bluuebunny/crossref_metadata_2025 huggingface dataset:
B-033 Real World Assessment of the Impact of Infectious Disease Assays on Workflow Capabilities of Siemens Atellica IM Analyzers
Authors: Abou-Diwan C , Hempton R , Clouet J , Diabate D , Aguanno J
Published: October 2024

Background

Instrument immunoassay throughputs publicized in the industry are often theoretical, performed in relatively smaller scale, and/or in the best case generated only with fast assays, not representing the typical assay mix of routine activity. Infectious disease (ID) serology assays typically have long analytical times and have the potential to influence throughput capabilities and turnaround time (TAT) of other assays with shorter analytical times. The objective of this study is to utilize real world evidence across a large fleet of Atellica® IM 1300 and IM 1600 analyzers representing variously sized laboratories, using variations of ID assay mixes, to assess the impact on TAT on select STAT immunoassays.

Methods

Assay mix, test volumes and TAT data was mined from the Atellica® Smart Remote Services (SRS), a Siemens Healthineers proprietary remote connectivity platform over 3 distinct 14-day time windows. Real world data from >1800 Atellica IM and >8 million tests were queried per time window for the following ID assays: HIV, Hepatitis B, Hepatitis C, TORCH, Syphilis (long analytical time) and a selection of non-ID immunoassays: hs-troponin I (TNIH), Thyroid Stimulating Hormone (TSH3UL), total HCG (ThCG), and B-Type Natriuretic Peptide (BNP) (short analytical time). Median TAT for short assay was analyzed with 6 variations of ID assay mix (0%, <10%, <20%, <30%, <40%, <50%) in the run representing increasing percentages of assays requiring longer incubation times. TAT was represented as barcode to result and aspiration to result.

Results

The median TAT for TNIH remained consistent at 10.1 minutes across increasing % of ID assays (N=100961). The median TAT for TNIH for platforms not running ID assays (83237) remained consistent at 10.03 minutes. The median TAT for TSH remained consistent at 14.02 minutes across increasing % of ID assays (N=1183344). The median TAT for TSH for platforms not running ID assays (N=480219) remained consistent at 13.98 minutes. The median TAT for ThCG remained consistent at 10.28 minutes across increasing % of ID assays (N=24677). The median TAT for ThCG for platforms not running ID assays (N=79275) remained consistent at 10.27 minutes. The median TAT for BNP remained consistent at 10.1 minutes across increasing % of ID assays (N=42949). The median TAT for BNP for platforms not running ID assays (N=14990) remained consistent at 10.03 minutes.

Conclusions

Throughput and TAT on the Atellica IM Analyzer is relatively unaffected by mix of longer-incubation and shorter-incubation assays. The dual incubation rings allow more flexibility in the mix of incubation times with predictable and consistent TAT for all assays including STAT.
B-050 A comparison of two semi-quantitative tests, Abbott’s Advise DX SARS-CoV-2 IgG II and Beckman Coulter’s Access SARS-COV-2 IgG II, for measuring IgG antibody levels after Sars-CoV-2 Pfizer-BioNTech vaccination
Authors: Niklinski W , Niklinska E , Siddiqui S , Ferrer Peace D
Published: October 2024

Background

Using 219 samples collected from volunteer employees of our lab, obtained in different times after Sars-CoV-2 Pfizer-BioNTech vaccination, we compared two semi-quantitative tests:

Methods

Abbott's AdviseDx SARS-CoV-2 IgG II and Beckman Coulter’s Access SARS-CoV-2 IgG II assay. Both assays detect IgG antibodies to the receptor binding domain of the S1 subunit of the spike protein of SARS-CoV-2 in serum and plasma of tested individuals. For the Beckman test, AMR is from 0 to 450 AU/ml with cut off for positive test 10 AU/ml; for the Abbott test, AMR is from 0 to 25000 AU/ml with cut off for positive test 100 AU/ml.

Results

Using a fitted regression line, it appears that the best correlation between these two tests was found in the lower value range, below 25AU/ml for Beckman test and 4000 AU/ml for Abbott test (R-squared value of 0.842 and y=87.165x). For higher antibody levels, the result distribution resembles a binary pattern, which we find very interesting. We will discuss possible explanations of this finding.

Conclusions
B-065 Comparative Analysis of 14-3-3η Autoantibody Assays on Luminex Platform for Diagnosing Axial Spondyloarthritis
Authors: Sidhu N , Maksymowych W P , Wichuk S , Marotta A
Published: October 2024

Background

The pathophysiological significance of extracellular 14-3-3η antigen and its autoantibodies (AAbs) is well-documented in autoimmune rheumatologic disorders. Use of 14-3-3η protein blood tests is common in diagnosing and managing rheumatoid arthritis (RA). Prior studies have established the diagnostic and prognostic value of 14-3-3η AAbs in RA and axial spondyloarthritis (AS), particularly in differentiating AS patients from healthy individuals and in relation to disease severity and progression. This study explores the performance of a novel assay platform in the context of AS diagnosis, especially in younger patients who are most responsive to early treatment interventions.This research aims to evaluate the discriminative accuracy of the 14-3-3η AAb assay on the Luminex® platform, a widely recognized clinical tool, in distinguishing AS patients from healthy subjects, and to compare its performance with that of the Meso Scale Discovery® (MSD) research-use only (RUO) platform.

