Adult Reference Intervals Research Articles

Thyrotropin reference interval in older adults.

It is estimated that by the year 2050, 16% of the world's population will be 65 years old and above. As the global aging population continues to grow, there is an increasing focus on thyroid disorders among older individuals. Thyrotropin is widely used in diagnosing subclinical thyroid diseases due to its high sensitivity as an indicator of changes in thyroid function. However, thyrotropin levels change with age, and different reference intervals have been proposed in various studies. The variation in thyrotropin ranges among older adults is probably caused by the heterogeneity of the studied population. This review aims to provide an overview of the existing literature on thyrotropin reference intervals in older adults and their distinction as adaptive or pathologic. Recent research indicates that older individuals may have slightly elevated levels of thyrotropin and higher upper limits of reference intervals. Therefore, a higher thyrotropin threshold for diagnosing and treating subclinical hypothyroidism in the elderly seems reasonable.

Advanced lipid testing in children: a call for pediatric reference intervals

Abstract Introduction Abnormal serum lipid levels in childhood are associated with dyslipidemia and increased risk of cardiovascular disease in adulthood. High prevalence of childhood obesity in the US has increased concerns about the adverse effects of abnormal lipids in children, prompting recommendations for universal lipid screening in adolescents. While specialized analysis of lipoproteins by nuclear magnetic resonance (NMR) has been predominately used in adults with risk factors for CVD, our laboratory also receives pediatric samples for NMR testing, most commonly associated with diagnostic codes for hyperlipidemia and/or abnormal weight gain. Currently adult-based reference ranges for the NMR lipoprotein measurements are used in children. The objective of this pilot study was to compare lipoprotein profiles of healthy adults and children and to assess the impact of reference intervals for children on clinical interpretation of pediatric results. Methods Serum samples were collected from 60 healthy children, ages 1 – 17 years, and 148 healthy adults, ages 19 – 64 years old. NMR lipoprotein analysis was performed using the Axinon lipoFIT by NMR assay on a 600 MHz NMR (Bruker). Statistical analysis was conducted in Excel and GraphPad Prism. Reference intervals (RIs) were determined in EP Evaluator as the central 95% interval. Results The levels of atherogenic low-density lipoprotein particle number (LDL-P) and small LDL-P (sLDL-P) were significantly lower in children compared to adults: 783±222 vs 1212±412 nmol/L and 302±142 vs 498±306 nmol/L, respectively (p<0.00001). Additionally, LDL size (LDL-s) was significantly larger in children than adults (21.23±0.29 vs 21.06±0.44 nm, p=0.006), reflecting prevalence of less dense LDL-P in the former group. Pediatric samples also had lower number of anti-atherogenic high-density lipoprotein particles (HDL-P) compared to adults: 29.4±4.6 vs 33.5±4.6 µmol/L, p<0.00001. The significant differences in the number and size of lipoprotein particles between adults and children implies that currently used adult reference intervals might not be appropriate for evaluating pediatric NMR samples. Therefore, we estimated RIs for our heathy pediatric and adult cohorts and applied these RIs to our retrospective data of 618 samples from children 1-17 years old, which were submitted for NMR lipoprotein testing in recent years. The analysis showed that using the adult RIs, 37% and 27% of pediatric samples would not flag for abnormally elevated LDL-P and sLDL-P, respectively; but they would be flagged based on the RI derived from our pediatric cohort. Moreover, 12% pediatric samples flagged for low HDL-P would have normal HDL-P levels if pediatric RIs are used instead of adult RIs. Conclusions Use of adult reference intervals in children may result in misclassification of lipid status and underestimation or overestimation of dyslipidemia and CVD risk in children. This pilot study highlights the need for pediatric reference intervals to guide interpretation of advanced lipid testing in children.

Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study.

As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over. A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had nohistory of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time. A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8-77.3) years. We propose a RI of 0.34-3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI. From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use.

