bluuebunny/crossref_metadata_2025_split huggingface dataset:
A-009 Analytical Characterization of a Novel NT-proBNP Assay on a Central Laboratory Platform
Authors: Christenson R H , Alahapperuma D , Allen B R , Guidi J L , Headden G , Peacock W F , Winden N , Januzzi J L 
Published: October 2024

Abstract

Background
N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) or B-type Natriuretic Peptide (BNP) assay(s) are widely measured with a Class 1, Level of Evidence A recommendation in professional heart failure (HF) guidelines for diagnosis and prognosis. We present the analytical characteristics of the first NT-proBNP assay on Beckman Coulter platforms.

Methods
Measurements were conducted with the Access NT-proBNP assay, a one-step sandwich immunoenzymatic assay using monoclonal capture and detection antibodies, on the DxI 9000 Immunoassay Analyzer with Lithium Heparin (LiHep) plasma samples. Performance was characterized according to CLSI guidelines for: Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ), linearity, imprecision (repeatability, reproducibility) and matrix comparison with LiHep, EDTA and serum. Reference intervals (RI) were evaluated in a healthy, adult U.S. population comprised of 675 subjects with 54.6% females, 79.1% White and 15.1% Black individuals. Exclusion criteria included elevated cardiac troponin, abnormal eGFR and cardiac medications. The 97.5th percentile RI upper limit was defined for age-stratified ranges of &lt;50, 50-75, and &gt;75 years old.

Results
Performance was LoB=1.1ng/L; LoD=4.8ng/L; LoQ=4.8ng/L; linearity=35,000ng/L. Repeatability ranged from 1.5%-3.5% and reproducibility from 2.3%-7.9% in seven samples ranging from 38ng/L to 23,848ng/L. Matrix measurement regression (n=68) yielded slopes of 1.00, 1.01; intercepts -0.03 to -2.63; r=0.98. Table 1 shows that NT-proBNP values increase with age and women generally have higher values than men.

Conclusions
The LoB, LoD and LoQ demonstrate highly sensitive low-end characteristics. Repeatability and reproducibility show excellent performance across a wide measurement range. NT-proBNP values are known to be age dependent, and the age-stratified 97.5th percentile RI upper limits were 162 ng/L for &lt;50 years, 311 ng/L for 50-70 years, and 457 ng/L for &gt;75 years. This novel Access NT-proBNP assay offers robust analytical performance as an aid to clinical HF management in acute settings.
A-014 Fifth Generation Troponin T is Unaffected by Extreme Levels of Lipemia and Icterus
Authors: Zakrajsek J A , Zakrajsek J T , Benefit S , McShane A J 
Published: October 2024

Abstract

Background
The tissue specific cardiac isoform of troponin (cTnT) originates exclusively from the myocardium; therefore, it is used as the primary diagnostic biomarker for myocardial infarction. Lipemia, caused by elevated lipoprotein particles, and icterus, caused by elevated bilirubin, are common endogenous interferences that can lead to erroneous results. According to the instructions for use (IFU), recovery is acceptable when bilirubin levels are ≤25 mg/dL (conjugation not specified) and intralipid levels are ≤1500 mg/dL. However, it is common in large hospital settings to observe higher levels for these potential interferents. The purpose of this study was to determine whether 5th generation cTnT results are negatively impacted by extreme levels of lipemia or conjugated or unconjugated bilirubin.

Methods
cTnT interference studies were performed on a cobas e602 (Roche Diagnostics). Low, mid, and high cTnT sample pools at approximate concentrations of 20 ng/L, 100 ng/L, and 1000 ng/L were split into target and control pools. To evaluate the effect of lipemia, target pools were spiked with intralipid solution to achieve a lipemia index (LI) ranging from 1500-2000 (correlates poorly with mg/dL triglycerides). Samples were analyzed in triplicate for cTnT and serum indices. To evaluate the effect of icterus, target pools were spiked with conjugated or unconjugated bilirubin to achieve an icterus index (II) ranging from 30-55 (approximately equal to mg/dL bilirubin). Samples were analyzed in triplicate for cTnT, conjugated and unconjugated bilirubin, and serum indices. Interference was determined by calculating the variance between the average target and corresponding control result.

