Browsing by Author "Subota, Vesna (16319788700)"

Factors associated with provoked PE may influence a biomarker's predictive value for the primary outcome. The aim of this study was to investigate the value of BNP, cTnI, CRP and D-Dimer measurements taken soon after hospital admission for the prediction of 30-day PE-caused death in patients with spontaneous versus provoked PE.Data were extracted from a pool of 726 consecutive PE patients enrolled in the multicenter Serbian PE registry. Blood concentrations of BNP, cTnI, CRP and D-dimer were measured during the first 24 h of hospitalization. BNP blood level had strong predictive value for the primary outcome in spontaneous PE (c-statistics 0.943, 95% CI 0.882–1.000, p = .001) and a slightly lower predictive outcome in provoked PE (c-statistics 0.824, 95% CI 0.745–0.902, p < .001). NRI and IDI showed that none of the markers, when added to BNP, could improve Cox regression prediction models for 30-day PE-related mortality in either the spontaneous or provoked PE group. Blood levels of BNP measured during the first 24 h of hospital admission had an excellent predictive value for 30-day PE-related mortality in spontaneous PE and slightly lower predictive value in provoked PE, whereas CRP, cTnI and D-Dimer did not contribute significantly to the predictive value of BNP in either group. © 2019 Elsevier B.V.

Factors associated with provoked PE may influence a biomarker's predictive value for the primary outcome. The aim of this study was to investigate the value of BNP, cTnI, CRP and D-Dimer measurements taken soon after hospital admission for the prediction of 30-day PE-caused death in patients with spontaneous versus provoked PE.Data were extracted from a pool of 726 consecutive PE patients enrolled in the multicenter Serbian PE registry. Blood concentrations of BNP, cTnI, CRP and D-dimer were measured during the first 24 h of hospitalization. BNP blood level had strong predictive value for the primary outcome in spontaneous PE (c-statistics 0.943, 95% CI 0.882–1.000, p = .001) and a slightly lower predictive outcome in provoked PE (c-statistics 0.824, 95% CI 0.745–0.902, p < .001). NRI and IDI showed that none of the markers, when added to BNP, could improve Cox regression prediction models for 30-day PE-related mortality in either the spontaneous or provoked PE group. Blood levels of BNP measured during the first 24 h of hospital admission had an excellent predictive value for 30-day PE-related mortality in spontaneous PE and slightly lower predictive value in provoked PE, whereas CRP, cTnI and D-Dimer did not contribute significantly to the predictive value of BNP in either group. © 2019 Elsevier B.V.

Congenital hypofibrinogenemia and afibrinogenemia are usually associated with an increased risk of bleeding, but occurrence of arterial or venous thrombosis has also been reported in individuals with fibrinogen deficiency. This study reports on a 25-year-old patient with hypofibrinogenemia (fibrinogen 0.6 g/l) and congenital thrombophilia due to heterozygous factor V Leiden mutation who developed spontaneous deep-vein thrombosis (DVT) in the right lower extremity. Regardless of hypofibrinogenemia, he was receiving anticoagulant therapy over 6 months, with no occurrence of bleeding. His father is also a heterozygous carrier of factor V Leiden, but with normal fibrinogen level and he remained asymptomatic despite having experienced surgery in the past. This case, as well as data from literature, suggests that risk of thrombosis in carriers of factor V Leiden mutation is not counterbalanced by moderate congenital hypofibrinogenemia, and that antithrombotic prophylaxis should not be omitted in high-risk situations for occurrence of thrombosis in patients with coinheritance of hypofibrinogenemia and factor V Leiden mutation. Copyright © Lippincott Williams & Wilkins.

