Correlation of High-Sensitivity Cardiac Troponin I Values and Cardiac Radiation Doses in Patients with Left-Sided Breast Cancer Undergoing Hypofractionated Adjuvant Radiotherapy with Concurrent Anti-HER2 Therapy.

Anti HER2 therapy and left breast adjuvant radiation therapy (RT) can both result in cardiotoxicity. The aim of this study was to evaluate the influence of radiation dose on cardiac structures on the values of the early cardiotoxicity marker high-sensitivity cardiac troponin I (hscTnI) in patients with HER2-positive left breast cancer undergoing adjuvant concomitant antiHER2 therapy and radiotherapy, and to establish a correlation between the hscTnI values and cardiac radiation doses. Sixty-one patients underwent left breast hypofractionated radiotherapy in parallel with anti-HER2 therapy: trastuzumab, combined trastuzumab-pertuzumab or trastuzumab emtansine (T-DM1). The hscTnI values were measured prior to and upon completion of radiotherapy. A significant increase in hscTnI was defined as >30% from baseline, with the second value being 4 ng/L or higher. Dose volume histograms (DVH) were generated for the heart, left ventricle (LV) and left anterior descending artery (LAD). The hscTnI levels were corelated with radiation doses on cardiac structures. An increase in hscTnI values was observed in 17 patients (Group 1). These patients had significantly higher mean radiation doses for the heart (p = 0.02), LV (p = 0.03) and LAD (p = 0.04), and AUC for heart and LV (p = 0.01), than patients without hscTnI increase (Group 2). The patients in Group 1 also had larger volumes of heart and LV receiving 2 Gy (p = 0.01 for both) and 4 Gy (p = 0.02 for both). LAD differences were observed in volumes receiving 2 Gy (p = 0.03), 4 Gy (p = 0.02) and 5 Gy (p = 0.02). The increase in hscTnI observed in patients receiving anti-HER2 therapy after adjuvant RT was positively associated with radiation doses on the heart, LV and LAD.

Elective Central Compartment Lymph Node Dissection Does not Increase the Risk of Postoperative Hypoparathyroidism in Patients Treated for Differentiated Thyroid Cancer.

AIM: The aim of this study was to compare the incidence of postoperative hypoparathyroidism in two groups of patients who were treated for differentiated thyroid cancer. METHODS: A retrospective analysis of 179 patients who were treated for differentiated thyroid cancer in our institution from January 2011 until December 2018 was performed. Only patients initially treated with total thyroidectomy and those who did not have preoperatively confirmed central compartment and lateral neck lymph node metastases were included in this study. Two main groups of patients were analysed. The patients who were treated with total thyroidectomy and elective central compartment lymph node dissection simultaneously were included in the first group. The patients who were treated only with total thyroidectomy were included in the second group. The rate of transitory and persistent postoperative hypoparathyroidism was compared between the two groups. RESULTS: A total of 117 patients (65.4%) underwent total thyroidectomy and elective central compartment lymph node dissection simultaneously (TT + CCLNd group). The remaining 62 patients (34.6%) underwent total thyroidectomy only (TT group). A total of 22.6% patients in the TT group developed postoperative hypoparathyroidism compared with 25.6% in the TT + CCLNd group. The rate of persistent hypoparathyroidism in the TT and TT + CCLNd groups was 3.2% and 6.0%, respectively. The difference in the rate of transient and persistent postoperative hypoparathyroidism was not statistically significant between the two groups. Within the TT + CCLNd group, 82.9% of patients underwent ipsilateral paratracheal lymph node dissection and 17.1% underwent bilateral paratracheal lymph node dissection. The rate of postoperative hypoparathyroidism was analysed in those two subgroups of patients and did not prove to be statistically significant. DISCUSSION: While its impact on the local recurrence rate is still controversial, elective central compartment lymph node dissection could be a great tool for selection of patients who could profit from adjuvant radioiodine treatment. On the other hand, central compartment lymph node dissection could potentially increase the risk of hypoparathyroidism due to involuntary injury to parathyroid glands and/or their blood supply. Our study did not find a statistically significant difference regarding postoperative hypoparathyroidism between patients who underwent central compartment lymph node dissection compared with patients who underwent total thyroidectomy only. Our data are not in accordance with some of the previously published studies. CONCLUSION: Our results demonstrated that elective central compartment lymph node dissection is a safe procedure and does not significantly increase the risk of postoperative hypoparathyroidism when it is performed simultaneously with total thyroidectomy.