Results

Conclusions
cTnT has a high lipemia and icterus tolerance with recoveries &lt;10% for all three cTnT concentrations.
A-029 Evaluation of the Analytical Performance of Four Assays Used for Diabetes on the Atellica CI Analyzer
Authors: Frenna J , Maher K , Warnock J , Riverso N , Tyler C , Arrode-Bruses G , Leipold H , Snyder J 
Published: October 2024

Abstract

Background
The Atellica® CI Analyzer is an automated, high-throughput integrated chemistry and immunoassay analyzer utilizing both Atellica® CH and Atellica® IM Assays. This study evaluated the analytical performance of the Atellica IM C-peptide (CpS) and Insulin (IRI) Assays, and the Atellica CH Enzymatic Hemoglobin A1c (A1c_E) and Fructosamine (Fruc) Assays on the Atellica CI Analyzer.

Methods
Precision studies were performed according to CLSI EP05-A3 using native and contrived human serum samples, except for the A1c_E assay using native and contrived human whole blood samples. One aliquot of each sample pool was tested in duplicate in two runs per day ≥2 hours apart on each analyzer for ≥20 days. Precision was evaluated using reagent lot and system combination varying between one to three reagent lots and one to three systems depending on the assay tested. Method comparison (MC) studies were performed using three reagent lots according to CLSI EP09c. Individual native and contrived human serum or whole blood (A1c_E) samples were analyzed using the Atellica IM Cps, IRI Assays on the Atellica IM Analyzer, the Atellica CH A1c_E, Fruc Assays on the Atellica CH Analyzer and the four Atellica IM and CH Assays presented on the Atellica CI Analyzer.

Results
Representative precision and MC results for each assay are listed in the table. For the four assays tested, repeatability and within-lab %CVs were &lt;2.8% and &lt;3.2%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusions
Evaluation of the Atellica IM Cps, IRI and Atellica CH A1c_E, Fruc Assays using the Atellica CI Analyzer demonstrated good precision and equivalent performance compared to the same assays on their respective Atellica CH and Atellica IM Analyzers.
A-034 Evaluation of the Analytical Performance of Five Chemistry Assays on the Atellica CI Analyzer
Authors: Lewisch S , Camacho J , Wilkins G , Gupta P , Shalhoub V , Snyder J 
Published: October 2024

Abstract

Background
The Atellica® CI 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® CH Alpha-1-antitrypsin (AAT), Ammonia (AMM), Amylase_2 (AMY_2), Cholinesterase_2 (CHE_2), Lipase (Lip) Assays on the Atellica CI Analyzer.

Methods
The Atellica CI assays use the same reagents and calibrators as the Atellica CH assays. Precision studies were performed according to CLSI EP05-A3 using human urine (AMY_2), serum (AAT, AMY_2, CHE_2, Lip), and plasma (AMM) samples. One aliquot of each sample pool was tested in duplicate in two runs per day for 20 days. MC studies were performed according to CLSI EP09-A3. Samples were analyzed using the Atellica CH and Atellica CI Analyzers.

Results
Across the five assays, repeatability CVs were &lt;5.7% and within-laboratory CVs were &lt;8.2%. Representative precision, and MC results observed for each assay across indicated sample ranges are presented in the table. Slopes determined using the Deming linear regression model were approximately equal to 1.

Conclusions
Atellica CH AAT, AMM, AMY_2, CHE_2, and Lip Assays on the Atellica CI Analyzer demonstrated good precision and equivalent performance to the same assays on the Atellica CH Analyzer.
A-046 Quantification of Corticosteroids and Androgens in Serum, utilizing Waters MassTrak™ Steroid Serum Sets 2 & Sets 3 for Clinical Research
Authors: Moran L , Tobin N , Foley D , Breen N , Davey L 
Published: October 2024

Abstract

Background
Steroid hormones encompass a large class of small molecules that play a central role in metabolic processes, such as the regulation of sexual characteristics, blood pressure, and inflammation. Enzymes that form part of the steroid biosynthetic pathway are pivotal in these metabolic processes, and their dysfunction can be examined through the correct measurement of steroid hormones in a clinical research setting. The availability of lyophilized calibrators and QCs reduces sample preparation time, aids in method harmonization, and assists with metrological traceability in accordance with ISO15189:2022, when used alongside an analytically selective chromatographic method.