A-227 One Step Toward Implementation of Advanced Lipoprotien Testing in Children: A Pilot Study on Pediatric Reference Ranges

Abstract Background Abnormal serum lipid levels in childhood are associated with dyslipidemia and increased risk of cardiovascular disease in adulthood. High prevalence of childhood obesity in the US has increased concerns about the adverse effects of abnormal lipids in children, prompting recommendations for universal lipid screening in adolescents. While specialized analysis of lipoproteins by nuclear magnetic resonance (NMR) has been predominately used in adults with risk factors for CVD, our laboratory also receives pediatric samples for NMR testing, most commonly associated with diagnostic codes for hyperlipidemia and/or abnormal weight gain. Currently adult-based reference ranges for the NMR lipoprotein measurements are used in children. The objective of this pilot study was to compare lipoprotein profiles of healthy adults and children and to assess the impact of reference intervals for children on clinical interpretation of pediatric results. Methods Serum samples were collected from 60 healthy children, ages 1 - 17 years, and 148 self-identified healthy adults, ages 19 - 64 years old. NMR lipoprotein analysis was performed using the Axinon lipoFIT by NMR assay on a 600 MHz NMR (Bruker). Statistical analysis was conducted in Excel and Graph Pad Prism. Reference intervals (RIs) were determined in EP Evaluator as the central 95% interval. Results The levels of atherogenic low-density lipoprotein particle number (LDL-P) and small LDL-P (sLDL-P) were significantly lower in children compared to adults: 783±222 vs 1212±412 nmol/L and 302±142 vs 498±306 nmol/L, respectively (p<0.00001). Additionally, LDL size (LDL-s) was significantly larger in children than adults (21.23±0.29 vs 21.06±0.44 nm, p=0.006), reflecting prevalence of less dense LDL-P in the former group. Pediatric samples also had lower number of anti-atherogenic high-density lipoprotein particles (HDL-P) compared to adults: 29.4±4.6 vs 33.5±4.6 µmol/L, p<0.00001. The significant differences in the number and size of lipoprotein particles between adults and children implies that currently used adult reference intervals might not be appropriate for evaluating pediatric NMR samples. Therefore, we estimated RIs for our heathy pediatric and adult cohorts and applied these RIs to our retrospective data of 618 samples from children 1-17 years old, which were submitted for NMR lipoprotein testing in recent years. The analysis showed that using the adult RIs, 37% and 27% of pediatric samples would not flag for abnormally elevated LDL-P and sLDL-P, respectively; but they would be flagged based on the RI derived from our pediatric cohort. Moreover, 12% pediatric samples flagged for low HDL-P would have normal HDL-P levels if pediatric RIs are used instead of adult RIs. Conclusions Use of adult reference intervals in children may result in misclassification of lipid status and underestimation or overestimation of dyslipidemia and CVD risk in children. This pilot study highlights the need for pediatric reference intervals to guide interpretation of advanced lipid testing in children.

Thyroid function tests in healthy kittens aged between 2 and 16 weeks.

This study aimed to determine thyroid hormone concentrations in a cohort of healthy kittens due to the paucity of information in the literature, and the potential for congenital hypothyroidism (CH) to contribute to fading kitten syndrome (FKS). The serum concentrations of total thyroxine (TT4), free thyroxine (fT4), total triiodothyronine (TT3), free triiodothyronine (fT3) and thyroid-stimulating hormone (TSH) were measured in 19 healthy kittens aged 2-16 weeks. Mean TT4, fT4, TT3 and fT3 concentrations significantly differed across age groups. Mean TT4 and fT4 concentrations peaked at 6 and 5 weeks of age, respectively. The TT4 concentration exceeded the adult cat reference interval (ACRI) in 54% (32/59) of samples at week 6, with the highest TT4 concentration being 7.1 µg/dl (91 nmol/l). Mean TT3 and fT3 concentrations also peaked at 6 weeks of age. Mean TT3 concentration started below the ACRI until 4 weeks of age, after which it remained within the ACRI. The mean fT3 concentration was within the ACRI at all ages. The mean TSH concentration did not differ across age groups and remained within the ACRI in nearly 100% of samples. Peak TT4, fT4, TT3 and fT3 concentrations in healthy kittens at 5 and 6 weeks of age are likely due to changes in the maternal transfer of thyroid hormones after weaning and organ system development. Knowing healthy neonatal and pediatric thyroid hormone concentrations in a cohort of kittens might help a veterinarian interpret thyroid hormone levels when trying to rule out CH in a kitten with FKS.

