Publications by authors named "Sanja Stankovic"

92 Publications

Biochemical, carcass and meat quality alterations associated with different degree of lung lesions in slaughtered pigs.

Prev Vet Med 2021 Mar 15;188:105269. Epub 2021 Jan 15.

University of Belgrade, Faculty of Veterinary Medicine, Department of Food Hygiene and Technology, Bulevar Oslobodjenja 18, 11000, Belgrade, Serbia. Electronic address:

This study examined the relationship between lung lesion severity and presence of antibodies of various respiratory pathogens, and the effects of lung lesion severity on growth performance, biochemical indicators, total aerobe counts, and carcass and meat quality indicators in total of 240 slaughter pigs originating from two farms with similar rearing conditions. Lung lesion severity was calculated based on the degree of pneumonia and pleurisy in slaughtered pigs. Two-step cluster analysis was used to place individual pigs to four clusters according to pneumonia and pleurisy scores: no lung lesions (cluster 1); mild lung lesions (cluster 2); moderate lung lesions (cluster 3); and severe lung lesions (cluster 4). ANOVA and post hoc pairwise comparisons using Tukey's test were performed to assess the differences between clusters in examined variables. Multivariate linear regression analysis was run to identify associations between lung lesions and examined variables. There was a strong evidence of association between the absence of lung lesions and increased albumin, sodium and chloride levels, daily weight gain, live weight, hot carcass weight, cold carcass weight, loin thickness and carcass lean content, and decreased haptoglobin, CK and LDH levels. Also, pigs without lung lesions produced the highest percentage of red, firm and nonexudative pork. Pigs having severe lung lesions had the highest percentage of simultaneously seropositive samples to SIV, PRRSV, PCV-2, PRCV, APP and M. hyopneumoniae. There was a strong evidence of association between the presence of severe lung lesions and decreased lactate, glucose, sodium, chloride and albumine levels, daily weight gain, live weight, hot carcass weight, cold carcass weight, loin thickness and carcass lean content, and increased CK, LDH and haptoglobin levels. There was a strong evidence of association between the presence of severe lung lesions in slaughered pigs and increased meat pH and sensory colour scores, and decreased drip, thawing and cooking losses and L* and b* values, which led to the highest occurrence of moderate DFD and DFD pork. There was a strong evidence of association between the presence of mild lung lesions in slaughtered pigs and decreased meat pH and sensory colour scores, and increased drip, thawing and cooking losses, L* and b* values, which led to the highest occurrence of moderate PSE and PSE pork. In conclusion, the presence of lung lesions, irrespective of severity, was significantly associated with alterations in the biochemical indicators, growth performance and carcass and meat quality in slaughtered pigs.
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http://dx.doi.org/10.1016/j.prevetmed.2021.105269DOI Listing
March 2021

Hepcidin Is a Reliable Marker of Iron Deficiency Anemia in Newly Diagnosed Patients with Inflammatory Bowel Disease.

Dis Markers 2020 28;2020:8523205. Epub 2020 Nov 28.

Clinic of Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia.

Results: There was a high statistically significant difference between IBD patients and controls in levels of hepcidin ( < 0.01). Namely, serum hepcidin levels were significantly higher in the control group. There was no statistically significant correlation of serum hepcidin with CRP, Mayo score, or CDAI, respectively ( > 0.05). However, we have found a statistically significant negative correlation of sTfR and TIBC with hepcidin ( < 0.01).

Conclusion: Results of our study suggest that hepcidin is a reliable marker of IDA in patients with IBD, and it could be used in routine clinical practice when determining adequate therapy in these patients.
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http://dx.doi.org/10.1155/2020/8523205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737436PMC
November 2020

The role of MIF in hepatic function, oxidative stress, and inflammation in thioacetamide-induced liver injury in mice: Protective effects of betaine.

Curr Med Chem 2020 Nov 4. Epub 2020 Nov 4.

Institute of Pathophysiology ''Ljubodrag Buba Mihailović'', Faculty of Medicine, University of Belgrade. Serbia.

Background: Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that contributes to the inflammatory response to chemical liver injury. This cytokine exhibits pro- and anti-inflammatory effects depending on etiology and stage of liver disease.

Objective: Our study aimed to investigate the role of MIF in oxidative stress and the inflammation in the liver, and modulatory effects of betaine on MIF in thioacetamide (TAA)-induced chronic hepatic damage in mice.

Methods: The experiment was performed on wild type and knockout MIF-/- C57BL/6 mice. They were divided into groups: Control; Bet-group, received betaine (2% wt/v dissolved in drinking water); MIF-/- mice group; MIF-/-+Bet; TAA-group, received of TAA (200 mg/kg b.w.), intraperitoneally, 3x/week/8 weeks); TAA+Bet; MIF-/-+TAA, and MIF-/-+TAA+Bet. In TAA- and Bet-treated groups, animals received in the same previous doses. After eight weeks of treatment, blood samples were collected for biochemical analysis and liver specimens were prepared for assessment the parameters of oxidative stress and inflammation.

Results: In MIF-/-mice, TAA reduced transaminases, -glutamyltranspeptidase, bilirubin, malondaldehyde (MDA), oxidative protein products (AOPP), total oxidant status (TOS), C-reactive protein (CRP), IL-6, IFN- , and increased of thiols and total antioxidant status (TAS). Betain attenuates mechanism of MIF-mediated effects in TAA-induced liver injury, reducing transaminases, -glutamyltranspeptidase, bilirubin, MDA, AOPP, TOS, CRP, IL-6, IFN-g and increasing thiols.

Conclusion: MIF is mediator in hepatotoxic, pro-oxidative and proinfammatory effects of TAA-induced liver injury. MIFtargeted therapy could potentially mitigate the oxidative stress and inflammation in the liver, but the exact mechanism of its action requires further investigation. Betaine increases antioxidative defense and attenuates hepatotoxic effects of MIF, suggesting that betaine can be used for the prevention and treatment of liver damage.
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http://dx.doi.org/10.2174/0929867327666201104151025DOI Listing
November 2020

Update on current practice in laboratory medicine in respect of natriuretic peptide testing for heart failure diagnosis and management in Europe. The CARdiac MArker guideline Uptake in Europe (CARMAGUE) study.