Methods

Sera from 49 AS patients and 25 healthy controls (HC), previously assessed using the MSD platform, were reanalyzed using a new Luminex 14-3-3η AAb assay. These samples were sourced from the Follow Up Research Cohort in Axial Spondyloarthritis (FORCAST) Prognostic Cohort. Spearman correlations were employed for variable analysis, and the Mann-Whitney U-test was used to compare AAb levels between groups. Receiver Operating Characteristic (ROC) Area Under Curve (AUC) analyses were conducted for both assay platforms, with a specific focus on patients aged 45 and under.

Results

The AS patient group had a mean age (SD) of 44 (13) years, with 67% male representation. The median (IQR) disease duration was 19 (10-24) years, and median (IQR) C-reactive protein (CRP) levels were 9.6 (4.3 - 24.8) mg/L. Median (IQR) 14-3-3η AAb levels were significantly higher in AS patients at 136 U/μl (48 - 408) compared to HCs at 54 (28 - 161) U/μl, p=0.02. ROC AUC analysis for the MSD RUO platform showed an AUC of 0.67 (95% CI, 0.55 - 0.79), and for the Luminex platform, an AUC of 0.66 (95% CI, 0.53 - 0.80), indicating comparable performance across platforms. In the subgroup of AS patients aged ≤45 years, the Luminex assay demonstrated an AUC of 0.74 (95% CI, 0.61-0.88), p=0.003. Combination of 14-3-3η AAbs and CRP was able to identify 90% of AS patients. No correlation between the two markers was observed (r= -0.14, p=0.38).

Conclusions

The Luminex-based 14-3-3η AAb assay exhibits equivalent discriminative capability to the MSD RUO assay in differentiating AS patients from healthy individuals. The combined use of 14-3-3η AAbs and CRP, identifying 90% of AS patients, highlights the potential of these biomarkers as complementary diagnostic and prognostic tools in AS, meriting further research.
B-070 Supar: what UACR and GFR don't say…
Authors: Valaperta S , Gamba S , Leo C , Moioli V , Saiaci C , Marozzi R , Alessio M
Published: October 2024

Background

Soluble urokinase-type plasminogen activator receptor (suPAR) is the circulating form of a three domain membrane protein expressed on a variety of cells, including immunologically active cells, endothelial cells, and podocytes. Diabetic nephropathy (DN) typically manifests with impaired glomerular filtration and microalbuminuria and progresses to end-stage renal disease. The study investigated whether high levels of suPAR may be added to KDIGO models that includes estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) to give more information about diabetic patients at higher risk of DN occurrence.

Methods

We measured plasma suPAR levels in 142 patients (67F/75M, median age 67 years) admitted to our hospital to check their glucose and glycated A1c hemoglobin (HbA1c) levels. We also recorded information about UACR and eGFR, and the relationship between suPAR levels and these parameters was investigated together with the distribution of suPAR levels according to KDIGO category risk of CKD.

Results

Among our study population, according to KDIGO risk category, 80 patients were at low risk, 47 were at moderate risk and 13 were at high risk of CKD. Mean plasma suPAR levels are 4.613±3.331 ng/mL, and significant correlation between suPAR and eGFR (P=0.0001) and between suPAR and HbA1c (P=0.0026) were found, while there is not a significant correlation with UACR (p=0.207) . According to KDIGO category risk, suPAR levels significantly increased from low to high risk, in particular, the increase is higher between the first two category (4.176 vs 6.285 ng/mL) risk compared to the highest (7.557 vs 7.427 ng/mL). We classified the 80 patients at low risk for KDIGO according suPAR levels divided into 4 quartiles according to literature (S. Salim Hayek et Al 2015) and 52 of them had suPAR levels in the third and fourth quartiles. Moreover, among these 52 patients, only 5 had HbA1c levels over the therapeutic target of 53 mmol/mol.

Conclusions

We identified an association between elevated plasma suPAR levels and a decline in the eGFR. However, we did not find a correlation with UACR, this is because suPAR levels are associated with a prospective membrane damage through interference with podocyte migration and apoptosis. According to this analysis, suPAR is a possible best candidate marker to stratify those patients who, according to the KDIGO criteria, are at low risk and have good glycemic compensation, but suPAR levels suggest a more careful follow-up.
B-072 Analytical Evaluation of a Novel Fully Automated Multiplexed Microarray Immunoassay for the Simultaneous Detection of Eleven Autoantibodies Associated with Connective Tissue Diseases in a Spanish Reference Laboratory
Authors: Gomez G , Pérez-Artes R , Fischer C , Viñas-Giménez L , Sanz-Martínez M
Published: October 2024

Background

Detection of different autoantibodies is key in the identification of autoimmune diseases; however, most available devices are either individual tests and/or manual/semi-automated. Development of fully-automated multiplexed devices for autoantibody testing is needed. We evaluated the analytical performance of the novel MosaiQ® AiPlex CTD (AiPlex-CTD) microarray, used with the fully-automated MosaiQ system, for simultaneous qualitative detection of eleven autoantibodies associated with connective tissue diseases (CTD), compared with selected CE-marked devices.