Determination of pediatric and adult reference intervals for neurofilament light chain (NfL) in blood and a comparison to other recent studies

Determination of pediatric and adult reference intervals for neurofilament light chain (NfL) in blood and a comparison to other recent studies

Derivation of Russian-specific reference intervals for complete blood count, iron markers and related vitamins.

This study aimed to establish reference intervals (RIs) for Russian adults for hematological parameters including related iron markers and vitamins. Sources of variation of reference values (RVs) and needs for secondary exclusion were explored for proper derivations of RIs. Following the harmonized protocol of the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL), 506 healthy Russians (age 18-80; 46% male) were recruited. Complete blood counts (CBC) and leukocyte differentials, iron markers, vitamin B12, and folate were measured by Beckman Coulter's analyzers. Sources of variation were analyzed by multiple regression analysis, and ANOVAs, and the need for partitioning RVs was decided accordingly. Two schemes of excluding latent anemia were compared: (1) latent abnormal values exclusion method (LAVE) based on associations among CBC parameters, or (2) explicit exclusion of individuals with either ferritin or iron below the respective lower limit of the manufacturer. RIs were determined by the parametric method using two-parameter Box-Cox formula. Gender-specific RIs were required for most analytes, while age-specific RIs were set only for ferritin in females. A BMI-related increase in RVs was prominently observed for reticulocyte parameters, hence we chose to exclude individuals with BMI>28 kg/m2 when establishing the RIs. The LAVE method was more effective in excluding individuals with latent anemia, than exclusion based on low ferritin and/or iron values. International comparison revealed that Russian RIs featured a lower side shift of platelet counts. Similar to African countries, Russian RIs for total leukocyte and neutrophil counts were lower compared to most of other countries. RIs for the Russian population for 34 hematological and related parameters were established using up-to-date methods proposed by C-RIDL. Reducing the influences of latent anemia and obesity on RIs was crucial for erythrocyte parameters. Low levels of Russian RIs observed for platelet and neutrophil counts need further investigation.

Exchangeable serum copper: Adult and pediatric reference intervals and in vitro stability in a nordic cohort

Wilson disease (WD) is a rare genetic disorder characterized by copper overload, primarily affecting the liver and brain, and the organ damage is believed to be caused by non-ceruloplasmin-bound copper (NCC). Accurate and early diagnosis is important for prognosis. Recently, a method for the measurement of NCC, exchangeable serum copper (CuEXC), was developed and shown to be a promising marker of WD, especially as the fraction of total copper, relative exchangeable copper (REC). This study aimed to validate the CuEXC extraction method and establish reference intervals for CuEXC and REC, as well as to examine short- and long-term stability of CuEXC in serum samples.The adult reference interval for CuEXC was 0.61–1.62 µmol/L and for REC 3.0–9.7 % based on 120 blood donors. Based on 88 children, the reference intervals for CuEXC was 0.45–1.16 µmol/L. The intervals for REC were 1.8–5.8 % for children <10 years and 2.3–8.5 % for children ≥10 years. Regarding stability, CuEXC increased following a logarithmic scale in uncentrifuged serum and exceeded the permissible difference of 10 % after 4 h. With long-term freezing at −20 °C, CuEXC was stable for 1.7 months.In conclusion, reference intervals for CuEXC and REC were established and confirmed to be substantially lower in children. Accurate reference intervals are important to ensure timely diagnosis of WD. Finally, our findings on stability have important implications and highlight the need for standardization of the pre-analytical handling of CuEXC samples in order to obtain comparable results within and between laboratories both for clinical and research use.

