Laboratory policies and practices for thyroid function tests in Croatia: survey on behalf of Working Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

Introduction: Laboratory plays important part in screening, diagnosis, and management of thyroid disorders. The aim of this study was to estimate current laboratory preanalytical, analytical and postanalytical practices and policies in Croatia. Materials and methods: Working Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine designed a questionnaire with 27 questions and statements regarding practices and protocols in measuring thyroid function tests. The survey was sent to 111 medical biochemistry laboratories participating in external quality assurance scheme for thyroid hormones organized by Croatian Centre for Quality Assessment in Laboratory Medicine. Data is presented as absolute numbers and proportions. Results: Fifty-three participants returned the questionnaire. Response rate varied depending on question, yielding a total survey response rate of 46-48%. All respondents perform thyroid stimulating hormone (TSH). From all other thyroid tests, most performed is free thyroxine (37/53) and least TSH-stimulating immunoglobulin (1/53). Laboratories are using nine different immunoassay methods. One tenth of laboratories is verifying manufacturer's declared limit of quantification for TSH and one third is verifying implemented reference intervals for all performed tests. Most of laboratories (91%) adopt the manufacturer's reference interval for adult population. Reference intervals for TSH are reported with different percentiles (90, 95 or 99 percentiles). Conclusion: This survey showed current practices and policies in Croatian laboratories regarding thyroid testing. The results identified some critical spots and will serve as a foundation in creating national guidelines in order to harmonize laboratory procedures in thyroid testing in Croatia.

Testing the Institute of Medicine (IOM) recommendations on maternal reproductive health and associated neonatal characteristics in a transitional, Mediterranean population.

BACKGROUND: High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are significant risk factors for maternal and neonatal health. AIM: To assess pre-pregnancy BMI and GWG during pregnancy and their association with different maternal and neonatal characteristics in the transitional Mediterranean population from the Eastern Adriatic islands. SUBJECTS AND METHODS: Two hundred and sixty-two mother-child dyads from the CRoatian Islands' Birth Cohort Study (CRIBS) were included in the study. Chi-square test, ANOVA, and regression analysis were used to test the association between selected characteristics. RESULTS: In total, 22% of women entered pregnancy as overweight/obese and 46.6% had excessive GWG. Pre-pregnancy overweight and obesity were significantly associated with elevated triglycerides uric acid levels, and decreased HDL cholesterol in pregnancy. Excessive GWG was associated with elevated fibrinogen and lipoprotein A levels. Women with high pre-pregnancy BMI and GWG values were more likely to give birth to babies that were large for gestational age (LGA), additionally confirmed in the multiple logistic regression model. CONCLUSION: High maternal pre-pregnancy BMI and excessive GWG were both significantly associated with deviated biochemical parameters and neonatal size. More careful monitoring of maternal nutritional status can lead to better pre- and perinatal maternal healthcare.

The Role of Urotensin-II in Obesity and Metabolic Syndrome in Pediatric Population.

BACKGROUND: Urotensin-II (U-II) is a short cyclic peptide that is widely recognized as one of the most potent vasoconstrictors. U-II plays a role in the pathophysiology of MS, participating in the development of essential hypertension, insulin resistance, hyperglycemia, and a proinflammatory state. METHODS: This study comprised 52 obese children and adolescents with a body mass index (BMI) z score > 2, aged 10 to 18 years. Serum levels of U-II were assessed using an enzyme-linked immunosorbent assay along with other standard biochemical parameters. RESULTS: Elevated serum levels of U-II were recorded in the group of obese subjects with MS when compared with the group of obese subjects without MS (4.99 (8.97-3.16) vs. 4.17 (5.17-2.03) ng/mL, median and IQR, p = 0.026). Furthermore, a subgroup of study subjects with high blood pressure had significantly higher U-II levels in comparison with the normotensive subgroup (4.98 (7.19-3.22) vs. 3.32 (5.06-1.97) ng/mL, p = 0.027), while the subgroup with a positive family history of high blood pressure had significantly higher U-II levels when compared with subjects who had a negative family history of elevated blood pressure (5.06 (6.83-4.45) vs. 3.32 (6.13-2.21) ng/mL, p = 0.039). CONCLUSIONS: To the best of the author's knowledge, this is the first study on the levels of U-II in obese children and adolescents, including a possible link to MS.

Circulating sST2 and catestatin levels in patients with acute worsening of heart failure: a report from the CATSTAT-HF study.

