bluuebunny/crossref_metadata_2025 huggingface dataset:
A-003 Point of Care BNP Values Obtained by the Abbott i-STAT are not Interchangeable With Laboratory Determined Values Using Beckman DXI 800 Analyzer
Authors: Zinn K , Boyd M , Dasgupta A
Published: September 2023

Background

B-type natriuretic peptide (BNP) is used as a biomarker of heart failure. In our hospital, point of care (POCT) BNP test is performed on whole blood using the i-STAT (Abbott, Abbott Park, IL) while in clinical laboratory, the DXI 800 analyzer is used (Beckman, Brea, CA) for determination of BNP in EDTA plasma. Sometimes clinicians interchangeably use POCT BNP with laboratory BNP test for monitoring heart failure patients, but values are sometimes significantly different causing diagnostic confusion. We compared POCT BNP values in 88 patients with laboratory-based BNP values analyzed between less than one hour to less than 12 h. In addition, 12 specimens were simultaneously analyzed for POCT BNP and lab-based BNP. No additional blood was drawn from patients and medical record was not accessed. The study had exempt status: by the IRB of University of Kansas Medical Center.

Methods

POCT BNP values were obtained using the i-STAT analyzer following manufacturer’s protocol. It is a two-site enzyme-linked immunosorbent assay (ELISA) with an analytical measurement range of 15–5000 pg/mL. In the laboratory BNP concentrations were obtained using the DXI 800 analyzer. It is also a sandwich immunoassay with the analytical measurement range of 5–5000 pg/mL.

Results

Overall comparison using lab-based BNP as x-axis and POCT BNP as y-axis produced the following regression equation; y = 1.48 x − 23.45 (n = 88, r = 0.96) indicating that although POCT BNP values correlated well with lab-based BNP values, POCT values showed an average 48% positive bias. When specimens analyzed within 4 h were compared, the regression equation was: y = 1.40 x + 74.12 (n = 20, r = 91) and when specimens analyzed within 1 h were compared, the regression equation was: y = 1.56 + 59.0 (n = 23, r = 0.97). In contrast, when 12 specimens were analyzed simultaneously using POCT and lab-based BNP, using x-axis as the lab-based BNP and y-axis as the POCT BNP, the following regression equation was observed: y = 1.83 x − 102.8 (n = 12, r = 0.99).

Conclusion

Higher positive bias in specimens analyzed simultaneously indicates true positive bias with POCT BNP compared to lab-based BNP because lab-based BNP in real patients were ordered later after POCT BNP. To our knowledge i-STAT BNP values were never compared with DXI 800 BNP values. We communicated with our clinicians not to use lab-based BNP test and POCT BNP in monitoring patients being treated for heart failure interchangeably. POCT BNP can be used for initial screening to identify potential patients with heart failure.
A-006 Evaluation of the ADVIA Centaur NT-proBNPII Assay Vs Standard-of-care Natriuretic Peptide Testing in the Emergency Department
Authors: Snyder J , Bermel S , Brown C , Cooper C
Published: September 2023

Background

The Siemens Healthineers ADVIA Centaur® NT-proBNPII (PBNPII) assay* was developed for in vitro diagnostic use in the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur XP Immunoassay System. Siemens Healthineers performed a clinical study to evaluate the ADVIA Centaur XP PBNPII assay in an Emergency Department (ED) patient population. The study also involved collection of standard-of-care (SOC) natriuretic peptide (NP) results, either NT-proBNP or BNP.

Objective

To compare results from the ADVIA Centaur PBNPII assay in ED populations with SOC NP results and adjudicated diagnosis of heart failure.

Methods

3128 subjects were enrolled from 30 ED sites. Blood was collected at time of enrollment for subsequent ADVIA Centaur PBNPII measurement; results from SOC NP testing were obtained from chart review. Available SOC testing was performed within 24 h of enrollment draw for all except four patients. Adjudication of acute HF (de novo or worsening) or non-acute HF was determined by an independent central adjudication panel of expert clinicians.

Results

Of the 3128 patients in the ED study, 1646 (52.6%) had an SOC BNP test performed, 1020 (32.6%) had an SOC NT-proBNP test performed, and 462 (14.8%) had neither. Agreement between the SOC NP results and PBNPII results was assessed based on concordance using cutoffs described in heart failure guidelines that include an indeterminate zone (1). For those tested with SOC NT-proBNP, there was 94.7% concordance, 5% partial concordance (indeterminate by one assay and positive or negative by the other), and 0.3% discordance. For those tested with SOC BNP, there was 73.8% concordance, 25.5% partial concordance, and 0.7% discordance. Agreement with adjudication was virtually identical for both the PBNPII assay and SOC PBNP at 63% concordance, 17% partial concordance, and 20% discordance. For those tested with SOC BNP, there was 63% concordance, 29.5% partial concordance, and 7.5% discordance, while in this same population the PBNPII assay had 67.8% concordance, 15.7% partial concordance, and 16.5% discordance.

Conclusion

Upon comparison of ADVIA Centaur PBNPII assay results to SOC NP testing in an ED population, Siemens Healthineers concludes that the ADVIA Centaur PBNPII assay performs similarly to commercial natriuretic peptide assays in routine use. These results agree with publications comparing diagnostic testing of NT-proBNP and BNP for suspected heart failure (2).

*Disclaimer

The products/features mentioned herein are not commercially available in all countries. Their future availability cannot be guaranteed.
A-011 High Sensitive Troponin Assays for Differentiating the Patients with Unstable Angina from Stable Angina
Authors: Kim Y , Cho H , Kim S , Lee H , Kwon H , Lee J
Published: September 2023

Background

There have been no cardiac biomarkers used in the diagnosis of unstable angina. In this study, we examined high sensitive troponin T and I as a marker to differentiate the patients with unstable angina from the patients with stable angina.

