Vatroslav Šerić

Falsely elevated serum oestradiol due to exemestane therapy

In this study, we present a case of falsely elevated oestradiol (E2) concentration, determined by two immunoassays, in a breast cancer patient receiving exemestane therapy. The positive bias of immunochemical measurements was revealed using liquid chromatography tandem mass spectrometry which showed undetectable E2 concentration. The discrepancy is expected to be a consequence of the structural resemblance of E2 and exemestane sharing the same steroidal backbone. Inaccurate laboratory findings in therapy monitoring, as in this case, may lead to unnecessary changes of therapy.

Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL)

Abstract Background: Acute pyelonephritis is a severe disease which is sometimes difficult to recognize based on clinical symptoms and routinely available diagnostic tests, especially in young children. The aim of this study was to assess the diagnostic value of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a biomarker of acute pyelonephritis. Methods: In this case-control study we analyzed 134 children (median age 2.5 years) who were admitted to the Pediatric Clinic of University Hospital Centre Osijek, Croatia. Eighty of them had acute pyelonephritis, while 54 children had febrile state of different etiology including cystitis and they represented the control group. uNGAL, white blood cells, C-reactive protein, urinanalysis, urine culture, kidney ultrasound and a dimercaptosuccinic acid scintigraphic scan were done for each child. uNGAL was measured using chemiluminiscent microparticle immunoassay on ARHITECT i1000SR (Abbott Diagnostics, IL, USA). Results: uNGAL values were significantly higher in children with acute pyelonephritis compared to the control groups (113.6 ng/mL vs. 10.2 ng/mL, p<0.001). A receiver operating characteristic curve comparison was done for tested parameters and encouraging results were obtained for uNGAL (AUC=0.952). A cut-off value of 29.4 ng/mL had 92.5% sensitivity and 90.7% specificity. We showed that uNGAL can also serve in differentiating acute pyelonephritis from cystitis (cut-off 38.5 ng/mL), and for differentiation of cystitis from febrile states with etiology other than urinary tract infection (UTI) (cut-off 20.4 ng/mL). Conclusions: uNGAL can be a useful diagnostic biomarker in acute pyelonephritis in children, but also in differentiating cystitis from febrile states other than UTI.

Association of Wnt Inhibitors, Bone Mineral Density and Lifestyle Parameters in Women with Breast Cancer Treated with Anastrozole Therapy

Aim: To determine the levels of Wnt inhibitors in patients treated with aromatase inhibitors (AIs) prior to therapy and to investigate their association with bone mineral density (BMD) and lifestyle parameters. Methods: 137 breast cancer patients were divided into a group treated with 1 mg of anastrozole and a group w/o anastrozole therapy. Serum concentrations of sclerostin and dickkopf1 (DKK1) were measured by ELISA. BMD was measured by dual-energy X-ray absorptiometry (DXA). Lifestyle factors were investigated by a self-reported questionnaire. Results: Sclerostin was significantly higher in the AI-treated group (31.8 pmol/L vs. 24.1 pmol/L; p < 0.001), whereas DKK1 was significantly lower in the AI-treated group (24.3 pmol/L vs. 26.02 pmol/L; p < 0.001). Total hip and femoral neck BMD were significantly lower in the AI-treated group. Conclusion: AI treatment was associated with increased levels of sclerostin and decreased levels of DKK1.

Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations

Abstract Background: Carbohydrate sulfotransferases (CHST) were shown to be involved in carcinogenesis. The aim of the study was to assess the diagnostic value of serum CHST7 concentration in differentiation between lung cancer and non-malignant pulmonary inflammations. Methods: Clinical case-control study involving 125 participants was conducted: the control group containing cases of pneumonia and chronic obstructive pulmonary disease was compared to the lung cancer group composed of primary and metastatic cancers. Serum concentrations of CHST7 and routinely used markers including carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (CYFRA 21-1) and neuron-specific enolase (NSE) were determined for each participant using immunochemical methods. Statistical association, receiver operating characteristic (ROC) analysis and cross-validation were used for the evaluation of CHST7 either as a standalone biomarker or as a part of a biomarker panel. Results: In comparison to the control group, serum CHST7 was elevated in lung cancer (p<0.001), but no differences between the overall stages of primary cancers were detected (p=0.828). The differentiation performance in terms of ROC area under curve (AUC) was 0.848 making CHST7 superior biomarker to the NSE (p=0.031). In comparison to CEA and CYFRA 21-1, the performance differences were not detected. CHST7 was not correlated to other biomarkers, and its addition to the routine biomarker panel significantly improved the cross-validated accuracy (85.6% vs. 75.2%) and ROC AUC (p=0.004) of the differentiation using a machine learning approach. Conclusions: Serum CHST7 is a promising biomarker for the differentiation between lung cancer and non-malignant pulmonary inflammations.

