Browsing by Author "Kilercik, Meltem"

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A new haematocytometric index: Predicting severity and mortality risk value in COVID-19 patients
(PUBLIC LIBRARY SCIENCE, 2021-01-01) Kilercik, Meltem; Demirelce, Ozlem; Serdar, Muhittin Abdulkadir; Mikailova, Parvana; Serteser, Mustafa
Introduction Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus, is a major public health concern spanning from healthy carriers to patients with life-threatening conditions. Although most of COVID-19 patients have mild-to-moderate clinical symptoms, some patients have severe pneumonia leading to death. Therefore, the early prediction of disease prognosis and severity is crucial in COVID-19 patients. The main objective of this study is to evaluate the haemocytometric parameters and identify severity score associated with SARS-CoV-2 infection. Methods Clinical and laboratory records were retrospectively reviewed from 97 cases of COVID-19 admitted to hospitals in Istanbul, Turkey. The patient groups were subdivided into three major groups: Group 1 (Non-critical): 59 patients, Group 2 (Critical-Survivors): 23 patients and Group 3 (Critical-Non-survivors):15 patients. These data was tested for correlation, including with derived haemocytometric parameters. The blood analyses were performed the Sysmex XN-series automated hematology analyser using standard laboratory protocols. All statistical testing was undertaken using Analyse-it software. Results 97 patients with COVID-19 disease and 935 sequential complete blood count (CBC-Diff) measurements (days 0-30) were included in the final analyses. Multivariate analysis demonstrated that red cell distribution width (RDW) (>13.7), neutrophil to lymphocyte ratio (NLR) (4.4), Hemoglobin (Hgb) (<11.4 gr/dL) and monocyte to neutrophil ratio (MNR) (0.084) had the highest area under curve (AUC) values, respectively in discrimination critical patients than non-critical patients. In determining Group 3, MNR (<0.095), NLR (>5.2), Plateletcount (PLT) (>142 x10(3)/L) and RDW (>14) were important haemocytometric parameters, and the mortality risk value created by their combination had the highest AUC value (AUC = 0.911, 95\% CI, 0886-0.931). Trend analysis of CBC-Diff parameters over 30 days of hospitalization, NLR on day 2, MNR on day 4, RDW on day 6 and PLT on day 7 of admission were found to be the best time related parameters in discrimination non-critical (mild-moderate) patient group from critical (severe and non-survivor) patient group. Conclusion NLR is a strong predictor for the prognosis for severe COVID-19 patients when the cut-off chosen was 4.4, the combined mortality risk factor COVID-19 disease generated from RDW-CV, NLR, MNR and PLT is best as a mortality haematocytometric index.
ANALYSIS OF CHANGES IN PARATHYROID HORMONE AND 25 (OH) VITAMIN D LEVELS WITH RESPECT TO AGE, GENDER AND SEASON: A DATA MINING STUDY
(SCIENDO, 2017-01-01) Serdar, Muhittin A.; Can, Basar Batu; Kilercik, Meltem; Durer, Zeynep A.; Aksungar, Fehime Benli; Serteser, Mustafa; Coskun, Abdurrahman; Ozpinar, Aysel; Unsal, Ibrahim
Background: 25 (OH) vitamin D3 (25(OH) D) and parathyroid hormone (PTH) are important regulators of calcium homeostasis. The aim of this study was to retrospectively determine the cut-off for sufficient 25(OH) D in a four-season region and the influence of age, seasons, and gender on serum 25(OH) D and PTH levels. Methods: Laboratory results of 9890 female and 2723 male individuals aged 38.8 +/- 22.1 years who had simultaneous measurements of 25(OH) D and PTH were retrospectively analyzed by statistical softwares. Serum 25(OH) D and PTH levels were measured by a mass spectrometry method and by an electrochemiluminescence immunoassay, respectively. Results: Mean serum 25(OH) D levels showed a sinusoidal fluctuation throughout the year and were significantly (p < 0.01) higher in summer and autumn. On the other hand, PTH levels were significantly higher (p < 0.01) in women and showed an opposite response to seasonal effects relative to 25(OH) D. Lowest levels of 25(OH) D were detected in people aged between 20 and 40 years whereas PTH hormone levels were gradually increasing in response to aging. The significant exponential inverse relationship that was found between PTH and 25(OH) D (PTH = (exp)(4.12-0.064{*}(sqrt)(25(OH) D)) (r=-0.325, R-squared=0.105, p < 0.001)) suggested that the cut-off for sufficient 25(OH) D should be 75 nmol/L. Conclusions: Our retrospective study based on large data set supports the suitability of the currently accepted clinical cut-off of 75 nmol/L for sufficient 25(OH) D. However, the issue of assessing Vitamin D deficiency remains difficult due to seasonal variations in serum 25(OH) D. Therefore, PTH measurements should complement 25(OH) D results for diagnosing Vitamin D deficiency. It is imperative that seasonally different criteria should be considered in future.
