Browsing by Author "Milošević, Goran (55608514200)"

Background/Aim. The cause of eosinophilia often remains unelucidated. The aim of the study was to analyze causes and treatment approaches in children with eosinophilia in pediatric tertiary care hospital. Methods. The medical records of children investigated for eosinophilia (based on the International Classification of Diseases code D72.1) were retrospectively reviewed in the University Children’s Hospital, Belgrade, Serbia, from December 2011 to December 2022. A total of 105 children (62 boys; male:female ratio was 1:4) aged one month to 16.5 years (median 7.7 years) were diagnosed with eosinophilia. After excluding 15 of them due to incorrectly assigned diagnosis based on relative eosinophil number only, the remaining 90 children were grouped according to the severity of eosinophilia (mild, moderate or severe). Results. Serological analysis confirmed toxocariasis in six (6.7%) patients, while two (2.2%) had a confirmed nematode infestation (Ascaris lumbricoides and Enterobius vermicularis, respectively). Thirty-two (35.6%) children with eosinophilia and three with no true eosinophilia were diagnosed with helminthiasis ex juvantibus. Eosinophilia was ultimately explained by allergic/atopic conditions [19 (21.1%)], drug reactions [four (4.4%)], bacterial infections [nine (8.9%)], hematological problems [five (5.5%)], Apstrakt Uvod/Cilj. Uzrok eozinofilije često ostaje nerasvetlјen. Cilj rada bio je da se analiziraju uzrok i terapijski pristup kod dece sa eozinofilijom u pedijatrijskoj bolnici tercijarnog stepena zbrinjavanja. Metode. Retrospektivno je analizirana medicinska dokumentacija dece koja su ispitivana zbog eozinofilije (naznačene šifrom D72.1 na osnovu Međunarodne klasifikacije bolesti) u Univerzitetskoj dečjoj klinici u Beogradu, Srbija, u periodu od decembra 2011. do decembra 2022. Dijagnozu eozinofilije imalo je ukupno 105 dece (62 dečaka; odnos autoimmune disorders [three (3.3%)], unrelated congenital disorders (one), or as an isolated finding [seven (7.8%)]. In addition, one of the children without an increased absolute eosinophil number was diagnosed with eosinophilic esophagitis. A total of 56 (53.3%) children received anthelminthic treatment: 9 (90.0%) with severe eosinophilia, 19 (51.4%) with moderate, 23 (53.5%) with mild, and 5 (33.3%) children with no true eosinophilia. Most (42) of the children were given mebendazole only, while the remaining 14 (eight with severe, three with moderate, and three with mild) were also initially treated with mebendazole but subsequently shifted to albendazole due to the persistence of eosinophilia. In all treated children, eosinophilia and other relevant findings (if any) subsided in a matter of a few days to a few weeks after initializing treatment. Conclusion. Our results support the recommendation that unexplained eosinophilia of all levels of severity requires a standardized diagnostic approach. The results also provide some support for a potential rational basis for ex juvantibus administration of anthelminthic drugs in a fraction of children with eosinophilia without an obvious etiological explanation. © 2024 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Introduction Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory condition characterized by fever, cytopenias, hepatosplenomegaly and hemophagocytosis. HLH may be primary or secondary to infection, autoimmune disease or malignancy. Hypertriglyceridemia is a common abnormality in HLH and one of the HLH-2004 diagnostic criteria. Case Outline We present an infant with severe hypotonia and hypoproteinemic edema who also had extreme hypertriglyceridemia (21 mmol/l) and was diagnosed with HLH based on six of eight HLH- 2004 criteria (fever, hepatosplenomegaly, bicytopenia, hypertriglyceridemia with hypofibrinogenemia, sIL-2R > 2400 IU/ml, hemophagocytosis). The presence of IgM antibodies to Epstein–Barr virus and cytomegalovirus indicated a probable infectious trigger. The child was cured by the HLH-2004 protocol for secondary HLH (consisting of dexamethasone and cyclosporine). He was also found to have low serum hydroxycobalamin levels, promptly corrected upon hydroxycobalamin administration. Conclusion The presented case history underlines the need to ascertain the presence or absence of each of the eight HLH-2004 criteria in any patient suspected to suffer from HLH. © 2015, Serbia Medical Society. All rights reserved.

Introduction Intensive treatment protocols used for non-Hodgkin lymphoma in children lead to eventfree survival rates ranging from 80% to 90%. However, the results are less successful in developing countries. Lymphoblastic lymphoma (LBL) is the second most frequent type of lymphoma in children, contributing with about one third to all non-Hodgkin lymphoma in childhood. Objective The aim of the study was to evaluate the results of LBL treatment in University Children’s Hospital (UCH), Belgrade. Methods A retrospective analysis of patient records at UCH from 1997 to 2015 was carried out in patients aged 0–18 years, in whom the diagnosis of LBL had been established. Twenty-two children were included in the analysis. Results Mean age at diagnosis was 10 years, with preponderance of male patients. All patients were treated according to Berlin-Frankfurt-Munster-based chemotherapy protocols. With median follow-up of 91.5 months, five-year probability of event-free survival was 79.5% for all patients, while overall survival was 81.8%. Conclusion Our results, although slightly inferior to those of leading international groups, reflect a good treatment outcome in our patients. © 2016, Serbia Medical Society. All rights reserved.

