bluuebunny/crossref_metadata_2025_split huggingface dataset:
A-118 Sigma Metric Performance of Chemistry Assays on 4 Instrument Systems
Authors: Berman M , Dechert J 
Published: October 2024

Abstract

Background
Chemistry panels play a crucial role in determining a person’s general health and well-being. These tests evaluate electrolyte balance and the status of several major organs. The Comprehensive Metabolic Panel (CMP) and Lipid Panel constitute approximately 87% of the blood tests prescribed in medical laboratories. Laboratories monitor assay performance by performing proficiency testing using quality controls (QC). College of American Pathologists (CAP) data is useful for laboratories to compare their proficiency testing performance to other laboratories and instrument systems. Sigma metrics serve as a valuable tool for laboratories to assess the quality and accuracy of their tests. Sigma scores vary from 0 to 6, with the 6 score designated as world-class performance, 5 as excellent, 4 as good, 3 as marginal, and 2 as poor. The analytical performance of 16 clinical assays from Abbott, Beckman, Roche, and Siemens instrument systems were compared using Sigma metrics.

Methods
Sigma metrics of 16 chemistry analytes were compared across 4 instruments system using CAP data from three reports (C-A 2023, C-C 2023 and C-B 2022). The 4 systems evaluated were Abbott Alinity ci, Beckman AU, Roche COBAS c500/c303 and Siemens Atellica CH. Method imprecision was estimated for each assay using the cumulative coefficient of variation or standard deviation for each assay at a single QC concentration and calculating the average sigma. Since sigma levels can be concentration-dependent, an equivalent CAP sample concentration was chosen for each instrument system evaluation. Method bias was estimated by evaluating each method QC mean to the peer group mean. Sigma values were calculated for each method as Sigma = (TEa - |Bias|) / Precision using the allowable total error from 2014 Clinical Laboratory Improvement Amendments (CLIA) proposed acceptance limits. Average Sigma values were generated for each analyte and graded as an optimal Sigma score.

Results
The sigma scores varied across assays and instrument systems. Abbott demonstrated the best overall performance. Specifically, the Abbott Alinity system had the highest number (7/16, 44%) of assays at 5 sigma or higher, with Siemens showing the lowest number of assays at 5 Sigma or higher (1/16, 6%). Of the 16 assays evaluated, Abbott has the fewest assays at or below the 3 sigma threshold (5/16) when compared to Roche (7/16), Beckman (7/16), and Siemens (9/16). Sigma scores were comparable between the Abbott ARCHITCT and Alinity clinical chemistry systems.

Conclusions
Sigma metrics are useful in assessing the performance of clinical assays. Assays with high Sigma have better performance due to lower imprecision and higher accuracy. None of the instrument systems demonstrated optimal six sigma performance for all analytes. However, Abbott demonstrated the best overall performance.
A-123 Comparative Assessment of Unmanned High-Speed Aerial Vehicles in Medical Logistics: Blood Sample Transportation Amidst Weather Variability
Authors: Stierlin N R , Hemmerle A , Risch M , Risch L 
Published: October 2024

Abstract

Background
Drones, as an innovative technology, hold transformative potential in the field of medical logistics, especially in the transportation of sensitive medical materials like blood samples. This study aimed to assess and compare the impact of high-speed drone transportation with conventional car transportation on the integrity and preanalytics of blood samples, taking into account various blood materials and analytes.

Methods
Blood samples, including EDTA whole blood, serum, and plasma anticoagulated with Citrate and Lithium-Heparin transported as whole blood, were subjected to transportation via both drone and car. Drone flights were tested under diverse weather conditions (ranging between 4 and 20 degrees Celsius), and results were compared to samples stored without transportation. The maximum drone speed exceeded 100 km/h. A total of 28 analytes were tested on Serum, 20 on EDTA, 26 on Lithium-Heparin, and 5 on Citrate blood. Statistical analyses were performed using Passing Bablok and Bland-Altman methods.

