Browsing by Author "Skoric, Dejan (6602687814)"

Hodgkin Lymphoma is a complex malignancy with unique features, primarily affecting children and young adults. The disease’s sensitivity to radiation therapy and the young age of onset underscore the importance of optimizing treatment strategies to minimize both acute and long-term toxicities associated with radiotherapy. In light of these considerations, our study aimed to evaluate whether [18 F]FDG-PET/CT assessment at interim and end-of-treatment timings, in comparison to conventional CT scans, led to a decrease or increase in unnecessary patient exposure to radiotherapy. The study involved 61 pediatric patients diagnosed and treated for Hodgkin lymphoma at our institution between 2009 and 2022. Patients were categorized into two groups based on treatment protocols: Group 1 received conventional CT imaging protocols, while Group 2 received [18 F]FDG-PET/CT-based protocols. The results demonstrated that [18 F]FDG-PET/CT-based protocols led to a reduction in the frequency of radiotherapy compared to conventional CT imaging (32% vs. 52%). This statistically significant difference highlights the potential benefits of [18 F]FDG-PET/CT in guiding treatment decisions and reducing unnecessary radiation exposure. Our research re-emphasize the potential of [18 F]FDG-PET/CT as a valuable tool in the management of pediatric patients with Hodgkin lymphoma in terms of more precise diagnosis and reduction of unnecessary treatment and toxicities. © Indian Society of Hematology and Blood Transfusion 2024.

Objective: The incidence of the 22q11.2 microdeletion among children who have at least two out of five major clinical criteria for 22q11.2 deletion syndrome. Design: Prospective study. Setting: University Children’s Hospital in Belgrade, Serbia between 2005 and 2014. Participants: 57 patients with clinical characteristics of 22q11.2 deletion syndrome. Methods: Standard G-banding cytogenetic analysis was performed in all children, and the 22q11.2 genomic region was examined using fluorescence in situ hybridization (FISH). For patients with no deletion detected by FISH, multiplex ligationdependent probe amplification (MLPA) analysis was also done in order to detect cryptic deletions of this region and to analyze other genomic loci associated with phenotypes resembling the syndrome. A selected group of patients diagnosed to have 22q11.2 microdeletion by FISH underwent MLPA testing in order to characterize the size and position of deletion. Outcome Measure: The frequency of 22q11.2 microdeletion among children with at least two of the five major characteristics of 22q11.2 deletion syndrome (heart malformations, facial dysmorphism, T-cell immunodeficiency, palatal clefts and hypocalcemia/hypoparathyroidism) Results: Typical 22q11.2 microdeletion was detected in 42.1% of patients; heart malformation were identified in all of them, facial dysmorphism in 79.2%, immunological problems in 63.6%, hypocalcemia in 62.5% and cleft palate in 8.3%. Conclusions: A higher detection rate compared to one-feature criterion is obtained when at least two major features of 22q11.2 deletion syndrome are taking into consideration. The criteria applied in this study could be considered by centers in lowincome countries. © 2016, Indian Academy of Pediatrics.

BACKGROUND: Therapy-induced leukemia is a well-known clinical syndrome occurring as a late complication in patients treated with cytotoxic therapy. OBSERVATION: We herein present results of analysis of common gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) genes in a 10-year-old boy who developed very rare type of cancer, mixed phenotype acute leukemia, 6 years after treatment of acute lymphoblastic leukemia. CONCLUSIONS: Impairment in function of GST and MTHFR enzymes found in our patient may have contributed to the development of secondary mixed phenotype acute leukemia, although precise mechanism remains elusive. © 2014 by Lippincott Williams & Wilkins.

Immune thrombocytopenic purpura (ITP) is an acquired immune-mediated bleeding disorder characterized by isolated low platelet (PLT) counts. Immune thrombocytopenic purpura pathogenesis involves multiple immune mechanisms causing PLT destruction and inadequate production. Owing to impaired immune homeostasis, ITP patients can develop other than anti-PLT autoantibodies even in the absence of clinical signs of autoimmune disease, such as anti-thyroglobulin (TG) and anti-thyroperoxidase (TPO) antibodies. Our objective is to determine the prevalence of antithyroid antibodies (ATAs) in the population of pediatric ITP patients, and the differences in ATA positivity prevalence in newly diagnosed/persistent ITP, and chronic ITP patient subgroups, as well as to establish the impact of ATA positivity on the treatment outcomes. A cross-sectional observational study was conducted involving 75 pediatric patients diagnosed with ITP and 60 healthy controls, carried out over a period of 11 years. The prevalence of ATA was significantly higher in ITP patients compared with controls (28% vs 5%, P <.05). Initial PLT count was significantly lower in ATA-positive patients, but the treatment response did not differ between ATA-positive and ATA-negative patients. To conclude, our study confirmed that ITP patients have a higher prevalence of ATA compared with the healthy pediatric population; however, no association was found between ATA positivity and disease duration or treatment outcomes. Our findings suggest that ATA screening may not be prognostic for ITP in pediatric population, but further research with larger cohorts may be beneficial to elucidate the role of ATA in ITP pathogenesis and management. © The Author(s) 2024.