Clin Chim Acta 2020 Dec 28;511:59-66. Epub 2020 Sep 28.

Clinical Chemistry, HUS Diagnostic Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland. Electronic address:

Background: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) initiated the CArdiac MARker Guidelines Uptake in Europe (CAMARGUE) Study to survey if current biomarker testing for heart failure (HF) in Europe is in accordance with up-dated guidelines.

Methods: A web-based questionnaire was distributed to clinical laboratories via European biochemical societies in 2019. Questions covered the type of natriuretic peptide (NP) assays performed, decision limits for HF, and opinion concerning requirement of different thresholds in patients with renal failure or obesity.

Results: There were 347 participating laboratories mostly from European countries with 266 offering NP testing. NP testing was increased from 67% to 77% between 2013 and 2019. NT-proBNP remained the preferred biomarker. Recommended decision limits were implemented for BNP (85%) and better focused for NT-proBNP (40%) than in the previous survey. The survey revealed that laboratorians are willing to support the translation of adjusted cut-off values for age, gender and for patients with conditions like renal insufficiency.

Conclusion: Guidelines stimulate clinical laboratories to offer NP testing with high value for the diagnosis and management of HF, and to present adjusted medical decision limits. Future guidelines should encourage the use of personalized cut-offs for some confounding factors.
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http://dx.doi.org/10.1016/j.cca.2020.09.030DOI Listing
December 2020

Prediction of adverse maternal outcomes of early severe preeclampsia.

Pregnancy Hypertens 2020 Oct 17;22:144-150. Epub 2020 Sep 17.

Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Objectives: Assess soluble FMS-like tyrosine kinase-1/placental growth factor ratio (sFlt-1/PlGF) diagnostic accuracy for predicting adverse maternal outcome in patients with early severe preeclampsia, and whether its predictive performance is superior to full preeclampsia integrated estimate of risk score (PIERS).

Study Design: Prospective study enrolled patients with early severe preeclampsia (defined by American College of Obstetricians and Gynaecologists 2013 guidelines) admitted to the Clinic for Obstetrics and Gynaecology, Clinical Center of Serbia intensive care unit. Patients underwent delivery to terminate preeclampsia within 48 h of admission. PIERS was generated and blood samples taken at admission. Multiple pregnancies and gestational ages outside 24-34 weeks were excluded. sFlt-1 and PlGF serum concentrations were measured using Elecsys® assays and cobas e 601 analyser. Maternal complications were recorded for seven days post-delivery.

Main Outcome Measures: Diagnostic accuracy (sensitivity and specificity), and predictive performance (receiver operating characteristic area under curve [AUC]) vs. PIERS, of sFlt-1/PlGF for predicting adverse maternal outcome.

Results: Of 89 patients enrolled, 61 were evaluable. Median frequency of adverse maternal outcomes within seven days of delivery was two. Median sFlt-1/PlGF and PIERS were 521·0 and 5·0%, respectively. sFlt-1/PlGF showed greater correlation with complication number than PIERS (Spearman's rho: 0·728 [p < 0·001] and 0·134 [p = 0·304], respectively). AUC for sFlt-1/PlGF and PIERS were 0·853 and 0·628, respectively. A 377·0 sFlt-1/PlGF cut-off was optimal for predicting complications (75·0% sensitivity; 92·3% specificity).

Conclusions: sFlt-1/PlGF correlated more closely with number of adverse maternal outcomes than PIERS, and was a superior predictor of maternal complications.
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http://dx.doi.org/10.1016/j.preghy.2020.09.009DOI Listing
October 2020

Collaborative AI and Laboratory Medicine integration in precision cardiovascular medicine.

Clin Chim Acta 2020 Oct 4;509:67-71. Epub 2020 Jun 4.

Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia; Emerging Technologies Division-MHBLM Committee, International Federation Clinical Chemistry and Laboratory Medicine (IFCC), Italy.

Artificial Intelligence (AI) is a broad term that combines computation with sophisticated mathematical models and in turn allows the development of complex algorithms which are capable to simulate human intelligence such as problem solving and learning. It is devised to promote a significant paradigm shift in the most diverse areas of medical knowledge. On the other hand, Cardiology is a vast field dealing with diseases relating to the heart, the circulatory system, and includes coronary heart disease, cerebrovascular disease, rheumatic heart disease and other conditions. AI has emerged as a promising tool in cardiovascular medicine which is aimed in augmenting the effectiveness of the cardiologist and to extend better quality to patients. It has the ability to support decision‑making and improve diagnostic and prognostic performance. Attempt has also been made to explore novel genotypes and phenotypes in existing cardiovascular diseases, improve the quality of patient care, to enablecost-effectiveness with reducereadmissionand mortality rates. Our review addresses the integration of AI and laboratory medicine as an accelerator of personalization care associated with the precision and the need of value creation services in cardiovascular medicine.
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http://dx.doi.org/10.1016/j.cca.2020.06.001DOI Listing
October 2020

Lipid profile and left ventricular geometry pattern in obese children.

Lipids Health Dis 2020 May 26;19(1):109. Epub 2020 May 26.

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, 281/289 Rzgowska St., 93-338, Lodz, Poland.

Background: Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular and all-cause mortality. Previous studies reported conflicting results concerning the relationship between serum lipid levels and left ventricular geometry pattern. We sought to explore the relationship between standard serum lipid profile measures with left ventricular geometry pattern in obese children.