Background/Aim. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are important biomarkers of exposure to organophosphorus and carbamate insecticides. Since the estimation of the level of cholinesterase inhibition depends on the normal values which may vary in different populations, it is important to determine them in our population, which so far has not been done. Therefore, the aim of this study was to determine the reference values for AChE and BuChE in a healthy population of adults in the Republic of Serbia. Methods. The AChE activity was measured by spectrophotometry (λ = 412 nm), using a modified Ellman’s method. BuChE activity was determined by the integrated chemical system (Dimension RxLMax) with ready-made reagent cartridge for analysis. The examinees were healthy voluntary blood donors from the Institute of Transfusiology and Hemobiology, Military Medical Academy in Belgrade, Serbia. Statistical Package for Social Sciences (SPSS) software program was used for data processing. Results. In the group of 851 persons, there were 728 males and 123 females. The mean age was 39.1 ± 11.6 years. For all of them, erythrocyte AChE activity was done while BuChE was determined in 205 persons (169 males and 36 females). Their mean value of acetylcholinesterase activity was 8,090.6 ± 1,976.7 IU/L, and of butyrylcholinesterase activity was 14,556.6 ± 4,078.1 U/L. Due to lack of normal data distribution in male group (both enzymes), reference ranges were estimated as 2.5 and 97.5 percentiles. Conclusion. The results of this pilot study on cholinesterase in healthy population in the Republic of Serbia which has now been done for the first time, indicate the need for considering their wider ranges of when estimating the severity of poisoning. However, further study for BuChE with the inclusion of a larger number of females and data for body weight of the examinees, in order to get more precise reference limits, is suggested. © 2017, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

Background/Aim. The evaluation of blood levels of cardiac troponin I (cTnI), D-dimer, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) on admission and during the treatment of pulmonary embolism (PE) are the part of routine diagnostic process and estimation of mortality risk. The aim of this study was to evaluate the predictive value of these biomarkers on admission for all-cause 30-day mortality in consecutive PE patients regarding whether they classified as spontaneous, transiently provoked, or permanently provoked PE. Methods. This retrospective analysis was gained from the data of 590 PE patients from the Serbian University Multicenter Pulmonary Embolism Registry (SUPER). Patients had at least one of these biomarkers (BNP, CRP, cTnI, and D-dimer) measured during the first 24 hours upon admission. Results. Receiver operating characteristic (ROC) curve analyses demonstrated that BNP had the highest prognostic accuracy for 30-day mortality in patients (n = 219) who had data for all examined biomarkers. BNP provided an AUC of 0.785 (p < 0.001). Separately, BNP had the highest c-statistic for all three groups of patients. CRP had a modest predictive value for the 30-day all-cause mortality in the group with transient provoked PE. Troponin I had a very modest predictive value for the 30-day all-cause mortality only in patients with spontaneous PE, and D-dimer was a very weak predictor of this end-point only in patients with persistent provoked PE. Conclusion. Patients with spontaneous, transient provoked, and persistent provoked PE have a significantly different profile of blood biomarkers level with different prognostic significance for early all-cause mortality. © 2021 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Background/Aim. Acute pulmonary embolism (PE) is a potentially life threating event, but there are scarce data about genderrelated differences in this condition. The aim of this study was to identify gender-specific differences in clinical presentation, the diagnosis and outcome between male and female patients with PE. Methods. We analysed the data of 144 consecutive patients with PE (50% women) and compared female and male patients regarding clinical presentation, electrocardiography (ECG) signs, basic laboratory markers and six-month outcome. All the patients confirmed PE by visualized thrombus on the multidetector computed tomography with pulmonary angiography (MDCTPA), ECG and echocardiographic examination at admission. Results. Compared to the men, the women were older and a larger proportion of them was in the third tertile of age (66.0% vs 34.0%, p = 0.008). In univariate analysis the men more often had hemoptysis [OR (95% CI) 3.75 (1.16–12.11)], chest pain [OR (95% CI) 3.31 (1.57–7.00)] febrile state [OR (95% CI) 2.41 (1.12–5.22)] and pneumonia at PE presentation [OR (95% CI) 3.40 (1.25–9.22)] and less likely had heart decompensation early in the course of the disease [OR (95%CI) 0.48 (0.24–0.97)]. In the multivariate analysis a significant difference in the rate of pneumonia and acute heart failure between genders disappeared due to strong influence of age. There was no significant difference in the occurrence of typical ECG signs for PE between the genders. Women had higher level of admission glycaemia [7.7 mmol/L (5.5–8.2 mmol/L) vs 6.9 mmol/L (6.3–9.6 mmol/L), p = 0.006] and total number of leukocytes [10.5 × 109/L (8.8-–12.7 × 109/L vs 8.7 × 109/L (7.0–11.6 × 109/L)), p = 0.007]. There was a trend toward higher plasma level of brain natriuretic peptide in women compared to men 127.1 pg/mL (55.0–484.0 pg/mL), p = 0.092] vs [90.3 pg/mL (39.2–308.5 pg/mL). The main 6-month outcomes, death and major bleeding, had similar frequencies in both sexes. Conclusion. There are several important differences between men and women in the clinical presentation of PE and basic laboratory findings which can influence the diagnosis and treatment of PE. © 2016, Vojnosanitetski Pregled. All rights reserved.