In diploid populations of size N, there will be 2 Nμ mutations per nucleotide (nt) site (or per locus) per generation (μ stands for mutation rate). If either the population or the coding genome double in size, one expects 4 Nμ mutations. What is important is not the population size per se but the number of genes (coding sites), the two being often interconverted. Here we compared the total physical length of protein-coding genomes (n) with the corresponding absolute rates of synonymous substitution (K S), an empirical neutral reference. In the classical occupancy problem and in the coupons collector (CC) problem, n was expressed as the mean rate of change (K CC). Despite inherently very low power of the approaches involving averaging of rates, the mode of molecular evolution of the total size phenotype of the coding genome could be evidenced through differences between the genomic estimates of K CC [K CC=1/(ln n + 0.57721) n] and rate of molecular evolution, K S. We found that (1) the estimates of n and K S are reciprocally correlated across taxa (r=0.812; p≪ 0.001); (2) the gamete-cell division hypothesis (Chang et al. Proc Natl Acad Sci USA 91:827-831, 1994) can be confirmed independently in terms of K CC/K S ratios; (3) the time scale of molecular evolution changes with change in mutation rate, as previously shown by Takahata (Proc Natl Acad Sci USA 87:2419-2423, 1990), Takahata et al. (Genetics 130:925-938, 1992), and Vekemans and Slatkin (Genetics 137:1157-1165, 1994); (4) the generation time and population size (Lynch and Conery, Science 302:1401-1404, 2003) effects left their "signatures" at the level of the size phenotype of the protein-coding genome. © The Japan Society of Human Genetics and Springer-Verlag 2005.

In diploid populations of size N, there will be 2 Nμ mutations per nucleotide (nt) site (or per locus) per generation (μ stands for mutation rate). If either the population or the coding genome double in size, one expects 4 Nμ mutations. What is important is not the population size per se but the number of genes (coding sites), the two being often interconverted. Here we compared the total physical length of protein-coding genomes (n) with the corresponding absolute rates of synonymous substitution (K S), an empirical neutral reference. In the classical occupancy problem and in the coupons collector (CC) problem, n was expressed as the mean rate of change (K CC). Despite inherently very low power of the approaches involving averaging of rates, the mode of molecular evolution of the total size phenotype of the coding genome could be evidenced through differences between the genomic estimates of K CC [K CC=1/(ln n + 0.57721) n] and rate of molecular evolution, K S. We found that (1) the estimates of n and K S are reciprocally correlated across taxa (r=0.812; p≪ 0.001); (2) the gamete-cell division hypothesis (Chang et al. Proc Natl Acad Sci USA 91:827-831, 1994) can be confirmed independently in terms of K CC/K S ratios; (3) the time scale of molecular evolution changes with change in mutation rate, as previously shown by Takahata (Proc Natl Acad Sci USA 87:2419-2423, 1990), Takahata et al. (Genetics 130:925-938, 1992), and Vekemans and Slatkin (Genetics 137:1157-1165, 1994); (4) the generation time and population size (Lynch and Conery, Science 302:1401-1404, 2003) effects left their "signatures" at the level of the size phenotype of the protein-coding genome. © The Japan Society of Human Genetics and Springer-Verlag 2005.

22q11.2 microdeletion is the most common microdeletion in humans. The purpose of this study was to evaluate postoperative outcome in children with 22q11.2 microdeletion who had undergone complete surgical correction of a congenital heart defect. The study included 34 patients who underwent complete correction of conotruncal heart defects. Of these, 17 patients diagnosed with 22q11.2 microdeletion represent the investigated group. Another 17 patients without 22q11.2 microdeletion represent the control group. Investigated and control groups differ significantly for total length of stay in the hospital (average 37.35 and 14.12 days, respectively); length of postoperative stay in the intensive care unit (average 10.82 and 6.76 days, respectively); sepsis (eight and two patients, respectively); administration of antibiotics (15 and seven patients, respectively); duration of antibiotic therapy (average 17.65 and 14.59 days, respectively); occurrence of hypocalcemia (16 and 0 patients, respectively); and initiation of peroral nutrition during the postoperative course (average 10.29 and 3.88 days, respectively). No difference was found for duration of ventilatory support (average 6.12 and 4.24 days, respectively), administration of total parenteral nutrition, and postoperative mortality rate. The study results suggest that genotype of 22q11.2 microdeletion affects postoperative outcome after cardiac surgery. Possible targets for intervention in postoperative intensive care management are prevention and treatment of systemic infections, monitoring, and treatment of hypocalcemias, rational administration of antibiotics and careful planning of nutrition. Consequently, this could shorten patients’ intensive care stay and overall duration of hospitalization. © 2017, Springer Science+Business Media, LLC.