Laboratory Puzzle of Oxidative Stress, Parameters of Hemostasis and Inflammation in Hospitalized Patients with COVID-19.

Bearing in mind that coronavirus disease (COVID-19) is associated with a wide range of laboratory abnormalities, the aim of this study was to examine the importance of determining the parameters of oxidative stress and antioxidant protection as well as markers of inflammation and hemostasis in hospitalized patients with COVID-19. The study population included 105 patients with severe COVID-19 and 65 healthy control subjects. The parameters of oxidative stress and the activity of enzymes of the antioxidant system were determined from the obtained samples using spectrophotometric methods. Standard laboratory methods were performed for the determination of the biochemical and hematological parameters. Patients with COVID-19 showed a significantly higher level of pro-oxidative parameters (hydrogen peroxide (H2O2) and the index of lipid peroxidation in the form of thiobarbituric acid-reactive substances (TBARSs)) and a significantly lower activity of the antioxidant system (catalase (CAT)). Patients with COVID-19 had significantly higher values of inflammation parameters (C-reactive protein (CRP), procalcitonin (PCT), ratio of the number of neutrophils to lymphocytes (NLR), and ratio of the number of platelets to lymphocytes (PLR)) and parameters of hemostasis (activated partial thromboplastin time (aPTT), prothrombin time (PT), D-dimer, fibrinogen) than the control healthy subjects. In addition, changes in hemostatic parameters correlated positively with inflammatory markers in the group of patients with COVID-19. The early determination of hemostasis parameters and the parameters of inflammation can help in the prediction of poor prognosis in COVID-19 patients.

Children's Internet use and physical and psychosocial development.

Introduction: Internet use (IU) commonly refers to sedentary lifestyle and may be addictive, especially among children. The aim of this study was to investigate the relationship between IU and some aspects of child physical and psychosocial development. Methodology: We conducted a cross-sectional survey by using a screen-time based sedentary behavior questionnaire and Strengths and Difficulties Questionnaire (SDQ)-among 836 primary school children in the Branicevo District. The children's medical records were analysed for vision problems and spinal deformities. Their body weight (BW) and height (BH) were measured and body mass index (BMI) was calculated as BW in kilograms divided by BH in meters squared (kg/m2). Results: The average age of respondents was 13.4 (SD 1.2) years. The mean duration of daily Internet use and sedentary behavior was 236 (SD 156) and 422 (SD 184) minutes, respectively. There was no significant correlation between daily IU and vision problems (near sightedness, farsightedness, astigmatism, strabismus), and spinal deformities. However, daily Internet use is significantly associated with obesity (p < 0.001) and sedentary behavior (p = 0.01). There was significant correlation between emotional symptoms with total Internet usage time, and total sedentary score (p < 0.001 for both, r = 0.141 and r = 0.132, respectively). There was a positive correlation between the total sedentary score of children and hyperactivity/inattention (r = 0.167, p < 0.001), emotional symptoms (r = 0.132, p < 0.001), and conduct problems (r = 0.084, p < 0.01). Conclusion: In our study, children's Internet use was associated with obesity, psychological disturbances and social maladjustment.

Can MDCT Enhancement Patterns Be Helpful in Differentiating Secretory from Non-Functional Adrenal Adenoma?

Background and Objectives: Primary adrenal tumors (AT) are a heterogeneous group of neoplasms due to their functional heterogeneity, which results in the diverse clinical presentation of these tumors. The purpose of this study was to examine cross-sectional imaging characteristics using multi-detector computed tomography (MDCT) to provide insight into the lesion characterization and functional status of these tumors. The radionuclide imaging using Technetium-99m radiolabeled hydrazinonicotinylacid-d-phenylalanyl1-tyrosine3-octreotide (99mTc-HYNIC-TOC), was also used in the diagnostic evaluation of these tumors. Materials and Methods: This cross-sectional study included 50 patients with confirmed diagnoses of AT (21 hormone-secreting and 29 non-functional) at the University Clinical Center, Kragujevac, Serbia, during the 2019-2022 year period. The morphological and dynamic characteristics using MDCT were performed, using qualitative, semi-quantitative, and quantitative analysis. Absolute washout (APW) and relative washout (RPW) values were also calculated. A semi-quantitative analysis of all visual findings with 99mTc-HYNIC-TOC was performed to compare the tumor to non-tumor tracer uptake. Results: A statistically significant difference was found in the MDCT values in the native phase (p < 0.05), the venous phase (p < 0.05), and the delayed phase (p < 0.001) to detect the existence of adrenal tumors. Most of these functional adrenocortical lesions (n = 44) can be differentiated using the delayed phase (p < 0.05), absolute percentage washout (APW) (p < 0.05), and relative percentage washout (RPW) (p < 0.001). Furthermore, 99mTc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumor existence (p < 0.001). There is a positive correlation between radionuclide imaging scan and APW to detect all AT (p < 0.01) and adrenocortical adenomas as well (p < 0.01). Conclusions: The results can be very helpful in a diagnostic algorithm to quickly and precisely diagnose the expansive processes of the adrenal glands, as well as to learn about the advantages and limitations of the mentioned imaging modalities.

Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience.

Introduction: Peptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment. Methodology: We retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups. Results: A total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively. Conclusion: The study's results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly.

Clinical usefulness of 99mTc-HYNIC-TOC, 99mTc(V)-DMSA, and 99mTc-MIBI SPECT in the evaluation of pituitary adenomas.