Background/Aim. Previous studies have confirmed a positive correlation between homocysteine levels and a greater risk for acute coronary syndrome and stroke, but there are no available data to support an association between homocysteine and inflammatory markers and the severity of coronary artery disease according to the clinical SYNTAX score in patients with stable angina. The aim was to determine the association between homocysteine and inflammatory biomarker levels: interleukin (IL)-6, high sensitive C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR) and the severity of coronary artery disease according to clinical SYNTAX score. Methods. Eighty-two patients with stable angina pectoris (average age 65 ± 8 years, 28.9% females) underwent coronary angiography and were divided into three groups according to the clinical SYNTAX score: the group I < 22 (39 patients), the group II 23–32 (16 patients), the group III > 33 (27 patients). The severity and complexity of coronary artery disease were calculated by clinical SYNTAX score, multiplying the SYNTAX score with the modified ACEF score, based on the patients’ left ventricular ejection fraction, age and creatinine clearance (derived with Cockcroft–Gault equation). Results. Homocysteine levels were significantly higher in patients with high clinical SYNTAX score [the group I: median (interquartile range – IQR): 10.20 (3.97), the group II: 10.45 (5.77), the group III: 14.70 (7.50), p = 0.005]. Patients in the group III had significantly higher homocysteine levels compared to the group I (p = 0.001). We also found a positive association between inflammatory biomarkers (IL-6, hsCRP, fibrinogen, ESR) and the severity of coronary artery disease according to the clinical SYNTAX score (p = 0.017, 0.001, 0.032, 0.049 respectively). We detected significantly lower plasma levels of vitamin B12 in the group III and group II in comparison with the group I (the group I: median (IQR): 238 (160), the group II: 171 (160), the group III: 172 (102), p = 0.022), which indicates its important role in homocysteine metabolism. Conclusion. The elevated plasma levels of homocysteine, IL-6, hsCRP, fibrinogen, ESR were detected in patients with high clinical SYNTAX score (> 33). Our results showed that hyperhomocysteinemia and some inflammatory biomarkers can predict more severe and extensive coronary artery disease in stable angina patients. © 2021 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Objective: To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3). Methods: This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of β-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses. Results: RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient’s global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (β = 0.206, P = 0.014; β = 0.192, P = 0.009; β = 0.121, P = 0.005; β = 0.148, P = 0.007; β = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R2), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (β = 0.090, P = 0.022; β = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2–2.5) vs. 1.2 (0.8–1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9–1.9) vs. 1.2 (0.8–1.4), P = 0.375]. Conclusions: RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors. © 2021, The Author(s).

Objective: To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3). Methods: This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of β-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses. Results: RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient’s global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (β = 0.206, P = 0.014; β = 0.192, P = 0.009; β = 0.121, P = 0.005; β = 0.148, P = 0.007; β = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R2), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (β = 0.090, P = 0.022; β = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2–2.5) vs. 1.2 (0.8–1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9–1.9) vs. 1.2 (0.8–1.4), P = 0.375]. Conclusions: RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors. © 2021, The Author(s).