Discrepancies between two total IgE assays and difference in reference intervals in healthy adults

ObjectiveTo compare total immunoglobulin (Ig) E assay performance characteristics between Abbott Architect and Siemens Immulite test systems. Reference intervals were also determined for both platforms in an American population of healthy adults. MethodsAgreement of the two total IgE assays was evaluated in a cohort of 331 subjects with normal complete blood count (CBC) and comprehensive metabolic panel (CMP) results. Reference intervals were established in 302 subjects after exclusion of atopic individuals on the Abbott Architect and Siemens Immulite test systems. ResultsWe demonstrated a 32% positive bias for total IgE quantitation on the Siemens Immulite platform compared to the Abbott Architect, despite both methods calibrated against the same WHO international reference material (75/502), Furthermore, the upper limit of the reference interval (95th percentile) was determined to be higher for the Siemens Immulite assay compared to the Abbott Architect (132 and 102 IU/mL, respectively). ConclusionDespite the use of a common WHO reference material for total IgE assay calibration, significant differences in quantitation was observed between two FDA-cleared test systems. Given that, it is warranted for clinical laboratories to verify vendor established reference intervals and adjust accordingly based on internal assessment of the normal range.

Indirect Determination of Hematological Reference Intervals in Healthy Moroccan Adults Using Outpatient Data.

Reference intervals are essential for the interpretation of clinical laboratory tests and patient management. This study aims to determine age and gender reference intervals of complete blood count (CBC) in the Moroccan population by using the indirect approach. The study used data of ostensibly healthy adults collected retrospectively using the laboratory information system (LIS) of the Laboratory for Research and Medical Analysis of the Fraternal Royal Gendarmerie in Rabat (Morocco), between January 2018 and February 2020. The study included 5,898 men and 10,172 women ranging in age from 18 to 90 years. The lower and upper reference limits of CBC parameters were calculated using the nonparametric technique, as suggested by the Clinical and Laboratory Standards Institute (CLSI). All hematological parameters showed no clinically significant gender-related differences, except small differences in the values of hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). There were also no clinically significant agerelated differences for median values of all hematology analytes in both genders, except for platelet count (PLT) that continued to decline with increasing age in men and women, and Red blood cell count (RBC), Hematocrit (HCT), and hemoglobin (HB) that tended to increase with age but decrease in older age groups in men while they tended to increase with age in women. The indirect method can be used to establish reference intervals for CBC, with appropriate selection criteria and statistical tools. Our findings differed from the reference ranges provided in the textbook and also in other countries' reports.

Updated adult ferritin reference intervals based on a large, healthy UK sample, measured on Roche Cobas series analysers.

There is a lack of standardization of reference intervals (RIs) for ferritin across laboratories, particularly for postmenopausal women. Depending on the RI used, there can be more than a 4-fold difference in the upper limit of normal between laboratories, resulting in potential misinterpretation. This retrospective study used a large dataset of blood test results from 25,425 healthy participants aged 18 to 97 over a 7-year period. Exclusion criteria were used to screen out individuals with conditions known to affect iron metabolism or raise ferritin as part of the acute phase response. Distributions were assessed using density and Q-Q plots, and age-banded cut-offs were determined. The non-parametric method was used to establish RIs for sex and age bands. For females, 4 age bands were established (18-39, 40-49, 50-59 and 60+). For males, 2 bands were identified (18-39 and 40+). Performance against a validation dataset, followed by an expansive validation against an inclusive dataset, demonstrated the robustness of the derived RIs. This study addresses the inconsistency in serum ferritin RIs by presenting intervals based on demographic parameters. This approach can potentially enhance the accuracy of interpreting serum ferritin levels, assisting clinicians in identifying patients requiring further evaluation.