Methods

AiPlex-CTD microarrays (AliveDx, Switzerland) were prepared by printing antigens onto functionalized glass chips. Microarrays consisting of 2 separate sides (1 side was printed, leaving the other side available for future addition of antigens) were assembled into magazines (containing 250 microarrays) for processing on the MosaiQ 125 instrument. Serum samples from a Spanish refence laboratory, characterized as reactive to ≥1 autoantibodies using Quanta Flash® CTD Screen (Werfen, Spain) or as non-reactive by FIDISTM Connective Profile (Theradiag, France). All samples were tested with AiPlex-CTD. Positive percent agreement (PPA) and negative percent agreement (NPA), overall and for individual analytes were calculated.

Results

Compared with Quanta Flash® CTD Screen, AiPlex-CTD showed PPA ranging from 80% for Sm to 100% for SS-A 60, TRIM21, U1RNP, Jo-1 and Scl-70. No reactive samples were available for Sm/RNP and Ribosomal P. Compared with FIDIS, NPA ranged from 95% for dsDNA, Scl-70 and CENP-B and 100% for SS-A 60, TRIM21, SS-B, Sm, Sm/RNP, U1RNP, Jo-1 and Ribosomal P. Performance details for individual analytes are shown in the Table.

Conclusions

In this sample cohort, AiPlex-CTD demonstrated high concordance with the compared CE-marked devices for the automated qualitative detection of the autoantibodies included in the assay, which is line with previous observations in a larger cohort using FIDIS and other CE-marked devices. This high throughput multiplexed platform has the potential to help optimize CTD testing by simplifying complex testing pathways.
B-074 Comparative Evaluation of Clinical Utility between Indirect Immunofluorescence and Immunoassay Methods for Antineutrophil Cytopalsmic Antibody Detection
Authors: Jeon S , Park J , Choi H , Nah E , Choi H , Kee S
Published: October 2024

Background

ANCA testing is essential for the diagnosis of vasculitis, commonly using indirect immunofluorescence(IIF) and immunoassay(IA) methods. Recent guidelines recommend IA as the primary test for suspected GPA and MPA, but actual practice varies among physicians. Here, we retrospectively analyzed ANCA test results, focusing on new cases of ANCA-associated vasculitis, and compared the utility of IIF and IA to guide appropriate test selection.

Methods

From January 2022 to July 2023, 24 new cases of ANCA-associated vasculitis were diagnosed. We checked whether ANCA testing was performed and the results, and compared the turnaround time(TAT) and costs. IIF ANCA tests were performed on a computer-based automated instrument(Helios), and IA ANCA tests were performed on automated instruments(Alegria, Phadia 250) with MPO antigen and PR3 antigen tested simultaneously in a bundled prescription.

Results

Among the 24 cases, there were 6 GPA, 7 MPA, 7 EGPA, and 4 ANCA-associated GN, with varying diagnostic sensitivities. GPA and EGPA had different ANCA positivity rates than previously reported, suggesting potential ethnic variations in ANCA expression and positivity rates. The test sequence and results, summarized in Table 1, showed 21 out of 22 cases had identical concordance between methods, with an excellent concordance rate (kappa value=0.83). TAT for IIF was 3,452 minutes, and for IA was 1,491 minutes for the whole period, but IA TAT increased to 2,748 minutes after implementing a days-of-the-week testing system. Test costs, with a relative value score of 118.99 for IIF and 156.05 for IA, indicated IA cost approximately 2.6 times higher, considering the bundled prescription of both antigens for IA ANCA testing.

Conclusions

Evaluating the utility of both methods for ANCA detection, our study highlights high inter-method agreement in ANCA-associated vasculitis. Considering overall cost and turnaround time, IIF ANCA testing remains effective as a screening test, demonstrating standalone effectiveness.
B-076 Detection of KLHL11 Autoantibodies Using a New Cell-based Indirect Immunofluorescence Assay
Authors: Weiss J , Mindorf S , Jäger D , Sabater L , Pitsch J , Baumgartner T , Becker A J , Budhram A , Honnorat J , Saschenbrecker S , Dalmau J , Komorowski L
Published: October 2024

Background

Autoantibodies against kelch-like protein 11 (KLHL11) were first described in 2019 as markers of paraneoplastic encephalitis. Early diagnosis and treatment are imperative to improve prognosis and outcome of affected patients. Rat brain immunohistochemistry was reported to be not useful in routine screening for KLHL11 antibodies. This study evaluates the performance of a new recombinant cell-based assay for the standardized detection of KLHL11-specific IgG and reports the characteristics of the examined patients.

Methods

Serum (n=9), CSF (n=5) and/or plasmapheresis (n=1) samples from 10 patients with clinical presentations compatible with anti-KLHL11 encephalitis as well as sera from 100 healthy blood donors were analyzed using a prototype indirect immunofluorescence assay (IFA; EUROIMMUN) based on recombinant HEK293 cells expressing human KLHL11.

Results

KLHL11 autoantibodies were detected at high titers in all samples (serum >1:1,000; CSF >1:320; plasma >1:100,000) from all (10/10) patients but in none (0/100) of the blood donors, indicating 100% sensitivity and specificity. Anti-KLHL11-positive patients had a median age of 52 years (range 27-71) and 80% were male. The most common reported clinical presentations were cerebellar syndrome (ataxia), brainstem diencephalic encephalitis, rhombencephalitis and limbic encephalitis. Testicular or ovarian tumors were found in 87.5% (7/8) of the cases with available results from malignancy screening.