Patients And Methods: In this cross-sectional study, a total of 70 obese children were examined. Fasting blood samples were taken to measure total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TGs), glucose, and insulin. Based on these values TG/HDL ratio, BMI and HOMA index were calculated. We also measured the average 24-h ambulatory systolic blood pressure (SBP) and two-dimensional (2/D) transthoracic echocardiography was performed to determine left ventricular mass index (LVMI) and relative wall thickness (RWT). Multiple regression analyses were conducted to explore relationships between study variables and the LVMI or RWT as outcome variables. The final model with LVMI included TG/HDL ratio, BMI, 24 h-average SBP, age and sex, while for the RWT we included BMI, insulin, age and sex.

Results: Our study included 70 children (65.71% boys and 34.29% girls) median age (14 years, IQR = 12-16)." We demonstrated independent and positive association of TG/HDL ratio, BMI and 24 h-average SBP with LVMI (effect = 3.65, SE = 1.32, p < 0.01; effect = 34.90, SE = 6.84, p < 0.01; effect = 0.32, SE = 0.12, p < 0.01, respectively). On the other hand, in model with RWT as outcome variable, only BMI and insulin were significantly linked (BMI: effect = 13.07, SE = 5.02, p = 0.01 Insulin: effect = 2.80, SE = 0.97).

Conclusion: Increased TG/HDL ratio in obese children is associated with the development of eccentric left ventricular hypertrophy while increased BMI and insulin were associated with concentric left ventricular hypertophy.
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http://dx.doi.org/10.1186/s12944-020-01285-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251900PMC
May 2020

How well do laboratories adhere to recommended guidelines for dyslipidaemia management in Europe? The CArdiac MARker Guideline Uptake in Europe (CAMARGUE) study.

Clin Chim Acta 2020 Sep 23;508:267-272. Epub 2020 May 23.

Department of Clinical Chemistry, HUSLAB, Helsinki University Hospital, Helsinki, Finland.

Background: The CArdiac MARker Guidelines Uptake in Europe Study (CAMARGUE) initiated by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) aims to survey the current use of evidence-based guidelines for dyslipidemia testing in Europe.

Methods: In 2019 a web-based questionnaire was distributed via EFLM National Societies to clinical laboratories in Europe. Questions covered pre-analytics, analytical methods, measurement units, flagging of decision thresholds, and use of decision-enhancing comments.

Results: Returns were obtained from 452 laboratories from 28 countries. Most laboratories always use nonfasting blood samples for lipid assays (66%). Lipid profiles are reported in mmol/L by 59% of the laboratories, mainly from 14 countries promoting the use of SI units. Important differences in flagging of decision thresholds were observed, with less than half of the laboratories applying the guideline-recommended LDL cholesterol threshold. Only 17% of the laboratories add an alert comment when familial hypercholesterolemia is suspected and 23% when risk of pancreatitis from hypertriglyceridemia is high.

Conclusions: There are marked differences among laboratories in Europe in terms of pre-analytical, analytical, and post-analytical lipid management that could have an important clinical impact. This relates to different availability of assays or different laboratory practices on reporting and flagging of lipid profiles.
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http://dx.doi.org/10.1016/j.cca.2020.05.038DOI Listing
September 2020

Folic acid affects cardiometabolic, oxidative stress, and immunohistochemical parameters in monocrotaline-induced rat heart failure.

Can J Physiol Pharmacol 2020 Oct 30;98(10):708-716. Epub 2020 Apr 30.

Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Heart failure (HF) is one of the major cardiovascular causes of death worldwide. In this study, we explored the effects of folic acid (FA) on cardiometabolic, oxidative stress biomarker changes, and the activity of proliferation marker Ki67 in monocrotaline-induced HF. The research was conducted during a 4 week period using five experimental groups (eight animals per group): blank solution exposed controls (C1: 1 mL/kg physiological saline, 1 day; C2: 1 mL/kg physiological saline, 28 days), monocrotaline (MCT) induced HF (50 mg/kg MCT), FA (5 mg·kg·day FA), and MCT+FA (50 mg/kg MCT, 5 mg·kg·day FA). Superoxide dismutase and glutathione peroxidase activities together with total glutathione and parameters of oxidative damage of proteins were determined in cardiac tissue as well as cardiometabolic parameters in plasma or serum. The total glutathionylation was determined by Western blot and proliferation marker Ki67 was assessed by immunohistochemistry. The right ventricular (RV) wall hypertrophy and Ki67 positivity, accompanied by a significant increase of troponin T, has been shown in MCT-induced HF. The antioxidant effect of FA was reflected through superoxide dismutase activity, reduced Ki67 positivity in the RV wall, and a slightly decreased total glutathionylation level.
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http://dx.doi.org/10.1139/cjpp-2020-0030DOI Listing
October 2020

Identifying Physiological Stress Biomarkers for Prediction of Pork Quality Variation.

Animals (Basel) 2020 Apr 2;10(4). Epub 2020 Apr 2.

Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, University of Belgrade, Bulevar oslobodjenja 18, 11000 Belgrade, Serbia.

This study assessed the potential use of various physiological stress biomarkers as indicators of carcass and meat quality traits in 240 pigs subjected to the standard marketing conditions and minimal stressful antemortem handling using Pearson correlations. The most important pork quality traits (pH and temperature, water holding capacity, and color) had limited correlations with stress metabolites (lactate, glucose), stress hormones (cortisol, adrenocorticotropic hormone), stress enzymes (creatine kinase, aspartate amino transferase, alanine amino transferase), electrolytes (sodium, chloride), and acute-phase proteins (haptoglobin, C-reactive protein, albumin), indicating poor reliability in predicting pork quality. Albumin level was moderately positively correlated with live weight, hot carcass weight, cold carcass weight, and back fat thickness. Alanine amino transferase level was moderately positively correlated with live weight, hot carcass weight, and cold carcass weight. Cortisol level was moderately positively correlated with live weight, hot carcass weight, cold carcass weight, and back fat thickness, and moderately negatively correlated with the lean carcass content. Increased lactate dehydrogenase level was moderately correlated with decreased drip and cooking loss. In conclusion, lactate dehydrogenase could help pork producers predict pork quality variation, while cortisol, alanine amino transferase, and albumin could be useful in prediction of carcass quality.
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http://dx.doi.org/10.3390/ani10040614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222799PMC
April 2020

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens-An Insight From Translational Studies.