Proofs for implementation of higher HE4 and ROMA index cut-off values in ovarian cancer preoperative stratification.

This study aimed to identify and quantify the clinical significance of the HE4 and ROMA index in patients with an adnexal tumour. We recruited 159 women and the HE4 and CA125 were measured with an electrochemiluminescence immunoassay in the sera. We used the Kolmogorov-Smirnov test, Mann-Whitney's test and logistic regression to interpret the data. In the premenopausal group (n = 57), the ROC analysis (with cut-off: 86.1 pmol/L for HE4; 40.7 U/L for CA125 and 21.9% for ROMA) demonstrated the superior prognostic potential of those markers when the higher cut-offs used are compared to producers. The AUC for HE4/CA125/ROMA were 0.846/0.867/0.846, respectively. The HE4/ROMA showed 85.7% sensitivity and 94% specificity. In the postmenopausal group (n = 102), the ROC analysis cut-off values were: 99.8 pmol/L for HE4; 45.8 U/L for CA125 and 38.4% for ROMA. AUC for HE4/CA125/ROMA were 0.928/0.899/0.927, respectively. HE4 had an 86.1% sensitivity at 92.4% specificity, while ROMA showed an 88.9% sensitivity at a 90.9% specificity. Impact Statement What is already known on this subject? The incidence of ovarian cancer has been increasing, despite the improvement of diagnostic, operative and therapeutic procedures. As a part of the multiparametric approach, the HE4 and ROMA index improve the diagnostic sensitivity and specificity of CA125 in the detection of ovarian cancer. What the results of this study add? The evaluation of HE4 and ROMA efficacy in the preoperative stratification was made by logistic regression analysis. The better prognostic potential of ROMA index, in patients with present adnexal mass, was obtained using our higher cut-offs for the ROMA index (21.9% for premenopausal and 38.4% for postmenopausal) in comparison to the producer's (11.7% for premenopausal and 29.9% for postmenopausal). The HE4 and ROMA index had 14.29 +LR, 0.15 -LR, 67% PPV and 97.9% NPV in the premenopausal patients. In the postmenopausal group, the HE4 had 11.37 +LR, 0.15 -LR, 75.6% PPV and 92.4% NPV, the ROMA showed 9.78 +LR, 0.12 -LR, 91.2% PPV and 95.2% NPV. What the implications are of these findings for clinical practice and/or further research? Application of a higher cut-off for HE4/CA125/ROMA index can significantly reduce the percentage of FP and FN in the preoperative stratification of ovarian cancer and justify speculations about this subject in the future.

Antioxidant supplementation and serum lipids in patients with Graves' disease: effect on LDL-cholesterol.

The effect of supplementation with a fixed combination of antioxidants (beta-carotene, selenium, vitamins C and E) on serum lipids was monitored in patients with newly detected Graves' disease. Measurements were made prior to the commencement of therapy and after 30 and 60 days. Patients were randomized into two groups. Test group comprised patients who received antioxidant supplementation in addition to methimazole, while patients treated with methimazole only were in the control group. The concentration of total and HDL-cholesterol increased significantly in test and control groups (p < 0.05) but these groups did not differ significantly. Concentration of LDL-cholesterol increased significantly in the test group only (p < 0.005) and was significantly different from the control group 60 days after the commencement of therapy (p < 0.005). Significant increase in the LDL-cholesterol concentration in the test group requires further investigations.

Correlation of cardio-ankle vascular index, ten-year risk assessment and other atherosclerosis risk factors.