Conclusions

The new cell-based IFA enables the sensitive and specific detection of KLHL11 autoantibodies, thus supporting the diagnosis of patients with predominantly paraneoplastic brainstem cerebellar syndrome. Future studies will evaluate assay performance in larger patient cohorts to address the reported association of KLHL11 autoimmunity with a wider spectrum of syndromes and tumors.
B-079 Characterization of an isoelectric focusing method for detection of IgG oligoclonal banding in paired cerebrospinal fluid and serum specimens
Authors: Hosseini S , Beatty P , Remaley A T , Duh S , Christenson R H
Published: October 2024

Background

Qualitative assessment of IgG-specific oligoclonal banding (OCB) in paired serum and cerebrospinal fluid (CSF) samples is useful for evaluating inflammatory conditions of the central nervous system such as multiple sclerosis. Here we characterized the performance of an IgG-specific method using isoelectric focusing on agarose gel matrix for the detection of OCB in paired serum and CSF samples.

Methods

Specimens of 20 paired, simultaneously collected CSF and serum patient samples were tested on Sebia (Hydrasys 2 System) provided by the National Institutes of Health (NIH) Diagnostic Laboratories. We tested these paired samples using the Helena IgG IFE-20 kit (SPIFE® Touch) method and the results were read by two independent individuals blinded to each other’s assessments. The results were compared to the NIH results for agreement. Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) were calculated. Analytical sensitivity of the Helena assay was assessed via serial dilutions of a CSF OCB positive sample (total IgG 4.5 mg/dL).

Results

Figure 1 shows serum and CSF pairs for the control (A), two example positive OCB patients (B & D) and a negative OCB patient (C). The Helena assay was concordant with Sebia for 11/12 positive OCB patients (PPA 91.6%) and 8/8 negative subjects (NPA 100%). 20-fold was the highest dilution that remained positive.

Conclusions

OCB detection using paired serum and CSF samples and isoelectric focusing electrophoresis is considered the preferred method. The Helena IgG IFE-20 assay is such a method and showed high PPA and NPA concordance with the Sebia System. Thus, the Helena OCB assay can be considered an accurate and analytically sensitive method for assessing OCB in serum and CSF.
B-086 Evaluation of Long-Term Adaptive Immune Responses Specific to SARS-CoV-2: Effect of Various Vaccination and Omicron Exposure
Authors: Oh E , Kang H , Jung J , Lee J , Ko G , Park H , Choi A
Published: October 2024

Background

The immune response to SARS-CoV-2 becomes increasingly complex as individuals receive different combinations of vaccines and encounter breakthrough infections. Our study aims to describe the immunogenicity observed over a two-year period in healthy individuals who completed two-dose series and then experienced booster and/or Omicron infection.

Methods

In June 2023, we recruited 78 healthcare workers who had previously participated in clinical research initiated in March 2021 at a single medical center. At 1, 5, 11, and 25 months after second dose, we assessed SARS-CoV-2-specific humoral and cellular immune responses using commercially available immunoassays and surrogate virus neutralization tests, along with interferon gamma (IFN-γ)-based enzyme-linked immunosorbent spot (ELIspot) assay using SARS-CoV-2 spike peptide pools.

Results

As the humoral immune response was monitored longitudinally, robust antibody production persisted after the third antigen exposure, in contrast to the rapid decline observed between the second and third dose injections. All immune metrics tended to increase as the number of vaccine doses increased. We also found a trend toward increased humoral immune response in the homologous mRNA-based vaccine group and enhanced cellular immune response in the vector-based primary series with mRNA booster heterologous combination group. Interestingly, no significant difference was found between Omicron exposure through breakthrough infection and bivalent vaccination. Omicron exposure significantly increased the breadth of neutralizing activity, while it did not significantly alter the cross-reactivity in the cellular immune response.

Conclusions

We identified individuals with diminished neutralization, aiding decisions for future vaccination prioritization. In addition, our findings suggest the role of cellular immunity as an important correlate of long-term protection through cross-reactivity to emerging variants.
B-093 Analytical performances of a novel fluorescent immunoassay of anti-Müllerian hormone and establishment of the reference intervals in Chinese children
Authors: Jiang L , Li L , Shen L , Li M , Zhu W , Lu D , Zhou Y
Published: October 2024

Background

Anti-Müllerian Hormone (AMH) plays a important role in children growth and the concentrations change with age as well as gender. This study aimed to evaluate the analytical performances of a novel AMH assay based on the cycle enhanced fluorescence immunoassay (CEFIA) and establish the pediatric reference intervals of AMH

Methods

The experiments on imprecision, sensitivity, linearity, linear range and comparison were carried out to evaluate the analytical performances. Furthermore, the concentrations of serum AMH in 238 females and 346 males aged 0-18 years were measured by the Pylon AMH assays and the reference ranges for ages group were calculated using robust methods.

Results

The repeatability and the within-laboratory imprecision CVs of the assay were 3.7% and 6.4% at at 2.25 ng/mL, and 4.6% and 6.4% at 15.49 ng/mL, respectively. The sensitivity of the assay (LoB =0.05 ng/mL, LoD= 0.1 ng/mL and LoQ= 0.3 ng/mL) was verified. The AMH Pylon assays showed good linearity within the detection range (between 0.1 and 24 ng/ml) and can report up to 480 ng/mL with 20x pre-dilution of samples. The AMH concentrations of serum samples measured by the Pylon assays correlated to those measured by the Elecsys assays. In the males under 18 years old, the AMH levels were high at birth (0-1 month: median 95.10 ng/mL) and continued to increase to a peak between 7 months to one year old (median 158.80 ng/mL) before they started to decrease with age to the lowest level between 15 and 18 years old (median 6.31 ng/mL). On the other side, the serum AMH concentrations in females were low at birth (0-1 month: median 0.20 ng/mL) and increased with age (15-18 years old: median 3.03 ng/mL). The reference intervals were provided for each gender and age groups,respectively.

