate the incidence, modalities of treatment and outcome in paediatric patients with traumatic brain injury (TBI). Methods A retrospective cross-sectional study including 353 paediatric patients with head injury was carried out in the Department of Neurosurgery of University Clinical Centre Sarajevo during the period 1 July 2006 - 30 June 2012 (72 months). For each patient the lowest Glasgow Coma Scale (GCS) was established and the patient was accordingly classified as suffering from mild, moderate or severe TBI. Neuroimaging data included computer tomography (CT). Survival rates and method of treatment were compared according to age group, and matched with the total number of patients examined. Results A total of 353 children with head trauma were identified. A severe TBI (GCS < 8) was found in 33 (out of 353) children, mostly in the age group 11-18. Falls were the most common cause of trauma, followed by traffic accidents. Falls were the most common mechanism in the infants, preschool, and school children up to 10 years old; children aged 11-18 showed a higher rate of traffic accidents comparing to children younger than 3 years. Of 353 patients, 49 (13,9%) required surgical procedure, 304 (86.1%) were threated conservatively. Survival rate was 96.6 %. Conclusion The majority of hospitalized patients qualify for medical treatment and surgical intervention is reserved for selected cases. Thus, the adequate pre-hospital care is essential.

Longterm Antiepileptic Therapy and Bone Health: Implications for Patients with Brain Tumors.

OBJECTIVE: The objective of our study was to investigate the effects of carbamazepine (CBZ) and lamotrigine (LTG) treatment on bone metabolism in epileptic patients. PATIENTS AND METHODS: A cross-sectional study was performed on normal controls (N=30) and 100 patients with symptomatic epilepsy caused by a primary brain tumor, divided into two groups according to the treatment: LTG monotherapy group (N=50) and CBZ monotherapy group (N=50). For each participant serum levels of 25-OHD and osteocalcin (OCLN) were measured, and bone mineral density (BMD) was evaluated by the dual-energy X-ray absorptiometry method. RESULTS: There was no statistically significant difference in the average values of vitamin D in serum between the CBZ and LTG groups (Vitamin D CBZ 17.03±12.86 vs. Vitamin D LTG 17.97±9.15; F=0.171, P=0.680). There was no statistically significant difference in the average values of OCLN between the CBZ and LTG groups (OCLN CBZ 26.06±10.87 vs. OCLN LTG 27.87±28.45; F=0.171, P=0.674). The BMD value was lower in both groups using antiepileptic agents compared to the controls, but when comparing the CBZ group to the LTG group, a statistically significant difference was only observed for the Z score (T-score CBZ: 0.08± 1.38 vs. T-score LTG: 0.37± 1.02; F=1.495, P=0.224; Z score CBZ: -0.05±1.17 vs. Z. score CBZ: 0.38±0.96; F=4.069, P=0.046) (Table 3). CONCLUSION: The choice of antiepileptic agents for treating seizures in patients with brain tumors should be carefully evaluated in relation to their impact on bone health. These patients could benefit from supplementation and regular measurement of biochemical markers of bone turnover and BMD.

Sepsis Caused by Bacterial Colonization of Migrated Distal Ventriculoperitoneal Shunt Catheter into the Pulmonary Artery: A First Case Report and Literature Review.

BACKGROUND: Migration of distal ventriculoperitoneal (VP) shunt catheter into another body part has been described as a potentially serious surgical complication. We present the first case of sepsis caused by transcardial and pulmonary migration of a distal catheter into the heart and pulmonary artery, which was subsequently colonized by Klebsiella pneumoniae. CASE REPORT: A 56-year-old man underwent VP shunt insertion for hydrocephalus that developed after the surgery for intracranial meningioma. Three years later, he was admitted to department for infectious diseases because of persistent fever. Klebsiella pneumoniae was isolated from the blood cultures. Computed tomography (CT) of the thorax showed migration of the distal catheter into the heart and pulmonary artery. The migrated shunt catheter was retrieved without any complication with the assistance of a cardiovascular surgeon; microbiologic analysis confirmed that the catheter was colonized with K. pneumoniae. We decided to delay new VP shunt placement because of the positive blood cultures, and 3 weeks after the surgery, the patient was without signs of increased intracranial pressure and without any heart problems. CONCLUSION: Migration of a distal VP shunt catheter into the heart should be considered in patients with a previously placed VP shunt presenting with cardiopulmonary problems, arrhythmia, and/or fever. Neurosurgeons should be involved as soon as possible, and a multidisciplinary approach is warranted.

Effect of Long-term Carbamazepine Therapy on Bone Health.

