Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSILs), but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3 months of supplementation with 600 mg of ALA on antioxidant and lipid status parameters in 100 patients with LSILs were investigated in a randomized, placebo-controlled study. The obtained results are discussed in terms of patients’ initial metabolic status and diet quality (particularly nutritional intake of antioxidants). The obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted in a small but statistically significant increase in serum low density lipoprotein (LDL), and the observed effect was significantly affected by the initial lipid status of the participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

Low-grade squamous intraepithelial lesion (SIL) is a cytologic diagnosis etiologically related to human papilloma virus (HPV) infection that leads to the release of inflammation mediators, the formation of reactive oxygen species (ROS) and decreased levels of antioxidants in tissues, which is why antioxidants might be considered effective against SIL progression. This randomized double-blind placebo-controlled study aimed to investigate the effectiveness of alpha-lipoic acid (ALA) supplementation (600 mg/day) on the regression of low-grade SIL in 100 patients. Low-grade SIL was determined after the cytological screening, colposcopic examination and targeted biopsy and histological confirmation of cytological–colposcopic diagnosis. Inflammation parameters and the presence of HPV were determined by standard laboratory methods. Dietary and lifestyle habits were investigated using a standardized and validated semi-quantitative food questionnaire (FFQ). ALA supplementation significantly reduced the proportion of patients with low-grade cytological abnormalities, in comparison to placebo. Given the obtained level of significance (p < 0.001), the presented results indicate that short-term ALA supplementation shows a clinically significant effect on cervical cytology. Future studies should focus on the use of innovative formulations of ALA that might induce bioavailability and therapeutic efficiency against HPV infection and the investigation of synergistic effects of concurrent dietary/lifestyle modification and ALA supplementation in both low-grade and high-grade SIL.

Objective - To assess 25(OH)D status in children with Multisystem Inflammatory Syndrome (MIS-C) associated with SARSCoV-2 infection, and the association between serum levels of 25(OH)D and inflammatory marker values.Patients and methods - This retrospective study was conducted at the Clinic for Children’s Diseases, University Clinical Center, Tuzla in the period from November 2020 to November 2021.Results - The study included 23 children with MIS-C with a median age of 6.9 years, and 22 children with acute SARS-CoV-2 infection, with a median age of 1.1 years. Both groups of children had low serum levels of 25(OH)D in the range of deficiency; median levels of 25(OH)D in MIS-C children were lower (median 44.60 nmol/L) than in children with acute SARS-CoV-2 infection - median 52.45 nmol/L. There was no statistically significant difference in 25(OH) D levels between the two groups of children included in the study (P=0.33). The same number of children in both groups had adequate serum levels of 25(OH)D. The children in both groups had elevated markers of inflammation, but we did not find a significant correlation between the values of 25(OH)D and the inflammatory marker values.Conclusion - Deficiency of 25(OH) D could be one of the precipitating factors that lead to the development of both MIS-C - related SARS-CoV-2 and more severe forms of acute infection. 25(OH)D enriched food, as well as supplementation with 25(OH)D, should be considered a long-term strategy in all high-risk children and adolescents.

As we know, the Philadelphia chromosome (Ph) is a highly specific marker for chronic myeloid leukemia (CML). This hematological disease is characterised by the formation of the BCR/ABL1 fusion gene, usually with typical translocation pattern including 9q34 and 22q11. In this paper we describe a 55 years old female patient with typical clinical and haematological signs of CML and a chromosome 9 differing from that which normally participates in translocation t(9;22). The karyotype of this Ph positive patient is characterised by pericentric inv(9)(p13q34) of the der(9)t(9;22)(q34;q11). Reverse transcriptase-polymerase chain reaction revealed a e14a2 type of BCR/ABL1 fusion transcript. As a consequence of this unusual translocation, FISH also found the separation of the ABL1/BCR1 fusion gene on chromosome 9. On reviewing the literature, to date only 10 Ph-positive leukemia patients have been noticed to have pericentric inversion inv(9)(p22q34)der(9)t(9;22)(q34;q11). No one case has been described with pericentric inversion inv(9)(p13q34) of the der(9)t(9;22)(q34;q11). This indicate that pericentric inv(9)(p13q34) of the der(9)t(9;22)(q34;q11) is a novel, rare, chromosomal abnormality in Phpositive CML.

