Browsing by Author "Ignjatović, Svetlana (55901270700)"

Purpose: Graves’ orbitopathy (GO) is a complex inflammatory disease of the orbit. A potential link between cholesterol metabolism and the occurrence of GO is possible, but still unexplored. This study aims to investigate patients’ lipid status, fatty acid content, and cholesterol homeostasis markers, all in relation to the clinical phenotype of GO. Methods: This cross-sectional study enrolled 89 consecutive patients with GO of varying degrees of activity and severity. Conventional lipid parameters were measured using routine biochemical methods. Concentrations of cholesterol synthesis and cholesterol absorption markers were analyzed by a GC-FID method. The percentage composition of individual fatty acids was determined by GC-FID. Total concentration of thyrotropin-receptor antibodies was measured by a binding immunoassay (Roche Diagnostics), while their stimulating activity (TSAb) was quantified using a cell-based bioassay (Quidelortho). Results: HDL-C concentration was significantly lower in patients with an active GO compared to an inactive form of GO (p = 0.032). The ApoB/ApoA1 ratio was significantly higher in a more severe GO (p = 0.029). Also, a positive correlation between LDL-C and TSAb levels (ρ = 0.255, p = 0.019) was observed. Lathosterol concentration significantly increased in more severe GO cases (p = 0.045). Moreover, the level of cholesterol synthesis-to-absorption index (CSI/CAI) positively correlated with CAS score (ρ = 0.232, p = 0.048). Palmitic acid was significantly associated with active GO (p = 0.012). The levels of desmosterol, lathosterol, CSI/CAI, and oleic acid were significantly associated with TSAb levels. Conclusions: Alterations in patients’ lipid profile and the cholesterol homeostasis were associated with a worse clinical phenotype of GO. © The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE) 2025.

Purpose: Graves’ orbitopathy (GO) is a complex inflammatory disease of the orbit. A potential link between cholesterol metabolism and the occurrence of GO is possible, but still unexplored. This study aims to investigate patients’ lipid status, fatty acid content, and cholesterol homeostasis markers, all in relation to the clinical phenotype of GO. Methods: This cross-sectional study enrolled 89 consecutive patients with GO of varying degrees of activity and severity. Conventional lipid parameters were measured using routine biochemical methods. Concentrations of cholesterol synthesis and cholesterol absorption markers were analyzed by a GC-FID method. The percentage composition of individual fatty acids was determined by GC-FID. Total concentration of thyrotropin-receptor antibodies was measured by a binding immunoassay (Roche Diagnostics), while their stimulating activity (TSAb) was quantified using a cell-based bioassay (Quidelortho). Results: HDL-C concentration was significantly lower in patients with an active GO compared to an inactive form of GO (p = 0.032). The ApoB/ApoA1 ratio was significantly higher in a more severe GO (p = 0.029). Also, a positive correlation between LDL-C and TSAb levels (ρ = 0.255, p = 0.019) was observed. Lathosterol concentration significantly increased in more severe GO cases (p = 0.045). Moreover, the level of cholesterol synthesis-to-absorption index (CSI/CAI) positively correlated with CAS score (ρ = 0.232, p = 0.048). Palmitic acid was significantly associated with active GO (p = 0.012). The levels of desmosterol, lathosterol, CSI/CAI, and oleic acid were significantly associated with TSAb levels. Conclusions: Alterations in patients’ lipid profile and the cholesterol homeostasis were associated with a worse clinical phenotype of GO. © The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE) 2025.

Introduction Every clinical trial has to meet all ethical criteria in addition to the scientific ones. The basic ethical principles in the clinical trials are the following: nonmaleficence, beneficence, respect for autonomy and the principle of justice. Objective The aim of the study was to analyse clinical cases with the outcomes leading to the changes in regulatory-ethical framework related to the clinical trials, as well as the outcomes of key clinical trials that influenced the introduction of the ethical principles into clinical trials. Methods This was a descriptive research (methods of analysis and documentation; desk analysis of the secondary data). Results By analysing the cases from the secondary sources as well as clinical and ethical outcomes, it may be noticed that the codes, declarations and regulations have been often preceded by certain events that caused their adoption. Moral concern and public awareness of the ethical issues have initiated not only the development of numerous guidelines, codes, and declarations, but also their incorporation into the legislative acts. Conclusion It is desirable that ethical instruments become legally binding documents, because only in this way will be possible to control all phases of the clinical trials and prevent abuse of the respondents.