Int J Mol Sci 2020 Mar 16;21(6). Epub 2020 Mar 16.

Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia.

Estrogen signaling plays an important role in pituitary development and function. In sensitive rat or mice strains of both sexes, estrogen treatments promote lactotropic cell proliferation and induce the formation of pituitary adenomas (dominantly prolactin or growth-hormone-secreting ones). In male patients receiving estrogen, treatment does not necessarily result in pituitary hyperplasia, hyperprolactinemia or adenoma development. In this review, we comprehensively analyze the mechanisms of estrogen action upon their application in male animal models comparing it with available data in human subjects. Sex-specific molecular targets of estrogen action in lactotropic (PRL) cells are highlighted in the context of their proliferative and secretory activity. In addition, putative effects of estradiol on the cellular/tumor microenvironment and the contribution of postnatal pituitary progenitor/stem cells and transdifferentiation processes to prolactinoma development have been analyzed. Finally, estrogen-induced morphological and hormone-secreting changes in pituitary thyrotropic (TSH) and adrenocorticotropic (ACTH) cells are discussed, as well as the putative role of the thyroid and/or glucocorticoid hormones in prolactinoma development, based on the current scarce literature.
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http://dx.doi.org/10.3390/ijms21062024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139613PMC
March 2020

Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM.

Atherosclerosis 2020 02 9;294:46-61. Epub 2020 Jan 9.

Department of Clinical Chemistry, HUSLAB, Helsinki University Hospital, Helsinki, Finland.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total - HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDL cholesterol is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDL cholesterol shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDL cholesterol decline poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apolipoprotein B measurement can detect elevated LDL particle numbers often unidentified on the basis of LDL cholesterol alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.
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http://dx.doi.org/10.1016/j.atherosclerosis.2019.12.005DOI Listing
February 2020

Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM.

Clin Chem Lab Med 2020 03;58(4):496-517

Department of Clinical Chemistry, HUSLAB, Helsinki University Hospital, Helsinki, Finland.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total - HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.
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http://dx.doi.org/10.1515/cclm-2019-1253DOI Listing
March 2020

Using the RISK-PCI Score in the Long-Term Prediction of Major Adverse Cardiovascular Events and Mortality after Primary Percutaneous Coronary Intervention.

J Interv Cardiol 2019 24;2019:2679791. Epub 2019 Oct 24.

Coronary Care Unit, Clinical Centre of Serbia, Emergency Hospital, Belgrade, Serbia.

Background/aim: The RISK-PCI is a simple score for the prediction of 30-day major adverse cardiovascular events (MACE) and mortality in patients treated with primary PCI (pPCI). The aim of the present study is to evaluate the prognostic performance of the RISK-PCI score in predicting MACE and mortality in the long-term follow-up of STEMI patients treated with pPCI.

Method: The present study enrolled 2,096 STEMI patients treated with pPCI included in the RISK-PCI trial. Patients presenting with cardiogenic shock were excluded. The composite end-point MACE comprising cardiovascular mortality, nonfatal reinfarction and stroke. Patients were followed up at 6 years after enrollment.

Results: One-year and 6-year MACE occurred in 229 (10.9%) and 285 (13.6%) patients, respectively; and 1-year and 6-year mortality occurred in 128 (6.2%) and 151 (7.2%) patients, respectively. The RISK-PCI score was an independent predictor for 1-year MACE (HR 1.24, 95% CI 1, 18-1.31, < 0.001), 6-year MACE (HR 1.22, 95% CI 1.16-1.28, < 0.001), 1-year mortality (HR 1.21, 95% CI 1.13-1.29, < 0.001), and 6-year mortality (HR 1.23, 95% CI 1.15-1.31, < 0.001). The discrimination of the RISK-PCI score to predict 1-year and 6-year MACE and mortality was good: for 1-year MACE c-statistic 0.78, for 6-year MACE c-statistic 0.75, for 1-year mortality c-statistic 0.87, and for 6-year mortality c-statistic 0.83. The nonsignificant Hosmer-Lemeshow goodness-of-fit estimates for 1-year MACE (=0.619), 6-year MACE (=0.319), 1-year mortality (=0.258), and 6-year mortality (=0.540) indicated a good calibration of the model.

Conclusion: The RISK-PCI score demonstrates good characteristics in the assessment of the risk for the occurrence of MACE and mortality during long-term follow-up after pPCI.
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http://dx.doi.org/10.1155/2019/2679791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854242PMC
February 2020

Retraction of: The Effect of a Gender Difference in the Apolipoprotein E Gene DNA Polymorphism on Serum Lipid Levels in a Serbian Healthy Population.

Clin Chem Lab Med 2020 02;58(3):e94

"Vinca" Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, P.O. Box 522, YU-11001 Belgrade, Yugoslavia.

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http://dx.doi.org/10.1515/cclm-2019-8899DOI Listing
February 2020

4th ESPT Conference: pharmacogenomics and personalized medicine - research progress and clinical implementation.

Pharmacogenomics 2019 10;20(15):1063-1069

Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.

The Fourth European Society of Pharmacogenomics and Personalized Therapy biennial conference was organized in collaboration with the Italian Society of Personalized Medicine (SIMeP) and was held at Benedictine Monastery of San Nicolò l'Arena in Catania, Sicily (Italy) on 4-7 October 2017. The congress addressed the research progress and clinical implementation in pharmacogenomics and personalized medicine. The Fourth European Society of Pharmacogenomics and Personalized Therapy congress brought together leading international scientists and healthcare professionals actively working in the fields of pharmacogenomics and personalized therapy. Altogether, 25 speakers in 15 session comprehensively covered broad spectrum of pharmacogenetics and pharmacogenomics research, clinical applications in different clinical disciplines attended by 270 delegates.
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http://dx.doi.org/10.2217/pgs-2019-0095DOI Listing
October 2019

Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers.