Conclusions

The Pylon AMH assays showed good analytical performances, and the AMH reference intervals in chinese children determined may provide a basis for the use in clinical diagnosis and treatment of related diseases.
B-095 The level of procalcitonin is a biomarker for differentiation between pathogenic and non-pathogenic bacteria
Authors: Deebukkham S , Pamarapa A , Permsripong N
Published: October 2024

Background

Sepsis is caused by bacteria infected in the bloodstream and the body’s inability to control inflammation. Procalcitonin (PCT) is a biomarker of infection in patients with sepsis, the severity of the infection, and whether the patient is responding to therapy. Thus, diagnostics and early treatment are very important for doctors and patients. In a hospital concerned with sepsis in patients, a doctor ordered a PCT level and hemoculture before treating an antibiotic on a patient whose doctor suspects sepsis. The objective of this study is to compare the PCT level in the blood and hemoculture results in patients.

Methods

In this study, we evaluated the patients who suspected sepsis disease and were admitted to the Uttaradit Hospital, Thailand, between October 2022 and October 2023. The patients were divided into two groups: those with positive hemoculture results (sepsis group) and those with negative hemoculture results (non-sepsis group). The PCT levels in the blood were measured on Alinity ci analyzers and compared between the two groups to determine if there was a significant difference. Additionally, clinical data such as age and gender were collected to assess their potential impact on PCT levels and hemoculture results.

Results

The results of the study showed that the sepsis group had significantly higher PCT levels compared to the non-sepsis group. And the difference in PCT levels between the sepsis and non-sepsis groups was considerably more marked for patients older than 60. Furthermore, there was no significant difference in PCT levels based on gender in either group.

Conclusions

This finding suggests that measuring PCT levels could potentially serve as a diagnostic tool for identifying sepsis in patients. A patient age may be a contributing factor to the severity of sepsis and could potentially be used as a marker for early detection and intervention in older patients. Further research is needed to validate these results and explore the clinical implications of using PCT as a biomarker for sepsis diagnosis.
B-107 Advancing Parasitology Laboratory Quality and Processes Through Artificial Intelligence (AI) and Automation
Authors: Feres M C , Siqueira F S , Pereira C d , de Martino M C , Ramadan-Boscolo D R , de Andrade S S , Tufik S
Published: October 2024

Background

This research emphasizes the profound impact of intestinal parasitic infections on developing countries, particularly in regions such as sub-Saharan Africa, South and Central America, China, and East Asia. With over 1.5 billion people globally affected and 450 million facing serious illness and a mortality rate of 155,000 cases per year, the socio-economic hindrances posed by these infections necessitate innovative approaches for control and eradication. The integration of artificial intelligence (AI) and machine learning (ML) into parasitology, exemplified by the “Automated Diagnosis of Intestinal Parasites” (ADIP), from brazilian Portuguese “Diagnóstico Automatizado de Parasitas Intestinais” (DAPI) system, showcases a paradigm shift. This advanced system, combining simple and complex decision-making mechanisms, demonstrates promising results, achieving high agreement compared to TF-Test (three fecal test).

Methods

Data were extracted through reports from the laboratory information system (LIS) from January-December 2023. TF-test was replaced by ADIP system in October 2023. Data were analyzed using Microsoft Excel software, with a bibliographic survey in national and international repositories.

Results

The parasitology laboratory of AFIP implemented artificial intelligence (AI) with ADIP equipment associated with system LIS automation, automating the analysis of approximately 38,000 monthly stool samples. The ADIP classification, image analysis and subsequent algorithm allowed a reduced examination time, since approximately 90% of samples could be released automatically, optimizing the whole process. In addition, after a three-month period using only ADIP, positivity results increased from 7,63% (TF-test) to 9,53%. Our database is periodically reviewed by specialized professionals who validate positive results, ensuring the security of information obtained by artificial intelligence, bringing efficiency, safety, and quality to the laboratory processes.

Conclusions

Artificial intelligence (AI) in parasite identification and the automated results system promises a bright future. Collaboration between the scientific community and data scientists is crucial to enhance laboratory processes. Through these tools, it is possible to focus on continuous improvements, increased efficiency, and, most importantly, without sacrificing accuracy and result quality. With new technologies associated with the parasitology field, detailed records can be ensured, previously challenging to obtain, showcasing each step from result acquisition to issued report. Process improvement in parasitology brings optimizations, suggesting the potential for team reduction without compromising quality and improving the takt time.
B-113 Beckman Coulter DxI 9000 immunoassay analyzer assay performance meets new CLIA 2024 performance goals with highest proportion of Six Sigma performance amongst all major manufacturers
Authors: Westgard S
Published: October 2024

Background

The Clinical Laboratory Improvement Act (CLIA) proficiency testing (PT) criteria will be updated in July 2024 with some goals tightening by up to 40%. It is assumed, but not known, that all assays and instruments will be able to achieve these goals.