Background/Aim. Preeclampsia (PE) belongs to the group of hypertensive disorders in pregnancy with the global average incidence of 2.16%. It is considered as one of the leading causes of maternal and neonatal morbidity and mortality worldwide. The goal of this study was to assess the potential association between Val158Met catechol-o-methyltransferase (COMT), tumor necrosis factor-alpha (TNF-α) -857 C>T, tumor necrosis factor receptor 1 (TNFR1) 36 A>G, interleukin-1alpha (IL-1α) 4845 G>T and interleukin-10 (IL-10) -1082 A>G polymorphisms and risk of early-onset preeclampsia (PE) and its complications. Methods. The study included 47 early-onset PE patients, which were grouped by disease severity and by size for gestational age and 47 control cases. The Val158Met polymorphism was genotyped by polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) analysis and inflammatory cytokine polymorphisms by the Sanger sequencing method. Results. The COMT Met allele as well as IL-1α T showed a protective role, decreasing the risk of early-onset PE after age and body mass index (BMI) adjustments. The detected interactions between the COMT Met and IL-10 A alleles, as well as between the COMT Met and TNF-α T alleles were insignificant after age and BMI adjustments. Conclusion. COMT and IL-1α may be used as candidate genes for early-onset PE and its severe form and small for gestational age (SGA) complications. © 2017, Inst. Sci. inf., Univ. Defence in Belgrade. All Rights Reserved.

Objectives: Several clinical studies of severe necrotizing pancreatitis (SNP) suggest profound activation of coagulation as well as activation of the fibrinolytic system. The aim of this study was to evaluate the hemostatic derangements in patients who were managed for SNP. Methods: Forty-one operated-on patients with SNP were analyzed regarding clinical outcome and activation of the coagulation systems. Serial measurement of coagulation, anticoagulation, and fibrinolysis parameters: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin III (AT III), protein C, plasminogen activator inhibitor-1 (PAI-1), D-dimer, α 2 -antiplasmin, and plasminogen were performed on days 1, 3, 5, 7, 10, and 14 after the initial operation. According to treatment outcome at the end of study, groups of 26 survivors and 15 nonsurvivors were compared. Results: Nonsurvivors had significantly lower levels of activity of protein C and AT III, and higher concentrations of D-dimer and PAI-1 than survivors. The other measured parameters did not show significant differences between the compared groups of patients. Conclusions: Changes in protein C, AT III, D-dimer and PAI-1 levels indicate exhaustion of fibrinolysis and coagulation inhibitors in patients with poor outcome during the course of SNP.

Objectives: Several clinical studies of severe necrotizing pancreatitis (SNP) suggest profound activation of coagulation as well as activation of the fibrinolytic system. The aim of this study was to evaluate the hemostatic derangements in patients who were managed for SNP. Methods: Forty-one operated-on patients with SNP were analyzed regarding clinical outcome and activation of the coagulation systems. Serial measurement of coagulation, anticoagulation, and fibrinolysis parameters: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin III (AT III), protein C, plasminogen activator inhibitor-1 (PAI-1), D-dimer, α 2 -antiplasmin, and plasminogen were performed on days 1, 3, 5, 7, 10, and 14 after the initial operation. According to treatment outcome at the end of study, groups of 26 survivors and 15 nonsurvivors were compared. Results: Nonsurvivors had significantly lower levels of activity of protein C and AT III, and higher concentrations of D-dimer and PAI-1 than survivors. The other measured parameters did not show significant differences between the compared groups of patients. Conclusions: Changes in protein C, AT III, D-dimer and PAI-1 levels indicate exhaustion of fibrinolysis and coagulation inhibitors in patients with poor outcome during the course of SNP.

