bluuebunny/crossref_metadata_2025_split huggingface dataset:
A-048 Reference Interval and Clinical Performance Studies for Vitros® Immunodiagnostic Products Intact PTH II Assay to Aid in Diagnosis of Calcium and Parathyroid Disorders and Intraoperative Testing
Authors: Hirsch B M , Gardner A , Potter L , Fish R , Woeller E , Atienza J , Ding Q 
Published: October 2024

Abstract

Background
Intact parathyroid hormone (iPTH) measurements aid in the differential diagnosis of hypercalcemia, hypocalcemia, and parathyroid disorders. The National Academy of Clinical Biochemistry has established guidelines for intraoperative PTH testing to monitor surgical success during parathyroidectomies. Studies were conducted to define the reference interval and clinical performance of the Vitros Immunodiagnostic Products Intact PTH II (Vitros iPTH II) assay, using samples from healthy individuals and patients with conditions commonly requiring iPTH testing, including intraoperative cases.

Methods
The reference interval study was conducted in accordance with Clinical and Laboratory Standards Institute (CLSI) guideline EP28-A3c in serum samples from 134 healthy individuals. For the clinical performance study, serum samples from individuals with hypoparathyroidism, primary hyperparathyroidism, chronic renal failure (secondary or tertiary hyperparathyroidism), hypercalcemia, hypercalcemia of malignancies, and hypocalcemia were tested. Intraoperative samples used were collected from parathyroidectomy patients in series at each surgical timepoint along with the standard plasma samples used to determine surgical success.

Results
The reference samples were composed of 134 serum donors that met all inclusion/exclusion criteria for healthy donors and had a normal test result on calcium, TSH, alkaline phosphatase, creatinine, and phosphate assays. The reference interval for iPTH was determined to be 14.2-75.2 pg/mL. The results in various disease states demonstrated the clinical performance of the Vitros iPTH II assay. Of 32 intraoperative sample series included in the study, three samples demonstrated no intraoperative decrease in iPTH due to surgical failures. Consistent with the goal of the parathyroidectomy procedure, at least a 50% decrease in iPTH was observed between the presurgical and post-excision samples in all other sample series. The clinical concordance with the Roche PTH assay used intraoperatively in these procedures was 100%.

Conclusions
Defining the reference interval for a normal healthy population and results from the intended use population demonstrated that the Vitros iPTH II assay can be used as an aid in the diagnosis of calcium and parathyroid disorders and intraoperative testing.
A-060 Assessing Glucose Stability: A Comparison of Citrate/NaF, NaF, and Gel Separator Vacuum Tubes in Routine Medical Laboratory Practice
Authors: Kosova S 
Published: October 2024

Abstract

Background
In cases where a glycolysis inhibitor is not utilized, blood cells in vitro can consume glucose. Although current guidelines suggest using citrate-buffered inhibitors or ice-water slurry to mitigate this, practical and financial constraints often hinder adherence to these recommendations. Our objective was to evaluate the difference in glucose concentration in our routine sample management by employing Citrate buffered/NaF, NaF, and Gel Barrier tubes.

Methods
In this study, we utilized Greiner FCmix citrate-buffered NaF and EDTA tubes (3 mL), Becton Dickinson NaF and EDTA tubes (4 mL), and Becton Dickinson SSTII Gel Barrier tubes (5 mL). Following venipuncture, the tubes were transferred to the laboratory and centrifuged within 30 minutes. Glucose levels of 46 patients' samples were measured using a Cobas 6000 system (c501) employing the Glucose Hexokinase method, which exhibits an intermediate coefficient of variation (CV) of approximately 1.5% and no significant bias, as confirmed by monitoring with Biorad EQAS.

Results
The mean plasma glucose difference between Citrate-buffered tubes and NaF tube samples was 2.8 mg/dL with a 95% confidence interval (CI) ranging from 2.2 to 3.4 mg/dL (Mean: 0.16 mmol/L; CI: 0.12 - 0.19 mmol/L). The difference in paired samples of NaF plasma and Gel Barrier tubes serum glucose was 3.2 mg/dL with a CI of 2.5 - 3.9 mg/dL (Mean: 0.18 mmol/L; CI: 0.14 - 0.22 mmol/L). Lastly, the mean difference in Citrate-buffered plasma and serum Gel barrier tubes for 46 paired samples was 6.0 mg/dL with a CI of 5.2 - 6.7 mg/dL (Mean: 0.33 mmol/L; CI: 0.29 - 0.37 mmol/L).