Methods

A total of 816 patients (59 AMI, 94 unstable angina, 99 stable angina, 623 healthy individuals) were included. All patients had glomerular filtration rate of ≥60 mL/min/1.73 m2. Leftover serum samples were obtained from the patients who visited The Catholic University of Korea, St Vincent’s Hospital from April to November, 2019. Cardiac troponin was measured using Beckman Coulter Access high sensitivity cTnI assay, Abbott Architect high sensitive TnI assay, and Roche Elecsys Troponin T-high sensitive assay.

Results

The 99th percentile URLs (Upper Reference Limits) of Beckman Coulter cTnI, Abbott cTnI, and Roche cTnT are 9.8 ng/L, 17.9 ng/L, and 16.4 ng/L, respectively. In the 99 patients with stable angina, 9.1% (9/99), 5.1% (5/99), and 6.1% (6/99) of the patients showed higher values than each the 99th percentile URL with Beckman Coulter cTnI, Abbott cTnI, and Roche cTnT, respectively. In the 94 patients with unstable angina, 24.5% (23/94), 24.5% (23/94), and 25.5% (24/94) showed higher values than each the 99th percentile URL with Beckman Coulter cTnI, Abbott cTnI, and Roche cTnT, respectively. There are significant differences between the frequencies of the patients with stable angina and unstable angina showing higher values of cardiac troponins than each the 99th percentile URL.

Conclusion

High sensitive troponins could be a useful marker for the differentiation of the patients with unstable angina from stable angina.
A-020 Evaluation of the Analytical Performance of BNP and NT-proBNP Assays on the Atellica CI 1900 Analyzer
Authors: Rhea-McManus J , Ozgen N , Leipold H
Published: September 2023

Background

The Atellica® CI 1900 Analyzer is an automated, high-throughput integrated chemistry and immunoassay analyzer employing both Atellica CH and Atellica IM assays. This study was designed to evaluate the analytical performance of the Atellica IM B-type Natriuretic Peptide (BNP) and NT-proBNP (PBNP) assays* on the Atellica CI 1900 Analyzer.

Methods

The Atellica CI 1900 BNP and PBNP assays use the same reagents and calibrators as the Atellica IM assays. Precision and method comparison were used as performance indicators for the Atellica CI 1900 Analyzer. Precision studies were performed according to CLSI EP05-A3 and method comparison according to CLSI EP09-A3 using native and contrived human plasma (BNP) and serum (PBNP) samples. One aliquot of each sample pool was tested in duplicate in two runs per day >2 h apart on each analyzer for >20 days. BNP and PBNP were evaluated with one reagent lot on two systems. For the method comparison, individual native and contrived human plasma samples (BNP) or native human serum samples (PBNP) were analyzed using the Atellica IM BNP and PBNP assays on both the Atellica IM and Atellica CI 1900 Analyzers.

Results

Representative precision and MC results for each assay are listed in the table. For the two assays tested, repeatability and within-lab %CVs were <2.5% and <3.0%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusion

Evaluation of the Atellica IM BNP and PBNP assays using the Atellica CI 1900 Analyzer demonstrated acceptable precision and equivalent performance compared to the same assays on the Atellica IM Analyzer.
A-024 Evaluation of the Analytical Performance of Thyroid-stimulating Hormone, Free Triiodothyronine, and Free Thyroxine Assays on the Atellica CI 1900 Analyzer
Authors: Zhang H , Quintanilla M , Guo M , Rhea-McManus J , Leipold H
Published: September 2023

Background

The Atellica® CI 1900 Analyzer is an automated, mid-throughput integrated chemistry and immunoassay analyzer utilizing both Atellica CH and Atellica IM assays. This study evaluated the analytical performance of the Atellica IM Thyroid Stimulating Hormone 3 Ultra™ (TSH3-UL), Free Triiodothyronine (FT3), and Free Thyroxine (FT4) assays* on the Atellica CI 1900 Analyzer.

Methods

The Atellica CI 1900 TSH3-UL, FT3, and FT4 assays use the same reagents and calibrators as the Atellica IM assays. Precision and method comparison studies were performed according to CLSI EP05-A3 and CLSI EP09-A3 using native and contrived human serum (TSH3-UL, FT3, and FT4) and plasma (TSH3-UL) samples. One aliquot of each sample pool was tested in duplicate in two runs per day >2 h apart on each analyzer for ≥20 days. FT3 and FT4 were evaluated with one reagent lot on two systems. TSH3-UL was evaluated with two reagent lots on two systems. For the method comparison, individual native human serum samples were analyzed using the Atellica IM TSH3-UL, FT3, and FT4 assays on both the Atellica IM and Atellica CI 1900 Analyzers.

Results

Representative precision and MC results are listed for each assay in the table. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusion

Evaluation of the Atellica IM TSH3-UL, FT3, and FT4 assays using the Atellica CI 1900 Analyzer demonstrated good precision and equivalent performance compared to the same assays on the Atellica IM Analyzer.

*The products/features mentioned herein are not commercially available in all countries. Their future availability cannot be guaranteed.
A-029 Modeling the Effect of Step Changes in Glucose on %Glycated Albumin vs Time
Authors: Stickle D F , DiNatale G J , Molinaro R
Published: September 2023

Background

Glycated albumin (GA) is often referred to as being a reflection of glucose exposure over the past 20–30 days. We examined this premise from a theoretical standpoint using a model for formation of GA and simulation of the effects of step changes in glucose concentration ([G]).

