TY  - JOUR
AU  - Mitrović, Miloš
AU  - Stanković-Popović, Verica
AU  - Tolinački, Maja
AU  - Golić, Nataša
AU  - Soković Bajić, Svetlana
AU  - Veljović, Katarina
AU  - Nastasijević, Branislav
AU  - Soldatović, Ivan
AU  - Svorcan, Petar
AU  - Dimković, Nada
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S1051227622001522
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1753
AB  - ObjectiveAltering dysbiotic gut flora through synbiotic supplementation has recently been recognized as a potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study.MethodsA total of 34 nondialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15 and 45 mL/minute, were randomized either to an intervention group (n = 17), receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n = 17), receiving placebo during 12 weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins, total serum indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high-sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultraperformance liquid chromatography. The stool microbiome analysis was performed using the 16S ribosomal ribonucleic acid gene sequencing approach.ResultsSynbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus, and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS –21.5% vs. 5.3%, P < .001), improved estimated glomerular filtration rate (ΔeGFR 12% vs. 8%, P = .029), and decreased level of high-sensitivity C-reactive protein (–39.5 vs. –8.5%, P < .001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted.ConclusionSynbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients.
T2  - Journal of Renal Nutrition
T2  - Journal of Renal NutritionJournal of Renal Nutrition
T1  - The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial
EP  - 288
IS  - 2
SP  - 278
VL  - 33
DO  - 10.1053/j.jrn.2022.07.008
ER  - 

@article{
author = "Mitrović, Miloš and Stanković-Popović, Verica and Tolinački, Maja and Golić, Nataša and Soković Bajić, Svetlana and Veljović, Katarina and Nastasijević, Branislav and Soldatović, Ivan and Svorcan, Petar and Dimković, Nada",
year = "2023",
abstract = "ObjectiveAltering dysbiotic gut flora through synbiotic supplementation has recently been recognized as a potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study.MethodsA total of 34 nondialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15 and 45 mL/minute, were randomized either to an intervention group (n = 17), receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n = 17), receiving placebo during 12 weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins, total serum indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high-sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultraperformance liquid chromatography. The stool microbiome analysis was performed using the 16S ribosomal ribonucleic acid gene sequencing approach.ResultsSynbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus, and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS –21.5% vs. 5.3%, P < .001), improved estimated glomerular filtration rate (ΔeGFR 12% vs. 8%, P = .029), and decreased level of high-sensitivity C-reactive protein (–39.5 vs. –8.5%, P < .001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted.ConclusionSynbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients.",
journal = "Journal of Renal Nutrition, Journal of Renal NutritionJournal of Renal Nutrition",
title = "The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial",
pages = "288-278",
number = "2",
volume = "33",
doi = "10.1053/j.jrn.2022.07.008"
}

Mitrović, M., Stanković-Popović, V., Tolinački, M., Golić, N., Soković Bajić, S., Veljović, K., Nastasijević, B., Soldatović, I., Svorcan, P.,& Dimković, N.. (2023). The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial. in Journal of Renal Nutrition, 33(2), 278-288.
https://doi.org/10.1053/j.jrn.2022.07.008

Mitrović M, Stanković-Popović V, Tolinački M, Golić N, Soković Bajić S, Veljović K, Nastasijević B, Soldatović I, Svorcan P, Dimković N. The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial. in Journal of Renal Nutrition. 2023;33(2):278-288.
doi:10.1053/j.jrn.2022.07.008 .

Mitrović, Miloš, Stanković-Popović, Verica, Tolinački, Maja, Golić, Nataša, Soković Bajić, Svetlana, Veljović, Katarina, Nastasijević, Branislav, Soldatović, Ivan, Svorcan, Petar, Dimković, Nada, "The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial" in Journal of Renal Nutrition, 33, no. 2 (2023):278-288,
https://doi.org/10.1053/j.jrn.2022.07.008 . .