Results
For Serum samples, the correlation coefficient (r) ranged from 0.830 to 1.000, and slopes varied from 0.913 to 1.111. Five analytes (total bilirubin, Calcium, Ferritin, Kalium, and Sodium) exhibited discrepancies between the negative control and the transported sample, with r lower than 0.800, slopes not between 0.8 and 1.2, and mean (%) not between +/- 10%. However, no significant differences were noted between drone and car transportation.
Similar patterns emerged for EDTA, Lithium-Heparin, and Citrate samples, with r ranging from 0.829 to 0.997, 0.939 to 0.998, and 0.830 to 1.000, respectively. Slopes ranged from 0.956 to 1.051, 0.938 to 1.085, and 0.913 to 1.111. Despite identifying a few discrepancies in specific analytes, no significant differences were observed between transportation methods.

Conclusions
n comparison to transportation by car, drone transportation of blood samples did not lead to alterations in concentrations of commonly used analytes. Notably, instances of differences before and after transportation were attributed to the transportation process itself rather than the mode of transportation. This suggests that the use of drones for medical sample transport can be deemed comparable to, if not superior to, traditional car transportation methods.
A-124 Sustainable Transport: Assessing Environmental Impact in Medical Sample Transit via Drones and Vehicles
Authors: Stierlin N R , Hemmerle A , Risch M , Risch L 
Published: October 2024

Abstract

Background
This research explores the ecological implications associated with different methods of transporting medical samples, specifically focusing on drones, combustion cars, and electric cars within two laboratories in central European countries. With the primary goal of assessing and comparing CO2 consumption, delivery time, and overall environmental impact, the study aims to provide a basis for adopting sustainable practices in healthcare logistics.

Methods
The transportation of medical samples occurred between two laboratories in the Principality of Liechtenstein and Switzerland, utilizing authorized aerial and road routes. Various weather conditions and distances were considered for sample transports using different vehicles (8 combustion cars, two electric cars, and one drone model). Energy consumption was documented, and the CO2 footprint was calculated based on data from the Swiss Federal Office for the Environment (FOEN) for both imported and renewable electricity. Comparative analyses were conducted to quantify the environmental impact of each transportation method.

Results
In terms of CO2 footprint, combustion cars exhibited a CO2 release of 159.5 g/km, while electric cars showed 3.43g (2.15 to 4.08% of combustion cars). Drones demonstrated a minimal 0.09g CO2 emission per kilometer (0.066% of combustion car CO2 emission; 2.6% of electric car CO2 emission). The distance traveled by drones was significantly shorter (16.7% to 50%). Additionally, the efficiency of drone transport was emphasized by its ability to avoid traffic jams and associated detours, resulting in time savings ranging from 31.25 to 50% per delivery when comparing transport times during rush hour and regular hours in the selected setting.

Conclusions
The integration of drone technology emerges as a crucial strategy for establishing a “green laboratory.” The substantial reduction in CO2 emissions and enhanced delivery efficiency position drone transport as a sustainable and operationally effective solution for medical sample logistics, offering shorter delivery times. These findings highlight the potential for transformative change in healthcare logistics, aligning with the global shift towards sustainability and green practices.
A-144 Liquid chromatography multiple reaction monitoring-based assay for quantitative assessment of fibrinogen levels in clinical samples
Authors: Chavan S , Bokka R , Venkataraman S , Peterson J , Tange J , Leger R , Seheult J , Pruthi R , Chen D , Pandey A 
Published: October 2024

Abstract

Background
Fibrinogen plays a critical role in hemostasis and is essential to clot formation. Changes in the quantity or activity of fibrinogen can lead to disorders affecting coagulation. Thus, it is essential to precisely quantify fibrinogen levels to differentiate between hyperfibrinogenemia in hypercoagulable disorders and dysfibrinogenemia, hypo/afibrinogenemia, and irregular bleeding. Current diagnostic tests that use antibodies to detect fibrinogen or activity-based measures are susceptible to interference from heparin contamination, hemolysis, and hyperbilirubinemia. Here, we evaluated the use of targeted proteomics for developing a quantitative assay for fibrinogen in plasma samples.