Arch Med Sci 2019 Sep 23;15(5):1138-1146. Epub 2018 Nov 23.

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.

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 (rs10741657), (rs10877012), (rs7041; rs4588), and (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 rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover, 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 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.
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http://dx.doi.org/10.5114/aoms.2018.79682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764301PMC
September 2019

The influence of subchronic co-application of vitamins B6 and folic acid on cardiac oxidative stress and biochemical markers in monocrotaline-induced heart failure in male Wistar albino rats.

Can J Physiol Pharmacol 2020 Feb 10;98(2):93-102. Epub 2019 Sep 10.

Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

The aim of this study was to test the hypothesis that subchronic co-application of vitamins B6 and folic acid (FA) could affect heart failure (HF) induced by monocrotaline (MCT), with the modulation of oxidative stress parameters and cardiometabolic biomarkers. Biochemical and histomorphometric analyses were assessed in blank solution-exposed controls (C1 physiological saline 1 mL/kg, 1 day, = 8; C2 physiological saline 1 mL/kg, 28 days, = 8), MCT-induced HF MCT 50 mg/kg, = 8), B6+FA (vitamin B6 7 mg·kg·day, FA 5 mg·kg·day; = 8), and MCT+B6+FA (MCT 50 mg/kg, vitamin B6 7 mg·kg·day, FA 5 mg·kg·day; = 8) in male Wistar albino rats (body mass 160 g at the start). Superoxide dismutase and glutathione peroxidase activities, thiol-, carbonyl groups, and nitrotyrosine were determined in cardiac tissue. Echocardiography was performed to confirm MCT-induced HF. The right ventricular wall hypertrophy, accompanied with significant increase of troponin T and preserved renal and liver function, has been shown in MCT-induced HF. However, these effects were not related to antioxidant effects of vitamin B6 and FA, since several parameters of oxidative stress were more pronounced after treatment. In this study, co-application of vitamins B6 and FA did not attenuate hypertrophy of the right ventricle wall but aggravated oxidative stress, which is involved in HF pathogenesis.
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http://dx.doi.org/10.1139/cjpp-2019-0305DOI Listing
February 2020

The Effects of Folic Acid Administration on Cardiac Oxidative Stress and Cardiovascular Biomarkers in Diabetic Rats.

Oxid Med Cell Longev 2019 11;2019:1342549. Epub 2019 Jun 11.

Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

The aim of this study was to examine the effects of folic acid administration on the antioxidant enzyme (superoxide dismutase (SOD) and catalase (CAT)) activities, lactate and malate dehydrogenase (LDH and MDH) activities, and certain LDH and MDH isoform distribution in the cardiac tissue of diabetic Wistar male rats. Diabetes mellitus (DM) was induced by streptozotocin (STZ). There were five groups: C1-control (physiological saline 1 ml/kg, i.p. one day), C2-control with daily physiological saline treatment (1 ml/kg, i.p. 28 days), DM-diabetes mellitus (STZ 100 mg/kg in physiological saline, i.p. one day), FA-folic acid (5 mg/kg in physiological saline, i.p. 28 days), and DM+FA-diabetes mellitus and folic acid group (STZ 100 mg/kg in physiological saline, i.p. one day, and folic acid 5 mg/kg in physiological saline, i.p. 28 days). After four weeks, animal hearts were isolated for measurement of enzyme activities, as well as for histomorphometry analyses. An elevated glucose level and a decreased insulin level were obtained in the DM group. SOD, CAT, and MDH activities were elevated in the DM group, while there was no difference in LDH activity among the groups. In all tested groups, four LDH and three MDH isoforms were detected in the heart tissue, but with differences in their relative activities among the groups. Left ventricular cardiomyocyte transversal diameters were significantly smaller in both diabetic groups. Folic acid treatment of diabetic rats induced a reduced glucose level and reduced CAT, SOD, and MDH activities and alleviated the decrease in cardiomyocyte diameters. In conclusion, increased activities of antioxidant enzymes and MDH may be the consequence of oxidative stress caused by DM. Administration of the folic acid has a protective effect since it leads to reduction in glycemia and activities of the certain examined enzymes in the rats with experimentally induced DM.
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http://dx.doi.org/10.1155/2019/1342549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594301PMC
January 2020

The effect of folic acid administration on cardiac tissue matrix metalloproteinase activity and hepatorenal biomarkers in diabetic rats .

Can J Physiol Pharmacol 2019 Sep 11;97(9):893-901. Epub 2019 Jul 11.

Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Diabetes mellitus (DM) is a metabolic disorder that causes severe complications. Thus, the aims of this study were to investigate the influence of DM and folic acid treatment on liver and renal biomarkers, and heart remodeling through evaluation of cardiac matrix metalloproteinase (MMP) activity. There were 4 groups: control (physiological saline 1 mL/kg, i.p., 28 days), DM (streptozotocin [STZ] 100 mg/kg in physiological saline, i.p., 1 day), folic acid (FA; 5 mg/kg, i.p., 28 days), and DM+FA (STZ 100 mg/kg, i.p., 1 day and folic acid 5 mg/kg, i.p., 28 days). Our results demonstrated increased aminotransferase and alkaline phosphatase activity, urea and creatinine concentration, and decreased albumin and fibrinogen concentration in the DM group. MMP-2 relative activity was elevated in the DM and FA groups; MMP-9 was decreased in the DM and increased in the FA group. The folic acid treatment of diabetic rats did not change aminotransferase activity; it alleviated the increase in alkaline phosphatase and the decrease in albumin and fibrinogen concentration, and reduced MMP-2 activity; however, it increased urea and creatinine concentration. In conclusion, folic acid treatment of diabetic rats has cardio- and hepato-protective effects. However, its dosing should be carefully considered because of possible renal damage.
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http://dx.doi.org/10.1139/cjpp-2019-0027DOI Listing
September 2019

Nailfold capillary morphology and platelet function in patients with exfoliative glaucoma.