Background: Polycystic ovary syndrome (PCOS) is a cardiometabolic disorder whose features include dyslipidemia, increased oxidative stress (OS, oxy) and chronic inflammation. The aim of this study was to investigate the ability of a summary score for dyslipidemia, OS and inflammation (the DOI score) to discriminate PCOS patients from healthy individuals and to evaluate the effect of obesity on individual scores and the DOI score in patients. Methods: Lipid status parameters, OS status parameters (advanced oxidation protein products; total oxidative status; prooxidant-antioxidant balance; malondialdehyde; total protein sulphydryl groups and paraoxonase 1 activity) and CRP were measured in 114 patients and 50 controls using standardised assays. The DOI score was calculated as the sum of dyslipidemia, oxy and inflammation scores, determined as Z-score values for every subject in relation to the controls. Results: PCOS patients had significantly higher oxy-score compared to controls (P<0.001). In addition, the DOI score was significantly higher in PCOS patients (P<0.001) as the dyslipidemia (P<0.05) and inflammatory scores (P<0.001) were greater. According to ROC analysis, the oxy-score showed better diagnostic accuracy in discriminating PCOS patients compared to the DOI score (AUC>0.9, P<0.01). Furthermore, obesity affected the risk scores in patients, especially the DOI score (significantly higher DOI scores in such patients, P<0.001). Conclusion: PCOS patients had greater dyslipidemia, chronic inflammation and OS compared to controls and could be segregated using all four scores. Our data suggest that weight gain could be the common factor responsible for induction and propagation of dyslipidemia, OS and inflammation in PCOS patients. © 2018 Iva Perović Blagojević et al., published by Sciendo.

Background: Polycystic ovary syndrome (PCOS) is a cardiometabolic disorder whose features include dyslipidemia, increased oxidative stress (OS, oxy) and chronic inflammation. The aim of this study was to investigate the ability of a summary score for dyslipidemia, OS and inflammation (the DOI score) to discriminate PCOS patients from healthy individuals and to evaluate the effect of obesity on individual scores and the DOI score in patients. Methods: Lipid status parameters, OS status parameters (advanced oxidation protein products; total oxidative status; prooxidant-antioxidant balance; malondialdehyde; total protein sulphydryl groups and paraoxonase 1 activity) and CRP were measured in 114 patients and 50 controls using standardised assays. The DOI score was calculated as the sum of dyslipidemia, oxy and inflammation scores, determined as Z-score values for every subject in relation to the controls. Results: PCOS patients had significantly higher oxy-score compared to controls (P<0.001). In addition, the DOI score was significantly higher in PCOS patients (P<0.001) as the dyslipidemia (P<0.05) and inflammatory scores (P<0.001) were greater. According to ROC analysis, the oxy-score showed better diagnostic accuracy in discriminating PCOS patients compared to the DOI score (AUC>0.9, P<0.01). Furthermore, obesity affected the risk scores in patients, especially the DOI score (significantly higher DOI scores in such patients, P<0.001). Conclusion: PCOS patients had greater dyslipidemia, chronic inflammation and OS compared to controls and could be segregated using all four scores. Our data suggest that weight gain could be the common factor responsible for induction and propagation of dyslipidemia, OS and inflammation in PCOS patients. © 2018 Iva Perović Blagojević et al., published by Sciendo.

Background. The diagnosis of Balkan endemic nephropathy (BEN) is often made using Danilovic's criteria. The aim of this study was to determine the prevalence, sensitivity, specificity, and predictive value of Danilovic's criteria and several additional indices. Methods. The study included 19 BEN patients, 23 BEN-suspected patients, 34 patients with other kidney diseases, and 23 healthy controls. The sensitivity and specificity of Danilovic's criteria was calculated, and these criteria, in addition to age, sex, blood pressure, creatinine clearance, glucosuria, urine osmolality, alkaline phosphatase, alpha 1-microglobulin, fractional sodium excretion, tubular phosphate reabsorption, kidney length, and volume, were combined in a logistic regression. Results. All examined persons were from a BEN-affected village (criterion 1), and all BEN, BEN-suspected patients, and 12/23 healthy controls were from BEN families (criterion 2). None of the remaining Danilovic's criteria was found in the healthy controls. The prevalence of proteinuria, low specific gravity, and anemia (criteria 3-5) differed insignificantly among the patient groups. Azotemia and shrunken kidney (criteria 6 and 7) were significantly more frequent in BEN than in other patients. Only proteinuria showed high sensitivity and specificity in differentiating BEN and BEN-suspected patients from healthy persons, but no criteria differentiated BEN or BEN-suspected from other kidney diseases. Proteinuria is a significant predictor of both BEN and BEN-suspected vs. healthy persons, and alpha 1-microglobulinuria is a significant predictor of BEN vs. other kidney diseases. Conclusion. Danilovic's criteria enabled a diagnosis of BEN only in chronic renal failure and differential diagnosis between BEN and healthy persons but not between BEN and other kidney diseases. Out of the examined indices of proximal tubular disorders, only alpha 1-microglobulinuria significantly discriminated BEN from other kidney diseases. Copyright © Informa Healthcare.