Methods
A quantitative clinical research method utilizing Waters MassTrak Steroid Serum Sets 2 and 3, Cals & QCs and Waters Oasis™ PRiME HLB µElution plate technology for the extraction of testosterone, androstenedione, 17-hydroxyprogesterone (17- OHP), dehydroepiandrosterone sulfate (DHEAS), Cortisol, 11-deoxycortisol and 21-deoxycortisol from human serum samples. Chromatographic separation was performed on an Waters ACQUITY™ UPLC™ I Class Plus (FL-I) System, using an ACQUITY UPLC HSS T3 Column, accompanied by a Xevo™ TQ-S micro Mass Spectrometer.

Results
Accuracy (±6%) and precision (±10%) have been confirmed through comparison to External Quality Assurance (EQA) LC-MS/MS schemes, panels and QC material for all seven steroid hormones. All analytes were assessed at the low, medium and high concentrations for each MassTrak Steroid Serum Set, which yielded excellent results across the range (±10%). Deming and Linear regression analysis were performed. No statistically significant bias was observed for each compound, with a mean method bias of ±1.3% for Set 2 and ±1.0% for Set 3. The clinical research method was shown to be linear for all analytes over the calibration ranges specified, furthermore, calibration lines created using Set 2 and Set 3 were analysed over a five-day period and were linear with a co-efficient of determination of (r2) &gt; 0.999 for all analytes. Analytical sensitivity using Signal:Noise (S/N) of the low calibrator (Calibrator 1) of each set, was &gt;10:1 for each analyte across several analytical runs.

Conclusions
This evaluation has demonstrated that the MassTrak Steroid Serum Calibrator and Quality Control Sets 2 and 3 can provide precise and accurate quantification of steroid hormones in serum. An analytically sensitive and selective clinical research method has been developed for the analysis of testosterone, androstenedione, 17- OHP, DHEAS, cortisol, 11-deoxycortisol and 21-deoxycortisol in serum using Waters I-Class Xevo TQ-S micro system. For Research Use Only. Not for Use in Diagnostic Procedures.
A-140 Reducing cell count bias with the GloCyte® Automated Cell Counter for CSF: an observational study at Loyola University Medical Center
Authors: Maggiore J , Flasher J , Majkut N , Webb D , MacKenzie J 
Published: October 2024

Abstract

Background
Accurate STAT cerebrospinal fluid (CSF) cell counts are critical in supporting diagnoses of meningitis, malignancy, demyelinating disease, and hemorrhage. Limitations of automated analyzers to achieve acceptable linearity for the clinically relevant range has maintained manual CSF cell counting as the preferred method. Manual cell counting, performed with a hemocytometer and bright field microscope, is time-consuming, requires specialized skills and depends on human interpretation. This subjectivity inherently introduces the potential for non-random error in the enumeration of both total nucleated cells (TNC) and red blood cells in CSF by manual methods. The purpose of this study was to evaluate and compare the level of bias inherent in manual determination (TNC) in CSF as compared to the GloCyte Automated Cell Counter.

Methods
Result bias data for CSF specimens processed in the hematology lab at Loyola University Medical Center, a quaternary care 547-bed academic medical center in Maywood, IL, was analyzed for manual cell counting using a Neubauer-improved hemocytometer and GloCyte, an FDA-cleared cell counting device employing fluorescence technology to automate RBC and TNC counts in under 5 minutes, with linearity down to 0 cells/µL. Result bias was determined by defining the “expected result” for both GloCyte and hemocytometer as the initial cell count determined at a 1:5 dilution of a freshly-collected CSF sample and calculating the expected cell count for subsequent serial dilutions of 1:10, 1:20, 1:50, 1:100 for each method. The actual TNC count and the disparity of the actual result from the expected result was recorded as bias.

Results
Data are summarized below in the Table, and indicate a lower bias for GloCyte compared to manual counts across the range of dilutions.

Conclusions
This study demonstrates that GloCyte can be implemented as a means of effectively mitigating the reporting bias of CSF TNC counts performed with a Neubauer-improved hemocytometer.
A-196 Using Aggregated Proficiency Testing Results to Identify Systematic Error
Authors: Astles J R , Kirbiyik U 
Published: October 2024

Abstract

Background
Proficiency testing (PT) should identify systematic errors, which are likely to recur. The Clinical Laboratory Improvement Amendments of 1988 (CLIA) acceptance limits (ALs) include 3SD and concentration limits. We investigated the ability of PT to detect systematic error, especially as affected by the AL type.