PLoS One 2019 9;14(7):e0219505. Epub 2019 Jul 9.

Clinic for Eye Diseases, Clinical Center of Serbia, Belgrade, Serbia.

Purpose: The purpose of the present study was to evaluate the nailfold capillary morphological features in patients with exfoliative glaucoma (XFG) and compare them with those pertaining to primary open-angle glaucoma (POAG), normal controls and subjects with exfoliation syndrome (XFS). The second purpose was to investigate all parameters related to platelet function on the hemogram, including the platelet count (PLT), the mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) in patients with XFG. These parameters were subsequently compared with those belonging to normal controls, POAG and XFS subjects.

Methods: This case control study involved 152 consecutive patients that were examined at the Glaucoma Department of Clinic for Eye Diseases, Clinical Centre of Serbia, as the referral center for glaucoma in Serbia, between June 2016 and December 2017.

Results: Regarding capillaroscopic characteristics, statistically significant difference was found in capillary diameter and tortuosity between the XFG and POAG group (p = 0.050 and p = 0.035) and the XFG and NC group (p = 0.003 and p = 0.044), as well as in the distribution of capillary loops and avascular zones between the XFG and NC group (p = 0.014 and p = 0.004). The subjects with XFG had lower PLT values compared to POAG patients (p = 0.022).

Conclusions: In conclusion, to the best of our knowledge, this study marks the first attempt to evaluate capillary morphology as well as to investigate all parameters related to platelet function on the hemogram, in patients with newly diagnosed XFG. Our findings revealed nailfold capillary morphological vascular changes in XFG patients. The subjects with XFG had lower PLT values and a higher MPV serum parameter compared to normal controls and patients with POAG. Further research in this field should therefore aim to evaluate the consequences of the aforementioned microvascular abnormalities in patients with XFG.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219505PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615605PMC
March 2020

Serum heparan sulfate and chondroitin sulfate concentrations in patients with newly diagnosed exfoliative glaucoma.

PeerJ 2019 23;7:e6920. Epub 2019 May 23.

Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Background: Exfoliative glaucoma (XFG) is typically classified as a high-pressure type of secondary open-angle glaucoma that develops as a consequence of exfoliation syndrome (XFS). Exfoliation syndrome is an age-related, generalized disorder of the extracellular matrix characterized by production and progressive accumulation of a fibrillar exfoliation material (XFM) in intra- and extraocular tissues. Exfoliation material represents complex glycoprotein/proteoglycan structure composed of a protein core surrounded by glycosaminoglycans such as heparan sulfate (HS) and chondroitin sulfate (CS). The purpose of the present study was to investigate HS and CS concentrations in serum samples of patients with newly diagnosed XFG and compare the obtained values with those pertaining to newly diagnosed primary open-angle glaucoma (POAG), normal controls (NC) and subjects with XFS.

Methods: This case-control study involved 165 subjects, including patients with newly diagnosed XFG, patients with newly diagnosed POAG, subjects with XFS and age- and sex-matched NC. The study was conducted at the Glaucoma Department of Clinic for Eye Diseases, Clinical Centre of Serbia, as the referral center for glaucoma in Serbia.

Results: The mean age in the XFG, POAG, XFS and NC groups was 73.3 ± 9.0, 66.3 ± 7.8, 75.5 ± 7.0 and 73.5 ± 9.5 years, respectively, XFG vs. POAG, < 0.001. Mean serum HS concentrations in the XFG, POAG, NC and XFS groups were 3,189.0 ± 1,473.8 ng/mL, 2,091.5 ± 940.9 ng/mL, 2,543.1 ± 1,397.3 ng/mL and 2,658.2 ± 1,426.8 ng/mL respectively, XFG vs. POAG, = 0.001 and XFG vs. NC, = 0.032. Mean serum CS concentrations in the XFG, POAG, NC and XFS group were 43.9 ± 20.7 ng/mL, 38.5 ± 22.0 ng/mL, 35.8 ± 16.4 ng/mL and 43.3 ± 21.8 ng/mL, respectively, XFG vs. NC, = 0.041.

Conclusions: Our findings revealed greater HS and CS concentrations in XFG patients and XFS subjects compared to those without XFM. Implications of HS and CS in the pathophysiology of XFS and glaucoma should be studied further. Serum is easily accessible and should thus be explored as rich sources of potential biomarkers. Further research should aim to identify XFG biomarkers that could be utilized in routine blood analysis tests, aiding in timely disease diagnosis.
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http://dx.doi.org/10.7717/peerj.6920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535222PMC
May 2019

Impact of acute hyperglycemia on layer-specific left ventricular strain in asymptomatic diabetic patients: an analysis based on two-dimensional speckle tracking echocardiography.

Cardiovasc Diabetol 2019 06 3;18(1):68. Epub 2019 Jun 3.

Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, dr Subotića 13, Belgrade, 11000, Serbia.

Background: Hyperglycemia has detrimental effect on ischemic myocardium, but the impact of acute hyperglycemia on the myocardium in asymptomatic diabetic patients has not been fully elucidated. Thus, this follow-up study was aimed to investigate the effects and reversibility of acute hyperglycemia on regional contractile function of left ventricle (LV) in diabetic patients without cardiovascular disease.

Methods: The two-dimensional speckle tracking echocardiography (2D-STE), including multilayer strain analysis, was used for evaluation of global and regional LV function in asymptomatic, normotensive patients with uncomplicated diabetes, with acute hyperglycemia ( ≥ 11.1 mmol/l) (Group A, n = 67), or with optimal metabolic control (fasting plasma glucose < 7 mmol/l and HbA1c < 7%) (Group B, n = 20), while 20 healthy individuals served as controls (Group C). In group A, after 72 h of i.v. continuous insulin treatment (at the time euglycemia was achieved) (second examination) and after 3 months following acute hyperglycemia (third examination) 2D-STE was repeated.