Analysis of Serum Free Thyroxine Concentrations in Healthy Term Neonates Underlines Need for Local and Laboratory-Specific Reference Interval: A Systematic Review and Meta-Analysis of Individual Participant Data.

Background: Initial evaluation of the hypothalamus-pituitary-thyroid axis is done by measuring serum free thyroxine (fT4) and thyrotropin concentrations. For correct interpretation of these measurements, reliable age-specific reference intervals (RIs) are fundamental. Since neonatal fT4 RIs conforming to the Clinical and Laboratory Standards Institute guidelines are not available for all assays, we set out to create literature-based uniform age-specific neonatal fT4 RIs that may be used for every assay. Methods: For meta-analysis of individual participant fT4 concentrations, we systematically searched MEDLINE and Embase (search date December 6, 2023; PROSPERO registration CRD42016041871). We searched for studies reporting fT4 concentrations in healthy term newborns aged 2-27 days, born to mothers without thyroid disease in iodine-sufficient regions. Authors were invited to supply data. Due to standardization differences between assays, data could not be combined for meta-analysis directly, and we attempted to normalize the data using two distinct methods. Results: We obtained 4206 fT4 concentrations from 20 studies that used 13 different assays from 6 manufacturers. First, we set out to normalize fT4 data using the mean and standard deviation of (assay-specific) adult RIs. fT4 concentrations were transformed into Z-scores, assuming a normal distribution. Using a linear mixed-effects model (LMM), we still found a significant difference between fT4 concentration across studies (p < 0.001), after this normalization. As a second approach, we normalized the fT4 concentrations using data from a method/assay comparison study. We used the relationship between the Cobas assay and the other assays as a reference point to convert all values to Cobas values. However, this method also failed to produce consistent results, with significant differences between the normalized data (LMM p < 0.001). Conclusions: We conclude that our attempts at normalizing fT4 assay results were unsuccessful. Confounders related to our unsuccessful analysis may be assay related and/or biological. These findings have significant implications for patient care, since relying on RIs from literature may result in erroneous interpretation of results. Therefore, we strongly recommend to establish local RIs for accurate interpretation of serum fT4 concentrations in neonates.

Reference intervals for serum creatinine and urea in the adult western Sudanese population

Introduction: Serum creatinine and urea levels are affected by numerous factors such as ethnicity, environment, age, sex, and anthropometric measurements. The Clinical and Laboratory Standards Institute (CLSI) recommends that each laboratory should establish its own reference intervals for biochemistry and haematology. There are no local reference intervals for serum creatinine and blood urea in Sudan; instead, intervals derived from worldwide research are used. The purpose of this study was to determine the blood urea and serum creatinine reference intervals for healthy adults in the Western Sudanese population.&#x0D; Method: Randomly selected adult Sudanese residents of Al Fashir City who were from the Western Sudan states of Kordofan and Darfur were the subjects of a cross-sectional study conducted in September and October 2018. We recruited 153 participants. After giving their consent, they were evaluated using a questionnaire that collected medical history and demographic information. We used standard techniques to measure blood pressure, body mass index, urea, and creatinine. Kolmogorov-Smirnov tests were used to assess the distributions of the creatinine and urea values, and reference intervals calculated. T-tests were used to investigate differences of mean creatinine and urea levels by sex and age. IBM SPSS Statistics version 25 was used to analyse the data and p ≤ 0.05 was considered significant.&#x0D; Results: Overall, the reference intervals (Mean±1.96*SD) for serum creatinine and urea levels were 0.45-0.92 mg/dL and 7.6-27.9 mg/dL respectively, compared to international reference intervals adopted from the American Board of Internal Medicine (ABIM) serum creatinine (males 0.7-1.3, females 0.5-1.1 mg/dL) and blood urea (17.12-42.8 mg/dL for both sexes) and The Western Sudanese population’s mean serum creatinine and urea levels were, respectively, 0.69 mg/dL and 17.8 mg/dL. Male sex was associated with higher levels of both creatinine and urea (p&lt;0.001).&#x0D; Conclusion: This study documented lower reference intervals for creatinine and urea in the Western Sudanese population.