Conclusions
Following guidelines, Citrate-buffered/NaF tubes demonstrate efficacy as glucose stabilizers. When compared to NaF tubes alone within a 30-minute timeframe, the mean difference between the two types of tubes was 2.8 mg/dL. Although NaF tubes are no longer recommended for glucose testing in plasma, they still outperform gel barrier serum tubes by 3.2 mg/dL. Furthermore, compared to citrate/NaF Plasma, serum glucose levels were on average 6.0 mg/dL lower. The preanalytical sample stage poses a significant obstacle to its reliable use for diagnostic or monitoring purposes. Laboratories should consider transitioning to Citrate/NaF tubes, or employ mathematical corrections if utilizing gel separator tubes for glucose testing in their established preanalytical process.
A-063 Correlation of 1,5-anhydroglucitol (AG) with A1c: understanding this relationship in terms of an established physiological model for AG mass balance as a function of [glucose]
Authors: Stickle D , Delikkaya B N , Kyle P B 
Published: October 2024

Abstract

Background
Diet-derived 1,5-anhydroglucitol (AG) is an unmetabolizable glucose analogue present in plasma (reference interval: 7.4-32.5 µg/mL). In diabetes, hyperglycemia can accelerate AG excretion, producing an inverse relationship between A1c and AG. There are no established guidelines regarding use or interpretation of AG in diabetes, but it is often described as being useful for detection of short-term variation in [glucose]. We examined AG usage at our institution, and, additionally, analyzed the information content of AG as derived from an established model for the relationship between AG and [glucose].

Methods
Medical records were scanned for all combined orders for AG and A1c between September 2020 and August 2023. Estimated average glucose (eAG) was calculated from A1c [PMID: 18540046]. AG vs. A1c data were compared to calculations for AG vs. eAG using an established physiological model for AG mass balance [PMID: 9357814].

Results
Among 104 AG measurements, there were 93 AG/A1c measurement pairs (see Figure). 70% had elevated A1c (n=65). 43% had decreased AG (n=40), all with elevated A1c. Among all AG/A1c pairs, 66% (closed points; n=61) were within the boundaries of model calculations for AG when assuming a simple steady-state [glucose] equal to eAG, a normal glomerular filtration rate, and a normal AG ingestion rate. AG outside of these boundaries (34%; open points, n=32) were almost entirely above the upper boundary (32%; n=30), where results are consistent either with increased AG ingestion rate, decreased glomerular filtration rate, or a discrepancy between eAG and A1c. Only two points (2.2%) were compatible with interpretation of variation in prevailing glucose from eAG.

Conclusions
For our data, paired AG/A1c measurements were in majority well characterized by a physiological model based simply on steady-state (invariant) [glucose] equal to eAG as derived from A1c alone. Only a small fraction of AG results suggested possible variation in [glucose].
A-065 The CDC HoSt Certification Requirements Have Been Met for More Than Four Years by the Atellica IM, ADVIA Centaur Testosterone II and Dimension Vista LOCI Total Testosterone Immunoassays
Authors: Abou-Diwan C , Parker N , Pagliaro S , Lewisch S , Barczak E , Shalhoub V , Oduaran E , Freeman J 
Published: October 2024

Abstract

Background
The CDC Hormone Standardization (CDC HoST) Certification Program, is traceable to the primary testosterone Standard National Measurement Institute (NMI) M914. The Atellica® IM, ADVIA Centaur® Testosterone II (TSTII) and Dimension Vista® LOCI Total Testosterone (TTST) assays are enrolled in the program. Certification is a yearlong process of 40 blinded samples from the CDC, 10 for testing each quarter. If 4 consecutive quarters meet bias acceptance criteria of ± 6.4%, CDC certification is achieved.

Methods
Initially, to standardize the assay approximately 120 samples were obtained from CDC with CDC HoST ID-LC-MS dose values to value assign master curve standards. Multiple ADVIA Centaur TSTII reagent lots were tested with CDC patient samples. Internal master curve standards were assayed as unknowns and dose values assigned using the RLU (system generated units-Relative Light Units) to CDC ID-LC-MS dose relationship. For TSTII (2019- 2023), after standard value assignment, at least 179 CDC blinded samples were tested across all platforms. Each quarter, 10 blinded samples were tested in duplicate over 2 days. Similar procedures were followed for TTST. Results were analyzed by the CDC.