Using these new CLIA 2024 goals, estimates of current instrument group performance from an international proficiency testing (PT) survey have shown significant differences in quality, calling into question which assays can achieve the new CLIA goals. Currently, the highest performing diagnostic instrument achieves only 35.2% 6-Sigma, while the majority of instruments have less than 15% 6-Sigma performance indicating a higher probability of future PT failures.

Methods

Eighteen assays that will be governed by new CLIA 2024 goals were assessed for Sigma metric performance on the DxI 9000 immunoassay analyzer: Alpha Fetoprotein (AFP), Beta hCG, Carcinoembryonic antigen (CEA), Cortisol, Creatine Kinase MB (CK-MB), Estradiol, Ferritin, Folate, Follicle-Stimulating Hormone (FSH), Prolactin, Para-thyroid hormone (PTH), Total Prostate specific antigen (Total PSA), Testosterone, Thyroid Stimulating Hormone (TSH), Total Triiodothyronine (TT3),high sensitivity Troponin I, Total Thyroxine (TT4) and Vitamin B12.

Precision and bias were determined following CLSI EP5 and EP9 guidelines, measured across 3 reagent lots. CLIA 2024 PT criteria provides the allowable total error for the standard Sigma-metric calculation:

Sigma-metric = (TEa - |bias|) / SD

Performance of the other major analyzers was assessed using the methodology introduced in 2006 by Westgard JO and Westgard SA.

The Sigma-metric predicts future problems with PT and potential optimization of QC procedure opportunities, including fewer Westgard Rules, control levels, even reduced QC frequency and materials leading to less cost and time saved.

Results

Half (50%) of the assays on DxI 9000 achieves 6-Sigma, outperforming all other major manufacturers in the market who range from only 5% to 35% 6-Sigma. Further, over 78% of the DxI 9000 performance was 4Sigma and higher. Less than 8% of performance fell below 3-Sigma, which was observed at the extreme ends of the reportable range.

Conclusions

The DxI 9000 assay performance is well designed to meet CLIA 2024’s new PT criteria and has the highest prevalence of 6-sigma assay performance observed on market when compared to the top 5 major instrument manufacturers. Assays with Sigma metrics at 4-Sigma and higher are unlikely to face analytical PT difficulties and can be optimized for reduced Westgard Rules, control levels, and potentially even QC frequency.
B-132 Within limits - is my thyroid just plump, or are these reference intervals telling me something?
Authors: Bransfield A , Costelloe S J , Green A D
Published: October 2024

Background

Replacing immunoassay equipment brings challenges in the implementation of reference intervals (RIs). In 2023, Cork University Hospital (CUH) replaced Abbott Architect immunoassay analysers with Beckman Coulter DxI 9000 units. The manufacturer’s recommended reference intervals were applied as the DxI 9000 is new to the market. CUH reports ≈100,000 immunoassay results per month.

Methods

A minimum of 45 adult patient samples were run on the Abbott and Beckman Coulter platforms for each of sixteen analytes as part of method verification following the requirements of ISO 15189 and CLSI. The slope and intercept of the Passing-Bablok regression analyses were used to transform the Abbott RI and the newly modelled RIs compared to those provided by Beckman Coulter.

Results

Conclusions:

While the manufacturer’s RI was adopted initially, the modelled data have shown that for three analytes (PTH, HCG, Free T4) the modelled RI differs significantly from the manufacturer’s. This was judged by how patients would theoretically be classified. For these assays it is necessary to closely monitor patients in the initial three months post-go-live to ensure that the RIs are clinically acceptable. A comprehensive dialogue was undertaken with clinicians before and after the implementation to ensure they were aware of the changes. All modelling was performed on adult patient data. However, CUH has a large paediatric patient cohort, and for this group, the same RI transformations were performed, and discussions were held with paediatric teams. Introducing new platforms and RIs requires careful planning, education and an open dialogue with clinicians to ensure no compromise to patient care. RIs should be reviewed frequently for appropriateness.
B-138 A Harmonization Program Leading to Improved Accuracy and Precision of Hemoglobin A1c (HbA1c) Testing: A Six-Year Multi-Site, Multi-Instrument Review and Comparison
Authors: Meyers W , Amukele T , McCloskey T W , Phalen L E , Swenson C
Published: October 2024

Background

Across four global laboratory locations in North America, Europe, and Asia a quality control system was implemented in the measurement of Hemoglobin A1c (HbA1c). The intent was to improve accuracy and reduce imprecision, both being independent contributors to total analytical performance.

Methods

Quality control (QC) data, created during routine clinical operations, was used for this analysis. Analysis of QC data evaluated bias and precision separately and provided the ability to predict and monitor performance. The in-process harmonization program indicated a change in instrumentation was needed to meet and maintain a more stringent analytical error profile. The instrumentation change allowed for a before and after comparison across platforms.

Results

Use of a harmonized quality control system allowed for the visualization of the role bias and precision play in measurements. Improved performance was confirmed using native matrix samples tested routinely from participation in the National Glycohemoglobin Standardization Program. Independently assessing bias and precision highlighted the cumulative and offsetting effects that challenge quality assessment and risk mitigation. Bias appeared to have both a transient and systematic nature. The transient bias contributed to the overall normal distributive property of the quality data. In contrast, the systematic accumulation of bias appeared to occur slowly, over multiple reagent and calibration cycles. The accumulation of bias occurred in the direction of the assay drift. While precision commonly consumes the largest amount of analytical error within an instrument, the dual (negative and positive) nature of bias similarly affects the harmonization of an instrument group.