Background: Despite commercially improved, standardised routine methods used in medical laboratories, precision laboratory medicine lacks harmonisation of results to make the laboratory result useful for its intended purpose. Furthermore, to obtain reliable laboratory results and precise diagnoses, it is important and recommended that each laboratory confirms the analytical and clinical characteristics of the method used. This study aimed to evaluate the analytical and clinical performance of the IMMULITE®2000 TSI bridge immunoassay to determine autoreactive thyroid stimulating hormone receptor antibodies (SH-R-Ab). Methods: A total of 86 patients with clinically present Graves’ orbitopathy and 23 healthy volunteers as a control group were included in the study. The total TSH-R-Ab concentration was determined using an ECLIA (Elecsys Anti-TSHR Immunoassay Roche Diagnostics, GmbH, Mannheim, Germany) on the Cobas e411 analyser (Roche, Diagnostics, GmbH). The TSH-R-Ab concentration was measured using a CLIA method (IMMULITE TSI 2000, Siemens Healthcare Diagnostics, UK). The inaccuracy of the method was investigated using two levels of commercial control samples (low and high analyte concentration). Results: The results obtained meet the general minimum requirements for the analytical performance of laboratory methods (CV<5%). The overall laboratory inaccuracy was acceptable according to FDA guidelines (CV<20%). The results showed a statistically significant correlation between the analysed methods (r=0.9041, p < 0.0001) but with a relative bias of 24.5%. The best ratio of sensitivity and specificity determined by the ROC analysis (93.3% and 100%, respectively) was obtained for a cut-off value of 0.1215 IU/L, which is significantly lower compared to the cut-off value specified by the manufacturer (0.55 IU/L). Conclusions: The IMMULITE 2000 TSI bridge immunoassay for TSH-R-Ab quantification confirmed adequate precision, which is essential for routine use. However, further studies are required to evaluate its analytical specificity. © 2025 Society of Medical Biochemists of Serbia. All rights reserved.

Some observational studies indicate an association of 25-hydroxy vitamin D (25(OH)D) insufficiency and atherogenic cholesterol concentrations. The aim of this study was to investigate relationship between 25(OH)D concentrations and lipid parameters in end stage renal disease (ESRD) patients, separately for predialysis, hemodialysis and peritoneal dialysis patients. We have adjusted 25(OH)D concentrations for seasonal variability with cosinor analysis, and performed all further analysis using these corrected 25(OH)D concentrations. Concentrations of 25(OH)D and the lipid parameters were determined in 214 ESRD patients and 50 control group participants. The analysis included the measurement of 25(OH)D by HPLC, apolipoprotein (Apo) AI, ApoB and Lp(a) by nephelometry, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) by spectrophotometry and manually calculated ApoB/ApoAI and LDL-C/HDL-C ratio. ESRD patients with adjusted 25(OH)D concentrations of ≤ 50 nmol/L had significantly higher TC (P = 0.005) and ApoAI (P = 0.049). Significantly higher HDL-C (P = 0.011) and ApoAI (P = 0.020) were found in hemodialysis patients with the 25(OH)D concentrations of ≤ 50 nmol/L. The other analyzed lipid parameters differed significantly between predialysis, hemodialysis and peritoneal dialysis patients with 25(OH)D concentrations of < 50 nmol/L. Our study indicate the significant relationship between 25(OH)D repletion and optimal concentrations of lipid parameters in ESRD patients. Further research is necessary to explain whether joint evaluation of vitamin D status and lipid abnormalities could improve cardiovascular outcome in ESRD patients. © 2019 Society of Medical Biochemists of Serbia and Montenegro.