Biological variations of ADAMTS13 and von Willebrand factor in human adults
(CROATIAN SOC MEDICAL BIOCHEMISTS, 2014-01-01) Kilercik, Meltem; Coskun, Abdurrahman; Serteser, Mustafa; Inan, Deniz; Unsal, Ibrahim
Background: The ultra-large von Willebrand factor (vWF) multimers are very active and must be degraded by ADAMTS13 for optimal activity. A severe functional deficiency of ADAMTS13 has been associated with thrombotic thrombocytopenic purpura. The correct interpretation of patient vWF and ADAMTS13 plasma levels requires an understanding of the biological variation associated with these analytes. In the present paper, we aimed to determine the biological variation of ADAMTS13 and vWF in human adults. Materials and methods: Blood samples were collected weekly from 19 healthy subjects for 5 consecutive weeks. vWF activity and antigenicity were determined using aggregometric and immunoturbidimetric methods. ADAMTS13 antigenicity and activity were determined by ELISA. Results: The within-subject biological variations for vWF activity and antigenicity were 8.06\% and 14.37\%, respectively, while the between-subject biological variations were 18.5\% and 22.59\%, respectively. The index of individuality for vWF activity was 0.44, while vWF antigenicity was 0.64. Similarly, ADAMTS13 activity and antigenicity within-subject biological variations were 12.73\% and 9.75\%, respectively, while between-subject biological variations were 9.63\% and 6.28\%, respectively. The ADAMTS13 indexes of individuality were 1.32 and 1.55, respectively. Conclusion: We report high biological variation and individuality in vWF antigenicity and activity levels. However, ADAMTS13 antigenicity and activity displayed high biological variation, but low individuality. Thus, population-based reference intervals may be useful for monitoring ADAMTS13 antigenicity and activity, but not for vWF, which displays high individuality. These findings should be considered when determining the reference interval and other clinical variables associated with ADAMTS13 and vWF levels.
Comparative Effects of Blood and Crystalloid Cardioplegia on Cellular Injury and Oxidative Stress in Cardiovascular Surgery
(MEDICAL TRIBUNE INC, 2019-01-01) Ulugol, Halim; Aksu, Ugur; Kocyigit, Muharrem; Kilercik, Meltem; Karduz, Gulsum; Okten, Murat; Toraman, Fevzi
Purpose: The purpose of this study was to evaluate the effect of different cardioplegic solutions on endothelial integrity and oxidative stress in cardiovascular surgery. Methods: In this randomized prospective study, after ethics approval and informed consent, 60 surgical patients were included. Patients undergoing coronary bypass surgery were randomized into two groups as warm blood cardioplegia (n = 30) and cold crystalloid cardioplegia (n = 30) following the cross-clamping. Measurements were performed at three time points: before induction of anesthesia (Ti), at admission to intensive care unit (ICU) (T2) and at the 24th postoperative hour (T3). Besides biochemical routine hemodynamic monitoring, patients were assessed for the sialic acid (SA), ischemic-modified albumin (IMA), advanced oxide protein products (AOPPs), total thiol (SH), and free hemoglobin (fHb) level. Results: Neither crystalloid nor blood cardioplegia led to significant changes in the AOPPs, T-SH, and SA level (p >0.05). Crystalloid cardioplegia, however, increased IMA level compared to both baseline (p <0.01) and blood cardioplegia group (p <0.05). fHb levels were transiently increased in both groups at the second-time point (p <0.001). fHb level was lower in the crystalloid group compared to that in the other group (p <0.05) at T2. Conclusion: Cardioplegia type creates similar effects on glycocalyx integrity. However, myocardial protection could be provided with warm blood cardioplegia.