Methods
Ungradable, duplicate, and irregular scores were removed from 2008 to 2018 CLIA laboratory PT results. For analytes that had at least 200 events and at least 200 participating laboratories, we calculated the overall sample miss rate, the unsatisfactory event rate, i.e., less than 80, and event rates for Score 100 to 0. We used paired t-tests and the Wilcoxon Signed-Rank test to compare miss rates and unsatisfactory event rates between short- and long-term participants. We used the binomial distribution to model the expected event scores under the assumption that all errors may be independent (random); see Figure. For each analyte and each of the possible PT scores, we compared observed event scores with their expected values as a ratio.

Results
40,596 laboratories produced 15,140,128 event scores for 75 analytes. The distribution of event scores was over-weighted with higher-order event errors (Score 0 - Score 60) compared to the predicted distribution. Miss rates and unsatisfactory rates were significantly higher for short-term laboratories. Plotting the log ratio of observed versus expected rates for event scores showed that the degree of systematic effect increased progressively for each analyte. The magnitude of the effect was less for 3SD ALs.

Conclusions
In an event, PT errors are often dependent. Concentration and 3SD ALs were similarly sensitive to detect systematic error; both were more sensitive than ALs for qualitative or dilution assays. Expressing systematic error using PT data could help to identify remediable analytical issues.
A-204 Commitment to Sustainability From Laboratory Medicine
Authors: Yeoh A C , Saw M Y , Ngabedan R , Jamaluddin F A , Chew Y Y 
Published: October 2024

Abstract

Background
According to McGill University, sustainability means “meeting our needs without compromising the ability of future generations to meet their own needs”. Sustainable environmental practices improve water and air quality, reduce landfills, and increase renewable energy sources in the long term. In response to the growing urgency of global sustainability challenges, the healthcare industry is taking a step forward to reduce its environmental impact. University of Malaya Medical Centre (UMMC) is a government-funded teaching hospital and medical institution, which processes about 3.95 million chemistry and 371,000 immunoassay tests per year. This study aims to evaluate the sustainability aspects of Atellica Solution, focusing on water usage, power consumption, carbon dioxide emissions and plastic waste generations.

Methods
Power and water consumption for the analysers Advia Chemistry 2400 & XPT and Advia Centaur XPT were obtained from Atellica Solution using the year 2022 test volumes and compared with those of Siemens legacy system for the year 2019 test volumes. In addition, the reduction of plastic usage was also assessed for the year 2019 and 2022.

Results
With innovative Atellica Solution replacing Siemens legacy system, the data showed reduction in water and energy consumption by 36.44% and 47.74% respectively, whereas the annual throughput increased by 13.7%. By using Atellica INTELIQ QC management, fewer aliquot tubes were used and thus plastic waste was reduced by 168 kg. These reductions combined to lower CO2 emissions by about 16 tons.

Conclusions
Atellica Solution is designed for high throughput and sustainability, reducing water and energy consumption while also significantly reducing CO2 emissions. Furthermore, it enables faster, streamlined quality control management with Atellica INTELIQ QC management system. UMMC is strongly committed to minimizing laboratories’ environmental footprint and provide better access to care eventually contributing to the well-being of patients.
A-264 Validation of a Novel Real-Time PCR Assay for Identification of Mycobacterium species Isolates Recovered from Clinical Culture
Authors: Harris A B , Jadi R , Urban T J , Le T , Song K , Brochu H N , Iyer L K , Dale S E , Capraro G A , Boles D J 
Published: October 2024

Abstract

Background
Historically, clinical mycobacteriology laboratories used the nucleic acid hybridization-based AccuProbe assay manufactured by Hologic, Inc., to rapidly rule in or rule out Mycobacterium tuberculosis (MTB) and members of the M. avium-intracellulare complex (MAC). The clinical value of this test was in its ability to rapidly rule in/out MTB from positive broth cultures and allow the initiation of appropriate antimicrobial therapy and infection prevention practices. Recent discontinuation of this commercial assay left a gap in testing available for the rapid identification of these organisms, which allowed us to develop an in-house real-time PCR test.

Methods
A replacement assay was developed by Labcorp R & D based on real-time PCR amplification of extracted nucleic acids from positive culture growth. Aliquots from positive AFB VersaTREK broth cultures were heat inactivated, and nucleic acids were extracted using the MagNA Pure 24 (MP24) instrument (Roche). Real-time PCR using published primer probe sets (Rocchetti, et al 2016) was performed on the QuantStudio™ 7 (QS7) instrument (Applied Biosystems®). The assay was designed with three independent primer/probe sequence targets: one for MTB Complex (IS6110), one for MAC (ITS), and one pan-target for the Mycobacterium genus (16s rRNA).

