Longitudinal non-targeted metabolomic profiling of urine samples for monitoring of kidney transplantation patients.

The assessment of kidney function within the first year following transplantation is crucial for predicting long-term graft survival. This study aimed to develop a robust and accurate model using metabolite profiles to predict early long-term outcomes in patient groups at the highest risk of early graft loss. A group of 61 kidney transplant recipients underwent thorough monitoring during a one-year follow-up period, which included a one-week hospital stay and follow-up assessments at three and six months. Based on their 12-month follow-up serum creatinine levels: Group 2 had levels exceeding 1.5 mg/dl, while Group 1 had levels below 1.5 mg/dl. Metabolites were detected by mass spectrometer and first pre-processed. Univariate and multivariate statistical analyses were employed to identify significant differences between the two groups. Nineteen metabolites were found to differ significantly in the 1st week, and seventeen metabolites in the 3rd month (adjusted p-value < 0.05, quality control (QC) < 30, a fold change (FC) > 1.1 or a FC < 0.91, Variable Influence on Projection (VIP) > 1). However, no significant differences were observed in the 6th month. These distinctive metabolites mainly belonged to lipid, fatty acid, and amino acid categories. Ten models were constructed using a backward conditional approach, with the best performance seen in model 5 for Group 2 at the 1st-week mark (AUC 0.900) and model 3 at the 3rd-month mark (AUC 0.924). In conclusion, the models developed in the early stages may offer potential benefits in the management of kidney transplant patients.

Sex-related differences in within-subject biological variation estimates for 22 essential and non-essential amino acids.

BACKGROUND: Measurement of serum amino acid (AA) concentrations is important in particular for the diagnosis and monitoring of inborn errors of AA metabolism. To ensure optimal clinical interpretation of AAs, reliable biological variation (BV) data are essential. In the present study, we derived BV data for 22 non-essential, conditionally essential, and essential AAs and assessed differences in BV of AAs related to sex. METHODS: Morning blood samples were drawn from 66 subjects (31 males and 35 females) once a week for 10 consecutive weeks. All samples were analyzed in duplicate using liquid chromatography-tandem mass-spectrometry. The data were assessed for outliers, trends, normality and variance homogeneity analysis prior to estimating within-subject (CVI) and between-subject (CVG) BV. RESULTS: CVI estimates ranged from 9.0 % for histidine (male) to 33.0 % for taurine (male). CVI estimates in males and females were significantly different for all AAs except for aspartic acid, citrulline and phenylalanine, in most cases higher in females than in males. Apart from for arginine, CVG estimates in males and females were similar. CONCLUSIONS: In this highly powered BV study, we provide updated BV estimates for 22 AAs and demonstrate that for most AAs, CVI estimates differ between males and females, with implications for interpretation and use of AAs in clinical practice.

Biological variation estimates for serum neurofilament light chain in healthy subjects.

OBJECTIVES: Neurofilament light chain (NfL) is an emerging biomarker of neurodegeneration disorders. Knowledge of the biological variation (BV) can facilitate proper interpretation between serial measurements. Here BV estimates for serum NfL (sNfL) are provided. METHODS: Serum samples were collected weekly from 24 apparently healthy subjects for 10 consecutive weeks and analyzed in duplicate using the Siemens Healthineers sNfL assay on the Atellica® IM Analyzer. Outlier detection, variance homogeneity analyses, and trend analysis were performed followed by CV-ANOVA to determine BV and analytical variation (CVA) estimates with 95%CI and the associated reference change values (RCV) and analytical performance specifications (APS). RESULTS: Despite observed differences in sNfL concentrations between males and females, BV estimates remained consistent across genders. Both within-subject BV (CVI) for males (10.7%, 95%CI; 9.2-12.6) and females (9.1%, 95%CI; 7.8-10.9) and between-subject BV (CVG) for males (26.1%, 95%CI; 18.0-45.6) and females (30.2%, 95%CI; 20.9-53.5) were comparable. An index of individuality value of 0.33 highlights significant individuality, indicating the potential efficacy of personalized reference intervals in patient monitoring. CONCLUSIONS: The established BV estimates for sNfL underscore its potential as a valuable biomarker for monitoring neurodegenerative diseases, offering a foundation for improved decision-making in clinical settings.

Personalized and Population-Based Reference Intervals for 48 Common Clinical Chemistry and Hematology Measurands: A Comparative Study.

