Browsing by Author "Milin-Lazovic, Jelena (57023980700)"

Objectives: We sought to determine whether blended learning is an effective strategy for acquiring competence in public health biostatistics. Methods: The trial was conducted with 69 Masters’ students of public health attending the School of Public Health at University of Belgrade. Students were exposed to the traditional and blended learning styles. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course. Curriculum development was guided by competencies as suggested by the Association of Schools of Public Health in the European Region (ASPHER). Teaching methods were compared according to the final competence score. Results: Forty-four students were enrolled in the traditional method of education delivery, and 25 to the blended learning format. Mean exam scores for the blended learning group were higher than for the on-site group for both the final statistics score (89.65 ± 6.93 vs. 78.21 ± 13.26; p < 0.001) and knowledge test score (35.89 ± 3.66 vs. 22.56 ± 7.12; p < 0.001), with estimated large effect size (d > 0.8). Conclusions: A blended learning approach is an attractive and effective way of acquiring biostatistics competence for Masters of Public Health (MPH) graduate students. © 2017, Swiss School of Public Health (SSPH+).

Sarcoidosis is a granulomatous disease of unknown etiology that can affect almost any organ. Although the acute form can have spontaneous regression, a certain number of patients can have a chronic form, which leads to an increase in mortality and a decrease in the quality of life. Considering that the risk factors are still unknown, we wanted to compare the characteristics of patients with acute and chronic forms of sarcoidosis in Serbia in order to determine significant differences between them with hopes of contributing to everyday clinical practice. A total of 2380 patients treated in our clinic were enrolled in this study. They were separated into the following two groups: 1126 patients with acute form and 1254 patients with chronic form. They were further compared by gender, smoking status, radiological status, exposition, biomarkers for sarcoidosis, organ involvement, and other comorbidities; the distribution of patients according to regions of Serbia was also noted. Statistical significance was found in radiological findings (p < 0.001), biomarkers (calcium in 24 h urine p < 0.001; chitotriosidase p = 0.001), and the affliction of organs (p < 0.001). The differences noted in this paper could help improve our understanding of this disease. © 2024 by the authors.

Inferior vena cava (IVC) anomalies are uncommon congenital causes of deep vein thrombosis (DVT). KILT syndrome (kidney and IVC abnormalities with leg thrombosis) has only been described as case reports in the literature. Therefore, the characteristics, evaluation, and management of patients with KILT syndrome have not yet been standardized. This study aimed to systematically review and analyze the clinical and radiographic data and treatment of previously reported cases of KILT syndrome. In this systematic review, we performed a literature search of the PubMed, Scopus, and Web of Science databases in December 2023, with no restrictions on the publication date. After duplicate extractions, 4195 articles were screened. Case reports and case series reporting on KILT syndrome were included. In addition to previously published cases, we included a new case of a previously healthy 25-year-old man with KILT syndrome in the analysis. A total of 34 cases were therefore included in this study. The majority (76.5%) were male patients with a median age of 24 years. In most patients, unprovoked bilateral iliofemoral thrombosis was diagnosed, and 64.7% had left kidney abnormalities. Our study suggests that anomalies of the IVC should be suspected in all young patients, especially male patients, with proximal, recurrent, or idiopathic DVT. If an IVC anomaly is confirmed, the kidneys should be examined to monitor and preserve healthy kidneys in cases of KILT syndrome. The data collected from all patients emphasize the requirement of long-term anticoagulation and risk factor control. Surgical measures may be effective for treating symptomatic refractory cases. © The Author(s) 2024.

The hallmark alteration in α-synucleinopathies, α-synuclein, is observed not only in the brain but also in the peripheral tissues, particularly in the intestine. This suggests that endoscopic biopsies performed for colon cancer screening could facilitate the assessment of α-synuclein in the gastrointestinal (GI) tract. Using immunohistochemistry for α-synuclein, we assessed whether GI biopsies could be used to confirm an ongoing α-synucleinopathy. Seventy-four subjects with cerebral α-synucleinopathy in various Braak stages with concomitant GI biopsies were available for study. In 81% of the subjects, α-synuclein was seen in the mucosal/submucosal GI biopsies. Two subjects with severe cerebral α-synucleinopathy and a long delay between biopsy and death displayed no α-synuclein pathology in the gut, and 11 subjects with sparse cerebral α-synucleinopathy displayed GI α-synuclein up to 36 years prior to death. The finding that there was no GI α-synuclein in 19% of the subjects with cerebral α-synucleinopathy, and α-synuclein was observed in the gut of 11 subjects (15%) with sparse cerebral α-synucleinopathy even many years prior to death is unexpected and jeopardizes the use of assessment of α-synuclein in the peripheral tissue for confirmation of an ongoing cerebral α-synucleinopathy. © 2022 American Association of Neuropathologists, Inc. All rights reserved.