Results
Procedural verification was performed using 100 residual clinical specimens previously identified using the Hologic AccuProbe® assay. Categorical concordance was 97% (97/100). The three discrepant results were identified as MAC positive by PCR; however, these were not identified as MAC on the predicate assay. Analytical sensitivity for the PCR assay was established to be 1,000 CFU/mL for each target. Analytical specificity was assessed in vitro for nine Mycobacterium species, with no cross-reactivity observed. In vitro analysis of target detection in the presence of yeast (Candida glabrata) was also performed, and we saw no inhibition. Analysis of the primer/probe sets for all targets was performed in silico using XploreDB database of microbial genomes, with confirmed 100% matches for both MAC and MTB genomes compared to hundreds of species. By comparison, the PAN-Myco primer set showed decreased performance, having three mismatches (two on forward primer and one on the probe). As this target sequence is used as an Internal Control (IC) this was not problematic for overall assay performance. The assay demonstrated excellent precision (%CV) for each target: MTB = 0.74%, MAC = 1.10%, PAN-Myco = 3.19%.

Conclusions
Utilizing the depth of molecular methodologies available in our laboratories, we developed a rapid method for identification of MAC and MTB from positive broth cultures, which had excellent performance compared to the predicate assay. The PCR ID LDT test is now available and allows testing to continue with no interruption in patient care.
A-346 Evaluating 14-3-3η Detection in Finger Prick Blood Using Lateral Flow Technology: Advancing Clinical Laboratory Diagnostics
Authors: Sidhu N , Stojanovic V , Marotta A 
Published: October 2024

Abstract

Background
The protein 14-3-3η is a critical biomarker in the diagnosis and monitoring of autoimmune rheumatologic disorders, and its early detection is pivotal for patient outcomes. Previous research has established the significance of 14-3-3η as a biomarker, particularly in inflammatory polyarthritis, as well as patients’ and physicians’ interest in near-patient testing. While 14-3-3η is traditionally measured in serum via ELISA, this study explores the innovative use of lateral flow technology (LFT) for its detection in finger prick blood, addressing the urgent need for near-patient testing.This research aims to evaluate the technical and clinical performance of 14-3-3η measurement using LFT in comparison to standard ELISA methods, with an emphasis on its detectability in finger prick blood.

Methods
This study included two phases of testing involving patient serum and spiked whole blood. In the serum phase, 53 samples (19 NEG, ≤0.19 ng/mL, and 34 POS, 0.27 to 28 ng/mL 14-3-3η) were tested using LFT. LFT results were compared to JOINTstat® ELISA measurements for concordance. For whole blood, recombinant 14-3-3η and ELISA-positive serum samples were spiked into whole blood at increasing concentrations (0.4 to 3.2 ng/mL) and tested with LFT. Concordance criteria included visual inspection of test and control lines, with results captured and analyzed using a reference key card. The study was extended to assess 14-3-3η levels in consented patients with 22 matched finger prick and venous serum samples​​.

Results
In serum testing, LFT demonstrated 100% positivity in detecting 14-3-3η for POS samples. Among NEG samples, 85% tested negative, with 15% positive, indicating a strong concordance between LFT and ELISA. The LFT's ability to semi-quantitatively measure 14-3-3η was confirmed by a significant Kruskal-Wallis test (p&lt;0.0001) across four intensity groups. In whole blood testing, LFT correctly identified all samples spiked at concentrations ≥0.5 ng/mL. The Spearman correlation showed a strong and significant association (r=0.96 to 0.98, p=0.001) between LFT test line intensity and spiked 14-3-3η levels. Finally, the equivalence testing for finger prick and venous serum samples affirmed the LFT’s reliability, with a strong correlation (p&lt;0.0001), underscoring its potential for near-patient testing​​.

Conclusions
The study validates LFT as a reliable and semi-quantitative method for detecting 14-3-3η in finger prick blood, demonstrating strong concordance with traditional ELISA measurements. The findings support the feasibility of LFT in near-patient testing for early detection, prognosis, and monitoring of autoimmune diseases, paving the way for enhanced patient accessibility. Future research will focus on integrating this technology into routine clinical care and examining its impact on patient management and outcomes.