BACKGROUND: Personalized reference intervals (prRIs) have the potential to improve individual patient follow-up as compared to population-based reference intervals (popRI). In this study, we estimated popRI and prRIs for 48 clinical chemistry and hematology measurands using samples from the same reference individuals and explored the effect of using group-based and individually based biological variation (BV) estimates to derive prRIs. METHODS: 143 individuals (median age 28 years) were included in the study and had fasting blood samples collected once. From this population, 41 randomly selected subjects had samples collected weekly for 5 weeks. PopRIs were estimated according to Clinical Laboratory Standards Institute EP28 and within-subject BV (CVI) were estimated by CV-ANOVA. Data were assessed for trends and outliers prior to calculation of individual prRIs, based on estimates of (a) within-person BV (CVP), (b) CVI derived in this study, and (c) publically available CVI estimates. RESULTS: For most measurands, the individual prRI ranges were smaller than the popRI range, but overall about half the study participants had a prRI wider than the popRI for 5 or more out of 48 measurands. The dispersion of prRIs based on CVP was wider than that of prRIs based on CVI. CONCLUSION: The prRIs derived in our study varied significantly between different individuals, especially if based on CVP. Our results highlight the limitations of popRIs in interpreting test results of individual patients. If sufficient data from a steady-state situation are available, using prRI based on CVP estimates will provide a RI most specific for an individual patient.

Sepsis biomarkers for early diagnosis of bacteremia in emergency department.

INTRODUCTION: We compared the diagnostic values of individual and composite biomarkers used in the prediction of bacteremia in adult emergency department patients. METHODOLOGY: First-hour blood levels of C- reactive protein, procalcitonin, interleukin-6, lactate, lipopolysaccharide-binding protein and white blood cell count were collected from a 30-person control group and 47 adult patients. Patients included in this study were admitted to the emergency department on suspicion of sepsis. We categorized patients according to presence/absence of sepsis and bacteremia. Our control group was categorized as S-B -, septic patients with bacteremia were S+B+, and septic patients without bacteremia were S+B-. RESULTS: All biomarkers showed a statistically significant elevation when S+B- and S+B+ groups were compared with the S-B-. When S+B+ group was compared with the S+B- group only procalcitonin and lactate levels had statistically significant elevation (p < 0.005). Regression analysis demonstrated that lactate and procalcitonin were independently associated with having bacteremia in the state of sepsis and Hosmer-Lemeshow score was 0.772. The areas under the curve (AUC) values of biomarkers procalcitonin, lactate, C-reactive protein, combined 1 (procalcitonin+ lactate), and combined 2 (procalcitonin + lactate + C-reactive protein) were 0.773, 0.744, 0.523, 0.806, and 0.829 respectively. CONCLUSIONS: Combination of tests such as combined 1 or combined 2 were highly predictive of bacteremia in adult septic patients. Combined 2 demonstrated the best predictive performance and could be utilized as a tool to assist diagnosis of bacteremia before culture results are available.

Rapid detection of serum free light chains by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Introduction: Serum free light chain (FLC) measurements are increasingly prominent for patients with plasma cell disorders (PCDs) in screening, prognostic stratification, and monitoring therapy responses. Objectives: We aimed to develop a sensitive, reliable, and accurate method for diagnosing PCDs that can notably decrease the time and cost of current methods. Methods: Here, we present a novel approach for FLC measurement using immunoenrichment on micro-affinity chromatography in combination with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) detection. In this study, serum free kappa (κ) and free lambda (λ) light chain (LC) levels in the serum of 105 patients were compared between the nephelometric serum FLC quantification and MALDI-TOF MS detection. Results: Cohen's kappa coefficient between the MALDI-TOF MS-based method and the FLC assay revealed an almost perfect agreement in the case of normal (negative) results (κ = 0.92; 95% confidence interval (CI): 0.837 to 0.968) and a good agreement in the case of increased (positive) results (κ = 0.76; 95% CI: 0.608 to 0.870). In Spearman's correlation analysis, the best correlation was found between serum free κ/λ ratios (r = 0.628, 0.496 to 0.732; p <0.0001). Our method showed sensitivity (92.5%) and specificity (76.3%) for discrimination between the κ/λ FLC ratio compared to the serum FLC assay. Conclusion: The proposed method can significantly contribute to diagnosing and monitoring PCDs as it can significantly be time-saving, cost-effective in FLC measurement.

Early postnatal metabolic profile in neonates with critical CHDs.