Methods

A model for glycation of albumin parallels established models for formation of hemoglobin A1c, differing only in characterization of the age distribution for albumin. Probability of survival (P(s)) of albumin at a given age (t) is based on a first-order rate constant (ke) for elimination: P(s) = exp(-ke t) [Eqn.1], where ke = 4.08e-2/d (t(1/2) = 17 d). Probability of glycation (P(g)) at a given age is given by: P(g) = (1-exp(-k[G] t)) [Eqn.2]. There is a simple analytical solution for %GA for constant [G]: %GA = 100(1-w/z), where w = ke and z = (ke+k[G]). k = 9.77e-4/d/(mmol/L) reproduces reference values for %GA [PMID: 29436378], and for which %GA = 2.41(%A1c)-0.004 (r = 0.999, for A1c range = 5%–12%). For non-constant [G], %GA must be determined by simulation of changes in P(g) using Eqn.2, calculated in small time increments, dt. Using dt = 0.01 d, we calculated changes in %GA by simulation as a function of time for two scenarios involving step changes in [G] at time = 0: A. from 10 mmol/L to 15 mmol/L (%GA ultimately moves from 19.3% to 26.4%); B. from 15 mmol/L to 10 mmol/L (%GA ultimately moves from 26.4% to 19.3%).

Results

Figure shows the fractional transition of %GA between respective starting points and ultimate endpoints vs time for scenarios A and B. In both cases, transition at 30 days was approximately 80% of the ultimate full transition.

Conclusions

Physiological model-based calculations support that description of %GA as a reflection of [G] over the past 30 days is a very reasonable one under conditions in which [G] has changed.
A-042 Comparison of the Second-Generation Parathyroid Hormone Assays: ELSA-PTH and Alinity i Intact PTH
Authors: Kang J , Park J , Choi H , Kee S
Published: September 2023

Background

Measurement of parathyroid hormone (PTH) level is essential in diagnosing and treating hyper- and hypoparathyroidism. Because of the various presenting forms of PTH (biologically active full-length PTH and also PTH fragments) in the blood and the lack of standardization, there can be a difference in results between the assays even when the same assay generation is used. We compared the two second-generation PTH assays, ELSA-PTH and Alinity i Intact PTH, and evaluated the analytical performance of Alinity i Intact PTH, newly adopted in the laboratory.

Methods

For method comparison, 56 remnant samples of routinely ordered sera for the PTH test were collected. ESLA-PTH assay tested on Gamma-10 contains the anti-[39-84, amino acids] PTH antibody coated on the tube, which captures PTH in the sample and is measured by the radioactivity through the bound I125-labelled anti-[1-34] PTH antibody. Alinity i Intact PTH assay performed on Alinity i system uses the anti-[39-84] PTH antibody coated on a paramagnetic microparticle and is analyzed by the emitted light through the captured acridinium-labeled anti-[1-34] PTH antibody. The correlation between the two tests was evaluated. Additionally, precision, linearity, and reference range verification were analyzed to investigate the performance of the Alinity i Intact PTH assay.

Results

Of the 56 samples, 35 (62.5%) were requested by the Nephrology department for evaluating chronic kidney disease, 16 (28.6%) by the General surgery department during and after parathyroid and thyroid surgery, and 5 (8.9%) by other departments. 52.3% of the patients were female, and the median age was 61.5 years (interquartile range: 45.3–71). The median values of ELSA-PTH and Alinity i Intact PTH were 69.0 pg/mL and 101.9 pg/mL, respectively, and the PTH values of Alinity i Intact PTH were significantly higher (P < 0.0001) by the Wilcoxon test. The Pearson correlation coefficient (r) was 0.959, and the average difference between the two tests was 78.57 pg/mL. In Alinity i Intact PTH, the coefficient of variation obtained at each low (10.5 pg/mL), medium (66.6 pg/mL), high (254.6 pg/mL) levels were 1.9%, 2.4%, and 1.8% for repeatability, and 2.03%, 2.71%, and 2.65% for within-laboratory precision, respectively. Linearity was observed within the analytical measuring range of 3–3000 pg/mL. The reference range (15–68.3 pg/mL) recommended by the manufacturer was validated with 20 normal sera.

Conclusion

The PTH values of Alinity i Intact PTH were significantly higher than those of the ELSA-PTH, and both assays showed a strong correlation. Additionally, the Alinity i Intact PTH assay demonstrated acceptable analytical performance.
A-048 Accurate Measurement of Free Testosterone in Serum using Equilibrium Dialysis Coupled with ID-UHPLC-MS/MS
Authors: Zhou H , Ribera A , Danilenko U , Vesper H
Published: September 2023

Background

Assessment of free testosterone (FT) has been recommended in recent clinical practice guidelines as a biomarker for diagnosis and management of testosterone related disorders such as male testosterone deficiency due to hypogonadism and female androgen excess due to polycystic ovary syndrome (PCOS). FT is currently measured using direct commercial immunoassays, assays using equilibrium dialysis (ED) or other separation techniques. Though the ED approach is recognized as the recommended approach, it is laborious and technically challenging for routine clinical use. The CDC Clinical Standardization Program is developing a high throughput automated method using the ED procedure coupled with isotope dilution ultra-high-performance liquid chromatography tandem mass spectrometry (ID-UHPLC-MS/MS) that is suitable for routine patient care and large-scale epidemiologic studies.

Methods

Serum samples are dialyzed in a custom-designed multi-well plate against a protein-free HEPES buffer (pH 7.4) at 37 °C until equilibrium. After isolating endogenous FT from protein-bound testosterone by ED, isotope-labeled internal standard (13C3-testosterone) was added to the dialysate for quantification. Certified pure primary reference material (National Measurement Institute-M914) was used to prepare calibrators, enabling traceability and ensuring measurement trueness. FT was further isolated from the dialysate matrix using supported liquid extraction and a chromatographic separation from interfering compounds and quantitation by tandem MS.