BACKGROUND: The aim of this study was to evaluate the behavioral uptake and ability to diagnose pituitary adenoma (PA) using tumor-seeking radiopharmaceuticals, and to provide a semiquantitative analysis of tracer uptake in the pituitary region. PATIENTS AND METHODS: The study included 33 (13 hormonally active and 20 nonfunctioning) patients with PA and 45 control participants without pituitary involvement. All patients (n=78) underwent single photon emission computed tomography (SPECT) imaging with technetium-99m-labeled hydrazinonicotinyl-tyr-octreotide (Tc-HYNIC-TOC), dimercaptosuccinic acid (Tc(V)-DMSA) and hexakis-2-methoxyisobutylisonitrile (Tc-MIBI). A semiquantitative analysis of abnormal uptake was carried out by drawing identical regions of interest over the pituitary area and the normal brain on one transverse section that shows the lesion most clearly. The pituitary uptake to normal brain uptake (P/B) ratio was calculated in all cases. RESULTS: The result of this study confirms that the SPECT semiquantitative method, with all three tracers, showed statistically significant differences between the PA group and the controls. However, Tc-HYNIC-TOC scintigraphy could have the highest diagnostic yield because of the smallest overlap between the P/B ratios between adenoma versus nonadenoma participants (the receiver operating characteristic curve P/B ratio cut-off value was 13.08). In addition, only Tc-MIBI SPECT have the diagnostic potential to detect secreting PAs, with statistically significant differences between groups (P<0.001), with an receiver operating characteristic curve P/B ratio cut-off value of 16.72. CONCLUSION: A semiquantitative analysis of increased focal tracer uptake in the sellar area showed that Tc-HYNIC-TOC is a highly sensitive and reliable tumor-seeking agent for detecting PA, whereas Tc-MIBI SPECT is a highly sensitive and specific method in differentiating hormone-secreting pituitary tumor.

Influence of Different ß-Blockers on Platelet Aggregation in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy.

INTRODUCTION: The use of ß-blockers in the treatment of patients with coronary heart disease is associated with a decrease in the frequency of angina pectoris and mortality of patients. Due to the severity of the disease and previous cardiovascular interventions, many patients with coronary artery disease (CAD) use dual antiplatelet therapy to achieve greater inhibition of platelet aggregation. The influence of ß-blockers on platelet aggregation in patients using antiplatelet therapy is not well understood. OBJECTIVE: To examine the effect of different ß-blockers on platelet aggregation in patients on dual antiplatelet therapy. METHODOLOGY: The study included 331 patients who were treated at the Department of Cardiology, Clinical Center Kragujevac during 2011. Patients were divided into 4 groups depending on the type of ß-blockers that were used (bisoprolol, nebivolol, metoprolol, and carvedilol). Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test (to assess the effect of clopidogrel), ASPI test (to assess the effect of acetyl salicylic acid), TRAP test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP ASPI/TRAP (ASPI - aranchidonic acid induced aggregation, TRAP - thrombin receptor activating peptide) representing the degree of inhibition of platelet aggregation compared to the basal value. In consideration were taken the representation of demographic, clinical characteristics, laboratory parameters, and cardiovascular medications between the groups. RESULTS: Patients who used nebivolol had a significantly lower value of the ratio of ADP/TRAP (0.39 ± 0.30) compared to patients who used bisoprolol (0.48 ± 0.26; P = .038), and trend toward the lower values of ADP test (328.0 ± 197.3 vs 403.7 ± 213.2; P = .059), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. CONCLUSION: Patients with CAD on dual antiplatelet therapy who used nebivolol had significantly lower levels of residual ADP-induced platelet aggregation compared to baseline than patients who used bisoprolol.

Is there a link between Hashimoto's thyroiditis and primary hyperparathyroidism? A study of serum parathormone and anti-TPO antibodies in 2267 patients.

According to various authors, thyroid disorders like Hashimoto's thyroiditis (HT), diffuse goiter or multinodular goiter, Graves' disease, medullary or papillary carcinoma could be found in a number of patients with primary hyperparathyroidism (PHPT). This association is more common in elderly women. Neck irradiation, lithium treatment and elevated TSH levels have been suggested as some of the possible causes of this co-existance. The aim of this study was to investigate and determine the prevalence of patients having both HT and PHPT, and the possible relation between these two diseases. We conducted a prospective study during three and a half years. This study included 45,231 patients, which were referred by their general practitioner or endocrinologist, under suspicion of having thyroid and/or parathyroid disease. In these patients we measured serum levels of the following parameters: anti-thyroid peroxidase antibodies (antiTPO-Ab), anti-thyroglobulin antibodies (Tg-Ab), anti-TSH-receptor antibodies (TSHR-Ab), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium (Ca). In 2,267 of these 45,231 patients (5.01%) we noticed elevated antiTPO-Ab (3542±3407IU/mL), with statistical significant difference from normal values (normal range 0-70IU/mL), P<0.05, and normal levels of other antithyroid antibodies (Tg-Ab, TSHR-Ab). All patients with elevated antiTPO-Ab were assumed to have HT. Within this group, 43 patients (1.89%) also had elevated serum levels of PTH (112.4±33.2pg/mL, normal range 8-76pg/mL) as well as elevated serum levels of calcium (2.92±0.06mmol/L, normal range 2.2-2.65mmol/L). These laboratory findings, accompanied with clinical symptoms, satisfied the criteria for PHPT. The mean age in this subgroup was 60.5±12.2 years. All 2,267 patients had normal or slightly elevated TSH levels. In conclusion, although the reported rate of prevalence of PHPT in the general population is about 0.3%, our results indicated a 1.89% occurrence of PHPT in 2267 patients with HT in central Serbia. This may be due to the autoimmune inflammatory process in HT supporting PHPT to PTH or calcium supporting HT or to common genetical predisposition of both entities.