Introduction/Objective Next generation sequencing (NGS) technology has enabled genomic profiling of each patient. Growing knowledge in pharmacogenomics makes it possible to use NGS data for discovery of novel potential genetic markers for targeted therapy of many diseases, especially cancers. The aim of this study was to use targeted NGS to make a genetic profile of childhood acute lymphoblastic leukemia (cALL) in order to evaluate potential molecular targets for targeted therapy. Methods We analyzed DNA samples from 17 cALL patients using NGS targeted sequencing. Advanced bioinformatic analysis was used to identify novel mutations in analyzed genes and to predict their effect and pharmacogenomic potential. Results We identified nine variants that have not been previously reported in relevant databases, including two stop-gain variants, ABL1 p.Q252* and AKT1 p.W22*, one frameshift, STK11 p.G257fs*28, and six missense variants. We created three-dimensional models of four proteins harboring novel missense variants. We analyzed pharmacogenomic potential of each variant and found that two of them, STK11 c.1023G>T/ p.L341F and ERBB2 c.2341C>T/ p.R781W, are suitable candidates for targeted therapy. Conclusion Most new variants detected in this study were found in the genes associated with Ras signaling pathway, which is frequently mutated in cALL patients. Pharmacogenomic profiling of each cALL will be indispensable for novel therapy approaches. Detection and initial analysis of novel variants, presented in this study, will become a standard procedure for the design and development of individualized therapies for children with ALL, leading to improved patient outcomes. © 2018, Serbia Medical Society. All rights reserved.

Aim To determine changes in the quality of life associated with epilepsy in school-age children with newly diagnosed uncomplicated epilepsy over the first six months after diagnosis to find points relevant for the early prevention of deterioration in quality of life. Methods This prospective follow-up study, performed in University Children’s Hospital in Belgrade, enrolled 60 school-aged children with recently diagnosed epilepsy, along with their parents. The respondents completed the Children with Epilepsy Quality of Life immediately following the diagnosis of epilepsy and six months later. Results Significant decline was observed in the domains related to intrapersonal/emotional relationships by both children (P < 0.001) and their parents (P = 0.03), and in the need to keep epilepsy a secret as observed by parents (P = 0.04). Significant improvement was found in the Interpersonal/Social domain as rated by parents (P = 0.001). Total quality-of-life scores, as assessed by children and parents, did not change significantly. Conclusion Bearing in mind that stigma and intrapersonal struggles are the major factors affecting the quality of life in children with epilepsy, psychological and social support is highly recommended in the first six months following an epilepsy diagnosis. Since intrapersonal relationships improved over six months, compensating for other deteriorations in the quality of life, children with epilepsy should be encouraged to socialize with their peers and to join organizations and actions that encourage social contact. © 2024, Medicinska Naklada Zagreb. All rights reserved.

Background: Acute kidney injury (AKI) is a common complication in pediatric oncology patients, most often caused by nephrotoxic drugs. We aimed to assess whether levels of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), liver fatty acid binding protein (uL-FABP) and Vanin-1 (uVNN-1), individually and in combination-integrated could be early markers for cytotoxic treatment induced AKI. Methods: Children with different malignant diseases treated with cisplatin (CIS) or ifosfamide (IFO) were included. AKI was defined using pediatric KDIGO (Kidney Disease Improving Global Outcomes) criteria by comparing pretreatment serum creatinine (sCr) values with those acquired at 48 h after the first or second chemotherapy cycle. Five serum (at baseline, 2, 6, 24 and 48 h after treatment) and four urine samples (at baseline, 2, 6 and 24 h after treatment) were obtained. Urinary biomarkers (uBm) were normalized to urine creatinine. Results: Thirty-eight patients were assessed. Within 48 h following chemotherapy 6 (15.79%) patients experienced AKI. Patients with AKI were younger and tend to have lower baseline sCr values than patients without AKI, but these differences were not statistically significant. Compared to baselines, all uBm were significantly increased during the first 6 h while sCr concentrations did not change significantly during the study period. The median increases in uBm during the first 6 h after treatment were 529.8% (interquartile range – IQR, 63.9-1835.2%) – 2194.0% (IQR, 255.3-4695.5%) in AKI vs. 302.2% (IQR 114.6-561.2%) -429.8% (156.5–1467.0%) in non-AKI group depending of tested uBm. The magnitude of these changes over time didn’t differ significantly between groups. The area under receiver operator curve (AUC) for uL-FABP and uNGAL at 24 h after chemotherapy were 0.81 and 0.72, respectively. The ROC analysis revealed that the other individual biomarkers’ performance at any time-point wasn’t statistically significant (AUC < 0.7). A model of integrated-combined uBm, 2 h (AUC 0.78), 6 h (AUC 0.85) and 24 h after (AUC 0.92) treatment with CIS and/or IFO showed good utility for early AKI prediction. Conclusions: The results of this study support that the use of the uBm to improves early AKI prediction in patients receiving CIS and/or IFO containing chemotherapy. Further studies on larger comparable groups of patients are needed. © The Author(s) 2025.