Conclusions

Changing the way data is viewed to include assessments of bias improved performance and aided in the identification of opportunities to reduce analytical variances that results in inter- and intra-individual variation. Harmonization of instruments should include methods to assess and describe bias, independent of precision.
B-139 Ai-all inclusive, artificial intelligence cannot outsmart the clinical chemist
Authors: Ibrahim R , Chokkalla A K , Kumar S , Devaraj S
Published: October 2024

Background

The rise of Artificial intelligence (AI) tools and their ability to generate human-like answers in a conversational context has sparked massive interest in people with calls for their application in different areas like healthcare. We evaluated the utility of artificial intelligence-powered language models (Google Bard, ChatGPT 3.5 and GPT-4) compared to trainees and clinical chemists in responding to common laboratory questions in the broad area of Clinical Chemistry.

Methods

35 questions from clinical consultations, real-life case scenarios, and clinical chemistry questions were used to evaluate these AI tools alongside clinical chemistry trainees and clinical chemistry faculties. Responses were scored by a blind participant and scores assigned as either being correct, partially correct, or incorrect. Additionally, responses were ranked based on categories and years of experience.

Results

Of the 35 questions asked, all human participants performed better than the AI tools. The Senior Chemistry Faculty demonstrated superior accuracy with 100% of correct responses compared to 71.4, 82.9% and 90.5% of correct responses from the residents, fellows and junior chemistry faculty. Both Google Bard and ChatGPT 3.5 generated 60% correct responses while GPT-4 generated 71.4% correct responses respectively. Of the sub-categories examined, both Google Bard and GPT-4 did not achieve 100% accuracy in any subcategory while ChatGPT 3.5 achieved 100% accuracy in endocrinology. GPT-4 outperformed both Google Bard and ChatGPT 3.5 but performed poorly to human participants when both partially correct and incorrect indices were considered.

Conclusions

We evaluated the performance of the popular AI-tools in answering clinical chemistry questions compared to responses given by individuals specially trained in the field of laboratory medicine. Despite advances in AI-powered language models, they cannot replace a trained pathologist in answering clinical chemistry questions. Caution should be observed by people, especially those not trained in clinical chemistry, to interpret test results using these tools.
B-143 Using Big Data Analytics to Measure the Multi-year Consistency of Sigma Metrics for Vitros Oncology Assays
Authors: Miller J
Published: October 2024

Background

Sigma metrics assess lab quality by incorporating precision, accuracy and total error allowed (TEa). Sigma metrics report quality on a 0-6 scale, with 6 representing World-Class quality. Due to logistical constraints, Sigma metrics are often calculated with limitations such as a small number of analyzers, single reagent lot or short duration. QuidelOrtho developed a novel approach using big data analytics for the objective, automated calculation of Sigma metrics across thousands of Vitros analyzers running in real lab conditions. This approach was previously used to report the Sigma metric performance for 115 assays using data from 2022. Of particular interest is the consistency of quality levels for Vitros oncology assays assessed in the study. The aim of this analysis was to examine Sigma metrics for Vitros oncology assays and compare Sigma metrics to data from 2022.

Methods

The methods follow the previous approach using the same Python algorithm to extract worldwide QC data from Jan. to Nov. 2023 (inclusive). A QC fluid lot from the study period was selected for each analyte to align with the fluid level reported in the 2022 study, which was based on medical relevance. Metrics were calculated for each set of QC data that originated from a single analyzer, reagent lot and calibration curve; the median Sigma metric is reported in the Results. Proficiency testing limits were utilized as TEa limits where available, with preference to CLIA 2024 limits.

Results

The following assays reported Sigma metrics as >6 using both 2022 and 2023 data: alpha-fetoprotein, cancer antigen 125, carcinoembryonic antigen, prostate-specific antigen (PSA), free PSA, IgA, and IgG. Assays with higher metrics using 2023 data: cancer antigen 19-9 (5.0 vs >6) and IgM (5.3 vs >6). Assays with lower metrics using 2023 data: cancer antigen 15-3 (4.8 vs 4.4).

Conclusions

Vitros oncology assays report similar performance for 2022 and 2023. All Vitros oncology assays assessed report Sigma metrics of 4 or greater, indicating they achieve results within the corresponding allowable error.
B-158 Association between multiple heavy metals exposure and blood lipid levels: evidence from a cross-sectional study of Korean adults
Authors: Park H , Choi K , Kim H , Kim C , Lee M , Lee K
Published: October 2024

Background

Metals are ubiquitous in our environment and enter human body via various pathways, such as air, soil, food, water, etc. Increasing studies have found that metals are important risk factors in developing dyslipidemia. However, there is no consensus regarding the effects of co-exposure to multiple metals on blood lipid levels. We investigated both the joint and individual effects of this metal mixture exposure on human blood lipid levels.

Methods

Blood concentrations of four human toxic metals (Pb, Cs, Hg, and Cd) in 2,798 general populations from Korea were simultaneously determined as a measure of exposure. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to estimate associations of four blood metals and metals mixture with lipid profiles, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C).

Results

The mean age of the overall study population was 41.2 ± 9.85 years, and 66.9% were men. The prevalence of overweight or obesity, diabetes, and hypertension in the population was 62.5, 6.8, and 13.9%, respectively. In the multivariable linear regression model, the blood Cs was positively associated with TC and LDL-C(p < 0.05, all), and the blood Pb was positively associated with serum TG (p < 0.05, all). Also, the blood Cd was positively associated with serum HDL-C (p < 0.05, all). We did not identify any other obvious interaction between metals on the lipid profiles using a bivariate exposure-response function in BKMR.