TY  - JOUR
AU  - Mihaljević, Marina
AU  - Franić, Dusanka
AU  - Soldatović, Ivan
AU  - Lukić, Iva
AU  - Andrić-Petrović, Sanja
AU  - Mirjanić, Tijana
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Zeljić, Katarina
AU  - Gašić, Vladimir
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
AU  - Marić, Nadja P.
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1451
AB  - Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Psychoneuroendocrinology
T1  - The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls
VL  - 128
DO  - 10.1016/j.psyneuen.2021.105205
ER  - 

@article{
author = "Mihaljević, Marina and Franić, Dusanka and Soldatović, Ivan and Lukić, Iva and Andrić-Petrović, Sanja and Mirjanić, Tijana and Stanković, Biljana and Zukić, Branka and Zeljić, Katarina and Gašić, Vladimir and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav and Marić, Nadja P.",
year = "2021",
abstract = "Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Psychoneuroendocrinology",
title = "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls",
volume = "128",
doi = "10.1016/j.psyneuen.2021.105205"
}

Mihaljević, M., Franić, D., Soldatović, I., Lukić, I., Andrić-Petrović, S., Mirjanić, T., Stanković, B., Zukić, B., Zeljić, K., Gašić, V., Novaković, I., Pavlović, S., Adžić, M.,& Marić, N. P.. (2021). The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology
Pergamon-Elsevier Science Ltd, Oxford., 128.
https://doi.org/10.1016/j.psyneuen.2021.105205

Mihaljević M, Franić D, Soldatović I, Lukić I, Andrić-Petrović S, Mirjanić T, Stanković B, Zukić B, Zeljić K, Gašić V, Novaković I, Pavlović S, Adžić M, Marić NP. The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology. 2021;128.
doi:10.1016/j.psyneuen.2021.105205 .

Mihaljević, Marina, Franić, Dusanka, Soldatović, Ivan, Lukić, Iva, Andrić-Petrović, Sanja, Mirjanić, Tijana, Stanković, Biljana, Zukić, Branka, Zeljić, Katarina, Gašić, Vladimir, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, Marić, Nadja P., "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls" in Psychoneuroendocrinology, 128 (2021),
https://doi.org/10.1016/j.psyneuen.2021.105205 . .

TY  - JOUR
AU  - Miletić, Aleksandra
AU  - Ruml Stojanović, Jelena
AU  - Parezanović, Vojislav
AU  - Rsovac, Snežana
AU  - Drakulić, Danijela
AU  - Soldatović, Ivan
AU  - Mijović, Marija
AU  - Bosankić, Brankica
AU  - Petrović, Hristina
AU  - Borlja, Nikola
AU  - Milivojević, Milena
AU  - Marjanović, Ana
AU  - Branković, Marija
AU  - Cuturilo, Goran
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1414
AB  - Rapid and efficient diagnostics is crucial for newborns with congenital heart defects (CHD) in intensive care unit (ICU) but is often challenging. Given that genetic factors play a role in 20-30% cases of CHD, it is likely that genetic tests could improve both its speed and efficiency. We aimed to analyze the utility of rapid and cost-effective multiplex ligation dependent probe amplification analysis (MLPA) for chromosomal analysis in newborns with critical CHD. One hundred consecutive newborns admitted with critical CHD to the ICU were included in the study. Those with normal MLPA findings were further tested by chromosomal microarray and clinical exome sequencing. Overall, pathogenic/likely pathogenic variants were determined in ten (10%) newborns by MLPA, three (3%) by chromosomal microarray, and three (3%) by clinical exome sequencing. The most common variant detected was deletion of 22q11.2 region. Conclusion: MLPA is fast and cost-effective analysis that could be used as the first-tier test in newborns with critical CHD admitted to the ICU. What is Known: center dot MLPA is an established method for chromosome analysis in patients with CHD, but detection rate in newborns with critical CHD is unknown. What is New: center dot Study suggests that detection rate of casual variants using MLPA in newborns with critical CHD is 10%.
PB  - Springer, New York
T2  - European Journal of Pediatrics
T1  - Genetic evaluation of newborns with critical congenital heart defects admitted to the intensive care unit
EP  - 3227
IS  - 10
SP  - 3219
VL  - 180
DO  - 10.1007/s00431-021-04097-w
ER  - 