Results

The measurement ranges covered 0.2–1000 ng/dL for testosterone, with the bias within ±5% and precision less than 10% CV. A total of 45 samples with a wide range of total testosterone (TT, 21–912 ng/dL) and SHBG (11–129 nmol/L) were analyzed and showed the suitability of this assay to measure the serum free testosterone levels in normal, hypogonadal males as well as in the majority of normal females and females with androgen excess. The application of 48-well format plate and automated liquid handler system significantly improves the throughput of sample preparation. In addition, comparison of the TT results measured with the presented TT method with calculated TT concentrations, suggest that on average calculation overestimates TT concentration by 34%.

Conclusion

The described high throughput method for FT allows for sufficiently accurate and precise measurement for routine applications including large epidemiologic studies to help with establishing reference intervals.
A-057 Cerebrospinal Fluid Prolactin in Patients with Neurological Disorders
Authors: Hashim I A , Abraham E
Published: September 2023

Introduction

Prolactin a 23 kDa glycoprotein produced by the anterior pituitary among other cells with possible immunological properties. The presence and significance of prolactin in cerebrospinal fluid (CSF) is not widely known. This study examined prolactin levels in CSF from patients being investigated for neurological disorders.

Methods

CSF samples (leftover) from patients being investigated for neuropathy were obtained and stored at 4 °C or at −20 °C if not analyzed within one week of collection. Prolactin levels were measured using a high sensitivity prolactin ELISA (R and D Systems, Inc., MN, USA) according to manufacturer’s instructions. CSF samples reported total protein and glucose levels were obtained and correlated with measured prolactin levels. Statistical analysis were performed using NCSS statistical software.

Results

A total of 53 CSF (leftover samples) were analyzed for prolactin content. Prolactin was detectable and levels ranged from 2.68 ng/mL to 12.1 ng/mL (mean 4.49 ng/mL). Total protein ranged from 21 mg/dL to 219 mg/dL (mean 67.5 mg/dL). CSF glucose levels ranged from 16 mg/dL to 114 mg/dL (mean 63.9 mg/dL). Although there was poor (r = 0.66) but significant (P < 0.003) correlation between CSF prolactin and total protein levels, there was no correlation (r = −0.1) between CSF prolactin and CSF glucose levels (P = 0.6).

Conclusion

Prolactin levels was detected in CSF from patients being investigated for neurological dysfunction. There was correlation with total protein and glucose levels. The clinical significance of CSF prolactin is unknown and remains to be elucidated.
A-058 Frequency of Biochemical Assessment of Risk for Heart Failure among Diabetic Population
Authors: Joseph J , Neeley J , Hashim I A
Published: September 2023

Background

Diabetes remains a prevalent chronic health condition. Patients with diabetes have nearly twice the risk of developing heart failure as the general population and the American Diabetes Association recommends annual assessment by measuring N-terminal pro-B-type natriuretic peptide (NT-proBNP) or BNP among diabetic patients. We evaluated the frequency of biomarker assessment among our diabetic population.

Methods

Retrospective analysis of glycated hemoglobin (A1c) and NT-proBNP measured over a period of 21 months were performed. The frequency of NTproBNP assessment among patients with diagnostic A1c values were determined. Statical analysis were performed using Microsoft® Excel and NCSS® statistical software.

Results

A total of 74 973 A1c and 23 540 NT-proBNP measurements were performed during the study period. Among diabetics, 16% of patients received NT-proBNP testing with about 38% exhibiting elevated values.

Conclusion

This preliminary and retrospective study indicated that diabetic patients are receiving biochemical assessment for heart failure and that a significant number are of diagnostic value. It is not clear if other clinical modalities for heart failure assessment are in effect and if increased utility of biochemical assessment is required. Further studies are required to assess the utility among our patient’s population and on the best protocol to apply.
A-072 An All-Purpose Particle Enhanced Immunoturbidimetric Assay for the Comparable, Instrument-Independent Monitoring of Procalcitonin in the Management of Sepsis
Authors: Grimmler M
Published: September 2023

Introduction

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host immune response to infection. It is a global health concern and a leading cause of death worldwide, affecting an estimate of 48.9 million people every year. Procalcitonin (PCT) revealed to be an indispensable parameter for the management of sepsis. However, recent analysis of EQA survey results suggested crucial deviations of PCT measurements in Germany and studies by the IFCC Working Group on standardization of PCT stated the need for a higher-order reference measurement procedure.Here we present the evaluation of the all-purpose particle enhanced immunoturbidimetric assay (PETIA) of DiaSys, which can be easily applied to every high-throughput clinical chemistry analyzer. The high diversity of applications and datasets match current diagnostic and regulative needs (IVDR). Procalcitonin FS enables the equivalent and instrument-independent monitoring of PCT in the management of sepsis.

Methodology

Evaluation of Procalcitonin FS was performed on seven clinical chemistry analyzer platforms (Jeol BioMajesty® JCA-BM6010/C, DiaSys respons®920 and respons®940, Roche cobas c501, Abbott Architect c8000 and Alinity c, Beckman Olympus AU680). Measurements were performed according to Clinical and Laboratory Standards Institute (CLSI) protocols.