Treatment of fresh frozen plasma (FFP) by riboflavin (RB) and ultraviolet (UV) light inhibits nucleic acid replication, leading to inactivation of white blood cells (WBCs) and pathogens. The goal of this study was to compare the effects of pathogen reduction technology (PRT) treatment on the plasma protein content based on biochemical, immune and hemostatic characteristics in "typical" pre-storage vs. post-storage PRT-treatment setting.Following whole blood centrifugation, separated plasma units were: (a) inactivated and frozen (pre-storage setting or control group [CG]) or (b) immediately frozen (post-storage setting or study group [SG]) afterward thawed, inactivated and stored at -40. ±. 5. °C (cryostorage). Plasma units were inactivated by the Mirasol PRT system (TerumoBCT, USA). Using multi-laboratory techniques and equipments, biochemistry (Advia 1800; Siemens, Germany), IgM, IgG and IgA, complement components C3 and C4 (BNA II nefelometer analyzer; Siemens, Germany), as well as CH50 activity (Behring coagulation timer; Siemens, Germany) were investigated. Procoagulant and inhibitor factors, such as antithrombin-III (AT-III), and protein C (PC) were determined by BCS XP Coagulation system (Siemens, Germany). There were neither significant changes in final protein levels, nor any differences in plasma immunoglobulin levels investigated. In the final samples CH50 activity was reduced in both investigated groups. The plasma concentration of the complement C3 following post-storage treatment was significantly (p<. 0.05) higher than in pre-storage setting. There was a trend of depletion of procoagulant activities in both, pre-storage and post-storage PRT-treatment (initial vs. final values), but there were no significant differences between two groups. Results confirmed that AT-III was significantly higher after post-storage inactivation.In conclusion, this study confirmed that there were not clinically relevant intergroup (pre-storage vs. post-storage PRT-treatment) differences in plasma constituent levels. Post-storage treated FFP remains, protein quantity, and activity well, and therefore can be used in clinical practice. Previously cryostored or quarantine FFP units (despite the reduced quarantine period after NAT/PCR testing) could be safely and effectively inactivated, directly prior to clinical application. © 2013 Elsevier Ltd.

Aims: To examine the relationship between admission glucose (AG) level and short-term in-hospital mortality and to investigate the association between hyperglycemia and major bleeding in PE patients with and without DMT2. Methods: We evaluated 1165 patients with diagnosed acute PE with multi-detector computed tomography pulmonary angiography (MDCT-PA) enrolled in the Regional multicenter PE registry (REPER). The study population was classified to patients with diabetes mellitus type 2 (DMT2) and those without diabetes. According to quartiles of AG patients, both groups separately were categorized into four subgroups (DMT2 I: < 7.5 mmol/L; II: 7.5–10.0 mmol/L; III: 10.0–15.7 mmol/L; IV: > 15.7 mmol/L and (non-DMT2 I: < 5.5 mmol/L; II: 5.5–6.3 mmol/L; III: 6.3–7.9 mmol/L; IV: > 7.9 mmol/L). Results: All-cause mortality was higher in the DMT2 group (9.5% vs. 18.2%, p < 0.001), and PE-cause mortality was 6% for the patients without DMT2 and 12.4% for DMT2 patients (p = 0.02). The patients in the fourth AG quartiles in both groups, without DMT2 and with DMT2, had significantly higher all-cause and PE-cause in-hospital mortality compared with the first quartile. Rates of major bleeding were similar between the groups. On the multivariable analysis, after adjusting for age, gender and mortality risk, the adherence in the fourth AG quartile had an independent predictive value for all-cause death (HR 2.476, 95% CI 1.017–6.027) only in DM patients. Conclusion: In our cohort of patients with acute PE, diabetes was associated with increased rates for all-cause and PE-cause mortality. © 2021, Springer-Verlag Italia S.r.l., part of Springer Nature.

Aims: To examine the relationship between admission glucose (AG) level and short-term in-hospital mortality and to investigate the association between hyperglycemia and major bleeding in PE patients with and without DMT2. Methods: We evaluated 1165 patients with diagnosed acute PE with multi-detector computed tomography pulmonary angiography (MDCT-PA) enrolled in the Regional multicenter PE registry (REPER). The study population was classified to patients with diabetes mellitus type 2 (DMT2) and those without diabetes. According to quartiles of AG patients, both groups separately were categorized into four subgroups (DMT2 I: < 7.5 mmol/L; II: 7.5–10.0 mmol/L; III: 10.0–15.7 mmol/L; IV: > 15.7 mmol/L and (non-DMT2 I: < 5.5 mmol/L; II: 5.5–6.3 mmol/L; III: 6.3–7.9 mmol/L; IV: > 7.9 mmol/L). Results: All-cause mortality was higher in the DMT2 group (9.5% vs. 18.2%, p < 0.001), and PE-cause mortality was 6% for the patients without DMT2 and 12.4% for DMT2 patients (p = 0.02). The patients in the fourth AG quartiles in both groups, without DMT2 and with DMT2, had significantly higher all-cause and PE-cause in-hospital mortality compared with the first quartile. Rates of major bleeding were similar between the groups. On the multivariable analysis, after adjusting for age, gender and mortality risk, the adherence in the fourth AG quartile had an independent predictive value for all-cause death (HR 2.476, 95% CI 1.017–6.027) only in DM patients. Conclusion: In our cohort of patients with acute PE, diabetes was associated with increased rates for all-cause and PE-cause mortality. © 2021, Springer-Verlag Italia S.r.l., part of Springer Nature.