The effects of propolis and bee pollen supplementation on biochemical blood parameters of broilers

Abstract The aim of this study was to determine the effect of propolis and bee pollen on selected biochemical blood parameters in broiler chickens. This experimental study was conducted on 200 Ross 308 chickens of equally distributed sex, which were divided into five groups (a control group and four experimental groups). Throughout the whole study the control group of chickens was fed the control feed mixture while the feed mixture that was fed to the experimental groups of chickens contained additives (propolis and/or bee pollen, each supplemented separately or in combination in a certain proportion). The results obtained by this study are: significantly lower blood glucose, cholesterol and calcium levels (P < 0.001), as well as significantly lower triglycerides levels (P = 0.002), but also significantly higher sodium and chloride (P < 0.001), phosphorus (P = 0.004) and globulins levels (P = 0.027) in chickens of the experimental groups compared to the chickens of the control group on the 21st day of fattening. Furthermore, this study has found significantly lower blood glucose (P = 0.033) levels and significantly higher levels of total proteins and globulins (P = 0.003), as well as albumins (P = 0.040) in chickens of the experimental groups compared to the chickens of the control group on the 42nd day of fattening. It can be concluded that the application of propolis and bee pollen as additives in broiler feeds enables the production of more vital and healthier animals, which significantly improves the fattening of chickens.

Razina kemerina u krvi je povezana s volumenima trbušnog masnog tkiva izmjerenima pomoću magnetske rezonancije i čimbenicima stila života

Obesity is a low-grade chronic inflammatory state, in which a cytokine chemerin with its immunometabolic modulation has an important role. We aimed to study in a healthy population relationships between serum chemerin levels, lifestyle choices and magnetic resonance imaging (MRI) assessed volumes of abdominal visceral (VAT) and subcutaneous (SAT) adipose tissues, which have different cytokine expression profiles. Overall, 73 healthy participants undertook lifestyle questionnaire and underwent anthropometric measurements along with MRI scanning of abdominal SAT and VAT. Furthermore, complete blood count was determined along with chemerin and fibrinogen serum levels. Regression model for prediction of chemerin serum levels was built after controlling for sex, age and anthropometric measures. Median serum chemerin was 141 (125-195) ng/mL. Serum chemerin had a moderate positive correlation with SAT and VAT volumes. The two most important predictors of chemerin levels were MRI detected SAT and thigh circumference. Independently, chemerin levels were associated with smoking, preference of salty food, and favoring flavor/simplicity of preparation over nutritional value of the food. Serum chemerin seems to be more strongly correlated with the volume of abdominal SAT than VAT, with certain lifestyle choices influencing chemerin levels independently of abdominal fat.

Vitamin D Status in Renal Transplant recipients is not Associated with Erectile Dysfunction

Erectile dysfunction (ED) is a highly prevalent disorder among renal transplant recipients. Vitamin D deficiency (VDD) has been associated with several ED risk factors but only recently directly linked to ED. We conducted a study to investigate whether vitamin D serum levels were associated with the presence and severity of ED in 40 male patients that underwent deceased donor kidney transplantation (TX) from 2001 to 2013. Blood samples were collected on two seasonally distinct occasions and 25(OH)D concentration was assessed by radioimmunoassay. A 5-item version of the International Index of Erectile Function (IIEF-5) was used for ED evaluation and group stratification. We found comparable rates of ED (75%) and VDD (42.5%-62.5%) as in previously published studies. Serum levels of 25(OH)D did not differ between patients with and those without ED on both measurements (p=0.656 and p=0.914, respectively), or when comparing different ED severity groups. Duration of renal replacement therapy before TX and graft duration until analysis were longer in patients with ED (p=0.022 and p=0.05, respectively), but with the results being nonsignificant on logistic regression. In conclusion, we found no association of 25(OH)D concentration with the presence and severity of ED in renal transplant recipients. So far, there are no similar published data.

Statistical learning confirms the diagnostic significance of the anemia panel in breast cancer.

Abstract Background: Diagnostic value of available tumor markers, such as cancer antigen CA 15-3 and carcinoembryonic antigen (CEA) in breast cancer is limited. There is an ongoing search for additional, potentially better diagnostic blood markers with improved clinical utility. The aim of this study is to evaluate performance of the approach based on routine blood tests accompanied by a statistical learning tool to the diagnosis of breast cancer. Methods: Blood was collected from total of 104 subjects which were divided into two groups: breast cancer patients and a control group that consisted of asymptomatic volunteers and patients who had benign breast lesions at the time of blood collection. Random forest statistical learning method and the external method validation have been applied to evaluate diagnostic performance of 31 routine blood tests. Results: The applied statistical learning approach assigned the highest diagnostic importance to the anemia panel among all analyzed blood tests that also included CA 15-3. External validation has shown utility of selected statistical approach – we were able to select tests that provide a diagnostic accuracy comparable to some diagnostic tools described in literature and based on more demanding laboratory techniques, such as gene expression microarrays. Conclusions: Inclusion of tests for anemia significantly improves diagnostic accuracy for the breast cancer in comparison to the diagnostic accuracy of the CA 15-3 alone. Application of the random forests also enables the reduction of number of laboratory tests needed for the establishment of diagnosis. Differences in relevant test values between the cancer and control group are small but application of multiparametric statistical learning ensured diagnostic accuracy of 72.0% associated by a sensitivity of 64.7% and specificity of 84.9%.