Introduction: Sarcoidosis is a rare multisystem granulomatous disease with unknown etiology. The interplay of vitamin D deficiency and genetic polymorphisms in genes coding for the proteins relevant for metabolism of vitamin D is an important, but unexplored area. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in CYP2R1 (rs10741657), CYP27B1 (rs10877012), DBP (rs7041; rs4588), and VDR (rs2228570) genes and sarcoidosis, as well as the association between these SNPs and 25(OH)D levels in sarcoidosis patients. Material and methods: For that purpose we genotyped 86 sarcoidosis patients and 50 healthy controls using the PCR-RFLP method. Results: Subjects carrying the CC genotype of CYP27B1 rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover, DBP rs4588 AA genotype was shown to be a susceptibility factor, where carriers of this genotype had eight times higher odds for developing sarcoidosis. In addition, the A allele of the DBP gene (rs4588) was associated with lower levels of 25(OH)D in sarcoidosis patients. Conclusions: These results suggest that patients with vitamin D deficiency should be regularly tested for genetic modifiers that are related to sarcoidosis in order to prevent development of serious forms of sarcoidosis. Copyright © 2018 Termedia & Banach

The healthcare environment in Serbia has changed dramatically over a last two decades, pointing out the necessity of clinical informatics (CI) education for future MDs. Total of 77 students were enrolled and 72 (93.5%) have successfully finished this course during 4 academic years. Mean total score for all students was 83.4 ± 9.0 points, without difference between genders. We presented blended learning module as an effective way of gaining competences in CI and recommend this course to be required for future MDs. © 2020 European Federation for Medical Informatics (EFMI) and IOS Press.

The healthcare environment in Serbia has changed dramatically over a last two decades, pointing out the necessity of clinical informatics (CI) education for future MDs. Total of 77 students were enrolled and 72 (93.5%) have successfully finished this course during 4 academic years. Mean total score for all students was 83.4 ± 9.0 points, without difference between genders. We presented blended learning module as an effective way of gaining competences in CI and recommend this course to be required for future MDs. © 2020 European Federation for Medical Informatics (EFMI) and IOS Press.