Results
Correlation between the CDC assigned values and Atellica IM, ADVIA Centaur, and ADVIA Centaur CP TSTII assay results was strong across all quarters from 2019 to 2023 combined. TTST results were strong for 2023. Mean bias between TSTII and TTST results and CDC reference values was consistently &lt;6.4%. This enabled the TSTII assays to be CDC certified for a fourth consecutive year, and TTST for 2023. The table presents TSTII (2019-2023) and TTST (2014-2023) results.

Conclusions
The TSTII assay consistently achieved CDC certification from 2019 to 2023, while the TTST assay was initially certified in 2014. Siemens Healthineers is the only testosterone immunoassay manufacturer to be currently certified, the TSTII assay has achieved certification for four consecutive years.
A-084 Performance evaluation of Sentinel Diagnostics’ Ammonia Ultra assay on Beckman Coulter AU/DxC AU Systems
Authors: Brambilla S , Barazzutti A , Bordonaro F , Coghi A , Fusi E , Lucini R , Santos Cruz J 
Published: October 2024

Abstract

Background
The analytical performances of the Ammonia Ultra assay for in vitro quantitative enzymatic determination of Ammonia in human plasma have been evaluated on Beckman AU/DxC AU Systems. Ammonia, derived from the amino acids catabolism and from the action of intestinal bacteria on dietary proteins, is converted to non-toxic urea by the liver. An excess of ammonia can have toxic effects on the Central Nervous System with possible neurological disturbances. Elevated ammonia levels can also be observed in severe liver failure as may occur in Reye’s syndrome, viral hepatitis or cirrhosis.

Methods
Ammonia, in the presence of glutamate dehydrogenase (GLDH), combines with alpha-ketoglutarate and NADH to yield glutamate and NAD+. The decrease in 340 nm absorbance (NADH → NAD+) is proportional to the ammonia level in the examined plasma. The reagent contains excess of lactate dehydrogenase (LDH) to rapidly reduce endogenous pyruvate and avoid its interference with the assay system. Performances evaluation have been done following current CLSI guidelines protocols.

Results
3 calibrator lots and 2 reagent lots have been used for testing. For each test and among different combinations of reagents and calibrators, worst case has been reported in the table.

Conclusions
Analytical performances of Ammonia Ultra assay on Beckman AU/DxC AU Systems meet the requirements for its use as quantitative determination of Ammonia in human plasma and make this assay very suitable for the routine measurement of this analyte.
A-099 Case Study of a Patient With Heterophile Antibodies Interfering with Both Competitive and Immunometric Assays
Authors: Palamalai V , Nwaukwe A , Ramirez R 
Published: October 2024

Abstract

Background
Immunoassay results may be affected by the presence of interfering substances including heterophile antibodies. These heterophile antibodies can cause either an increase or decrease in the result based on assay design and antibody target. We report a case study wherein we identified several analytes whose results were either increased or decreased by heterophile antibodies in a patient.

Methods
74 year male presented to Endocrinology with history of hypocalcemia and his previous lab tests were suggestive for idiopathic hypoparathyroidism, Hashimoto’s disease and Addison’s disease raising physician concern for a possible Type 1 autoimmune endocrinopathy. Cortisol was ordered (for an ACTH stimulation test for adrenal insufficiency); upon testing the post-stimulation cortisol result was higher than the analytical measurement range (AMR), and so the sample was diluted 1:2 and repeated. The repeat cortisol result after correction for the dilution factor was well within the AMR and prompted an investigation for an interfering substance. Serial dilution of analytes was performed and send-out testing for the same with another immunoassay from a different manufacturer and/or mass spectrometry method where available were done.

Results
The results for most analytes did not match with the reference lab results. Serial dilution showed non-parallelism in the results. For most analytes, after dilution of the sample by 1:4 or 1:8 times, the interfering substance was diluted enough to obtain a result matching the reference lab result.