The aim of the study was to assess correlation of atherosclerosis severity as determined by two different methods of screening for atherosclerosis: (A) measurement of the cardio-ankle vascular index-CAVI by use of the VaseraVS-1500 vascular screening device, and (B) Framingham scale scoring. 52 subjects (28 male and 24 female) were enrolled in the study. Classification of study subjects into four quartiles based on theoretically calculated 10-year risk according to Framingham scale (medians: 1%, 3%, 4% and 15%) confirmed the risk increase to be associated with a statistically significant increase in CAVI, age and total cholesterol, and a statistically significant decrease in HDL-cholesterol (p < 0.001 all). Spearman correlation coefficients showed a statistically significant correlation of 10-year risk with CAVI (p = 0.0242; r = 0.4494). Study results suggested that simultaneous determination of CAVI and 10-year risk might prove justified. They are not contradictory, the more so, these two parameters showed a significant positive correlation. This test panel yields comprehensible, implying all the possible consequences and highly motivating information that may stimulate the person for lifestyle modification.

In vivo study of propolis supplementation effects on antioxidative status and red blood cells.

In vivo study has been conducted on 47 healthy women and men in order to investigate whether daily intake of powdered propolis extract during 30 days has any influence on the following blood parameters: activity of superoxide dismutase, glutathione peroxidase and catalase, concentration of plasma malondialdehyde, total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides, glucose, uric acid, ferritin and transferrin, together with routine red blood cell parameters. The effect of daily propolis intake seems to be time and gender related. For the men test group after the initial 15 days of propolis treatment, 23.2% (p=0.005) decrease in concentration of malondialdehyde was observed. After 30 days of treatment, statistically significant (p=0.010) 20.9% increase in superoxide dismutase activity and change in some of the red blood cell parameters were detected. For the women test group, the propolis treatment did not induce a change in any of the measured parameters.

The effect of antioxidant supplementation on superoxide dismutase activity, Cu and Zn levels, and total antioxidant status in erythrocytes of patients with Graves' disease.

The effects of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) on superoxide dismutase activity, copper and zinc concentrations, and total antioxidant status were monitored in erythrocytes derived from a group of patients with Graves' disease treated with methimazole, with respect to the rate of achieving euthyroidism. Thyroid-stimulating hormone (TSH), thyroid hormones and the above-mentioned parameters were measured before therapy, and on days 30 and 60 after therapy initiation. The patients receiving antioxidant supplementation along with methimazole therapy (group A, n = 27) achieved euthyroidism at a faster rate than those treated with methimazole alone (group B, n = 28). The activity of superoxide dismutase decreased significantly in both patient groups during the treatment; however, there was no significant difference between the groups. There was no significant change in the erythrocyte concentration of copper, whereas the zinc concentration and total antioxidant status showed significant between-group differences. The study results clearly show that antioxidant supplementation in the treatment of Graves' disease is justified, while zinc and total antioxidant status in erythrocytes seem to be sensitive indicators of the efficacy of supplemental therapy.

Supplementation with antioxidants in the treatment of Graves' disease: the effect on the extracellular antioxidative parameters.

In this study, the effect of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) on concentrations of antioxidative parameters in serum was monitored. Measurements were performed prior to the commencement of therapy and after 30 and 60 days in patients with Graves' disease treated with methimazole. Patients who received extra supplementation with antioxidants (group A, n = 29) attained euthyroidism faster than the patients treated only with methimazole (group B, n = 28). Statistically significant differences were achieved after supplementation with antioxidants for all investigated parameters (uric acid, transferrin, ferritin), except TAS and glucose. Nevertheless, due to the fact that all measured parameters remained within the range of referent values, they may not be proposed as reliable indicators of the level of oxidative stress in Graves' disease.

[Biochemical markers in acute coronary syndrome]. / Biokemijski biljezi akutnog koronarnog sindroma.