@article{
author = "Miletić, Aleksandra and Ruml Stojanović, Jelena and Parezanović, Vojislav and Rsovac, Snežana and Drakulić, Danijela and Soldatović, Ivan and Mijović, Marija and Bosankić, Brankica and Petrović, Hristina and Borlja, Nikola and Milivojević, Milena and Marjanović, Ana and Branković, Marija and Cuturilo, Goran",
year = "2021",
abstract = "Rapid and efficient diagnostics is crucial for newborns with congenital heart defects (CHD) in intensive care unit (ICU) but is often challenging. Given that genetic factors play a role in 20-30% cases of CHD, it is likely that genetic tests could improve both its speed and efficiency. We aimed to analyze the utility of rapid and cost-effective multiplex ligation dependent probe amplification analysis (MLPA) for chromosomal analysis in newborns with critical CHD. One hundred consecutive newborns admitted with critical CHD to the ICU were included in the study. Those with normal MLPA findings were further tested by chromosomal microarray and clinical exome sequencing. Overall, pathogenic/likely pathogenic variants were determined in ten (10%) newborns by MLPA, three (3%) by chromosomal microarray, and three (3%) by clinical exome sequencing. The most common variant detected was deletion of 22q11.2 region. Conclusion: MLPA is fast and cost-effective analysis that could be used as the first-tier test in newborns with critical CHD admitted to the ICU. What is Known: center dot MLPA is an established method for chromosome analysis in patients with CHD, but detection rate in newborns with critical CHD is unknown. What is New: center dot Study suggests that detection rate of casual variants using MLPA in newborns with critical CHD is 10%.",
publisher = "Springer, New York",
journal = "European Journal of Pediatrics",
title = "Genetic evaluation of newborns with critical congenital heart defects admitted to the intensive care unit",
pages = "3227-3219",
number = "10",
volume = "180",
doi = "10.1007/s00431-021-04097-w"
}

Miletić, A., Ruml Stojanović, J., Parezanović, V., Rsovac, S., Drakulić, D., Soldatović, I., Mijović, M., Bosankić, B., Petrović, H., Borlja, N., Milivojević, M., Marjanović, A., Branković, M.,& Cuturilo, G.. (2021). Genetic evaluation of newborns with critical congenital heart defects admitted to the intensive care unit. in European Journal of Pediatrics
Springer, New York., 180(10), 3219-3227.
https://doi.org/10.1007/s00431-021-04097-w

Miletić A, Ruml Stojanović J, Parezanović V, Rsovac S, Drakulić D, Soldatović I, Mijović M, Bosankić B, Petrović H, Borlja N, Milivojević M, Marjanović A, Branković M, Cuturilo G. Genetic evaluation of newborns with critical congenital heart defects admitted to the intensive care unit. in European Journal of Pediatrics. 2021;180(10):3219-3227.
doi:10.1007/s00431-021-04097-w .

Miletić, Aleksandra, Ruml Stojanović, Jelena, Parezanović, Vojislav, Rsovac, Snežana, Drakulić, Danijela, Soldatović, Ivan, Mijović, Marija, Bosankić, Brankica, Petrović, Hristina, Borlja, Nikola, Milivojević, Milena, Marjanović, Ana, Branković, Marija, Cuturilo, Goran, "Genetic evaluation of newborns with critical congenital heart defects admitted to the intensive care unit" in European Journal of Pediatrics, 180, no. 10 (2021):3219-3227,
https://doi.org/10.1007/s00431-021-04097-w . .

TY  - JOUR
AU  - Jovanović, Dragana
AU  - Marković, Jelena
AU  - Ceriman, Vesna
AU  - Perić, Jelena
AU  - Pavlović, Sonja
AU  - Soldatović, Ivan
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1341
AB  - Thymic epithelial tumors (TETs) include several anterior mediastinal malignant tumours: thymomas, thymic carcinomas and thymic neuroendocrine cancers. There is significant variety in the biologic features and clinical course of TETs and many attempts have been made to identify target genes for successful therapy of TETs. Next generation sequencing (NGS) represents a huge advancement in diagnostics and these new molecular technologies revealed that thymic neoplasms have the lowest tumor mutation burden among all adult malignant tumours with a different pattern of molecular aberrations in thymomas and thymic carcinomas. As for the PD-L1 expression in tumor cells in thymoma and thymic carcinoma, it varies a lot in published studies, with findings of PD-L1 expression from 23% to 92% in thymoma and 36% to 100% in thymic carcinoma. When correlated PD-L1 expression with disease stage some controversial results were obtained, with no association with tumor stage in most studies. This is, at least in part, explained by the fact that several diverse PD-L1 immunohistochemical tests were used in each trial, with four different antibodies (SP142, SP263, 22C3, and 28-8), different definition of PD-L1 positivity and cutoff values throughout the studies as well. There is a huge interest in using genomic features to produce predictive genomic-based immunotherapy biomarkers, particularly since recent data suggest that certain tumor-specific genomic alterations, either individually or in combination, appear to influence immune checkpoint activity and better responses as the outcome, so as such in some cancer types they may complement existing biomarkers to improve the selection criteria for immunotherapy.
PB  - Ame Publ Co, Shatin
T2  - Journal of Thoracic Disease
T1  - Correlation of genomic alterations and PD-L1 expression in thymoma
EP  - 7570
IS  - 12
SP  - 7561
VL  - 12
DO  - 10.21037/jtd-2019-thym-13
ER  - 