Methods
Four peptides each for alpha and gamma chains of fibrinogen were synthesized using FMOC chemistry on a Liberty Blue (CEM Corp) peptide synthesizer. A targeted multiple reaction monitoring (MRM) assay was developed and optimized using Dionex Ultimate 3000 HPLC connected to a TSQ Altis triple quadrupole mass spectrometer (Thermo Scientific). Evaluations were conducted using a range of standards, such as pure protein, WHO plasma and commercially available plasma with known fibrinogen amounts for the accurate quantitation of fibrinogen. Calibration curves were generated using different dilutions in various matrices. The repeatability and precision of the assay were evaluated across five different days. The plasma samples were processed and digested in a 96-well plate and subjected to C18 clean-up using a Bravo automated liquid handler (Agilent). All samples were spiked-in with corresponding heavy-labeled peptides prior to digestion with trypsin. Multiple reaction monitoring assays were performed on tryptic digests of plasma samples.

Results
Calibration curves using commercial plasma for all peptides showed linearity from 20 mg/dl to 1,308 mg/dl. This covers the entire clinical range including normal (200-350 mg/dl), deficient states (&lt;100 mg/dl) and excess production (&gt;350 mg/dl) that can be used for evaluation of bleeding disorders including consumption coagulopathy and hyperfibrinogenemia. Based on the overall performance in terms of linearity, limit of detection/quantitation, carryover and coefficient of variation (CV) across five different days, two peptides per chain were finally selected for developing the quantitative assay. The intra-assay variability was &lt;5% and intra-day CV was ∼20%. This assay is currently being tested on a variety of clinical samples representing a range of fibrinogen levels.

Conclusions
Our study focused on assessing whether multiplexed MRM assay could be implemented to measure fibrinogen levels in plasma. Our data indicate the feasibility of MRM-based assays for determining fibrinogen levels as an alternative to existing non-mass spectrometry-based activity or antigen assays.
A-149 Comparison of Mass Spectrometry to Sickle Solubility for Confirmation of Low Percentages of Hemoglobin S
Authors: Olson T , Rangan A , Kandler R , Pappas A , Yang B , Zhang X , Herrick J L 
Published: October 2024

Abstract

Background
Hemoglobin S (HbS) causes sickling disorders. In the laboratory, confirmation of HbS in patient samples with varying percentages is essential. Assessment is routinely performed using capillary electrophoresis (CE) and/or high-performance liquid chromatography. Sickle solubility (SS) exploits decreased solubility of HbS under reducing conditions and is a confirmatory test. SS is unreliable with low HbS, elevated HbF, severe anemia, erythrocytosis, hyperglobulinemia, extreme leukocytosis, hyperlipidemia, or increased serum proteins. Infant samples commonly have low percentages of HbS, high HbF, and limited sample volume. Intact globin chain Mass Spectrometry (MS) is used to identify abnormal hemoglobin variants by detecting the mass change (normal α/β/γ mass =15127/15867/15996 amu), respectively). MS has potential advantages in sensitivity and efficiency over SS and requires lower input sample volume. Herein we compare the utility of MS versus SS for confirmation of HbS.

Methods
Twenty-three EDTA-anticoagulated blood samples containing low percentages of HbS were identified. SS was performed on 30μL washed packed cells (requires 200μL whole blood) per standard methods. Intact Quadrupole Time-of-Flight MS (Accurate-Mass Q-TOF LC/MS 6520, Agilent Technologies, California) was performed using 10μL whole blood sample in acetonitrile solution reagent and results were compared. HbS and HbF levels were assayed by capillary electrophoresis (Sebia, France) per standard methods.

Results
Select results are summarized in Table 1. SS detected HbS percentages to 4.8% when HbF was low but not 6% HbS when Hb F is high. MS showed no HbF interference and identified HbS peaks (at 15837 amu) down to 3.1%. HbS percentages &lt;3.1 were undetected by both methods.