Introduction: The analysis of cell-free DNA (cfDNA) for genetic abnormalities is a promising new approach for the diagnosis and prognosis of pancreatic cancer patients. Insights into the molecular characteristics of pancreatic cancer may provide valuable information, leading to its earlier detection and the development of targeted therapies. Material and Methods: We conducted a systematic review and a meta-analysis of studies that reported cfDNA in pancreatic ductal adenocarcinoma (PDAC). The studies were considered eligible if they included patients with PDAC, if they had blood tests for cfDNA/ctDNA, and if they analyzed the prognostic value of cfDNA/ctDNA for patients’ survival. The studies published before 22 October 2020 were identified through the PubMED, EM-BASE, Web of Science and Cochrane Library databases. The assessed outcomes were the overall (OS) and progression-free survival (PFS), expressed as the log hazard ratio (HR) and standard error (SE). The summary of the HR effect size was estimated by pooling the individual trial results using the Review Manager, version 5.3, Cochrane Collaboration. The heterogeneity was assessed using the Cochran Q test and I2 statistic. Results: In total, 48 studies were included in the qualitative review, while 44 were assessed in the quantitative synthesis, with the total number of patients included being 3524. Overall negative impacts of cfDNA and KRAS mutations on OS and PFS in PDAC (HR = 2.42, 95% CI 1.95–2.99 and HR = 2.46, 95% CI: 2.01–3.00, respectively) were found. The subgroup analysis of the locally advanced and metastatic disease presented similar results (HR = 2.51, 95% CI: 1.90–3.31). In the studies assessing the pre-treatment presence of KRAS, there was a moderate to high degree of heterogeneity (I2 = 87% and I2 = 48%, for OS and PFS, respectively), which was remarkably decreased in the analysis of the studies measuring post-treatment KRAS (I2 = 24% and I2 = 0%, for OS and PFS, respectively). The patients who were KRAS positive before but KRAS negative after treatment had a better prognosis than the persistently KRAS-positive patients (HR = 5.30, 95% CI: 1.02–27.63). Conclusion: The assessment of KRAS mutation by liquid biopsy can be considered as an additional tool for the estimation of the disease course and outcome in PDAC patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Introduction: The analysis of cell-free DNA (cfDNA) for genetic abnormalities is a promising new approach for the diagnosis and prognosis of pancreatic cancer patients. Insights into the molecular characteristics of pancreatic cancer may provide valuable information, leading to its earlier detection and the development of targeted therapies. Material and Methods: We conducted a systematic review and a meta-analysis of studies that reported cfDNA in pancreatic ductal adenocarcinoma (PDAC). The studies were considered eligible if they included patients with PDAC, if they had blood tests for cfDNA/ctDNA, and if they analyzed the prognostic value of cfDNA/ctDNA for patients’ survival. The studies published before 22 October 2020 were identified through the PubMED, EM-BASE, Web of Science and Cochrane Library databases. The assessed outcomes were the overall (OS) and progression-free survival (PFS), expressed as the log hazard ratio (HR) and standard error (SE). The summary of the HR effect size was estimated by pooling the individual trial results using the Review Manager, version 5.3, Cochrane Collaboration. The heterogeneity was assessed using the Cochran Q test and I2 statistic. Results: In total, 48 studies were included in the qualitative review, while 44 were assessed in the quantitative synthesis, with the total number of patients included being 3524. Overall negative impacts of cfDNA and KRAS mutations on OS and PFS in PDAC (HR = 2.42, 95% CI 1.95–2.99 and HR = 2.46, 95% CI: 2.01–3.00, respectively) were found. The subgroup analysis of the locally advanced and metastatic disease presented similar results (HR = 2.51, 95% CI: 1.90–3.31). In the studies assessing the pre-treatment presence of KRAS, there was a moderate to high degree of heterogeneity (I2 = 87% and I2 = 48%, for OS and PFS, respectively), which was remarkably decreased in the analysis of the studies measuring post-treatment KRAS (I2 = 24% and I2 = 0%, for OS and PFS, respectively). The patients who were KRAS positive before but KRAS negative after treatment had a better prognosis than the persistently KRAS-positive patients (HR = 5.30, 95% CI: 1.02–27.63). Conclusion: The assessment of KRAS mutation by liquid biopsy can be considered as an additional tool for the estimation of the disease course and outcome in PDAC patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background and Objectives: Forceps delivery is a crucial obstetrical technique that has become increasingly underutilized in favor of cesarean delivery, despite the numerous complications related to cesarean sections. The major concerns with regard to assisted vaginal birth (AVB) are safety and long-term consequences. We aimed to investigate a neurological outcome of neonates and children at the age of 7 who were born via forceps delivery. This would greatly improve informed decision making for both mothers and obstetricians. Materials and Methods: A single-arm cohort study was conducted from January 2012 to December 2016 among 49 women and their children born via forceps delivery at the Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia. The Sarnat and Sarnat classification was used to evaluate the neurological status of neonates, and logistic regression analysis was employed to explore the association with perinatal factors. Long-term neurological outcomes were assessed using the Griffiths Mental Development Scale and a questionnaire for parents based on the Motor and Social Development (MSD) scale, which was derived from the Bayley-III Scale. Results: The main indication for forceps delivery was maternal exhaustion (79.6%), followed by fetal distress (20.4%). A pathological neurological status was observed in 16.3% of newborns, with pathological ultrasound of the CNS in 3%. A statistically significant association was observed with the Apgar score, with an odds ratio of 0.575 (95% CI: 0.407–0.813, p = 0.002) and perinatal asphyxia, with an odds ratio of 9.882 (95% CI: 1.111–87.902, p = 0.04). However, these associations were unlikely to be related to the mode of delivery. Long-term adverse neurological outcomes were seen in three cases, which accounts for 6.4%. These included mild disorders such as delayed milestone, speech delay, and motor clumsiness. Conclusions: The present study highlights the safety of forceps delivery regarding children’s neurological outcomes at 7 years of age. This is an important contribution to the modern management of labor, especially in light of increasing rates of cesarean deliveries worldwide. © 2024 by the authors.