@article{
author = "Jovanović, Dragana and Marković, Jelena and Ceriman, Vesna and Perić, Jelena and Pavlović, Sonja and Soldatović, Ivan",
year = "2020",
abstract = "Thymic epithelial tumors (TETs) include several anterior mediastinal malignant tumours: thymomas, thymic carcinomas and thymic neuroendocrine cancers. There is significant variety in the biologic features and clinical course of TETs and many attempts have been made to identify target genes for successful therapy of TETs. Next generation sequencing (NGS) represents a huge advancement in diagnostics and these new molecular technologies revealed that thymic neoplasms have the lowest tumor mutation burden among all adult malignant tumours with a different pattern of molecular aberrations in thymomas and thymic carcinomas. As for the PD-L1 expression in tumor cells in thymoma and thymic carcinoma, it varies a lot in published studies, with findings of PD-L1 expression from 23% to 92% in thymoma and 36% to 100% in thymic carcinoma. When correlated PD-L1 expression with disease stage some controversial results were obtained, with no association with tumor stage in most studies. This is, at least in part, explained by the fact that several diverse PD-L1 immunohistochemical tests were used in each trial, with four different antibodies (SP142, SP263, 22C3, and 28-8), different definition of PD-L1 positivity and cutoff values throughout the studies as well. There is a huge interest in using genomic features to produce predictive genomic-based immunotherapy biomarkers, particularly since recent data suggest that certain tumor-specific genomic alterations, either individually or in combination, appear to influence immune checkpoint activity and better responses as the outcome, so as such in some cancer types they may complement existing biomarkers to improve the selection criteria for immunotherapy.",
publisher = "Ame Publ Co, Shatin",
journal = "Journal of Thoracic Disease",
title = "Correlation of genomic alterations and PD-L1 expression in thymoma",
pages = "7570-7561",
number = "12",
volume = "12",
doi = "10.21037/jtd-2019-thym-13"
}

Jovanović, D., Marković, J., Ceriman, V., Perić, J., Pavlović, S.,& Soldatović, I.. (2020). Correlation of genomic alterations and PD-L1 expression in thymoma. in Journal of Thoracic Disease
Ame Publ Co, Shatin., 12(12), 7561-7570.
https://doi.org/10.21037/jtd-2019-thym-13

Jovanović D, Marković J, Ceriman V, Perić J, Pavlović S, Soldatović I. Correlation of genomic alterations and PD-L1 expression in thymoma. in Journal of Thoracic Disease. 2020;12(12):7561-7570.
doi:10.21037/jtd-2019-thym-13 .

Jovanović, Dragana, Marković, Jelena, Ceriman, Vesna, Perić, Jelena, Pavlović, Sonja, Soldatović, Ivan, "Correlation of genomic alterations and PD-L1 expression in thymoma" in Journal of Thoracic Disease, 12, no. 12 (2020):7561-7570,
https://doi.org/10.21037/jtd-2019-thym-13 . .

TY  - JOUR
AU  - Doknić, Mirjana
AU  - Gašić, Vladimir
AU  - Stojanović, Marko
AU  - Pavlović, Sonja
AU  - Marinković, Snežana
AU  - Miljić, Dragana
AU  - Pekić, Sandra
AU  - Manojlović-Gacić, Emilija
AU  - Damjanović, Dusan
AU  - Soldatović, Ivan
AU  - Petakov, Milan
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1404
AB  - Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.
PB  - Springer, New York
T2  - Pituitary
T1  - Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood
EP  - 408
IS  - 4
SP  - 400
VL  - 23
DO  - 10.1007/s11102-020-01049-9
ER  - 