Objective – To evaluate the suitability of diagnosing chronic recurrent multifocal osteomyelitis (CRMO) according to the Bristol diagnostic criteria and the clinical outcome of the children included in the study. Materials and Methods – Retrospectiveprospective study was conducted at the Clinic for Children’s Diseases, University Clinical Center Tuzla in the period from January 2018 to January 2020. The medical records of children treated CRMO were analyzed. Results – Eight children fulfilled the Bristol diagnostic criteria. The median age at disease onset was 10.7 years. All children had multifocal lesions which relapsed in 2 children, and predominantly affected regions were the pelvis, hips, femur, spine and shoulder girdle. Hematological and biochemical parameters were unremarkable, although ESR was elevated in 6/8 children; all children had CRP<30 mg/L. For 3 children lesions on plain radiography were observed; 49 lesions were verified on MRI (4 children had whole body MRI). Bone biopsy was performed in 2 children and it showed inflammatory changes. In 6/8 children treatment with NSAIDs was sufficient to control the disease during the 8-month period. However, two children had pain resistant to NSAID therapy, so they were treated with methotrexate and sulfasalazine. The child who received sulfasalazine treatment relapsed, so TNFα inhibitor (adalimumab) was used to control disease activity. No child received pamidronate. Conclusions – Our results showed that the use of the Bristol diagnostic criteria may obviate the need for a biopsy, shorten the time of diagnosis, save the bone from destruction, and avoid unnecessary treatments.

Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are detrimental, there is a lack of information on the toxicity of mixtures. In this study, two common heavy metals, lead and cadmium, were introduced individually and as mixtures to HL-60 and JURKAT cell lines for 24 hours. The study established that exposures to these two heavy metals induced cytotoxic and genotoxic effects on both cell lines. Also, cadmium exhibited a higher cytotoxic and genotoxic potential than lead. The cytotoxicity data of single metals were used to determine the mixtures interaction profile by using the effect additivity method. Metal mixtures showed synergistic effect in HL-60 cells and antagonistic effect in JURKAT cells, compared to individual metals. The combined effects should be considered in the risk assessment of heavy metal co-exposure and potency.

Children with atopic dermatitis (AD) usually develop symptoms when they reach the age of 6-7 years, but the risk of developing respiratory allergies, asthma and allergic rhinitis (AR) remains high. In most children with AD, the development of asthma and AR is associated with sensitization to food allergens and/or aeroallergens, while only a small percentage missed atopic diathesis. In about 35% of children with AD, food allergy is the provoking cause, and 60% of infants who had AD in the first 3 months of life were sensitized against aeroallergens by the age of 5. The aim of the study was to follow development of asthma and AR and to assess the most significant risk factors for developing respiratory allergy. A total of 114 children with AD were followed up for five years. At annual visits, the severity of disease, total immunoglobulin E (IgE) antibody values, skin prick tests, specific IgE antibodies to food allergens and aeroallergens, and absolute eosinophil count were assessed. Information on the family history of atopy and AD, feeding patterns during infancy, data on sensitivity to food allergens and/or aeroallergens, and on the occurrence of bronchial obstruction and nose symptoms were obtained. Asthma developed in 36 children, median age 7.7 years; 33 children had symptoms of AR, and 13 children with AD had both diseases associated; 38 children had sensitivity to food, of which 24 developed asthma and 13 AR; asthma developed in 18/23 children with sensitivity to aeroallergens, and almost an equal number of children developed AR. The increased absolute eosinophil count and specific IgE to aeroallergens and food allergens were the best asthma predictors, while AR predictors were family history and early onset of AD. In conclusion, children with AD are at a significant risk of developing respiratory allergies, and those with the increased absolute eosinophil count, positive specific IgE to aeroallergens and food allergens, heredity of AD, and early onset of AD are at the highest risk. Identification of risk factors will enable us to improve the treatments of AD in order to reduce the severity of disease and prevent manifestation of respiratory allergy.