INTRODUCTION: Recent research reported that prolonged use of AET is associated with changes in bone metabolism, with consequent reduction in bone mineral density (BMD) and increased risk of fractures. OBJECTIVES: Therefore, the aim of our study was to investigate the effects of carbamazepine on serum levels of 25 -hydroxyvitamin D and on biomarker of bone formation and resorption (serum levels of osteocalcin). MATERIAL AND METHODS: We measured serum levels of 25-OHD and osteocalcin (OCLN) in normal controls (n=30) and in epilepsy patients taking carbamazepine (CBZ) (n=50) in monotherapy for a period of at least twelve months. For each participant, mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry method. RESULTS: The average value of vitamin D in serum was significantly lower in CBZ group than in control group (Vit D 17.03+12.86 vs. 32.03+6.99, p=0.0001). The average value of osteocalcin in serum was significantly higher in CBZ group than in control group (26.06+10.78 vs. 19.64+6, 54, p=0.004).BMD value in CBZ group was significantly lower than in control group (T. score CBZ: 0.08+1.38 vs. T. score control: 0.73+ 1.13, p=0.031; Z score CBZ:-0.05+1.17 vs. Z. score control: 0.55+0.79, p=0.015). CONCLUSION: AEDs are associated with bone disease, as evidenced by biochemical abnormalities and decreased BMD. Patients on long-term antiepileptic therapy, especially with enzyme-inducing agents, could benefit of routine measurement of biochemical markers of bone turnover, and BMD measurement as part of osteoporosis investigation.

Relapsing Tumefactive Demyelination: A Case Report.

OBJECTIVE: We present a case of relapsing tumefactive demyelination in a young female patient, that posed a real diagnostic challenge, with a heterogeneous clinical picture, atypical for multiple sclerosis (MS) presentation, and neuroradiological manifestations with a high suspicion of neoplastic diseases. CASE REPORT: An 18-year old female patient presented to our Neurosurgical Out-patients' Clinic with symptoms atypical for multiple sclerosis, unremarkable neurological deficit, one tumefactive lesion on MRI, followed by relapse and another two lesions within a period of six months. We decided to perform biopsy of the tumefactive lesion with compressive effect. Serological and clinical data were negative for MS, and the patient did not respond well to corticosteroid therapy. Fresh frozen tumor tissue aroused a strong suspicion of gemistocytic astrocytoma, so total resection was done, but the definitive pathohistological examination confirmed tumefactive demyelination. CONCLUSION: For clinicians, it is important to consider demyelinating disease in the differential diagnosis of a tumorlike lesion of the central nervous system, in order to avoid invasive and potentially harmful diagnostic procedures, especially in younger patients.

Association Between - 675 ID, 4G/5G PAI-1 Gene Polymorphism and Pregnancy Loss: A Systematic Review.

INTRODUCTION: Several analysis for different population conclude that endothelial plasminogen activator inhibitor 1 gene polymorphism, -675 ID, 4G/5G PAI-1 (ref SNP ID: rs1799889, also described as rs34857375, has merged into rs1799762) may increase risk of pregnancy loss (PL). However, there is a disagreement as to the association 4G allele with pregnancy loss. AIM: Therefore, we decided to investigate the -675 ID, 4G/5G PAI-1 as a potential genetic factor linked to PL in European and worldwide populations. A systematic review of the scientific literature was conducted with the use of the PubMed and Scopus electronic databases (1991-present), using the following search terms: pregnancy loss, miscarriage, genetic risk of thrombophilia, rs1799889 PAI-1 gen, 4G/5G PAI-1 gene polymorphism, PAI-1 gene locus 4G/5G polymorphism. RESULTS: Among European populations, the statistically significant association between 4G allele and recurrent PL only in Czechs and Bulgarian women was found (p<0.002 and p=0.018, respectively); while, among populations outside Europe in Iranian, Tunisian and Turkish women (each p<0.001). CONCLUSIONS: We concluded, that both in Europe and elsewhere in the world, the high frequency of 4G allele in population, is not unambiguously linked with the risk of pregnancy loss.

Prevalence of F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms in Bosnian women with pregnancy loss.

The relationship between genetic risk factors of thrombophilia and pregnancy loss (PL) is being discussed. The focus has been on F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms that may predispose women to microthrombosis during the stages of embryo implantation and placentation. Although, the frequencies of these polymorphisms were reported in different populations, such studies have not yet been performed in Bosnian population. In this study, we determined the prevalence of F5 G>A (rs6025), F2 G>A (rs1799963) and MTHFR C>T (rs1801133) polymorphisms in Bosnian women. A total of 154 women with PL, mean age 33 (±5.4) years, were enrolled in the study. As a control group, 154 mothers [mean age 31.4 (±6.7) years] with at least one live-born child were included. We used real-time polymerase chain reaction (PCR) to determine the frequencies of F5 G>A and F2 G>A genotypes, and PCR-restriction fragment length polymorphism (RFLP) for analyzing MTHFR C>T genotypes. The frequency of heterozygotes for F5 and F2 was significantly higher in women with venous thrombosis (VT) compared to women without VT (p = 0.047 and p = 0.001, respectively). There was no significant difference in the distribution of MTHFR genotypes and alleles between these two groups. In addition, we observed no significant differences in the genotype and allele frequencies between the group with PL and control group, for all investigated polymorphisms. The allele frequencies for 1691A (F5), 20210A (F2), and 677T (MTHFR) reported in this study are consistent with the data obtained for other European countries, however, we were not able to confirm the association between the three polymorphisms and PL in Bosnian women.