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Item Utilization of biological variation data in the interpretation of laboratory test results - survey about clinicians' opinion and knowledge(CROATIAN SOC MEDICAL BIOCHEMISTRY \& LABORATORY MEDICINE, 2021-01-01) Emre, Humeyra Ozturk; Karpuzoglu, Fatma Hande; Coskun, Cihan; Sezer, Ebru Demirel; Ozturk, Ozlem Goruroglu; Ucar, Fatma; Cubukcu, Hikmet Can; Arslan, Fatma Demet; Deniz, Levent; Senes, Mehmet; Serteser, Mustafa; Yazici, Cevat; Yucel, Dogan; Coskun, AbdurrahmanIntroduction: To interpret test results correctly, understanding of the variations that affect test results is essential. The aim of this study is: 1) to evaluate the clinicians' knowledge and opinion concerning biological variation (BV), and 2) to investigate if clinicians use BV in the interpretation of test results. Materials and methods: This study uses a questionnaire comprising open-ended and close-ended questions. Questions were selected from the real-life numerical examples of interpretation of test results, the knowledge about main sources of variations in laboratories and the opinion of clinicians on BV. A total of 399 clinicians were interviewed, and the answers were evaluated using a scoring system ranked from A (clinician has the highest level of knowledge and the ability of using BV data) to D (clinician has no knowledge about variations in laboratory). The results were presented as number (N) and percentage (\%). Results: Altogether, 60.4\% of clinicians have knowledge of pre-analytical and analytical variationsItem Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects(WALTER DE GRUYTER GMBH, 2018-01-01) Coskun, Abdurrahman; Carobene, Anna; Kilercik, Meltem; Serteser, Mustafa; Sandberg, Sverre; Aarsand, Aasne K.; Fernandez-Calle, Pilar; Jonker, Niels; Bartlett, William A.; Diaz-Garzon, Jorge; Huet, Sibel; Kiziltas, Cansu; Dalgakiran, Ilayda; Ugur, Esra; Unsal, Ibrahim; Varia, E.F.L.M. Working Grp BiologicalBackground: The complete blood count (CBC) is used to evaluate health status in the contexts of various clinical situations such as anemia, infection, inflammation, trauma, malignancies, etc. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are required. The study aim was to define the BVs of CBC parameters employing a strict protocol. Methods: Blood samples, drawn from 30 healthy subjects (17 females, 13 males) once weekly for 10 weeks, were analyzed using a Sysmex XN 3000 instrument. The data were assessed for normality, trends, outliers and variance homogeneity prior to coefficient of variation (CV)-analysis of variance (ANOVA). Sex-stratified within-subject (CVI) and between-subjects (CVG) BV estimates were determined for 21 CBC parameters. Results: For leukocyte parameters, with the exception of lymphocytes and basophils, significant differences were found between female/male CVI estimates. The mean values of all erythrocyte-, reticulocyte- and platelet parameters differed significantly between the sexes, except for mean corpuscular hemoglobin concentration, mean corpuscular volume and platelet numbers. Most CVI and CVG estimates appear to be lower than those previously published. Conclusions: Our study, based on a rigorous protocol, provides updated and more stringent BV estimates for CBC parameters. Sex stratification of data is necessary when exploring the significance of changes in consecutive results and when setting analytical performance specifications.Item Melatonin in preservation solutions prevents ischemic injury in rat kidneys(PUBLIC LIBRARY SCIENCE, 2022-01-01) Coskun, Abdurrahman; Yegen, Cumhur; Arbak, Serap; Attaallah, Wafi; Gunal, Omer; Elmas, Merve Acikel; Ucal, Yasemin; Can, Ozge; Bas, Banu; Yildirim, Zeynep; Seckin, Ismail; Demirci, Sibel; Serteser, Mustafa; Ozpinar, Aysel; Belce, Ahmet; Basdemir, Gulcin; Moldur, Derya Emel; Derelioglu, Ecenur Izzete; Yozgatli, Tahir