For many years, cardiac markers have been used to assist cardiologists in the diagnosis and management of patients with cardiovascular disease. At first, enzyme activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase have been used in diagnosing patients with chest pain in order to differentiate those with acute myocardial infarction. In the field of cardiac markers, emphasis is currently put on the use of protein markers such as myoglobin, and cardiac troponin T or I. Troponins are very highly cardiac specific and their concentration in blood increase only from four to six hours after the onset of chest pain. Today we obligatorily use two markers, the first being the early one (myoglobin, isoform of creatine kinase), which is very sensitive and shows up in the circulation one to two hours after myocardial damage. Confirmation of myocardial damage can be obtained by definite markers (troponin I or T), which are highly specific of myocardial damage.

Antioxidants in patients with hyperthyroidism.

Hyperthyroidism is a hypermetabolic state accompanied by increased oxygen utilization, increased production of reactive oxygen species and consequentially measurable changes in antioxidative factors. Therefore, the activities of whole blood glutathione peroxidase (GPx) and erythrocyte superoxide dismutase (SOD), total antioxidant status (TAS) in serum and erythrocytes, and serum urate and transferrrin concentrations were determined in 70 women: 14 with newly diagnosed Graves' disease (group A); 28 with hyperthyroidism on therapy with methimazole (group B, divided into two subgroups, B1 and B2) and 28 healthy women (group C). In comparison with control group C, GPx activity was significantly decreased in all patient groups (p < 0.05), whereas SOD activity was significantly decreased in group A (p < 0.01) and significantly increased in group B (p < 0.01). In comparison with the control group, serum TAS activity was significantly decreased in group A, and erythrocyte TAS activity in all patient groups. Study results suggest that the impaired antioxidative factor balance leads to the development and presence of oxidative stress in women with hyperthyroidism. The severity of these alterations, considered contradictory by some authors, appears to depend on the use of therapy.

Supplementation with antioxidants in the treatment of Graves' disease; the effect on glutathione peroxidase activity and concentration of selenium.

BACKGROUND: The effect of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) was monitored on the speed of attaining euthyroidism in a group of patients with Graves' disease, treated with methimazole. METHODS: The activity of glutathione peroxidase in whole blood and the concentrations of selenium, pituitary and thyroid hormones in serum were measured, prior to commencement of therapy and after 30 and 60 days. RESULTS Patients who received supplementation with antioxidants in addition to therapy with methimazole (Group A, n=29) attained euthyroidism faster than the patients treated with only methimazole (Group B, n=28). The concentration of selenium in the serum of patients in Group A increased significantly during treatment (p<0.001), while there was no statistically significant change in the patients in Group B. The concentration of selenium in the serum between the groups differed statistically significantly 30 days (p<0.05) and 60 days (p<0.01) after the commencement of therapy. Activity of glutathione peroxidase in whole blood increased during treatment in both groups of patients. However, a statistically more significant increase occurred in Group A compared to Group B, 30 days after the commencement of therapy (p<0.01). CONCLUSION: The results of the study clearly indicate that supplementation with antioxidants in the treatment of Graves' disease is justified, particularly those containing selenium.

Paraoxonase activity and concentration of indicators of lipids status in the serum of cardiac patients.

In this research, we measured the activity of paraoxonase (basal and activated) enzyme, and components of lipid status components (total cholesterol, LDL cholesterol, HDL cholesterol and Apo A I) in the serum of patients, undergoing bypass surgery. We also tested how the applied EKC affected changes of defined indicators. Measuring of all the given parameters was conducted prior to the operation, 90 minutes, 1.5 hour, 6 hours, 24 hours and 72 hours, on 29 patients (11 of them did undergo myocardium revascularization with the application of EKC, while the rest of them did not). Activity of paraoxonase (both basal and activated) changes significantly during the postoperative period, in relation to pre-operative values, p < 0.05. Total cholesterol concentration is reduced in both examined groups, regardless of the application of EKC. This trend is also accompanied by LDL cholesterol concentration. On the other hand, HDL cholesterol concentration during post-operative period does not indicate any significant statistical change in relation to pre-operative values, while we noticed difference with regard to EKC application, 90 minutes after surgery. This change of lipid status indicator is partly due to heparin, a stimulator of lipoprotein lipase that was applied during the surgery. Our conclusion is that lipid profile changes significantly after the bypass surgery, mostly regardless of the application of EKC.