Results

The onboard stability reaches 8 weeks (with chimney) on BioMajesty® JCA-BM6010/C, 20 days on respons®920 and respons®940, 21 weeks on cobas c501, 9 weeks on Architect, 12 weeks on Olympus AU680 and 13 weeks on Alinity c. The calibration stability is 4 weeks (with chimney) on BioMajesty® JCA-BM6010/C, 2 weeks (with chimney) on respons®920 and respons®940, 21 weeks on cobas c501, 3 weeks on Architect, 5 weeks on Olympus AU680 and 10 weeks on Alinity c. The intra-assay precision (CV%) ranges from ≤4.57% on respons®920 up to ≤7.19% on respons®940. The Total Precision (CV%) ranges from ≤3.99% on cobas c501 up to ≤9.62% on Olympus AU680. LOB ranges from 0.07 ng/mL on BioMajesty® JCA-BM6010/C up to 0.130 ng/mL on Olympus AU680. LOQ ranges from 0.20 ng/mL on Architect up to 0.277 ng/mL on Olympus AU680. The reagent displayed a linear recovery up to 50 ng/mL and no prozone effect was detected up to 1000 ng/mL on all seven analyzers. The Passing & Bablok regression vs the reference test showed an excellent comparability/alignment between the methods (slope ≤1.11, intercept ≤0.156 ng/mL, R ≥ 0.986).

Conclusion

Evaluation work proves that DiaSys PETIA reagent Procalcitonin FS shows excellent performance on all seven clinical chemistry analyzers. In addition, the high comparability between the seven analyzers enables the reliable and instrument-independent monitoring of PCT in the management of sepsis, and thus offering a solution to the current landscape of deviating PCT measurement results.
A-085 Analytical Performance of BÜHLMANN sCAL® turbo, a New, Reliable and Precise High-Throughput Assay to Assess the Inflammatory Status of Patients
Authors: Melone A , Vogt D , Ohmann A , Moniz C , Eichmann M , Guschin D , Gerhold C , Schuster T
Published: September 2023

Background

Serum calprotectin plays an important pro-inflammatory role in the innate immune system and is a promising marker with several potential applications in rheumatoid arthritis, juvenile idiopathic arthritis and systemic onset juvenile idiopathic arthritis. Serum calprotectin can be a useful tool to monitor disease activity and predict treatment response in these patients.

Methods

The aim of this work was to evaluate the analytical performance of BÜHLMANN sCAL® turbo, a new turbidimetric test on clinical chemistry analyzers for the determination of calprotectin levels in serum. Assay characteristics were established according to CLSI guidelines (CLSI C28-A3, EP05-A3, EP07-A3, and EP09-A3). 111 samples were measured using 3 lots over 3 days and compared to another commercially available assay.

Results

The analytical measuring range from 0.23 to 15 µg/mL, extended to 225 µg/mL with an additional dilution in an automated rerun on a clinical chemistry analyzer, is suitable to address the described pathologies. 160 self-declared healthy adults (m/w) aged 18–83 years exhibit reference limits of 1.77 and 1.10 µg/mL when sampled either in a native tube or a gel separator tube and processed within 3.4 h after collection, respectively. With a within-laboratory precision up to 5.1% and a reproducibility up to 11.1% the method is precise, reliable and suitable for routine use. Tested concentrations of oral and injectable pharmaceuticals showed no interference. Hemolyzed samples are not recommended. It shows good comparison to an existing commercial assay with a bias of 12.5% (Bland-Altman) and a slope of 1.16 (Passing-Bablok).

Conclusion

A high-throughput test on clinical chemistry analyzers is now available with the turbidimetric BÜHLMANN sCAL® turbo allowing reliable and precise measurements of serum calprotectin levels.
A-088 Establish Laboratory Limit of Blank and Limit of Detection for LH Assay on the Ortho VITROS 3600 System
Authors: Su D , Wu H , Zhao Q
Published: September 2023

Background

In our lab, Luteinizing hormone (LH) was tested on VITROS 3600 system with manufacture’s declared limit of detection (LoD) 0.216 mIU/mL, limit of Blank (LoB) 0.0367 mIU/mL. It’s determined with NCCLS guideline EP17, false positives (α) less than 5% and false negatives (β) less than 1%, based on more than 700 determinations on several systems. Chinese government launched industry standard WS/T 514-2017, defining how a clinical laboratory establish its detection capability with stated proportions α = β = 5% and some other differences from EP17. Here we set up the LoB, LoD of VITROS 3600 LH assay in our lab based on Chinese industry standard.

Methods

a) LoB was designed to run 4 blank samples, LoD with 4 low positive samples, respectively with two VITROS LH kit lots, on one VITROS 3600, over two runs per day, for 3–4 days using two different calibrations, therefore we got 120 results (outliers omitted) for LoB and LoD respectively. b) Negative (blank) samples were matrix fetal bovine serum (FBS), low positive samples were in house produced, VITROS 3600 System was well maintained, fully calibrated and quality controlled. c) Data analysis: LoB and LoD sample data are not Gaussian, according to WS/T 514-2017, the LoB and LoD were computed with nonparametric statistics.

Results

Perform steps described in method for each lot reagents. LoB data distribution were non-Gaussian (as when truncated at zero). therefore the LoB can be determined by ranking the data in order from lowest to highest concentration and using the following equations, LOB = Pct100-α, here α is 0.05, P is 0.95, 60 determinations, each reagent lot arrangement position = 0.5 + 60*0.95 = 57.5, result was not an integer, LOB should be re-calculated = X57 + 0.5(X57-X58) = 0.5(X57 + X58). The final result for LoB is 0.0105.with proportions α = β = 5%, each reagent lot LoD determinations more than 50, thereof, K-S test is used for normality analysis. All results of both reagent lots have P-value less than 0.05, which means that the samples were not been generated from a normal distribution. According to WS/T 514-2017, the LoD is estimated with non-parametric statistical derivation method. All results are greater than LoB 0.0105, 0% results are lower than LoB which is less than stated probability 5%. The median value for lot 1990 is 0.0898, and lot 2010 0.0899, so LoD is 0.0899.