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, Mustafa
Introduction: 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.
Ischemia modified albumin: does it change during pneumoperitoneum in robotic prostatectomies?
(BRAZILIAN SOC UROL, 2016-01-01) Ozgen, Serpil Ustalar; Ozveren, Bora; Kilercik, Meltem; Aksu, Ugur; Ay, Binnaz; Tufek, Ilter; Kural, Ali Riza; Turkeri, Levent N.; Toraman, Fevzi
Background: The unique positioning of the patient at steep Trendelenburg with prolonged and increased intra-abdominal pressure (IAP) during robotic radical prostatectomy may increase the risk of splanchnic ischemia. We aimed to investigate the acute effects of IAP and steep Trendelenburg position on the level of ischemia modified albumin (IMA) and to test if serum IMA levels might be used as a surrogate marker for possible covert ischemia during robotic radical prostatectomies. Patients and Methods: Fifty ASA I-II patients scheduled for elective robotic radical prostatectomy were included in this investigation. Exclusion criteria: The patients were excluded from the study when an arterial cannulation could not be accomplished, if the case had to be converted to open surgery or if the calculated intraoperative bleeding exceeded 300ml. All the patients were placed in steep (45 degrees) Trendelenburg position following trocar placement. Throughout the operation the IAP was maintained between 11-14mmHg. Mean arterial blood pressure (MAP), cardiac output (CO) were continuously monitored before the induction and throughout the surgery. Blood gases, electrolytes, urea, creatinine, alanine transferase (ALT), aspartate transferase (AST) were recorded. Additionally, IMA levels were measured before, during and after surgery. Results: (1) MAP, CO, lactate and hemoglobin (Hb) did not significantly change in any period of surgery (p>0.05)
Personalized reference intervals - statistical approaches and considerations
(WALTER DE GRUYTER GMBH, 2022-01-01) Coskun, Abdurrahman; Sandberg, Sverre; Unsal, Ibrahim; Yavuz, Fulya G.; Cavusoglu, Coskun; Serteser, Mustafa; Kilercik, Meltem; Aarsand, Aasne K.
For many measurands, physicians depend on population-based reference intervals (popRI), when assessing laboratory test results. The availability of personalized reference intervals (prRI) may provide a means to improve the interpretation of laboratory test results for an individual. prRI can be calculated using estimates of biological and analytical variation and previous test results obtained in a steady-state situation. In this study, we aim to outline statistical approaches and considerations required when establishing and implementing prRI in clinical practice. Data quality assessment, including analysis for outliers and trends, is required prior to using previous test results to estimate the homeostatic set point. To calculate the prRI limits, two different statistical models based on `prediction intervals' can be applied. The first model utilizes estimates of `within-person biological variation' which are based on an individual's own data. This model requires a minimum of five previous test results to generate the prRI. The second model is based on estimates of `within-subject biological variation', which represents an average estimate for a population and can be found, for most measurands, in the EFLM Biological Variation Database. This model can be applied also when there are lower numbers of previous test results available. The prRI offers physicians the opportunity to improve interpretation of individuals' test results, though studies are required to demonstrate if using prRI leads to better clinical outcomes. We recommend that both popRIs and prRIs are included in laboratory reports to aid in evaluating laboratory test results in the follow-up of patients.
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.
Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients
(PUBLIC LIBRARY SCIENCE, 2020-01-01) Akgun, Emel; Tuzuner, Mete Bora; Sahin, Betul; Kilercik, Meltem; Kulah, Canan; Cakiroglu, Hacer Nur; Serteser, Mustafa; Unsal, Ibrahim; Baykal, Ahmet Tarik
COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared throughout the World and currently affected more than 9 million people and caused the death of around 470,000 patients. The novel strain of the coronavirus disease is transmittable at a devastating rate with a high rate of severe hospitalization even more so for the elderly population. Naso-oro-pharyngeal swab samples as the first step towards detecting suspected infection of SARS-CoV-2 provides a non-invasive method for PCR testing at a high confidence rate. Furthermore, proteomics analysis of PCR positive and negative naso-oropharyngeal samples provides information on the molecular level which highlights disease pathology. Samples from 15 PCR positive cases and 15 PCR negative cases were analyzed with nanoLC-MS/MS to identify the differentially expressed proteins. Proteomic analyses identified 207 proteins across the sample set and 17 of them were statistically significant. Protein-protein interaction analyses emphasized pathways like Neutrophil degranulation, Innate Immune System, Antimicrobial Peptides. Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified proteins are linked to alteration in the innate immune system specifically via neutrophil degranulation and NETosis.
Relationship between disease severity and serum IL-6 levels in COVID-19 anosmia
(W B SAUNDERS CO-ELSEVIER INC, 2021-01-01) Sanli, Deniz Esin Tekcan; Altundag, Aytug; Kandemirli, Sedat Giray; Yildirim, Duzgun; Sanli, Ahmet Necati; Saatci, Ozlem; Kirisoglu, Ceyda Erel; Dikensoy, Oner; Murrja, Edvin; Yesil, Atakan; Bastan, Serdar; Karsidag, Tamer; Akinci, Ibrahim Ozkan; Ozkok, Sezen; Yilmaz, Eren; Tuzuner, Filiz; Kilercik, Meltem; Ljama, Taner
Background: An association between IL-6 levels and cytokine storm syndrome in COVID-19 patients has been suggested. Cases with higher IL-6 levels have more rapid progression and a higher complication rate. On the other hand, COVID-19 cases with anosmia have a milder course of the disease. Objective: We aimed to investigate whether there is a relationship between serum IL-6 levels and presence of anosmia in COVID-19 patients. Methods: Patients with a confirmed diagnosis of COVID-19 based on laboratory (PCR) were stratified into two groups based on presence of olfactory dysfunction (OD). In all cases with and without anosmia
THE EFFECT OF RETICULOCYTE HEMOGLOBIN CONTENT ON THE DIAGNOSIS OF IRON DEFICIENCY ANEMIA: A META-ANALYSIS STUDY
(SOC MEDICAL BIOCHEMISTS SERBIA, 2022-01-01) Kilic, Merve; Ozpinar, Aysel; Serteser, Mustafa; Kilercik, Meltem; Serdar, Muhittin
Background: Iron deficiency anemia (IDA) is the most common type of anemia worldwide and has many adverse effects on life quality. This meta-analysis study aims to show that reticulocyte hemoglobin content (CHr) is more effective than routinely used parameters in the diagnosis of IDA. Methods: Comprehensive and systematic research was done using international databases including PubMed, Web of Science, Cochrane Library, Science Direct, and Google Scholar, which contain all articles published on IDA until December 29, 2020. Seventeen articles were included in the meta-analysis. Results: The analyses found the Cohens deffect size (Standardized Mean Difference) values of the parameters. Accordingly, CHr is 2.84 (95\% CI 2.36 to 3.31), mean corpus volume (MCV) is 2.46 (95\% CI 1.97 to 2.95), ferritin is 2.37 (95\% CI 1.63 to 3.11), and transferrin saturation (TSAT) is 3.76 (95\% CI 2.14 to 5.38). To diagnose IDA, the sensitivity value of the CHr concentration was found as 83.5\% (95\% CI 76.1 to 89.8), specificity value to be 91.8\% (95\% CI 85.5 to 96.4), and mean cut-off value as 28.2 pg. Conclusions: The results of our study reveal the findings that CHr is a better biomarker than MCV and ferritin used in determining IDA, and its efficacy is lower than TSAT. It is very important to use it routinely for the pre-diagnosis of IDA, which is very important for public health. The groups in the study are heterogeneous but contain bias. Therefore, meta analyses of studies with less heterogeneity of CHr are needed.
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 Biological
Background: 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.
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