Reference Intervals of Haematological Parameters for Apparently Healthy Adults in Northeast Ethiopia.

Clinical laboratory reference intervals play a vital role in evaluating overall well-being, tracking the progression of diseases, and detecting potential harmful effects and complications. Despite evidence revealing disparities, many African nations currently rely on reference intervals for blood analysis obtained mainly from Western populations. This practice increases the risk of misidentifying and misdiagnosing healthy individuals. The aim of this study was to establish common hematological parameters reference intervals for healthy adults in Northeast Ethiopia. This community-based cross-sectional study consisted of 328 individuals who were presumed to be in good health. To assess their blood-related characteristics, blood samples were collected and analyzed using the advanced Dirui BF-6500 analyzer, along with serological testing. In accordance with guidelines provided by the Clinical and Laboratory Standards Institute, the study employed a non-parametric approach to calculate the medians and 95% confidence intervals. To explore potential variations between males and females, a statistical test known as the Mann-Whitney U-test was used to compare the reference intervals. The established reference intervals were: white blood cells 3.5-11.3×109/L; red blood cells 4.0-6.1×1012/L; hemoglobin 11.2-17.5g/dL; hematocrit 35.4-52.0%; MCV 77.9-93.8fl; MCH 24.7-32.0pg; MCHC 306-349g/L; RDW-CV 12.1-13.8% and platelet 131-391×109/L. The reference values of monocytes, eosinophils, red blood cells, hemoglobin, hematocrit and RDW-CV in males were higher than females, while females had significantly higher platelet counts compared to males. The reference intervals discovered differed from the reference intervals now in use, those mentioned in earlier research in Ethiopia or other African nations, as well as those conducted on Western populations. In the adult demographic of Northeast Ethiopia, specific reference intervals for commonly observed hematological parameters were established, tailored to the local community. Consequently, these reference intervals hold the potential to enhance informed decision-making within this population, by providing valuable guidance when interpreting laboratory test outcomes.

A-033 Development and Validation of a Liquid Chromatography Tandem Mass Spectrometry Bioanalytical Method for Prostaglandin D2 in Serum or Urine

Abstract Background Prostaglandin D2 (PGD2) is a major prostaglandin produced by the brain and by mast cells, and plays a role in vasodilation (“niacin flush”) and in the development of allergic diseases such as asthma and alopecia. We sought to develop a bioanalytical method for multiple specimen types for PGD2 for clinical use. Methods An analytical method was developed using a TX-4 HPLC system (Thermo-Fisher) with Agilent® 1200 pumps (Agilent Technologies, Inc.) and a Sciex® 5500 (Danaher) triple quadrupole mass spectrometer. Calibration curve based on purified PGD2 (Cayman) was prepared in depleted serum (Golden West Biologicals). Sample preparation consisted of an initial isotope dilution using a deuterated heavy isotope internal standard (PGD2-2H4) followed by solid phase extraction, evaporation and reconstitution using a second heavy isotope (PGD2-2H9). Double-isotope dilution allows discrimination between extraction loss and ion suppression as causes of decreased ion current. A reversed phase C18 analytical column was used with an acidified water/acetonitrile/methanol solvent gradient to achieve chromatographic separation of physiological PGD2 from related isobaric metabolites include Prostaglandin E2. Negative mode electrospray ionization (ESI) was used for detection in Multiple Reaction Monitoring (MRM) mode. Results Analytical range was 1–1000 pg/mL (up to 5000 pg/mL with dilution). Inter-assay precision ranged from 8.8% to 10.2% and inter-assay accuracy ranged from 95.7% to 103.3%. Reference intervals for adults was developed using residual serum and urine specimens. No interference was observed in the presence of hemolysis, icteric or lipemia. No difference in result was observed when using collection tubes containing EDTA, Heparin or gel barriers. Conclusion A bioanalytical method for PGD2 has been fully validated for clinical use.