@article{
author = "Doknić, Mirjana and Gašić, Vladimir and Stojanović, Marko and Pavlović, Sonja and Marinković, Snežana and Miljić, Dragana and Pekić, Sandra and Manojlović-Gacić, Emilija and Damjanović, Dusan and Soldatović, Ivan and Petakov, Milan",
year = "2020",
abstract = "Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.",
publisher = "Springer, New York",
journal = "Pituitary",
title = "Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood",
pages = "408-400",
number = "4",
volume = "23",
doi = "10.1007/s11102-020-01049-9"
}

Doknić, M., Gašić, V., Stojanović, M., Pavlović, S., Marinković, S., Miljić, D., Pekić, S., Manojlović-Gacić, E., Damjanović, D., Soldatović, I.,& Petakov, M.. (2020). Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood. in Pituitary
Springer, New York., 23(4), 400-408.
https://doi.org/10.1007/s11102-020-01049-9

Doknić M, Gašić V, Stojanović M, Pavlović S, Marinković S, Miljić D, Pekić S, Manojlović-Gacić E, Damjanović D, Soldatović I, Petakov M. Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood. in Pituitary. 2020;23(4):400-408.
doi:10.1007/s11102-020-01049-9 .

Doknić, Mirjana, Gašić, Vladimir, Stojanović, Marko, Pavlović, Sonja, Marinković, Snežana, Miljić, Dragana, Pekić, Sandra, Manojlović-Gacić, Emilija, Damjanović, Dusan, Soldatović, Ivan, Petakov, Milan, "Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood" in Pituitary, 23, no. 4 (2020):400-408,
https://doi.org/10.1007/s11102-020-01049-9 . .

TY  - CONF
AU  - Marić, Nadja
AU  - Mihaljević, Marina
AU  - Franić, Dusanka
AU  - Soldatović, Ivan
AU  - Andrić, Sanja
AU  - Lukić, Iva
AU  - Mirjanić, Tijana
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Dobricić, Valerija
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1047
PB  - Oxford Univ Press, Oxford
C3  - Schizophrenia Bulletin
T1  - The signature of trauma in psychosis: a preliminary genetic and epigenetic analyses of fk506-binding protein 5 regulation
EP  - S66
SP  - S66
VL  - 43
UR  - https://hdl.handle.net/21.15107/rcub_vinar_7156
ER  - 

@conference{
author = "Marić, Nadja and Mihaljević, Marina and Franić, Dusanka and Soldatović, Ivan and Andrić, Sanja and Lukić, Iva and Mirjanić, Tijana and Stanković, Biljana and Zukić, Branka and Dobricić, Valerija and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav",
year = "2017",
publisher = "Oxford Univ Press, Oxford",
journal = "Schizophrenia Bulletin",
title = "The signature of trauma in psychosis: a preliminary genetic and epigenetic analyses of fk506-binding protein 5 regulation",
pages = "S66-S66",
volume = "43",
url = "https://hdl.handle.net/21.15107/rcub_vinar_7156"
}

Marić, N., Mihaljević, M., Franić, D., Soldatović, I., Andrić, S., Lukić, I., Mirjanić, T., Stanković, B., Zukić, B., Dobricić, V., Novaković, I., Pavlović, S.,& Adžić, M.. (2017). The signature of trauma in psychosis: a preliminary genetic and epigenetic analyses of fk506-binding protein 5 regulation. in Schizophrenia Bulletin
Oxford Univ Press, Oxford., 43, S66-S66.
https://hdl.handle.net/21.15107/rcub_vinar_7156

Marić N, Mihaljević M, Franić D, Soldatović I, Andrić S, Lukić I, Mirjanić T, Stanković B, Zukić B, Dobricić V, Novaković I, Pavlović S, Adžić M. The signature of trauma in psychosis: a preliminary genetic and epigenetic analyses of fk506-binding protein 5 regulation. in Schizophrenia Bulletin. 2017;43:S66-S66.
https://hdl.handle.net/21.15107/rcub_vinar_7156 .

Marić, Nadja, Mihaljević, Marina, Franić, Dusanka, Soldatović, Ivan, Andrić, Sanja, Lukić, Iva, Mirjanić, Tijana, Stanković, Biljana, Zukić, Branka, Dobricić, Valerija, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, "The signature of trauma in psychosis: a preliminary genetic and epigenetic analyses of fk506-binding protein 5 regulation" in Schizophrenia Bulletin, 43 (2017):S66-S66,
https://hdl.handle.net/21.15107/rcub_vinar_7156 .