Koray; Erdemgil, Yigit; Unsal, IbrahimTransplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCI which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63-1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.Item Exposure to Perchlorate in Lactating Women and Its Associations With Newborn Thyroid Stimulating Hormone(FRONTIERS MEDIA SA, 2018-01-01) Ucal, Yasemin; Sahin, Ozlem N.; Serdar, Muhittin; Blount, Ben; Kumru, Pinar; Muhcu, Murat; Eroglu, Mustafa; Akin-Levi, Cansu; Keles, Z. Zeynep Yildirim; Turam, Cem; Valentin-Blasini, Liza; Morel-Espinosa, Maria; Serteser, Mustafa; Unsal, Ibrahim; Ozpinar, AyselBackground: Perchlorate, thiocyanate, and nitrate can block iodide transport at the sodium iodide symporter (NIS) and this can subsequently lead to decreased thyroid hormone production and hypothyroidism. NIS inhibitor exposure has been shown to reduce iodide uptake and thyroid hormone levelsItem Iodine Status in Turkish Populations and Exposure to Iodide Uptake Inhibitors(PUBLIC LIBRARY SCIENCE, 2014-01-01) Ozpinar, Aysel; Kelestimur, Fahrettin; Songur, Yildiran; Can, Ozge; Valentin, Liza; Caldwell, Kathleen; Arikan, Ender; Unsal, Ibrahim; Serteser, Mustafa; Inal, Tamer; Erdemgil, Yigit; Coskun, Abdurrahman; Bakirci, Nadi; Sezgin, Ozlem; Blount, BenPerchlorate, nitrate, and thiocyanate are competitive inhibitors of the sodium iodide symporter of the thyroid membrane. These inhibitors can decrease iodine uptake by the symporter into the thyroid gland and may disrupt thyroid function. This study assesses iodine status and exposure to iodide uptake inhibitors of non-pregnant and non-lactating adult women living in three different cities in Turkey (Istanbul, Isparta and Kayseri). We measured iodine and iodide uptake inhibitors in 24-hr urines collected from study participants (N = 255). All three study populations were mildly iodine deficient, with median urinary iodine (UI) levels of 77.5 mu g/L in Istanbul, 58.8 mu g/L in Isparta, and 69.8 mu g/L in Kayseri. Perchlorate doses were higher in the study population (median 0.13 mu g/kg/day), compared with a reference population (median 0.059 mu g/kg/day), but lower than the U. S. EPA reference dose (0.7 mu g/kg/day). Urinary thiocyanate levels increased with increasing exposure to tobacco smoke, with non-smokers (268 mu g/L) significantly lower than light smokers (1110 mu g/L), who were significantly lower than heavy smokers (2410 mu g/L). This pilot study provides novel data indicating that study participants were moderately iodine deficient and had higher intakes of the iodide uptake inhibitor perchlorate compared with a reference population. Further investigation is needed to characterize the thyroid impact resulting from iodine deficiency coupled with exposure to iodide uptake inhibitors such as perchlorate, thiocyanate and nitrate.Item INCREASED MATERNAL LEPTIN LEVELS MAY BE AN INDICATOR OF SUBCLINICAL HYPOTHYROIDISM IN A NEWBORN(SOC MEDICAL BIOCHEMISTS SERBIA, 2022-01-01) Karpuzoglu, Hande; Ucal, Yasemin; Kumru, Pinar; Muhcu, Murat; Eroglu, Mustafa; Serdar, Muhittin; Serteser, Mustafa; Ozpinar, AyselBackground: Several factors may influence newborn thyroid-stimulating hormone (TSH) concentrations and cause subclinical hypothyroidism in a newborn. A sufficient level of leptin signalling is needed for the normal production of TSH and thyroid hormones by the thyroid gland. Our study aimed to investigate the correlation between maternal serum leptin concentration during the third trimester of pregnancy and newborn screening-TSH levels. Methods: This prospective cross-sectional study was conducted in obstetrics and gynaecology clinics of a state hospital between June and August 2013. Maternal venous blood samples were collected from 270 healthy pregnant women in the third trimester just before delivery. Measurements of maternal fT3, fT4, TSH, anti-thyroid peroxidase (TPO), and anti-thyroglobulin (anti-Tg) antibodies from serum samples were performed by chemiluminescence immunoassay. Maternal serum leptin levels were determined by ELISA. Dried capillary blood spots were used to measure newborn TSH levels. Results: Subjects were divided into two groups according to the neonatal TSH levels using a cut-point of 5.5 mIU/L. Median maternal serum leptin levels were significantly higher in newborns whose TSH levels were higher than >5.5 mIU/L {[}13.2 mg/L (1.3-46.5) vs 19.7 mg/L (2.4-48.5), p<0.05]. Serum leptin levels showed a negative correlation with maternal fT4 (r=0.32, p<0.05), fT3 (r=0.23, p<0.05), and a positive correlation with BMI (r=0.30, p<0.05). Conclusions: Our results suggest that high leptin levels in the third trimester of pregnancy influence maternal thyroid functions and might cause an increase in newborn TSH levels. Detection of high maternal serum leptin levels may be a reason for subclinical hypothyroidism.Item Personalized Reference Intervals in Laboratory Medicine: A New Model Based on Within-Subject Biological Variation(OXFORD UNIV PRESS INC, 2021-01-01) Coskun, Abdurrahman; Sandberg, Sverre; Unsal, Ibrahim; Cavusoglu, Coskun; Serteser, Mustafa; Kilercik, Meltem; Aarsand, Aasne K.BACKGROUND: The concept of personalized medicine has received widespread attention in the last decade. However, personalized medicine depends on correct diagnosis and monitoring of patients, for which personalized reference intervals for laboratory tests may be beneficial. In this study, we propose a simple model to generate personalized reference intervals based on historical, previously analyzed results, and data on analytical and within-subject biological variation. METHODS: A model using estimates of analytical and within-subject biological variation and previous test results was developed. We modeled the effect of adding an increasing number of measurement results on the estimation of the personal reference interval. We then used laboratory test results from 784 adult patients (>18 years) considered to be in a steady-state condition to calculate personalized reference intervals for 27 commonly requested clinical chemistry and hematology measurands. RESULTS: Increasing the number of measurements had little impact on the total variation around the true homeostatic set point and using >= 3 previous measurement results delivered robust personalized reference intervals. The personalized reference intervals of the study participants were different from one another and, as expected, located within the common reference interval. However, in general they made up only a small proportion of the population-based reference interval. CONCLUSIONS: Our study shows that, if using results from patients in steady state, only a few previous test results and reliable estimates of within-subject biological variation are required to calculate personalized reference intervals. This may be highly valuable for diagnosing patients as well as for follow-up and treatment.Item Rise of serum troponin levels following uncomplicated elective percutaneous coronary interventions in patients without clinical and procedural signs suggestive of myocardial necrosis(TERMEDIA PUBLISHING HOUSE LTD, 2016-01-01) Buturak, Ali; Degirmencioglu, Aleks; Surgit, Ozgur; Demir, Ali Riza; Karakurt, Huseyin; Erturk, Mehmet; Yazici, Selcuk; Serteser, Mustafa; Norgaz, Tugrul; Gorgulu, SevketIntroduction: The new definition of periprocedural myocardial infarction (type 4a MI) excludes patients without angina and electrocardiographic or echocardiographic changes suggestive of myocardial ischemia even though significant serum troponin elevations occur following percutaneous coronary intervention (PCI). Aim: To evaluate the incidence and predictors of serum troponin rise following elective PCI in patients without clinical and procedural signs suggestive of myocardial necrosis by using a high-sensitivite