Introduction: Preeclampsia (PE) is a pregnancy-associated, multi-organ, life-threatening disease that appears after the 20th week of gestation. The aim of this study was to perform a systematic review and meta-analysis to determine whether women with PE have disrupted miRNA expression compared to women who do not have PE. Methods: We conducted a systematic review and meta-analysis of studies that reported miRNAs expression levels in placenta or peripheral blood of pregnant women with vs. without PE. Studies published before October 29, 2021 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Standardized mean difference (SMD) was used as a measure of effect size. Results: 229 publications were included in the systematic review and 53 in the meta-analysis. The expression levels in placenta were significantly higher in women with PE compared to women without PE for miRNA-16 (SMD = 1.51,95%CI = 0.55–2.46), miRNA-20b (SMD = 0.89, 95%CI = 0.33–1.45), miRNA-23a (SMD = 2.02, 95%CI = 1.25–2.78), miRNA-29b (SMD = 1.37, 95%CI = 0.36–2.37), miRNA-155 (SMD = 2.99, 95%CI = 0.83–5.14) and miRNA-210 (SMD = 1.63, 95%CI = 0.69–2.58), and significantly lower for miRNA-376c (SMD = –4.86, 95%CI = –9.51 to –0.20). An increased level of miRNK-155 expression was found in peripheral blood of women with PE (SMD = 2.06, 95%CI = 0.35–3.76), while the expression level of miRNA-16 was significantly lower in peripheral blood of PE women (SMD = –0.47, 95%CI = –0.91 to –0.03). The functional roles of the presented miRNAs include control of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and angiogenesis. Conclusion: miRNAs play an important role in the pathophysiology of PE. The identification of differentially expressed miRNAs in maternal blood creates an opportunity to define an easily accessible biomarker of PE. Copyright © 2021 Cirkovic, Stanisavljevic, Milin-Lazovic, Rajovic, Pavlovic, Milicevic, Savic, Kostic Peric, Aleksic, Milic, Stanisavljevic, Mikovic, Garovic and Milic.

Introduction: Preeclampsia (PE) is a pregnancy-associated, multi-organ, life-threatening disease that appears after the 20th week of gestation. The aim of this study was to perform a systematic review and meta-analysis to determine whether women with PE have disrupted miRNA expression compared to women who do not have PE. Methods: We conducted a systematic review and meta-analysis of studies that reported miRNAs expression levels in placenta or peripheral blood of pregnant women with vs. without PE. Studies published before October 29, 2021 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Standardized mean difference (SMD) was used as a measure of effect size. Results: 229 publications were included in the systematic review and 53 in the meta-analysis. The expression levels in placenta were significantly higher in women with PE compared to women without PE for miRNA-16 (SMD = 1.51,95%CI = 0.55–2.46), miRNA-20b (SMD = 0.89, 95%CI = 0.33–1.45), miRNA-23a (SMD = 2.02, 95%CI = 1.25–2.78), miRNA-29b (SMD = 1.37, 95%CI = 0.36–2.37), miRNA-155 (SMD = 2.99, 95%CI = 0.83–5.14) and miRNA-210 (SMD = 1.63, 95%CI = 0.69–2.58), and significantly lower for miRNA-376c (SMD = –4.86, 95%CI = –9.51 to –0.20). An increased level of miRNK-155 expression was found in peripheral blood of women with PE (SMD = 2.06, 95%CI = 0.35–3.76), while the expression level of miRNA-16 was significantly lower in peripheral blood of PE women (SMD = –0.47, 95%CI = –0.91 to –0.03). The functional roles of the presented miRNAs include control of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and angiogenesis. Conclusion: miRNAs play an important role in the pathophysiology of PE. The identification of differentially expressed miRNAs in maternal blood creates an opportunity to define an easily accessible biomarker of PE. Copyright © 2021 Cirkovic, Stanisavljevic, Milin-Lazovic, Rajovic, Pavlovic, Milicevic, Savic, Kostic Peric, Aleksic, Milic, Stanisavljevic, Mikovic, Garovic and Milic.