Conclusions
Based on non-parallelism in serial dilution results, discordant results with other methods, and loss of interference after dilution it was determined that the most likely cause was a heterophile antibody. Formal testing using blocking antibodies was not done as it seemed that the reference lab used did not run our method and their assays were not affected by this particular heterophile antibody. Analysis of the assay designs and analyte results showed that competitive assays showed falsely high results, while immunometric assays showed falsely low results. The physician was contacted and the case discussed in detail and it was recommended that further testing on this individual be sent out to a reference lab using the alternate method or to use mass spectrometry based assays for further testing if needed. Today, the patient continues to have low calcium, high phosphate and an undetectable PTH suggestive of idiopathic hypoparathyroidism but his other endocrine functions are within normal limits.
A-100 Clinical Utility of Measuring Creatine Concentration in Erythrocyte
Authors: Nakahara T , Imada M , Kataoka H 
Published: October 2024

Abstract

Background
Shortened erythrocyte lifespan characterizes hemolytic anemia and impacts HbA1c values. Recently, erythrocyte creatine concentration (EC) measurement emerged as a new method to assess erythrocyte lifespan. However, literature reports conflicting findings regarding the association between erythrocyte lifespan and EC concentration. In our study, we noted low EC concentrations in renal diseases, typically linked to short erythrocyte lifespan, while iron deficiency anemia exhibited high EC concentrations. This contradicts established relationships, prompting a reevaluation of EC concentration assessment. The aim is to evaluate the clinical utility of EC concentration measurements by correlating them with various clinical parameters, including hematopoietic status.

Methods
EC concentrations were measured in 522 subjects (252 females, 270 males) aged 19 to 95 at Kawasaki Medical School Hospital. Medical records and laboratory test results from around one month before and after blood collection were used to create a database. Box-and-whisker plots illustrated EC concentration distribution for each disease, and scatter plots compared EC concentrations with laboratory parameters.

Results
EC concentrations were lower in renal diseases like Diabetes and Chronic Kidney Disease but higher in iron deficiency anemia (Fig. 1). Moreover, EC concentrations rose as hemoglobin concentrations declined, unaffected by CKD grade (Fig. 2).

Conclusions
While conventionally, high EC concentrations imply a short erythrocyte lifespan, our study noted the opposite trend. EC concentrations might not indicate erythrocyte lifespan but instead reflect hemoglobin synthesis. Investigating EC concentration's relationship with factors like iron and vitamin B12 involved in hemoglobin synthesis may unveil new clinical applications.
A-103 Analytical Performance Evaluation of Plasma NfL in a Clinical Diagnostic Laboratory
Authors: Frykman H , Mammel A , Pradip G , Hallett K , Mousavi A 
Published: October 2024

Abstract

Background
Neurofilament light chain (NfL) is a neuron-specific intermediate filament that is released at a consistent low level in normal individuals and increases with age and axonal injuries. NfL is a neurodegeneration biomarker in Alzheimer’s disease (AD), multiple sclerosis, stroke, traumatic brain injury and other neurodegenerative diseases (NDD). Here, we report the analytical performance of plasma NfL using high-sensitivity methodology in a clinical diagnostic laboratory.

Methods
The analytical performance, encompassing precision, detection limits, interference, and linearity, was evaluated. Plasma NfL levels were measured between July and October 2023 at Neurocode USA in Bellingham, WA, using a single Lumipulse G1200 instrument following CLSI guidelines, particularly for the utilization of the Fujirebio NfL Blood RUO assay as a laboratory-developed test for clinical analysis. A total of 100 healthy control samples, near the age of AD onset, were used to validate the reference ranges.

Results
The average plasma NfL concentrations varied from ≤ 8.4 to ≤ 37.9 ng/L among healthy individuals aged 20 to 80 years. The Plasma NfL assay exhibits analytical measurements, including a limit of blank (LoB) of 0.75 ng/L, a limit of detection (LoD) of 1.99 ng/ml, and a limit of quantification (LoQ) of 3.96 ng/L. Its linearity ranges from 11.08 to 741.58 ng/L, with intra-laboratory precision ≤ 9% CV. Stability is maintained at 4⁰C for ≤ 72 hours, at room temperature for ≤ 4 hours, at -20⁰C for ≤ 4 weeks, and at -80⁰C for ≤ 7 days, with freeze/thaw cycles tolerated within the specified time frame. Additionally, no interference was observed at the maximum concentrations tested for bilirubin, hemoglobin, and intralipid.