B-039 Method Performance Evaluation of the Siemens Atellica Cystatin C Assay on the CH930 Instrument

Abstract Background The National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease published recommendations on the implementation of the CKD-EPI 2021 equation to calculate eGFRcr without a race coefficient. Clinical practice recommendations also suggest increasing availability of Cystatin C testing which can be a more reliable marker of renal function than creatinine for select adults with eGFRcr near medical decision points and in situations where non-GFR factors may have a large effect on serum creatinine. This study evaluated the method performance characteristics of the Cystatin C assay on the Siemens Atellica CH930 analyzer. The assay measures agglutination of latex particles coated with anti-cystatin C antibody at 571/805 nm and is approved for determination of Cystatin C in serum and plasma (lithium heparin, and EDTA). Methods Cystatin C reagent lot 2114231 and calibrator lot 560956 were used in the study. Intra-run precision was evaluated using BioRad IntelliQ Immunology Control (Level 1 lot 68991, Level 2 lot 68993). Inter-run precision was evaluated over 20 consecutive days. Mean, SD, and CV were calculated and compared to manufacturer precision claims in the IFU and BioRad UNITY™ Interlab Reports. Linearity was evaluated using AUDIT MicroControls Cystatin C Linearity LQ (Lot 06901). Accuracy was evaluated by measuring 40 serum samples on the Atellica CH930 and Roche Diagnostics Tina-Quant Cystatin C Gen 2 assay. Acceptable criteria were defined as a calculated slope between 0.9–1.1 and r greater than 0.995. Appropriateness of the adult reference interval was evaluated with 20 female and 20 male presumably healthy donors. Acceptability was defined as less than 10% of results outside the proposed range. Results Intra-run CV ranged from 2.3–9.2% (Level 1 QC) and 1.2–2.6% (Level 2 QC) across four different CH930 instruments. Level 1 precision did not verify the manufacturer claim of ≤3.6% CV on 3 out of 4 instruments. Level 2 precision did not verify the manufacturer claim of ≤1.7% CV for any instrument tested. Using BioRad UNITY™ peer performance as targets, 3 of 4 instruments had CV ≤6.7% for Level 1 and all instruments had CV ≤2.8% for Level 2. Inter-run precision for Level 1 QC was ≤5.94% CV which was less than the BioRad Peer Group CV. Linearity material spanned 0.490–5.893 mg/L and results were within manufacturer’s expected ranges. Method comparison with the Roche Tina-Quant Gen 2 assay had a calculated slope of 0.954, intercept of 0.094, and r value equal to 0.9993. Thirty-nine of 40 results were within 10% of the reference method (range 0.74–5.45 mg/L). Verification of the reference interval using presumably healthy donors resulted in 5.3% (2/38) of results outside the proposed range. Conclusion With the exception of precision, all other manufacturer-claimed performance specifications for the Siemens Atellica Cystatin C assay were verified using four CH930 instruments at our institution.

Paediatric reference ranges for plasma chromogranin A.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare diseases with varied aggressiveness originating from endocrine cells belonging to the diffuse endocrine system and most often produce and secrete chromogranin A (CgA). CgA in plasma is therefore used to screen, diagnose, and monitor for NENs in both adults and children with sporadic or familial NENs. Plasma CgA was measured using the Brahms Kryptor assay in 268 healthy children/adolescents; 85 children were tested as part of a familial cancer screening program and 183 additional children younger than 20years of age underwent screening for allergies. Repeated measurements (month - years) was used to calculate the intra-individual variation. The dataset was analysed in R using the referenceInterval package. The plasma CgA concentration decreased with age and was 32-118µg/L for children aged 0-3years, 18-85 µg/L for children aged 4-13years, and 6-79µg/L for adolescents aged 14-19years. Earlier reported CgA reference intervals for adults have upper limits from 88 to 102µg/L while no lower limits have been reported. The median for the three groups were 78, 51, and 39µg/L, respectively. The median intra-individual variation was 14% (25%-centile 9.4%/75%-centile 21%). The reference interval will be useful when screening, diagnosing, and monitoring children for NENs respecting the limitations plasma CgA has.