In patients with pulmonary embolism (PE), the D-dimer assay is commonly utilized as part of the diagnostic workup, but data on D-dimer for early risk stratification and short-term mortality prediction are limited. The purpose of this study was to determine D-dimer levels as a predictive biomarker of PE outcomes in younger (<50 years of age) compared to older patients. We conducted retrospective analysis for 930 patients diagnosed with PE between 2015 and 2019 as part of the Serbian University Multicenter Pulmonary Embolism Registry (SUPER).All patients had D-dimer levels measured within 24 hours of hospital admission. The primary outcome was mortality at 30 days or during hospitalization. Patients were categorized into two groups based on age (≤ 50 and >50 years of age). Younger patients constituted 20.5% of the study cohort. Regarding all-cause mortality, 5.2% (10/191)of patients died in group under the 50 years of age; the short-term all-causemortality was 12.4% (92/739) in older group.We have found that there was significant difference in plasma D-dimer level between patients ≤ 50 years of age and older group (>50), p= 0.006.D-dimer plasma level had good predictive value for the primary outcome in younger patients (c-statistics 0.710; 95% CI, 0.640-0.773; p<0.031). The optimal cutoff level for D-dimer to predict PE-cause death in patients aged > 50 years was found to be 8.8 mg/l FEU(c-statistics 0,580; 95% CI 0.544-0.616; p=0.049). In younger PE patients, D-dimer levels have good prognostic performance for 30-day all-cause mortalityand concentrations above 6.3 mg/l FEU are associated with increased risk of death. D-dimer in patients aged over 50 years does not have predictive ability for all-caused short-term mortality. The relationship between D-dimer and age in patients with PE may need further evaluation. © 2023 Ljiljana Jovanovic et al., published by Sciendo.

In patients with pulmonary embolism (PE), the D-dimer assay is commonly utilized as part of the diagnostic workup, but data on D-dimer for early risk stratification and short-term mortality prediction are limited. The purpose of this study was to determine D-dimer levels as a predictive biomarker of PE outcomes in younger (<50 years of age) compared to older patients. We conducted retrospective analysis for 930 patients diagnosed with PE between 2015 and 2019 as part of the Serbian University Multicenter Pulmonary Embolism Registry (SUPER).All patients had D-dimer levels measured within 24 hours of hospital admission. The primary outcome was mortality at 30 days or during hospitalization. Patients were categorized into two groups based on age (≤ 50 and >50 years of age). Younger patients constituted 20.5% of the study cohort. Regarding all-cause mortality, 5.2% (10/191)of patients died in group under the 50 years of age; the short-term all-causemortality was 12.4% (92/739) in older group.We have found that there was significant difference in plasma D-dimer level between patients ≤ 50 years of age and older group (>50), p= 0.006.D-dimer plasma level had good predictive value for the primary outcome in younger patients (c-statistics 0.710; 95% CI, 0.640-0.773; p<0.031). The optimal cutoff level for D-dimer to predict PE-cause death in patients aged > 50 years was found to be 8.8 mg/l FEU(c-statistics 0,580; 95% CI 0.544-0.616; p=0.049). In younger PE patients, D-dimer levels have good prognostic performance for 30-day all-cause mortalityand concentrations above 6.3 mg/l FEU are associated with increased risk of death. D-dimer in patients aged over 50 years does not have predictive ability for all-caused short-term mortality. The relationship between D-dimer and age in patients with PE may need further evaluation. © 2023 Ljiljana Jovanovic et al., published by Sciendo.