Results: Global longitudinal strain (GLS) (- 19.6 ± 0.4%) in Group A was significantly lower in comparison to both groups B (- 21.3 ± 0.4%; p < 0.05) and C (- 21.9 ± 0.4%; p < 0.01) at baseline, while we could not detect the differences between groups B and C. Peak systolic longitudinal endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) layer strain were significantly lower in group A at baseline compared to both groups B and C. Deterioration in peak systolic circumferential strain was observed at basal LV level, in all three layers (Endo, Mid and Epi) and in mid-cavity LV level in Epi layer in group A in comparison to group C. Moreover, in group A, after euglycemia was achieved (at second and third examination) GLS, as well as peak longitudinal and circumferential strain remain the same.

Conclusion: Acute hyperglycemia in asymptomatic diabetic patients has significant negative effects on systolic LV myocardial mechanics primarily by reducing GLS and multilayer peak systolic longitudinal and circumferential strain which was not reversible after three months of good glycemic control.
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http://dx.doi.org/10.1186/s12933-019-0876-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545629PMC
June 2019

Impact on long-term mortality of access and non-access site bleeding after primary percutaneous coronary intervention.

Heart 2019 10 25;105(20):1568-1574. Epub 2019 May 25.

Department for Diagnostic and Catheterization Laboratories, Clinic for Cardiology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Objectives: The influence of the bleeding site on long-term survival after the primary percutaneous coronary intervention (PCI) is poorly understood. This study sought to investigate the relationship between in-hospital access site versus non-access site bleeding and very late mortality in unselected patients treated with primary PCI.

Methods: Data of the 2715 consecutive patients with ST-segment elevation myocardial infarction treated with primary PCI, enrolled in a prospective registry of a high volume tertiary centre, were analysed. Bleeding events were assessed according to the Bleeding Academic Research Consortium (BARC) criteria. The primary outcome was 4-year mortality.

Results: The BARC type ≥2 bleeding occurred in 171 patients (6.3%). Access site bleeding occurred in 3.8%, and non-access site bleeding in 2.5% of patients. Four-year mortality was significantly higher for patients with bleeding (BARC type ≥2) than in patients without bleeding (BARC type 0+1), (36.3% vs 16.2%, p<0.001). Patients with non-access site bleeding had higher 4 year mortality (50.7% vs 26.5%, p=0.001). After multivariable adjustment, BARC type ≥2 bleeding was the independent predictor of 4 year mortality (HR 2.01; 95% CI 1.49 to 2.71, p<0.001). Patients with a non-access site bleeding were at 2-fold higher risk of very late mortality than patients with an access site bleeding (HR 2.62; 1.78 to 3.86, p<0.001 vs HR 1.57; 1.03 to 2.38, p=0.034).

Conclusions: Both access and non-access site BARC type ≥2 bleeding is independently associated with a high risk of 4-year mortality after primary PCI. Patients with non-access site bleeding were at higher risk of late mortality than patients with access site bleeding.
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http://dx.doi.org/10.1136/heartjnl-2019-314728DOI Listing
October 2019

4th ESPT summer school: precision medicine and personalised health.

Pharmacogenomics 2019 05;20(7):471-474

CANSEARCH Research Laboratory, Department of Paediatrics, Faculty of Medicine, Geneva University, 1205 Geneva, Switzerland.

In September 2018, the European Society of Pharmacogenomics and Personalised Therapy (ESPT), with the support of the Swiss Personalized Health Network (SPHN), organized its 4th biennial summer school, entitled 'Precision Medicine and Personalised Health' (Campus Biotech, Geneva, Switzerland; www.esptsummerschool.eu/ ). The school's comprehensive and innovative educational program aimed to address the fundamentals of pharmacogenomics, the latest knowledge on established and new concepts in the field of precision medicine, as well as its advanced clinical applications in personalized health. The school consisted of 31 lectures, eight interactive workshops, visits to genome center and poster presentations, involving 40 speakers from distinguished international faculties. The meeting was a resounding success by generating informal environments between more than 80 participants from 26 different countries.
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http://dx.doi.org/10.2217/pgs-2019-0008DOI Listing
May 2019

Dual Roles of the Mineral Metabolism Disorders Biomarkers in Prevalent Hemodilysis Patients: In Renal Bone Disease and in Vascular Calcification.

J Med Biochem 2019 Apr 3;38(2):134-144. Epub 2019 Mar 3.

Clinical Centre of Serbia, Department of Nephrology, Belgrade, Serbia.

Background: Vascular calcification (VC) is highly prevalent in dialysis (HD) patients, and its mechanism is multifactorial. Most likely that systemic or local inhibitory factor is overwhelmed by promoters of VC in these patients. VC increased arterial stiffness, and left ventricular hypertrophy. Thus, the present study aimed to investigate the association of VC and myocardial remodeling and to analyze their relationship with VC promoters (fibroblast growth factor 23-FGF23, Klotho, intact parathormon-iPTH, vitamin D) in 56 prevalent HD patients (median values: age 54 yrs, HD vintage 82 months).

Methods: Besides routine laboratory analyzes, serum levels of FGF 23, soluble Klotho, iPTH, 1,25-dihydroxyvitamin D3; pulse wave velocity (PWV); left ventricular (LV) mass by ultrasound; and VCs score by Adragao method were measured.

Results: VC was found in 60% and LV concentric or eccentric hypertrophy in 50% patients. Dialysis vintage (OR 1.025, 95%CI 1.007-1.044, p=0.006) FGF23 (OR 1.006, 95% CI 0.992-1.012, p=0.029) and serum magnesium (OR 0.000, 95%CI 0.000-0.214, p=0.04) were associated with VC. Changes in myocardial geometry was associated with male sex (beta=-0.273, 95% CI -23.967 1.513, p=0.027), iPTH (beta 0.029, 95%CI -0.059-0.001, p=0.027) and vitamin D treatment (beta 25.49, 95%CI 11.325-39.667, p=0.001). Also, patients with the more widespread VC had the highest LV remodeling categories. PWV was associated patient's age, cholesterol, diastolic blood pressure, LV mass (positively) and serum calcium (negatively), indicating potential link with atherosclerotic risk.