Conclusions
With a reference range between ≤ 8.4 to ≤ 37.9 ng/L and exceptional analytical performance, the measurement of plasma NfL on a state-of-the-art instrument using CLSI guidelines, can be useful in the diagnosis and monitoring of AD and other NDD.
A-110 Analytical Performance Evaluation of Vitros® Immunodiagnostic Products Intact PTH II Assay
Authors: Hirsch B M , Gardner A , Potter L , Fish R , Woeller E , Atienza J , Ding Q 
Published: October 2024

Abstract

Background
Intact parathyroid hormone (iPTH) is indicated to aid in the diagnosis of hyperparathyroidism, hypoparathyroidism, differential diagnosis of hypocalcemia or hypercalcemia and for intraoperative measurement of iPTH levels. Studies were conducted to evaluate the analytical performance of the Vitros Immunodiagnostic Products Intact PTH II (Vitros iPTH II) assay by determining limit of detection (LoD), limit of quantitation (LoQ), and precision. A method comparison of the Vitros iPTH II assay against the Roche Elecsys PTH assay was also conducted.

Methods
The LoD and LoQ were determined consistent with CLSI EP17. Precision was evaluated consistent with CLSI EP05 using six patient pools for 20 days. Repeatability was determined using two replicates per run. Within-lab precision was determined using a single reagent lot and a single calibration. A quantitative comparison between the Vitros iPTH II assay on a Vitros 3600 system and the Roche Elecsys PTH assay on a Roche Cobas 8000 system was conducted in accordance with CLSI guideline EP09 using 206 endogenous patient samples. Samples were selected to cover the full measuring interval and were tested over a total of six non-consecutive days.

Results
The LoD for the Vitros iPTH II assay was determined to be 1.7 pg/mL. The claimed LoQ was determined using a precision profile approach with a %CV limit of 20% and set at 1.7 pg/mL. For mean parathyroid hormone (PTH) concentrations ranging from 15.9 to 4656 pg/mL, repeatability (within-run) percent coefficient of variation (%CV) ranged from 0.8% to 1.4% and within-lab %CV ranged from 1.5% to 3.0%. The method comparison of the Vitros iPTH II assay versus the Roche Elecsys PTH assay yielded a correlation coefficient of 0.991 and a Passing-Bablok regression slope of 1.01 and intercept of 0.3.

Conclusions
The Vitros iPTH II assay demonstrated acceptable analytical performance in these studies, with high correlation and close agreement to the Roche Elecsys PTH assay.
A-112 Reference Intervals for Serum Concentrations of N-Terminal Propeptide of Type-I Procollagen (PINP) for Greek Adult Population
Authors: Makris K , Trifonidi I , Tournis S , Chronopoulos E 
Published: October 2024

Abstract

Background
PINP is a sensitive indicator of the synthesis of type-I collagen. Serum PINP levels are affected by changes in bone metabolism and is a useful indicator of disease activity in Paget's disease, bone metastases of osteoblastic nature and in monitoring osteoporosis treatment. To interpret PINP, method and population specific reference intervals are needed. We aimed to determine reference intervals for serum concentrations of PINP for the Greek adult population.

Methods
We collected samples from 431 apparently healthy Greeks (140 men as well as 150 pre- and 139 post-menopausal women), who volunteered to participate in our study. Data on socio-demographic characteristics, medical histories and medications were collected and subjects with conditions or receiving medications that affecting bone metabolism were excluded. Dual-energy x-ray absorptiometry (DXA) used to measure bone mineral density (BMD) in all participants. All blood collections were performed in the morning after overnight fast. Measurements were performed by an automated chemiluminescent immunoassay on the Maglumi-X3 analyzer (Snibe, Shenzhen, China). This method measures the total-PINP in serum. The reference interval was defined as the central 95% range and determined according to CLSI guide C28-A3 using the MedCalc Software

Results
The table summarizes our results. DXA results revealed that 348 participants had normal BMD, 74 had osteopenia and 9 had osteoporosis which excluded from analysis. Since our data were not normally distributed (Shapiro-Wilk test) in any group and after the exclusion of outliers (Tukey test), we used the non-parametric method suggested by the CLSI guide in order to determine the reference intervals. Multiple regression analysis revealed that sex and menopausal status were factors affecting PINP values.

Conclusions
We provide reference intervals for the determination of PINP concentrations in serum for the Greek adult population using an automated immunoassay. Our data may aid to interpret bone turnover in the Greek adult population.