AIMS: Soluble suppression of tumourigenicity 2 (sST2) and catestatin (CST) reflect myocardial fibrosis and sympathetic overactivity during the acute worsening of heart failure (AWHF). We aimed to determine serum levels and associations of sST2 and CST with in-hospital death as well as the association between sST2 and CST among AWHF patients. METHODS AND RESULTS: A total of 96 AWHF patients were consecutively enrolled, while levels of sST2 and CST were determined and compared between non-survivors and survivors. Predictive values of sST2 and CST for in-hospital death were determined by the penalized multivariable Firth logistic regression. The diagnostic ability of sST2 and CST for in-hospital death was assessed by the receiver operating characteristic analysis and examined with respect to the N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and C-reactive protein. The in-hospital death rate was 6.25%. Serum sST2 and CST levels were significantly higher among non-survivors than survivors [146.6 (inter-quartile range, IQR 65.9-156.2) vs. 35.3 (IQR 20.6-64.4) ng/mL, P < 0.001, and 19.8 (IQR 9.9-28.0) vs. 5.6 (IQR 3.4-9.8) ng/mL, P < 0.001, respectively]. Both sST2 and CST were independent predictors of in-hospital death [Firth coefficient (FC) 6.00, 95% confidence interval (CI), 1.48-15.20, P = 0.005, and FC 6.58, 95% CI 1.66-21.78, P = 0.003, respectively], while NT-proBNP was not a significant predictor (FC 1.57, 95% CI 0.51-3.99, P = 0.142). In classifying non-survivors from survivors, sST2 provided area under the curve (AUC) of 0.917 (95% CI 0.819-1.000, P < 0.001) followed by CST (AUC 0.905, 95% CI 0.792-1.000, P < 0.001), while NT-proBNP yielded AUC of 0.735 (95% CI 0.516-0.954, P = 0.036). High-sensitivity cardiac troponin I and C-reactive protein were not found as significant classifiers of in-hospital death (AUC 0.719, 95% CI 0.509-0.930, P = 0.075, and AUC 0.682, 95% CI 0.541-0.822, P = 0.164, respectively). Among survivors, those with sST2 serum levels ≥35 ng/mL had significantly higher CST levels, compared with those with sST2 < 35 ng/mL (9.05 ± 5.17 vs. 5.06 ± 2.76 ng/mL, P < 0.001). Serum sST2 levels positively and independently correlated with CST levels in the whole patient cohort (ß = 0.437, P < 0.001). CONCLUSIONS: Elevated sST2 and CST levels, reflecting two distinct pathophysiological pathways in heart failure, might indicate impending clinical deterioration among AWHF patients during hospitalization and facilitate prognosis beyond traditional biomarkers regarding the risk of in-hospital death (CATSTAT-HF ClinicalTrials.gov Number NCT03389386).

Right Ventricular Free Wall Strain and Congestive Hepatopathy in Patients with Acute Worsening of Chronic Heart Failure: A CATSTAT-HF Echo Substudy.

Right ventricular (RV) function is an important predictor of prognosis in patients with heart failure. However, the relationship of the RV free wall longitudinal strain (RV FWS) and the degree of hepatic dysfunction during the acute worsening of heart failure (AWHF) is unknown. We sought to determine associations of RV FWS with laboratory liver function tests and parameters of RV function including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV FAC), maximal tricuspid jet velocity (TR Vmax), RV S' velocity, and estimated RV systolic pressure (RVSP). A total of 42 AWHF patients from the CATSTAT-HF study were stratified in two groups by the RV FWS median (-16.5%). Patients < RV FWS median had significantly prolonged international normalized ratio (INR; p = 0.002), increased total bilirubin (p < 0.001) and alkaline phosphatase (ALP; p = 0.020), and decreased albumin (p = 0.005) and thrombocytes (p = 0.017) compared to patients > RV FWS median. RV FWS independently correlated to total bilirubin (ß = 0.457, p = 0.004), ALP (ß = 0.556, p = 0.002), INR (ß = 0.392, p = 0.022), albumin (ß = -0.437, p = 0.013), and thrombocytes (ß = -404, p = 0.038). Similarly, TAPSE, RV FAC, and RV S' significantly correlated with RV FWS. In conclusion, RV impairment, reflected in reduced RV FWS, is independently associated with a higher degree of hepatic dysfunction among patients with AWHF (CATSTAT-HF ClinicalTrials gov number, NCT03389386).

Fetomaternal Hemorrhage: Can We Use Hemoglobin Electrophoresis as a Diagnostic Tool?

Fetomaternal hemorrhage (FMH) is usually detected by either the Kleihauer-Betke (KB) test or by 2 cytometry, the latter of which represents the gold standard of FMH diagnosis today. But what do we do when neither method is available? We present two cases of suspected FMH due to their characteristic signs and symptoms that were ultimately confirmed by hemoglobin electrophoresis (HE).

Reference intervals for six salivary cortisol measures based on the Croatian Late Adolescence Stress Study (CLASS).

INTRODUCTION: The aim of this nested study is to provide the reference intervals for already published measurements of salivary cortisol from the Croatian Adolescence Stress Study (CLASS). MATERIAL AND METHODS: A total of 969 individuals (372 males and 597 females) were included in the reference sample (age range: 18-21 years). Salivary cortisol concentrations were determined by the enzyme immunoassay (LUCIO-Medical ELISA Salivary Cortisol Kit, Nal von Minden, Germany) in the Department of Medical Laboratory Diagnostics, University Hospital Split. Nonparametric statistics were used for calculating the reference intervals (RIs) and 90% confidence intervals (90% CIs). RESULTS: The lower limits of RIs determined by the direct method were higher in females (> 10%) than in males for the cortisol concentrations at awakening (SCC0), 30 to 45 after awakening (SCC30-45) and at bedtime (SCCbedtime). The upper limits of RIs for the SCCbedtime were higher (> 10%) in males than in females. Females also had higher upper limits of RIs for the cortisol awakening response (CAR) and the diurnal cortisol slope (DCS) and higher lower limits of RIs for the CAR and the area under the curve with respect to ground (AUCG). The lower limits of RIs for the DCS were higher in males than in females. CONCLUSIONS: Obtained reference values open the arena for introducing salivary bioscience in Croatian clinical laboratory practice and provide important data for better understanding of gender differences in adaptation to stress during late adolescence.