Conclusion

The limit of detection (LoD) for VITROS LH assay in our lab is 0.0899 mIU/mL, the limit of Blank (LoB) is 0.0105 mIU/mL, determined with WS/T 514-2017, and with proportions of false positives(α) = false negatives (β) = 5%. In our lab the detection capability is surpass to what manufacture claimed in the IFU. It could be as following factors: singleton platform in our lab, with greater stated proportions, less determinations, and consistently assigned operator. So we can conclude that this system is fit for a more sensitive detection scenario, like pediatric patients.
A-102 Development and Validation of Turbidimetric Retinol Binding Protein (RBP) Assay
Authors: Jaquemar M , Safdari A , Nilsen T , Knüttel T , Havelka A
Published: September 2023

Background

Retinol-binding protein (RBP) is a non-glycosylated protein synthesized by the liver. The role of RBP is to transport retinol (vitamin A) from the liver to the target tissues. RBP is also a sensitive marker of undernutrition. Serum/plasma RBP levels decrease with Vitamin A deficiency, hepatocellular insufficiency, and severe inflammation. Serum/plasma RBP levels increase with renal failure, type-2 diabetes, and steatosis.

Methods

The immunoassay was developed and validated on the turbidimetric instrument Cobas c501 from Roche Diagnostics. The antibodies against RBP in the assay react with RBP in the sample, and the turbidity formed by formation of antibody-antigen complexes is measured at 340 nm and 700 nm. The analytical sensitivity was tested in a study including 4 samples, analysed in 3 replicates over 3 days using a protocol based on the CLSI guideline EP17. The limit of quantification (LoQ) is defined as the lowest concentration of an analyte that can be reliably detected and at which the total error meets the requirements for accuracy. Interference with triglycerides, haemoglobin and bilirubin was tested using a protocol based on the CLSI guideline EP07. Precision of the assay was tested in a 22-day precision study using a protocol based on the CLSI guideline EP05. 3 controls were measured 2 times a day in 2 replicates each time.

Results

The assay has a calibration range from 7.5 to 120 mg/L. Samples with higher concentrations are automatically diluted and reanalysed. No antigen excess was observed up to 600 mg/L. Precision achieved a total CV of <4 % for samples with concentrations in the range 34–63 mg/L. Analytical sensitivity of RBP was measured as 7.81 mg/L with a total error (TE) of ≤20%. No clinically relevant interference towards triglycerides (13 g/L), haemoglobin (6.9 g/L) and bilirubin (0.3 g/L) was observed.

Conclusion

The Gentian RBP assay is a turbidimetric assay based on the formation of antibody-antigen complexes and can be used for assessment of undernutrition, vitamin A deficiency, hepatocellular insufficiency, severe inflammation, renal failure, type-2 diabetes, and steatosis. The assay can be installed on high-throughput platforms from different manufacturers and provides accurate, cost efficient and fast results.
A-106 Sigma Metric Performance of Chemistries on the Abbott Alinity c Analyzer
Authors: Laryea E T , Nichols J H
Published: September 2023

Background

The analytical performance of the Abbott Alinity c (Abbott Park, IL) was compared to our current Abbott Architect analyzers using sigma metrics.

Methods

Sigma metrics of 28 chemistry analytes on our six Abbott Alinity analyzers was compared to three Abbott Architect 16 000 analyzers and one Architect 8000 analyzer using Bio-Rad Multiqual quality control (QC) (Hercules, CA). Method imprecision was estimated for each assay using the cumulative coefficient of variation (CV) of 12 months data for each analyzer at three QC concentrations and calculating the average sigma. Method bias was estimated by comparing each analyzer QC mean to peer group QC means. Sigma values were calculated for each method as (TEa—Bias%)/CV% using allowable total error (TEa) from three sources: the CLIA proficiency testing evaluation limits, Australasian Association of Clinical Biochemistry allowable limits of performance (RCPA quality assurance programs Pty limited, Adelaide, Australia) and desirable biological variation (Ricos C et al, Scand J Clin Lab Invest. 1999, 59(7):491–500). Average sigma values were generated for each analyte and graded as optimal >6 sigma; good 5–6 sigma; marginal 3–5 sigma; or poor <3 sigma.

Results

Assay sigmas varied across QC concentrations and between analyzers of the same platform. Na, Cl, and CO2 had the lowest sigma performance. Since the sigma calculations are dependent on TEa, tighter TEa limits (Ricos and RCPA) generated lower sigmas compared to the wider CLIA TEa limits especially for Ca, Cl, total bilirubin, CO2, Na, total protein, and HDL.

Conclusion

None of the chemistries met optimal six sigma performance for all analytes, concentrations of QC and sources of TEa. However, the assay performance between analyzer platforms was comparable.
A-110 Analytical Performance Evaluation of Diazo Bilirubin Assays on the Atellica CH Analyzer
Authors: Robinson C , Sinopoli A , Blagovcanin D , Rhea McManus J , Cheek J
Published: September 2023

Background

Measurements of bilirubin are used to evaluate liver function. The two most common methods to measure bilirubin are the diazo method (based on measuring the color of azobilirubin) and the vanadate method (based on chemical oxidation). Advantages and disadvantages of each method are well-documented in the literature. This study was designed to evaluate the analytical performance of two new diazo-based methods: the Atellica® CH Total Bilirubin (D_TBil)* assay and the Atellica CH Direct Bilirubin (D_DBil)* assay on the Atellica CH Analyzer.