Conclusions

Our finding suggests that combined exposure to this metal mixture may affect human blood lipid levels. Therefore, reducing exposure to heavy metals, such as Cs and Pb, should be a priority for the general population. However, future studies with a larger number of heavy metals are still needed to focus on the detrimental effects of single metals on lipid profiles as well as to identify key components.
B-167 Quantification of Thyroglobulin in Serum for Clinical Research using SISCAPA Workflow Combined with LC-MS/MS
Authors: Davey L , Foley D , Razavi M , Calton L J , Trudeau M , Wardle R , Mira N
Published: October 2024

Background

Accurate measurement of Thyroglobulin (Tg) using existing immunoassay-based techniques can be challenging in the presence of anti-Tg antibodies (TgAb), which can prevent the binding of Tg to assay antibodies thus leading to non-quantifiable Tg concentrations. The Stable Isotope Standards and Capture with Anti-Peptide Antibodies (SISCAPA™) Workflow combined with LC-MS/MS has been successfully employed to circumvent this problem by digesting the serum sample thus eliminating interfering TgAb and measuring a Tg-specific surrogate peptide instead.

Methods

Using a Andrew+™ Pipetting Robot, denaturation and reduction buffer was added to 250µL serum samples and incubated at 37°C. Internal standard and trypsin were added and samples incubated at 37°C. The samples were quenched with protease inhibitor and Anti-Tg FSP mAb SISCAPA was added to the serum samples and mixed for 60 minutes. Using a magnetic array plate, the beads were left to pull down, samples were discarded, and the beads were twice washed with PBS/CHAPS prior to elution with acetonitrile with formic acid. Using an ACQUITY™ UPLC™ I-Class PLUS FL System, samples were injected onto a Waters™ XSelect™ HSS T3 Column using a water/acetonitrile/formic acid gradient elution profile and the Tg FSP peptide was quantified using a Waters Xevo™ TQ Absolute Mass Spectrometer.

Results

The method demonstrated no significant carryover or matrix effects and was shown to be linear from 0.1 - 50 ng/mL. Analytical sensitivity investigations indicate the analytical sensitivity of this method would allow precise quantification (<20%) at 0.1 ng/mL with S/N (PtP) >10:1. Coefficients of variation (CV) for total precision and repeatability on 5 analytical runs for low, mid and high QCs were all < 9.5% (n = 25) for both automated and manual precision assessments. Comparison with samples from the UK NEQAS scheme demonstrated significant method bias of -40% for the developed LC-MS/MS method. Re-assignment of the calibrator concentrations using the EQA samples reduced the bias to -5.5%, indicating differences in the calibration materials used for these measurements.

Conclusions

A LC-MS/MS clinical research method for serum thyroglobulin was developed using SISCAPA, followed by analysis using ACQUITY UPLC I-Class PLUS FL System and the Xevo TQ Absolute Mass Spectrometer. The method provides analytical sensitivity down to 0.1 ng/mL from 250 µL serum, while providing sufficient sample for re-analysis. The method demonstrates excellent linearity across the calibration range, with no significant carryover, interferences, and matrix effects. Total reproducibility and repeatability of the method was ≤9.5% RSD for manual and automated sample preparation, using the Andrew+ Pipetting Robot. In addition, the Andrew+ Pipetting Robot can minimize user touch-time, allowing a full plate to be prepared within four hours without user intervention.
B-218 Inconclusive results in the Fetal Sex Determination from maternal plasma assay may indicate miscarriage
Authors: Levi J , Xavier T D , Caciatore M , Lourenço G P , Almeida S S , Andrade C E , Mello L A , Carpinetti M L , Batistutti V P , Osório P S
Published: October 2024

Background

The purpose of this study was to evaluate the miscarriage rates from patients presenting inconclusive results in a cell-free DNA fetal sex determination test at Dasa, a Brazilian laboratory, between 2021 and 2023.

Methods

In validating the fetal sex determination test, a Ct value range was established to assign the presence of the Y chromosome on maternal plasma and a gray zone for determining an inconclusive result. In this case, our operational procedure is to repeat the analysis from the beginning, due to plasma volume limitation. When the result remains inconclusive upon repetition a new sample is requested.After the 2nd sample collection with inconclusive results, cases are forwarded to specialized medical contact, when patient is informed and potential explanations for the rare situation of a repeat-indeterminate sex determination result are discussed.At the end of 2022, the need to widen the sex-determining range and consequently the inconclusive zone was routinely perceived. The main reason for this change was to reduce unnecessary repetitions.

Results

The adjustments of range reduced unnecessary repetition, requests for new samples and medical contacts (Table). Between 2021 and 2023 the median gestational age at 1st collect of medical contact was 9 weeks, and in cases of miscarriages was 10 (2022) and 8 weeks (2023).

Conclusions

The widening of the Y chromosome Ct range proved to be efficient on a routine basis without changing the result error rates, which since 2021 have remained at 0.05%. In addition to providing more precision to the assay, the newly established gray zone increased the positive predictive value for miscarriage. Our results, show that what was thought to be a limitation of the technique in determining the fetal sex may in fact, in many cases, be associated to fetal loss