Background and Objectives: Despite advances in surgical techniques, industry adjuncts, and cerebral perfusion techniques, the in-hospital mortality rate of type A acute dissection (TAAD) remains at 15–30%. This study aimed to investigate the influence of different extents of aortic resection on survival and quality of life (QoL) after long-term follow-up. Materials and Methods: A retrospective observational trial was performed, including 165 patients operated upon for TAAD. Patients were divided into two groups according to the extent of their aortic repair: the first group comprised patients who had ascending aorta replacement and the second included patients who had hemiarch or total arch replacement. The groups were compared with regard to their baseline characteristics, operative characteristics, survival, complications, and QoL during nine years of follow-up. Results: The mean follow-up time was 75.6 months (1–108 months). The mean survival in the ascending aorta repair group was 89.651 (81.242–98.061) months and was 54.801 (40.053–69.548) months in the hemiarch and arch group; the difference between the groups was significant (log-rank p < 0.001). The rate of new postoperative neurological deficits was statistically higher in the hemiarch and arch group (17.5% vs. 8.4%, p = 0.045), the most common being stroke, and was also more frequent in the hemiarch and arch group than in the ascending aorta group (with statistical significance (15.7% vs. 6.5%)). The mean SF-12 physical score from the QoL questionnaire was higher in the ascending aorta replacement group than in the hemiarch and arch group (50.1 ± 7.3 vs. 44.0 ± 11.9, p = 0.017). Additionally, the mean SF-12 mental score was higher in the ascending aorta replacement group (52.3 ± 7.3 vs. 47.1 ± 12.8, p = 0.032). Conclusions: A more aggressive approach involving aortic arch repair means a lower survival rate and lesser quality of life after long-term follow-up in comparison with the replacement of the ascending aorta. If clinically applicable, a more defensive strategy may be considered. © 2023 by the authors.

Background: The aim of this study was to examine the correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction. Methods: Between 2014 and 2022, we prospectively evaluated 81 consecutive spina bifida children with neurogenic bowel and bladder dysfunction (35 boys and 46 girls, mean age 9.5 ± 3.4 years). All patients underwent echosonographic measurement of transverse rectal diameter and urodynamic studies. Results: We found a strong negative correlation between transverse rectal diameter and maximum bladder capacity (r = −0.682, p < 0.001) and compliance (r = −0.690, p < 0.001). There was also a strong positive correlation between transverse rectal diameter and maximal detrusor pressure (r = 0.650, p < 0.001), leak point pressure (r = 0.793, p < 0.001), and PVR (r = 0.762, p < 0.001). In ROC analysis, transverse rectal diameter demonstrated good performance for distinguishing children with upper urinary tract deterioration, with an AUC of 0.857 (95% CI 0.761–0.953). A transverse rectal diameter ≥40 mm was 83.3% sensitive and 100% specific for the diagnosis of unfavorable urodynamic patterns. Conclusion: There is a correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction. Ultrasonographically assessed transverse rectal diameter of ≥40 mm may be used as a risk factor for upper urinary tract deterioration (unfavorable urodynamic findings). We suggest the transverse rectal diameter echosonographic measurement use as an integral part of the diagnostic approach in children with neurogenic bowel and bladder dysfunction, as it can help decision-making while waiting for urodynamic testing. Copyright © 2022 Milivojevic, Zelenovic, Milin-Lazovic, Radojicic, Laketic, Dasic, Milic and Radojicic.

Background: Inflammation, oxidative stress and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and to assess their relationship with lung function, symptom severity scores and recent acute exacerbations. Methods: In this observational cohort study, serum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 ratio in the peripheral blood of COPD patients with stable disease and healthy controls were determined, and their association with lung function (postbronchodilator spirometry, body plethysmography, single breath diffusion capacity for carbon monoxide), symptom severity scores (mMRC and CAT) and exacerbation history were assessed. Results: COPD patients (n = 98) had significantly higher levels of serum MMP-9 and TIMP-1 and a higher MMP-9/TIMP-1 ratio than healthy controls (n = 47) (p ≤ 0.001). The areas under the receiver operating characteristic curve for MMP-9, TIMP-1 and the MMP-9/TIMP-1 ratio for COPD diagnosis were 0.974, 0.961 and 0.910, respectively (all p < 0.05). MMP-9 and the MMP-9/TIMP-1 ratio were both negatively correlated with FVC, FEV1, FEV1/FVC, VC, and IC (all p < 0.05). For MMP-9, a positive correlation was found with RV/TLC% (p = 0.005), and a positive correlation was found for the MMP-9/TIMP-1 ratio with RV% and RV/TLC% (p = 0.013 and 0.002, respectively). Patients with COPD GOLD 3 and 4 presented greater MMP-9 levels and a greater MMP-9/TIMP-1 ratio compared to GOLD 1 and 2 patients (p ≤ 0.001). No correlation between diffusion capacity for carbon monoxide and number of acute exacerbations in the previous year was found. Conclusions: COPD patients have elevated serum levels of MMP-9 and TIMP-1 and MMP-9/TIMP-1 ratio. COPD patients have an imbalance between MMP-9 and TIMP-1 in favor of a pro-proteolytic environment, which overall indicates the importance of the MMP-9/TIMP-1 ratio as a potential biomarker for COPD diagnosis and severity. © 2023, The Author(s).