Conclusions
Overall, MS was superior to SS for confirming HbS, particularly in samples with low variant percentage and/or elevated HbF. MS is also optimal when sample volume is minimal, such as for infants. Percentages of HbS &lt;3% require methods such as IEF or DNA sequencing for confirmation.
A-154 Non-standard body fluid validation of d-dimer analysis of organox liver perfusate to support clinical evaluations of donor livers prior to transplantation
Authors: Koster H , Majkut N , Krum K , Maggiore J , Gant Kanegusuku A 
Published: October 2024

Abstract

Background
Non-standard body fluid analysis is considered a challenge to laboratories since very few have been approved by the FDA for routine testing. As medical procedures evolve, the laboratory must balance the requirement to uphold regulatory standards while also supporting procedures that improve patient care. The LUMC Liver Transplant Team recently implemented the use of the FDA-approved OrganOx Metra normothermic machine perfusion instrument for maintaining donor livers under physiologic conditions prior to transplantation. The team mitigates risk for biliary complications associated with fibrin microthrombi by perfusing a combination of alteplase rTPA with fresh frozen plasma and monitoring the prevalence of fibrin through the release of D-dimers over the course of ex situ normothermic preservation. Liver perfusate is not an FDA-approved specimen type for the analysis of D-dimer and requires laboratory verification as a compatible specimen for analysis.

Methods
The D-dimer HS 500 assay was performed on an ACL TOP 750 analyzer. Carry-over studies evaluated activated partial thromboplastin time (aPTT) of a normal control (citrated plasma) specimen initially, and repeatedly in-between sets of D-dimer measurements of heparinized perfusate specimen. Recovery studies were performed by mixing liver perfusate with citrated plasma spiked with D-dimer in known ratios, allowing for the calculation of an expected value of D-dimer.

Results
Carry-over studies measuring aPTTs of normal plasma specimens provided %CVs of 1 and 3%. Recovery of D-dimer in seven sets of independent add-mixture series (three mixed specimen per set) was on average 105% with a range from 95 to 113% recovery.

Conclusions
Concern for cross-contamination of perfusate specimen containing heparin anticoagulant on analyzers used to evaluate routine coagulation testing was mitigated by the results of the carry-over study, which provided %CV within the manufacturer limit for intraday precision. Recovery studies evaluating matrix effect for the analysis of D-dimer on liver perfusate generated under the LUMC liver transplant protocol indicated that the matrix of the perfusate did not impact D-dimer analysis, as compared to the FDA-approved specimen type.
A-159 Re-evaluating Ferritin Cutoffs for the Diagnosis of Iron Deficiency and Iron Deficiency Anemia
Authors: Troike K , McShane A J 
Published: October 2024

Abstract

Background
Iron deficiency (ID) is the most common nutrient deficiency in the world and iron deficiency anemia (IDA) is estimated to affect 1.24 billion people. Serum ferritin is an iron storage protein commonly used as a biomarker for ID and IDA. The ferritin lower limit of normal (LLN) defined in many clinical laboratories is lower than evidence-based cutoffs and may not detect ID and IDA with adequate sensitivity, particularly when sex-based reference intervals (RIs) are used. This may be due in part to the use of asymptomatic, iron-depleted individuals for RI studies. Recent efforts have been made to increase the LLN for ferritin to at least 30 ng/mL and re-evaluate sex based RIs to improve diagnosis of ID and IDA. In this study, we aimed to investigate LLN ferritin cutoffs for ID and IDA in our patient population.

Methods
Patient data from June 2022-May 2023 were collected with approval from the Institutional Review Board (IRB), including age, sex, and values for ferritin, iron, transferrin saturation, and hemoglobin. Patients were classified as iron replete (IR), ID, or IDA based on measurements for iron, transferrin saturation, and hemoglobin. IR patients were defined as having iron and transferrin saturation values within current RIs, while those below the cutoff were grouped as ID. ID and IDA were further classified based on hemoglobin values. A range of ferritin concentrations between 1 and 100 ng/mL were used to calculate true and false positive rates (TPR and FPR) and diagnostic accuracy (DA). Receiver operator characteristic (ROC) curve and J index analysis were used to define optimal ferritin cutoffs for ID and IDA.

Results
Data from 26,455 patients (65% female) were used in this study.