BACKGROUND: Cyanotic CHD is a life-threatening condition that presents with low oxygen saturation in the newborn period. Hypoxemia might cause alterations in the metabolic pathways. In the present study, we aimed to evaluate the early postnatal amino acid and carnitine/acylcarnitine profiles of newborn infants with cyanotic CHD. METHODS: A single centre case-control study was conducted. Twenty-seven patients with cyanotic CHD and 54 healthy newborn controls were enrolled. As part of the neonatal screening programme, results of amino acid and carnitine/acylcarnitine were recorded and compared between groups. RESULTS: Twenty-seven neonates with cyanotic CHD and 54 healthy newborns as controls were enrolled in the study. Cyanotic CHD neonates had higher levels of alanine, phenylalanine, leucine/isoleucine, citrulline, ornithine, C5, C5-OH; but lower levels of C3, C10, C12, C14, C14:1, C16, C16.1, C18, C5-DC, C6-DC, C16-OH, C16:1-OH when compared with the healthy controls. CONCLUSION: This study showed that there are differences between patients with cyanotic CHD and healthy controls in terms of postnatal amino acid and carnitine/acylcarnitine profiles.

Evaluation and comparison of eighteen SARS-CoV-2 antibody assays from seven different companies to assess its diagnostic role in SARS-CoV-2 infections.

The diagnostic performance of reverse transcriptase polymerase chain reaction (RT-PCR) decreases during the late acute stage of the corona virus disease (COVID-19) infection; hence, serological assays can be used for disease diagnosis in patients non-protected through vaccinations at this stage. The objective of this study was to assess the diagnostic accuracy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests in current/past infections, determine proper testing time, and check the accuracy of cutoff values. In this study, 18 Ig (immunoglobulin) G, IgM, IgA, and total antibody serological assays were performed using 839 samples. Positive sera (n=132) were collected during the first 5 months after the patients were symptomatic and tested positive for the SARS-CoV-2 RT-PCR test; they were grouped as 0-10, 10-15, >15 days according to the symptom onset. Negative sera (N=707) were obtained from patients with lupus before the pandemic. The performance of IgG and total antibody assays was better than those of IgA, IgM, and IgA-IgM for all post-symptom groups except for 0-10 days, which showed lower Ig assay sensitivity. During 10-15 and >15 days, >70% sensitivity to IgA, IgM, IgM-IgA assays and lower sensitivity were noted, respectively. The sensitivities of IgG and total antibody assays for group C were slightly lower than that of group B. There were no significant differences, but there were higher correlations between the methods or antigenic structures. Receiving operating characteristics (ROC) analysis revealed better cutoff values. For the diagnosis of late acute/past SARS-CoV-2 infection, serological tests can be performed on unvaccinated patients showing symptoms for ≥10 days. SARS-CoV-2 IgG and total antibodies were better diagnostic markers than IgM, IgA, and IgM+IgA, which were restricted to group B.

Melatonin in preservation solutions prevents ischemic injury in rat kidneys.

Transplantation 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-HCl 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.

Increased maternal leptin levels may be an indicator of subclinical hypothyroidism in a newborn.

Background: 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 µg/L (1.3 - 46.5) vs 19.7 µg/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.

Personalized reference intervals: from theory to practice.

Using laboratory test results for diagnosis and monitoring requires a reliable reference to which the results can be compared. Currently, most reference data is derived from the population, and patients in this context are considered members of a population group rather than individuals. However, such reference data has limitations when used as the reference for an individual. A patient's test results preferably should be compared with their own, individualized reference intervals (RI), i.e. a personalized RI (prRI).The prRI is based on the homeostatic model and can be calculated using an individual's previous test results obtained in a steady-state situation and estimates of analytical (CVA) and biological variation (BV). BV used to calculate the prRI can be obtained from the population (within-subject biological variation, CVI) or an individual's own data (within-person biological variation, CVP). Statistically, the prediction interval provides a useful tool to calculate the interval (i.e. prRI) for future observation based on previous measurements. With the development of information technology, the data of millions of patients is stored and processed in medical laboratories, allowing the implementation of personalized laboratory medicine. PrRI for each individual should be made available as part of the laboratory information system and should be continually updated as new test results become available.In this review, we summarize the limitations of population-based RI for the diagnosis and monitoring of disease, provide an outline of the prRI concept and different approaches to its determination, including statistical considerations for deriving prRI, and discuss aspects which must be further investigated prior to implementation of prRI in clinical practice.

The effect of reticulocyte hemoglobin content on the diagnosis of iron deficiency anemia: A meta-analysis study.

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 Cohen's 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.