Methods

Precision and method comparison (MC) were used as performance indicators for the diazo-based assays. Precision studies were performed according to CLSI EP05-A3. Human serum samples were spiked with either conjugated or unconjugated bilirubin. One aliquot of each sample pool was tested in duplicate in two runs per day >2 h apart for >20 days. MC studies were performed according to CLSI EP09-A3. For total bilirubin comparisons, human serum samples (n = 100) were analyzed using the Atellica CH D_TBil assay and the commercial Dimension® Total Bilirubin (TBI) assay. Direct bilirubin comparisons were performed by analyzing human serum samples (n = 100) using the Atellica CH D_DBil assay and the commercial ADVIA® Chemistry Direct Bilirubin_2 (DBil_2) assay.

Results

Representative precision and MC results for each assay across the indicated sample ranges are listed in the table. Over the two assays tested, repeatability and within-lab %CVs were <2.0% and <3.5%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusion

Evaluation of the Atellica CH D_TBil and D_DBil assays demonstrated good precision and equivalent performance compared to commercially available assays.
A-114 Mas™ Omni·Core™ Controls, Ready-to-use Tube Format
Authors: Adams N , Sunderraj M , Krishnaswami N , Crandall D , Zhang Y , Hu R
Published: September 2023

Background

The Thermo Fisher Scientific™ MAS™ Controls* are assayed controls to monitor assay performance within clinical laboratory settings. The user can compare observed results of controls with their expected ranges as a means of assuring consistent performance of both reagent and instrument.

The objective of developing MAS™ Ready-to-Use Tube Controls is to provide MAS™ controls in a new automation-friendly plastic tube format, as an alternative to the current glass vials. The MAS™ controls contained in the plastic tubes are intended to be used by core labs to be placed directly onto the analyzers, eliminating the need to aliquot into sample cups or other primary tubes.

In this presentation we summarize the results of MAS™ Omni·CORE™ in the new Ready-to-Use Tube Controls configuration.

Methods

The purpose of these studies is to verify material compatibility and acceptable product performance of MAS™ Omni·CORE™ in the new Ready-to-Use Tube Controls configuration.

The controls were also assessed for Fit/Form/Function on various platforms from manufacturers such as Siemens, Roche, Abbott, Ortho Clinical Diagnostics, Thermo Fisher Scientific, and Beckman.

Results

The MAS™ Omni·CORE™ Ready-to-Use Control results demonstrated comparable performance and Fit/Form/Function criterion of the specified platforms.

Torque/Leak, Cap Characterization, and Plastic Interaction studies yielded passing results per protocol criterion. The In-Use (CO2) study demonstrated acceptable “time-on-platform” performance of 9 h in 2–8°C (4 h at 25°C). The Extractables/Leachables study demonstrated passing results for all claimed analytes, with minor exceptions. All light sensitive analytes yielded passing results during the Light Transmission study.

Conclusion

To conclude, the MAS™ Omni·CORE™ Ready-to-Use Controls will contribute to the increased efficiency of core lab workflow by allowing the analyzer(s) to aspirate controls directly from the tube and allow for control storage in an on-board refrigeration unit after use.

*Availability of product in each country depends on local regulatory marketing authorization status.
A-116 Evaluation of Lp(a) Ultra assay for the Immunoturbidimetric Quantitative Determination of Lipoprotein (a) in Human Serum and Plasma With Siemens Healthineers Atellica CH 930 Analyzer
Authors: Cugini A , De Angelis L , Lucini R , Brambilla S
Published: September 2023

Objective

The aim of this study is to evaluate the analytical performances of the Lp(a) Ultra assay for the immunoturbidimetric quantitative determination of lipoprotein (a) in human serum and plasma on Siemens Healthineers Atellica CH 930 Analyzer.

Background

Lipoprotein (a) has been found in artery walls and can have atherogenic effects. Because of its structural similarity to plasminogen, it can also inhibit fibrinolysis and hence acts thrombogenically. High Lp(a) concentrations in serum correlate with premature manifestation of atherosclerosis and strokes. In combination with elevated LDL Cholesterol concentrations, the coronary risk increases approximately six-fold.

Methods

Lp(a) Ultra is a latex immunoassay manufactured by Sentinel Diagnostics and developed to measure Lp(a) levels. If the antigen-antibody reaction takes place between Lp(a) in the sample and the anti-Lp(a) antibodies, which have been adsorbed to latex particles, agglutination occurs. This agglutination is detected as an absorbance change, with the magnitude of the change being proportional to the quantity of Lp(a) contained in the sample.

Results

The Limit of Blank LOB (4 samples × 5 replicates × 3 runs) was ≤2.0 mg/dL. The Limit of Detection LOD (4 samples × 5 replicates × 3 runs) was ≤ 3.0 mg/dL. The Limit of Quantitation LOQ (8 dilution levels × 10 replicates × 3 runs) was ≤5.0 mg/dL at %CV lower than 20%. The Intra Assay (5 samples × 20 replicates × 3 runs) gave the following %CVs: 2.4% at 12.1 mg/dL, 0.8% at 30.3 mg/dL, 0.6% at 47.8 mg/dL, 0.5% at 58.8 mg/dL, 1.7% at 87.1 mg/dL. Total precision study (5 samples × 2 runs × 2 replicates × 20 runs) gave the following %CVs: 4.0% at 11.5 mg/dL, 3.6% at 21.7 mg/dL, 3.0% at 32.0 mg/dL, 2.8% at 42.2 mg/dL, 2.3% at 50.7 mg/dL. The test was linear up to 130 mg/dL. Calibration stability was up to 30 days. Reagent on board stability was up to 30 days. This application (y) was compared with the same test applied on Beckman Coulter AU680 Analyzer (x) and gave the following results: using Passing Bablok analysis: y = 0.8 + 1.0x; correlation coefficient (r) = 0.997; using Deming analysis: y = 1.0 + 1.0x; correlation coefficient (r) = 0.997; number of samples = 120. There is not Hook effect/antigen excess up to 600 mg/dL.