Conclusions: Despite to different risk factors for VC and myocardial remodeling, obtained results could indicate that risk factors intertwine in long-term treatment of HD patients and therefore careful and continuous correction of mineral metabolism disorders is undoubtedly of the utmost importance.
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http://dx.doi.org/10.2478/jomb-2018-0026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411002PMC
April 2019

The Inflammatory and Hemostatic Cardiovascular Risk Markers During Acute Hyperglycemic Crisis in Type 1 and Type 2 Diabetes.

J Med Biochem 2019 Apr 3;38(2):126-133. Epub 2019 Mar 3.

Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Background: We analyzed cardiovascular inflammatory (C-reactive protein (CRP), interleukin 6 (IL-6)), haemostatic (homocysteine) risk markers in lean and obese patients at admission and acute hyperglicemic crisis (AHC) resolving, involving diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS).

Methods: In that context, we included group A: N = 20 obese, B: N=20 lean patients with DKA; C: N = l0 obese, D: N=10 lean patients with HHS; E: N = 15 obese, F: N=15 lean controls. CRP IL-6, homocysteine were determined by ELISA.

Results: Our results showed that CRP IL-6, and homocysteine levels decreased in all groups: (A: p<0.001; B: p<0.001, C: p<0.05; D: p<0.001 mg/L), (A: p<0.001 B: p<0.001, C: p<0.001, D: p<0.01 pg/mL), (A: p<0.001, B: p <0.001; C: p<0.05, D: p=0.001 μmol/L), respectively, at resolving AHC. However, CRP persisted higher (p<0.001, p<0.01), IL-6 lower (p<0.05, p<0.001), while homocysteine levels turned out to be similar to controls.

Conclusions: AHC is associated with increased inflammatory and hemostatic cardiovascular risk markers. Also, insulin therapy in AHC has had more pronounced favorable effect on IL-6 and homocystein than on CRP.
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http://dx.doi.org/10.2478/jomb-2018-0024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410996PMC
April 2019

Combined Diagnostic Efficacy of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Mean Platelet Volume (MPV) as Biomarkers of Systemic Inflammation in the Diagnosis of Colorectal Cancer.

Dis Markers 2019 17;2019:6036979. Epub 2019 Jan 17.

Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Background: Systemic inflammation in colorectal cancer (CRC) may be reflected by neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV). This study was designed to investigate the efficiency of preoperative NLR, PLR, and MVP as a tool for the assessment of tumor characteristics in newly diagnosed patients with CRC.

Patients And Methods: For 300 patients and 300 healthy volunteers, complete blood counts with automated differential counts were performed. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; PLR was calculated by dividing the absolute platelet count by the absolute lymphocyte count. The diagnostic performance of NLR, PLR, and MVP was estimated by ROC curve.

Results: ROC curve analysis showed high diagnostic efficacy of NLR and PLR in CRC patients with cut-off values of 2.15 (AUC = 0.790, 95% CI 0.736-0.884, Se = 74.1%, and Sp = 73%) and 123 (AUC = 0.846, 95% CI 0.801-0.891, Se = 73.5%, and Sp = 80%) compared to healthy controls, respectively. The diagnostic efficacy of three combined markers was superior compared with individual markers (AUC = 0.904, 95% CI 0.812-0.989, Se = 96%, and Sp = 70%).

Conclusion: NRL, PLR, and MPV may be useful markers in diagnostic and early recognition of different stages of CRC; additionally combined all together have stronger diagnostic efficacy.
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http://dx.doi.org/10.1155/2019/6036979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360046PMC
June 2019

Vitamin D Is Inversely Related to Obesity: Cross-Sectional Study in a Small Cohort of Serbian Adults.

J Am Coll Nutr 2019 07 11;38(5):405-414. Epub 2019 Jan 11.

a Institute for Medical Research, Centre of Research Excellence in Nutrition and Metabolism , University of Belgrade , Beograd , Serbia.

: Vitamin D (vitD) mediates numerous health conditions other than bone health and mineralization. Its role in cardiometabolic condition is still inconclusive. : We conducted a cross-sectional study in 87 apparently healthy Serbian adults. We assessed their dietary intake, anthropometric and biochemical parameters, blood pressure, and vitD status (as serum 25-hydroxyvitamin D, 25(OH)D). Unexpectedly, the status was significantly higher in January than in July. Therefore, we pooled the data from two time points, to enhance the statistical power for carrying out association analyses. We employed linear regression models to evaluate the associations between vitD status and the obesity biomarkers of serum lipids and blood pressure. : Mean vitD intake of 3.85 ± 4.71 μg in the cohort was below recommended. Of the subjects in the pooled cohort, 60.58% were vitD deficient (with serum 25(OH)D below 50 nmol/L), with the majority of them being women who were overweight. VitD status tended to be inversely related to percent body fat and waist/height ratio in the crude regression model. After age and gender adjustment, the status was significantly related to waist circumference, waist/height ratio, and waist/hip ratio (β = -0.116, 95% confidence interval [CI]: -0.206, -0.025, β = -0.001, 95% CI: -0.001, 0.000, and β = -0.001, 95% CI: -0.001, 0.000, respectively). These associations remained only within women. Fully adjusted models supported the notion of vitD being independently associated with central adiposity, regardless of age, gender, and total obesity. : In apparently healthy adults with low vitD intake, vitD status was inversely associated with obesity parameters, pronouncedly in women. Our data support the need for development and implementation of public health policies on increasing vitD intake also as part of obesity management strategies.
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http://dx.doi.org/10.1080/07315724.2018.1538828DOI Listing
July 2019