Some observational studies indicate an association of 25-hydroxy vitamin D (25(OH)D) insufficiency and atherogenic cholesterol concentrations. The aim of this study was to investigate relationship between 25(OH)D concentrations and lipid parameters in end stage renal disease (ESRD) patients, separately for predialysis, hemodialysis and peritoneal dialysis patients. We have adjusted 25(OH)D concentrations for seasonal variability with cosinor analysis, and performed all further analysis using these corrected 25(OH)D concentrations. Concentrations of 25(OH)D and the lipid parameters were determined in 214 ESRD patients and 50 control group participants. The analysis included the measurement of 25(OH)D by HPLC, apolipoprotein (Apo) AI, ApoB and Lp(a) by nephelometry, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) by spectrophotometry and manually calculated ApoB/ApoAI and LDL-C/HDL-C ratio. ESRD patients with adjusted 25(OH)D concentrations of ≤ 50 nmol/L had significantly higher TC (P = 0.005) and ApoAI (P = 0.049). Significantly higher HDL-C (P = 0.011) and ApoAI (P = 0.020) were found in hemodialysis patients with the 25(OH)D concentrations of ≤ 50 nmol/L. The other analyzed lipid parameters differed significantly between predialysis, hemodialysis and peritoneal dialysis patients with 25(OH)D concentrations of < 50 nmol/L. Our study indicate the significant relationship between 25(OH)D repletion and optimal concentrations of lipid parameters in ESRD patients. Further research is necessary to explain whether joint evaluation of vitamin D status and lipid abnormalities could improve cardiovascular outcome in ESRD patients. © 2019 Society of Medical Biochemists of Serbia and Montenegro.

Background: Sleep deprivation, malnutrition and lack of physical activity are contemporary stress-related factors present in the student population. Stress activates the HPA and often suppresses the HPG axis, but also influences cytokine synthesis and consequently regulates immune response. Since magnesium deficiency facilitates negative pathophysiological consequences, a reasonable question imposes, wheth er Mg supplementation might correct the adrenal/go - n adal hormone balance and immuno-endocrine function. Methods: Fifteen male students were given 2 × 250 mg Mg for four weeks. Serum levels of FSH, LH, testosterone (T), ACTH and cortisol (C) were measured before and after supplementation and the T/C ratio was calculated. Furthermore, IL-6, red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC) and the WBC differential were measured. Results: Despite no change in the serum level of ACTH, a statistically significant (p<0.05) decrease in the serum cortisol level appeared, accompanied with an IL-6 level reduction (p<0.05) after Mg supplementation. Analysis of the pituitarygonadal axis hormones showed an increasing trend of the FSH level (p=0.087), and a significant increase (p<0.05) in the T/C ratio. An RBC count increase (p<0.001) was found, along with a decrease in the percentage of neutrophils (p<0.05), and a trend toward a lymphocyte percentage increase. Conclusions: The results suggest that chronic oral magnesium supplementation in male students improves the balance of pituitary-gonadal and pituitary-adrenal hormones and is involved in the regulation of the basal IL-6 level.

Background: Sleep deprivation, malnutrition and lack of physical activity are contemporary stress-related factors present in the student population. Stress activates the HPA and often suppresses the HPG axis, but also influences cytokine synthesis and consequently regulates immune response. Since magnesium deficiency facilitates negative pathophysiological consequences, a reasonable question imposes, wheth er Mg supplementation might correct the adrenal/go - n adal hormone balance and immuno-endocrine function. Methods: Fifteen male students were given 2 × 250 mg Mg for four weeks. Serum levels of FSH, LH, testosterone (T), ACTH and cortisol (C) were measured before and after supplementation and the T/C ratio was calculated. Furthermore, IL-6, red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC) and the WBC differential were measured. Results: Despite no change in the serum level of ACTH, a statistically significant (p<0.05) decrease in the serum cortisol level appeared, accompanied with an IL-6 level reduction (p<0.05) after Mg supplementation. Analysis of the pituitarygonadal axis hormones showed an increasing trend of the FSH level (p=0.087), and a significant increase (p<0.05) in the T/C ratio. An RBC count increase (p<0.001) was found, along with a decrease in the percentage of neutrophils (p<0.05), and a trend toward a lymphocyte percentage increase. Conclusions: The results suggest that chronic oral magnesium supplementation in male students improves the balance of pituitary-gonadal and pituitary-adrenal hormones and is involved in the regulation of the basal IL-6 level.