troponin assay (hsTnT). Material and methods: Three hundred and four patients (mean age: 60.8 +/- 8.8 years, 204 male) undergoing elective PCI were enrolled. Patients with periprocedural angina, electrocardiographic or echocardiographic signs indicating myocardial ischemia or a visible procedural complication such as dissection or side branch occlusion were excluded. Mild-moderate periprocedural myocardial injury (PMI) and severe PMI were defined as post-PCI (12 h later) elevation of serum hsTnT concentrations to the range of 14-70 ng/l and > 70 ng/l, respectively. Results: The median pre-procedural hsTnT level was 9.7 ng/l (interquartile range: 7.1-12.2 ng/l). Serum hsTnT concentration elevated (p < 0.001) to 19.4 ng/l (IQR: 12.0-38.8 ng/l) 12 h after PCI. Mild-moderate PMI and severe PMI were detected in 49.3\% and 12.2\% of patients, respectively. Post-procedural hsTnT levels were significantly higher in multivessel PCI, overlapping stenting, predilatation and postdilatation subgroups. In addition, post-procedural hsTnT levels were correlated (r = 0.340Item Early Postnatal Metabolic Profile in Neonates With Different Birth Weight Status: A Pilot Study(FRONTIERS MEDIA SA, 2021-01-01) Beken, Serdar; Abali, Saygin; Yildirim Saral, Neslihan; Guner, Bengisu; Dinc, Taha; Albayrak, Eda; Ersoy, Melike; Kilercik, Meltem; Halici, Muge; Bulbul, Ezgi; Kaya, Didem; Karabay, Melis; Ay, Zeynep Alize; Eksi, Gulten Zeynep; Benli Aksungar, Fehime; Korkmaz, Ayse; Serteser, MustafaIntroduction: Restricted or enhanced intrauterine growth is associated with elevated risks of early and late metabolic problems in humans. Metabolomics based on amino acid and carnitine/acylcarnitine profile may have a role in fetal and early postnatal energy metabolism. In this study, the relationship between intrauterine growth status and early metabolomics profile was evaluated. Materials and Methods: A single-center retrospective cohort study was conducted. Three hundred and sixty-one newborn infants were enrolled into the study, and they were grouped according to their birth weight percentile as small for gestational age (SGA, n = 69), appropriate for gestational age (AGA, n = 168), and large for gestational age (LGA, n = 124) infants. In all infants, amino acid and carnitine/acylcarnitine profiles with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were recorded and compared between groups. Results: LGA infants had higher levels of glutamic acid and lower levels of ornithine, alanine, and glycine (p < 0.05) when compared with AGA infants. SGA infants had higher levels of alanine and glycine levels when compared with AGA and LGA infants. Total carnitine, C0, C2, C4, C5, C10:1, C18:1, C18:2, C14-OH, and C18:2-OH levels were significantly higher and C3 and C6-DC levels were lower in SGA infants (p < 0.05). LGA infants had higher C3 and C5:1 levels and lower C18:2 and C16:1-OH levels (p < 0.05). There were positive correlations between free carnitine and phenylalanine, arginine, methionine, alanine, and glycine levels (p < 0.05). Also, a positive correlation between ponderal index and C3, C5-DC, C14, and C14:1 and a negative correlation between ponderal index and ornithine, alanine, glycine, C16:1-OH, and C18:2 were shown. Conclusion: We demonstrated differences in metabolomics possibly reflecting the energy metabolism in newborn infants with intrauterine growth problems in the early postnatal period. These differences might be the footprints of metabolic disturbances in future adulthood.Item Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity(PUBLIC LIBRARY SCIENCE, 2022-01-01) Kilercik, Meltem; Ucal, Yasemin; Serdar, Muhittin; Serteser, Mustafa; Ozpinar, Aysel; Schweigert, Florian J.Background Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation. Methods The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days
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