Kappa/Lambda light-chain typing in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease is a progressive neurodegenerative disorder characterized by memory loss and cognitive impairment. The diagnosis of Alzheimer's disease according to symptomatic events is still a puzzling task. Developing a biomarker-based, low-cost, and high-throughput test, readily applicable in clinical laboratories, dramatically impacts the rapid and reliable detection of the disease. OBJECTIVE: This study aimed to develop an accurate, sensitive, and reliable screening tool for diagnosing Alzheimer's disease, which can significantly reduce the cost and time of existing methods. METHODS: We have employed a MALDI-TOF-MS-based methodology combined with a microaffinity chromatography enrichment approach using affinity capture resins to determine serum kappa (κ) and lambda (λ) light chain levels in control and patients with AD. RESULTS: We observed a statistically significant difference in the kappa light chain over lambda light chain (κLC/λLC) ratios between patients with AD and controls (mean difference -0,409; % 95 CI:- 0.547 to -0.269; p<0.001). Our method demonstrated higher sensitivity (100.00%) and specificity (71.43%) for discrimination between AD and controls. CONCLUSION: We have developed a high-throughput screening test with a novel sample enrichment method for determining κLC/λLC ratios associated with AD diagnosis. Following further validation, we believe our test has the potential for clinical laboratories.

Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity.

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; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19. RESULTS: Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95% CI 1.019-30.867)) and ZnPP/L ratio (OR (74.313) (95% CI 1.081-5108.103)). CONCLUSIONS: For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.

Ex vivo study: is it possible to overcome the blurriness caused by holmium laser fragmentation of kidney stones?

Better endoscopic vision is mandatory for successful ureteroscopic stone operations to achieve shorter operating time. However, an important impairing factor for a good endoscopic view is the cloudiness of vision which was formed during laser fragmentation. Holmium laser fragmentation of calcium oxalate stones produces calcium carbonate solubility of which is dependent on pH, citrate, and phosphate. In this ex vivo research, the solubility of calcium carbonate has been investigated in solutions composed of various concentrations of citrate and phosphate buffered at different pH levels after laser fragmentation of calcium oxalate stones. Calcium oxalate stones were placed into the laboratory tubes filled with various concentrations of citrate-phosphate buffers with different pH values. Laser energy in dusting mode was applied to the stones and spectrophotometric measurement for optical density (OD) was calculated for each buffered solution for clarity comparison. In the first phase, solutions composed of four different molar concentrations of citrate-phosphate buffer (0.2, 0.3, 0.4 and 0.5 molars) at various pH levels were used. Then, the next phase of the study was designed to compare solutions demonstrating the lowest OD values with an isotonic saline solution. The results were most convenient at 0.5 molarity (pH = 6) followed by 0.4 molarity (pH = 7) in the first phase (OD values of 0.054 and 0.065, respectively). In the next phase, OD values of both buffered solutions were significantly lower than those of isotonic saline solution (p = 0). Two specific buffers have provided better optic visibility values after laser fragmentation supporting their use as an irrigation solution for the favor of less cloudiness.

Within- and between-subject biological variation data for serum zinc, copper and selenium obtained from 68 apparently healthy Turkish subjects.

OBJECTIVES: Trace elements (TrEL) are nutritionally essential components in maintaining health and preventing diseases. There is a lack of reliable biological variation (BV) data for TrELs, required for the diagnosis and monitoring of TrEL disturbances. In this study, we aimed to provide updated within- and between-subject BV estimates for zinc (Zn), copper (Cu) and selenium (Se). METHODS: Weekly serum samples were drawn from 68 healthy subjects (36 females and 32 males) for 10 weeks and stored at -80 °C prior to analysis. Serum Zn, Cu and Se levels were measured using inductively-coupled plasma mass spectrometry (ICP-MS). Outlier and variance homogeneity analyses were performed followed by CV-ANOVA (Røraas method) to determine BV and analytical variation estimates with 95% CI and the associated reference change values (RCV) for all subjects, males and females. RESULTS: Significant differences in mean concentrations between males and females were observed, with absolute and relative (%) differences for Zn at 0.5 µmol/L (3.5%), Cu 2.0 µmol/L (14.1%) and Se 0.06 µmol/L (6.0%). The within-subject BV (CVI [95% CI]) estimates were 8.8% (8.2-9.3), 7.8% (7.3-8.3) and 7.7% (7.2-8.2) for Zn, Cu and Se, respectively. Within-subject biological variation (CVI) estimates derived for male and female subgroups were similar for all three TrELs. Marked individuality was observed for Cu and Se. CONCLUSIONS: The data of this study provides updated BV estimates for serum Zn, Cu and Se derived from a stringent protocol and state of the art methodologies. Furthermore, Cu and Se display marked individuality, highlighting that population based reference limits should not be used in the monitoring of patients.

Personalized reference intervals - statistical approaches and considerations.

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.

A new haematocytometric index: Predicting severity and mortality risk value in COVID-19 patients.

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 x103/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.

Early Postnatal Metabolic Profile in Neonates With Different Birth Weight Status: A Pilot Study.

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.