Background: Up until now there have been contradictory data about the association between p.Val158Met catechol-O-methyltransferase (COMT) polymorphism and risk of preeclampsia (PE). The goal of this study was to assess the potential correlation between p.Val158Met COMT polymorphism and risk of early-onset PE, risk of a severe form of early-onset PE, as well as risk of small-for-gestationalage (SGA) complicating PE. Methods: The study included 47 early-onset PE patients and 47 control cases. Forty-seven early-onset PE patients were grouped by disease severity (33 patients with a severe form and 14 patients without severe features) and secondly by size for gestational age (12 patients with appropriate-for-gestational-age (AGA) and 35 patients with SGA size). p.Val158Met polymorphism was genotyped by PCR-RFLP analysis. Results: Allele analysis showed significant difference in COMT allele distribution between early-onset PE and control group as well as early-onset PE SGA and controls (p=0.04057 and p=0.0411 respectively). A statistically significant distribution difference between the severe form and form without severe features of early-onset PE patients was not observed (p>0.05). The highest difference observed was in the allele recessive model where COMT MetMet genotype was associated with decreased risk of early-onset PE (OR=0.281; 95%CI=0.092-0.7836) and PE complications including severe early-onset PE (OR= 0.304; 95%CI=0.086-0.944) and SGA early-onset PE (OR=0.284; 95%CI=0.081-0.874). Conclusions: COMT may be used as a candidate gene for early-onset PE and its severe form and SGA complications. © by Tijana Krnjeta 2016.

Background: Up until now there have been contradictory data about the association between p.Val158Met catechol-O-methyltransferase (COMT) polymorphism and risk of preeclampsia (PE). The goal of this study was to assess the potential correlation between p.Val158Met COMT polymorphism and risk of early-onset PE, risk of a severe form of early-onset PE, as well as risk of small-for-gestationalage (SGA) complicating PE. Methods: The study included 47 early-onset PE patients and 47 control cases. Forty-seven early-onset PE patients were grouped by disease severity (33 patients with a severe form and 14 patients without severe features) and secondly by size for gestational age (12 patients with appropriate-for-gestational-age (AGA) and 35 patients with SGA size). p.Val158Met polymorphism was genotyped by PCR-RFLP analysis. Results: Allele analysis showed significant difference in COMT allele distribution between early-onset PE and control group as well as early-onset PE SGA and controls (p=0.04057 and p=0.0411 respectively). A statistically significant distribution difference between the severe form and form without severe features of early-onset PE patients was not observed (p>0.05). The highest difference observed was in the allele recessive model where COMT MetMet genotype was associated with decreased risk of early-onset PE (OR=0.281; 95%CI=0.092-0.7836) and PE complications including severe early-onset PE (OR= 0.304; 95%CI=0.086-0.944) and SGA early-onset PE (OR=0.284; 95%CI=0.081-0.874). Conclusions: COMT may be used as a candidate gene for early-onset PE and its severe form and SGA complications. © by Tijana Krnjeta 2016.

Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age (x¯±SD=49.0±14.5) SD = 49.0 ± 14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and χ2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B12 were 4.13 (2.16) μg/L and 463.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and P<0.000 for folate and vitamin B12 respectively), depending on the cut-off used for classification (4.4, 6.6 and 8.0 μg/L-folate; 203 and 473 ng/L-vitamin B12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.

Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age (x¯±SD=49.0±14.5) SD = 49.0 ± 14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and χ2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B12 were 4.13 (2.16) μg/L and 463.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and P<0.000 for folate and vitamin B12 respectively), depending on the cut-off used for classification (4.4, 6.6 and 8.0 μg/L-folate; 203 and 473 ng/L-vitamin B12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.

Background: Thyrotropin receptor autoantibodies (TSH-R-Ab) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO. Methods: 87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and binding TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cell-based bioassay. Results: Compared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (r=0.893, p<0.001), compared to the bioassay (r=0.669, p<0.001). Conclusions: In patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays. © 2022 Sciendo. All rights reserved.

Background: Thyrotropin receptor autoantibodies (TSH-R-Ab) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO. Methods: 87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and binding TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cell-based bioassay. Results: Compared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (r=0.893, p<0.001), compared to the bioassay (r=0.669, p<0.001). Conclusions: In patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays. © 2022 Sciendo. All rights reserved.