Serum cobalamin and methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or other acute enteropathies.

Low serum cobalamin concentrations have been associated with ileal malabsorption in dogs with chronic enteropathy. Increased serum methylmalonic acid (MMA) concentrations indicate cobalamin deficiency on a cellular level. Few studies have evaluated serum cobalamin concentrations or methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or nonparvoviral acute enteropathies. Evaluate serum cobalamin and methylmalonic acid concentrations in juvenile dogs (6 weeks to 10 months old) with parvoviral enteritis or nonparvoviral acute enteropathy. Thirty-one juvenile dogs with parvoviral enteritis, 29 dogs with nonparvoviral acute diarrhea (NPVAD), and 40 healthy juvenile control dogs. Single-center, prospective, observational, cross-sectional study. Serum cobalamin and, when sufficient serum was available, MMA concentrations were measured. Most serum cobalamin concentrations were within the adult reference interval. Serum cobalamin concentrations in healthy dogs (median, 848 ng/L; range, 293-1912 ng/L) were significantly higher than in dogs with parvoviral enteritis (P = .0002; median, 463 ng/L; range, <150-10 000 ng/L) or dogs with NPVAD (P = .02; median, 528 ng/L; range, 160-8998 ng/L). Serum MMA concentrations were not significantly different between groups (healthy dogs: median, 796 nmol/L; range, 427-1933 nmol/L; parvoviral enteritis: median, 858 nmol/L; range, 554-3424 nmol/L; NPVAD: median, 764 nmol/L; range, 392-1222 nmol/L; P = .1). Juvenile dogs with parvoviral enteritis or NPVAD had lower serum cobalamin concentrations than healthy juvenile dogs. However, based on serum MMA concentrations cellular cobalamin deficiency was not apparent.

Establishing Pediatric Reference Ranges for Rotational Thromboelastometry.

The aim of our investigation was to establish normal pediatric reference intervals (PRIs) for rotational thromboelastometry (ROTEM) Delta assays in a representative group of healthy children, 0 to 18 years of age, at our institution. This was a prospective study of healthy pediatric patients undergoing elective minor surgery requiring placement of an intravenous cannula. The sample size for patients was 20 per age group of either sex from 5 different age groups based on coagulation system maturity: 0 to 6 or fewer months, more than 6 to 12 or fewer months, more than 1 year to 5 or fewer years, more than 5 to 11 or fewer years, and more than 11 to 18 or fewer years. ROTEM Delta assays assessed include the EXTEM, INTEM, and FIBTEM. We defined 2 sets of ROTEM PRIs for our patient population: one for patients 11 years or younger and one for children more than 11 years of age. For those 11 years or younger, the PRIs were derived from the 2.5th and 97.5th percentiles from the 0 to 11 age groups. For those older than 11 years, previously published adult reference intervals validated internally with adult normal samples were used. The 2 sets of PRIs were embedded into our electronic medical record, allowing clinicians to easily interpret their patient's ROTEM results against age-verified reference ranges, enabling them to make informed transfusion decisions.

Adult reference intervals for ceruloplasmin by Siemens BN II Nephelometer by Bhattacharya analysis

Background: Low ceruloplasmin may indicate Wilson’s disease or copper deficiency. Ceruloplasmin assays are not well harmonised, necessitating assay specific reference intervals (RI). The lower reference limit (LRL) in the Siemens BN II package insert (0.2 g/L) if reported to two significant figures was previously shown to be too high in Asian cities. However, studies from predominantly Caucasian populations were lacking.