Introduction: The treatment response and outcome in acute myeloid leukaemia (AML) is heterogeneous. Aim: To analyze the prognostic parameters of AML at presentation. Methods: The total sample of 44 AML patients was analyzed on the basis of age <55 and ≥55 years, sex, WBC count <50x10/9/l and ≥50x10/9/l, the Hb concentration <100 g/l and ≥100 g/l, PLT count <100x10/9/l and ≥100x10/9/l, Karnofsky score <60% and >60%, cytogenetics, CD56 expression, morphological type and types of treatment (standard and reduced induction chemotherapy, high–dose chemotherapy/stem cell transplantation – autologous and HLA matched, related, allogeneic, together and separately). Results: The age <55 years, Karnofsky score >60% and standard induction chemotherapy statistically correlated with the higher complete remission (CR) rates, longer relapse free survival (RFS), lower relapse rate (RR), and longer overall survival (OS) (p<0.01). The difference in terms of CR and RR between the sexes were not statistically significant (p<0.05), however women had statistically lower OS comparing to men (9.71±4.54 months vs. 38.03±9.17 months) (p<0.01). WBC count ≥ 50x10/9/l and the Hb concentration <100 g/l statistically correlated with shorter OS (p<0.05), while the WBC count ≥50x10/9/l statistically correlated with shorter RFS (p<0.05). The PLT count <100x10/9/l and ≥100x10/9/l was not found as prognostically significant for CR, RR, RFS, and OS (p<0.05). In comparison to the standard induction chemotherapy, both types of high dose chemotherapy/stem cell transplantation (HDT/SCT) (10/22), together and separately, resulted in longer RFS, lower RR, and longer OS (p<0.05). The frequency of cytogenetic risk was intermediate 81.6%, unfavorable 13.2%, and favorable 5.3%, respectively. CD56 + expression statistically correlated with the lower PLT count, higher RR, shorter RFS, and shorter OS (p<0.05). Statistical analysis of the cytogenetic risk and morphological types of AML were not possible due to the small number of patients in stratified groups. Conclusions: Female sex, the WBC count >50x10/9/l, the concentration of Hb <100 g/l, and CD56 + expression, at presentation of AML, should be considered as parameters of adverse risk, especially in latter decisions considering post-remission treatment with HDT/SCT.

Introduction: More than three decades after recognition of acquired immunodeficiency syndrome (AIDS) in the United States, the pandemic of human immunodeficiency virus (HIV) infection has dramatically changed the global burden of disease. Aim: The main goal of this research is retrospective analysis of epidemiological and clinical characteristics of 28 HIV infected patients, who were diagnosed and treated at the Clinic for Infectious Diseases in University Clinical Center Tuzla in the period from 1996 until the end of 2013. Subjects and Methods: Retrospective analysis was performed using the medical records of 28 HIV-infected persons. Two rapid tests were used for HIV testing: OraQuick Advance test, Vikia HIV1/2, Elisa combo test, HIV RNA test. AIDS disease was determined by using the criteria from WHO. Results: Among a total of 28 HIV-infected persons, 23 (82.14%) were males and 5 (17.86%) were females, with the male: female ratio of 4,6:1. In terms of the transmission route, a large proportion of cases were infected through heterosexual contact 19 (67.86%). At the time of the first visit, 16 (57.15%) patients showed asymptomatic HIV infection, 4 (14.28%) HIV infection with symptoms other than the AIDS defining diseases, and 8 (28.57) had AIDS. At the time of first hospital visit, the CD4 + cells count ranged from 40 to 1795/µl (conducted in 19 patients), and mean value of CD4 + cells was 365,31/µl, and mean HIV RNA titer was 287 118 copies/ml³. Of 28 HIV-infected persons 39 cases of opportunistic diseases developed in 12 patients (42.9%). In terms of the frequency of opportunistic diseases, tuberculosis (12 cases, 42.9%). Among a total of 28 HIV-infected patients, 6 (21.4%) of them died. Conclusion: This study characterizes the epidemiological and clinical patterns of HIV–infected patients in Tuzla region of Bosnia and Herzegovina to accurately understand HIV infection/AIDS in our region, in the hope to contribute in the establishment of effective HIV guidelines in the Tuzla region of B&H in the future.

The aim of this study was to analyze (i) ratios between pro-inflammatory cytokines interleukin 6 (IL-6), interleukin 1 (IL-1), tumour necrosis factor alpha (TNF-alpha) and anti-inflammatory cytokine interleukin 10 (IL-10) in patients with acute myocardial infarction (AMI) and stable angina pectoris (ii) as well as correlation between IL-6 and IL-10 in AMI and (iii) correlation between IL-6 and lipoproteins in AMI.The total of 71 patients were enrolled in this study, 41 of them with AMI (study group) and 30 with stable angina pectoris (control group). The concentrations of cytokines and lipoproteins were measured from blood samples. Pro-inflammatory to anti-inflammatory cytokine ratios were calculated by dividing concentrations of pro-inflammatory cytokines with IL-10. In statistical analyses we used descriptive statistics, normality tests and analysis of correlation.IL-6: IL-10 ratio is significantly higher in AMI than in stable angina (P < 0,001), TNF-alpha: IL-10 is also higher in study group but the difference is not significant. We found positive linear correlation between IL-6 and IL-10 (r =0,43; p = 0,015) and negative linear correlation between IL-6 and high density lipoprotein HDL (r = -0,47; p= 0,008) in AMI.IL-6: IL-10 ratio is higher in AMI than in stable angina. There is linear correlation between IL-6 and IL-10 and IL-6 and HDL in AMI.