Conclusions
These findings highlight the need to re-examine ferritin RIs in the context of ID/IDA, especially for those patients assigned female at birth.
A-161 Diagnosis of Lupus Anticoagulant Cases using Deep Neural Networks
Authors: Wang J , Leger R , Heikal N , Pruthi R , Chen D , Seheult J 
Published: October 2024

Abstract

Background
Laboratory identification of lupus anticoagulant (LAC) is critical for diagnosing antiphospholipid antibody syndrome, a common cause of unprovoked thromboembolic events and pregnancy morbidity. Commonly used clot-based assays for LAC include the dilute Russell’s viper venom time (DRVVT) and activated partial thromboplastin time (APTT), but these are susceptible to anticoagulant interferences. Despite standardization efforts, LAC interpretation remains challenging due to pre- and post-analytical complexity and limited expertise. This study explored the use of deep neural networks (DNN) to facilitate LAC diagnosis.

Methods
Retrospective data for LAC profiling with 13 features performed at Mayo Clinic between 2021 and 2022 was collected. The profiles of 7,202 patients were randomly divided into training (n=4608), validation (n=1153), and test cohorts (n=1441). Diagnostic outputs including LAC positivity (determined by DRVVT or APTT) and the presence of warfarin (WAR) and heparin (HEP), were confirmed by expert assessment. Three DNN architectures were developed and evaluated (Figure 1): (1) four single output DNN models with a domain knowledge driven selection of input features, (2) four single output DNN models using the same 13 inputs across all models, and (3) a multi-output DNN model. Model performance was evaluated using the F1 score and the index of balanced accuracy (IBA) for each output label.

Results
Architecture 1 achieved high diagnostic accuracy with IBA values of 0.989-1.000 for all four outputs and F1 scores of 0.945-0.991. Architecture 2 exhibited F1 scores of 0.902-0.973 and IBA values of 0.935-0.992. Architecture 3 achieved F1 scores of 0.933-0.967 and IBA values of 0.941-0.983.

Conclusions
All three architectures accurately classify LAC and common anticoagulation effects. The comparable performance of architectures 1 and 2 suggests that manual feature extraction is unnecessary. Given its relative simplicity and versatility, architecture 3 is the preferred choice for implementation in a clinical laboratory to standardize LAC diagnosis.
A-164 Establishment and Verification of Reference Intervals for Red Blood Cell Series and Total Leukocytes in Whole Blood Counts of Chilean Adults Using refineR and Multi Criteria Expectation Maximization Methods
Authors: Prieto C , Delgado H , Dias A C , Stevenson M , Díaz N , Arias S , Apablaza C 
Published: October 2024

Abstract

Background
This study aimed to define RIs for red blood cell series and total leukocytes in the complete blood count, in adult patients.

Methods
We used a sample of 822 patients aged 18 to 60 years, both female and male. The study focused on the red blood cell series (RBC Count, hemoglobin, Hematocrit, MCV, MCH, MCHC and RDW) and total leukocytes. RIs and respective 90% confidence intervals were estimated using the refineR method and a multi-criteria method combining the Expectation Maximization algorithm, mode, antimode analysis, an adapted Horn algorithm (5 cycles of Tukey's test with intermediate trimming and 2 cycles of Tukey's test with Box-Cox transformed data if applicable after analyzing Lambda, kurtosis, and skewness coefficients) and distribution truncation based on clusters and antimode. The RIs estimates using refineR and multi-criteria methods were compared to the manufacturer's specifications (Mindray). Flagging Rates were used to validate the method that estimates the most representative RI for the population served by the laboratory. Equivalence Interval and Bias Ratio were utilized to assess the practical relevance of sex-based partitioning.

Results
The method based on the multicriteria approach demonstrated the best performance, with flagging rates showing results lower than 4.7% and higher than 0.9% after the truncation of the results distribution. In general, the refineR method generated very narrow RIs, while the manufacturer's specifications resulted in very wide or shifted RIs, which do not adequately represent the data distribution profile. It was identified the need to partition by sex for the parameters Red Blood Cell Count, Hemoglobin, and Hematocrit, which is in agreement with the manufacturer's specifications.

Conclusions
The estimated RIs better represent the laboratory-served population, highlighting the importance of adhering to ISO 15189 normative requirements. This involves verifying and/or determining RIs to provide representative information of the served population, thereby aiding in medical decision-making.