Conclusions

Analytical performances of Lp(a) Ultra assay on Siemens Healthineers Atellica CH 930 Analyzer meet the requirements for its use as immunoturbidimetric quantitative determination of lipoprotein (a) in human serum and plasma and make this assay very suitable for the routine measurement of this analyte.
A-118 Evaluation of Mindray Cystatin C Assay
Authors: Bao Y , Hu J , Jiang M , Wang J , Dai J
Published: September 2023

Background

Cystatin C is a low molecular weight non-glycosylated alkaline protein, with a molecular weight of 13kDa. It is formed by all nucleated cells in human at a constant rate. The only pathway of Cystatin C in vivo is excretion through glomerular filtration and absorbed by proximal renal tubular epithelial cells, which was decomposed finally. Therefore, the concentration of Cystatin C in serum is almost not affected by external factors, such as weight, age, gender, etc. Compared with creatinine and urea, it is an ideal endogenous marker for monitoring glomerular filtration function. Currently, the most methods on the market for testing Cystatin C are either latex enhanced immunoturbidimetric method, or immunoturbidimetric method. These methods usually use polyclonal antibodies from different animal species, which are sometime susceptible to the interference from rheumatoid factors reported in the literature, resulting in false positive results. The anti-RF interference ability of this reagent was enhanced by selecting the optimal antibody and optimizing reagent formulation. This study evaluated performances of the Cystatin C assay on Mindray BS-2000M system.

Method

Mindray Cystatin C assay is based on latex immunno-agglutination. Latex nanoparticles were coated with anti-Cystatin C antibody. Reagent of this assay contains R1 buffer and R2 with latex particles coupled with anti-Cystatin C antibodies. The assay starts with R1 and sample incubation for 5 min and then R2 is added. After another 5 min of incubation, agglutination occurs, leading to turbidity increasing. The turbidity is measured at 570 nm. Multi-level (5-point) calibration is used. Cystatin C concentrations are obtained from the calibration curve with signals from the assay with patient samples. Following basic assay performances were evaluated: precision, limit of detection, linearity, method comparison, interference and high dose hook.

Results

The precision study followed EP05-03 protocol. The repeatability and within-lab CVs on the BS-2000M system with 2 QC and 3 patient samples were ranged from 0.9% to 5.3%, respectively. Limit of detection was 0.1 mg/L and linearity was given up to 8.63 mg/L. The assay (y) shows good accuracy when compared with Roche Cystatin C (x) assay on the cobas 701: y = 1.0055x - 0.0268 (r2 = 0.9994, n = 109). The assay showed no significant with bilirubin up to 40 mg/dL, with hemoglobin up to 500 mg/dL, with lipids up to 500 mg/dL, and with rheumatoid factors up to 1200 IU/mL that is about 0.3% out of a total of 55 184 samples collected from our customers in China with RF measurements. No prozone was observed with the assay up to the high cystatin C concentration of 800 mg/L tested.

Conclusion

From this evaluation, we confirmed that Mindray Cystatin C assay can measure serum Cystatin C precisely and accurately, and with good performance against rheumatoid factors interference. It is suitable for use in routine clinical laboratories.
A-122 Fluid Type (STILL) Matters: An Analysis of Quality Control Material Suitability for Measuring Eleven Body Fluid Analytes in the Clinical Laboratory
Authors: Fyffe-Freil R C , Baumann N A , Block D R
Published: September 2023

Background

Measuring the concentration of albumin, amylase, bilirubin, cholesterol, creatinine, glucose, lactate dehydrogenase (LDH), lipase, total protein(TP), triglycerides, and urea nitrogen(UN) in body fluids(BFs) provides important information to aid in clinical decision-making. The range of expected values of these analytes in BFs may not match serum, and the distribution by fluid type is not well described. Quality control (QC) materials are designed to reflect clinically relevant concentrations in blood. Hence, the measuring ranges for assays modified for BF testing vary in suitability. Laboratorians and manufacturers would benefit from understanding the overlap in BF and serum analyte concentrations. The aim of this study was to characterize the range of BF analyte concentrations compared to serum and assess the suitability of QC materials used on these assays.

Methods

A retrospective analysis was performed for the following analytes in BFs with reportable ranges(including maximum dilution factor): albumin = 0.2–12.0 g/dL(×2), amylase = 3–14 000 U/L(×100), bilirubin = 0.1–72.2 mg/dL(×2), cholesterol = 4–8000 mg/dL(×10), creatinine = 0.1–92.0 mg/dL(×4), glucose = 2–3375 mg/dL(×5), LDH = 10–9000 U/L(×10), lipase = 3–300 000 U/L(×1000), TP = 0.2–36.0 g/dL(×3), triglycerides = 4–8850 mg/dL(×10), and UN = 2–300 mg/dL(×3). Chemistry tests were run on a cobas® 6000 c501 (Roche Diagnostics,Indiana). Patient analyte concentration and fluid type results reported between 9/16/2019 and 1/27/2022 at all Mayo Clinic locations were extracted from an institutional database of electronic medical record data. Serum results were included for comparison. Descriptive statistical analyses (median and range) were performed with R (version 4.2.2)/R Studio(version 2022.12.0). QC materials for BF testing were purchased from Bio-Rad (Multilevel Qual, Levels 1 and 3; Hercules, CA, USA). Target concentrations are reported.

Results

Conclusion

BF median (range) concentrations are similar or higher for bilirubin, creatinine, glucose, lipase, and UN. Serum QC material is likely appropriate for these assays in BFs. BF median(range) concentrations are lower for albumin, cholesterol, TP, and triglycerides suggesting that serum QC material may not be well suited for BFs. The need for extended dilutions may impact BF amylase and lipase.