bluuebunny/crossref_metadata_2025_split huggingface dataset:
B-253 Using biomarkers in recurrent renal stone formers to detect silent stones
Authors: Gohel M , Ng C 
Published: October 2024

Abstract

Background
Glycosaminoglycans (GAGs) protect cells from binding of calcium oxalate (CaOx) crystals to prevent CaOx stone formation. Hyaluronan (HA) is a non-sulfated GAG with crystallization-promoting activity during renal stone formation. The excretion of urinary GAGs and HA were measured in stone-formers (SF), post-treated SF, and normal controls to reveal their relationship with renal stone disease.

Methods
Three groups were included - active SF, post-treated SF (SF after extracorporeal shock wave lithotripsy) and normal controls with 40 subjects in each group. Early morning urine was collected for each subject. The hexuronate content of the GAGs were measured by carbazole reaction and values for GAGs were standardized against creatinine. Individual GAGs extracts were then digested sequentially with Streptomyces hyaluronidase and chondroitinase ABC to yield the HA disaccharides for analysis by high performance liquid chromatography.

Results
Hexuronate content of GAGs were in the order of post-treated SF &lt; SF &lt;&lt; normal controls. SF had an enhanced urinary excretion of HA with no increase of urinary HA in post-treated SF group. However, both the SF and post-treated SF groups had increased proportion of HA (of total GAGs) compared to normal controls. Active-SF and post-treated SF groups had lower total GAGs content but increased proportion of HA than that of the normal controls indicating that urinary GAGs and HA are probably protective/risk factors, respectively, for renal stone disease.

Conclusions
The higher recurrence rate of renal stone disease may be due to the presence of sub-species of GAGs, HA, that becomes an accidental participant for renal stone formation. Concomitantly, other species of charged sulfated GAGs, which are protective to the cells and prevent crystal binding, are found to be in lesser content in active SF and post-treated SF. Clinicians can use these two markers, which are easily detectable (by ELISA) for prevention and monitoring of silent renal stone formation.
B-257 Dont go breaking my heart: use and misuse of beta-blockers in clinical and forensic casework (2019-2023)
Authors: Midthun K M 
Published: October 2024

Abstract

Background
Beta-adrenergic antagonists, or beta-blockers, are commonly prescribed for the treatment and prevention of a variety of cardiovascular issues and other health conditions. These include, but are not limited to heart failure, heart rhythm disturbances, high blood pressure, hypertension, anxiety, asthma, glaucoma, and migraines. Beta-blockers work by blocking access to beta-receptors, which then enhance or inhibit cellular activity and result in dilating blood vessels and relaxing the heart muscle. When misused, accidentally or intentionally, serious adverse effects including dizziness, seizure, heart failure, QTc prolongation, coma, and death can occur. In routine toxicology testing, beta-blockers are often reported qualitatively, which likely underestimates the reporting of related adverse events. We performed a retrospective review to evaluate quantitative levels of beta-blockers in blood and identify trends of potential misuse.

Methods
We queried our laboratory’s data management system from 2019-2023 for reported findings of beta-blockers in blood. Analytes were quantified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results were analyzed using Microsoft Office software.

Results
Blood results and a comparison of known therapeutic and adverse concentrations are shown in Table 1. Age and sex were reported in 50% and 74% of cases, respectively. Average age ranged from 43 years old (propranolol) to 59 years old (atenolol and metoprolol), without major differences between sexes. Overall use of beta-blockers was split evenly between men and women. Importantly, each analyte provided examples which far exceeded known therapeutic levels, with several cases submitted as potential overdoses.

Conclusions
Since beta-blockers are generally reported qualitatively during routine toxicology testing, concentrations are unknown. Quantitative testing has shown that beta-blocker concentrations often exceed known therapeutic ranges, which can lead to adverse effects and fatal outcomes. Physicians and death investigators should be aware of these adverse effects and the need for specialized testing in the event of suspected beta-blocker toxicity.
B-258 Rapid clozapine blood levels on the Beckman Coulter DxC 500 AU
Authors: Fritz J , Holler A , Wisnoski J , Hilaire M , Salamone S 
Published: October 2024

Abstract

Background
Clozapine is the most effective drug for treatment-resistant schizophrenia. Multiple guidelines strongly recommend clozapine therapeutic drug monitoring (TDM). Measuring clozapine blood levels provides essential information when there are questions of medication adherence, efficacy, toxicity, medication interactions, or concern over other factors that may influence clozapine levels. Turnaround time is essential for effective clinical decisions. However, with liquid-chromatography/mass spectrometry, clozapine levels can take days to report results. To address the medical need for a faster turnaround time, a rapid clozapine immunoassay was developed for automated clinical chemistry analyzers. The immunoassay measuring range is based on established APA Practice Guidelines and ASCP/AGNP Consensus Statement. We developed an analyzer application for the DxC 500 AU (time to first result &lt; 9 minutes) to expand the availability of rapid clozapine blood level testing.

Methods
The performance of the FDA-cleared clozapine assay was evaluated on the DxC 500 AU according to CLSI guidelines. Precision testing was performed with three clozapine spiked pools over five days with five replicates per sample. Precision sample recovery was assessed to their theoretical spike concentration. Linearity was verified with five spiked serum samples covering the measuring range. Method comparison was performed with 40 remnant patient samples vs. the Beckman Coulter AU480.

Results
Repeatability CV was ≤5.5% and within-laboratory precision CV was ≤6.1%. Individual deviation was ±20% and mean deviation was ±2% for all samples. Deviation from linearity was &lt;3%. Deming regression statistics for the method comparison were a slope of 0.987, an intercept of 5.7, and an R of 0.9948. The methods are statistically equivalent: the 99% confidence limits contained 1 and 0 for the slope and intercept respectively.

Conclusions
The precision, recovery, linearity, and method comparison results for clozapine on the DxC 500 AU demonstrate that the analyzer can be used to generate robust results for clozapine.
B-259 Cannabinoid Prevalence in Umbilical Cord Tissue Toxicity Testing
Authors: Reinhart A , Kacinko S L , Midthun K M 
Published: October 2024

Abstract

Background
Cannabis is rapidly becoming legalized in the United States. While its effects on the developing fetus are not fully understood, current recommendations advise against cannabis use and exposure during pregnancy due to its association with negative outcomes, such as preterm birth, fetal growth restriction, low birth weight, and developmental deficits. If drug exposure is suspected, umbilical cord tissue (UCT) testing is growing in frequency as a tissue of choice when testing infants. Neonatal testing protocols vary between hospitals, including both targeted or universal collection and targeted or universal testing of neonatal specimens. Based on the current environment of legalization, we were curious to see what the changes in cannabis use were over the previous five years, from 2019-2023.

Methods
We queried our laboratory information system for reported findings from screening and confirmatory umbilical cord testing, both of which were analyzed via liquid chromatography tandem-mass spectrometry (LC-MS/MS). Results were analyzed using R coding software.

Results
Overall, annually, 2019-2023 positivity rates for testing in general ranged from 41% - 44% positivity and maintained at 44% from 2020 onwards (n=90384 total workorders 2019-2023, n=40551 total positive workorders). Cannabinoids were starkly the most common drug found, accounting for 59-63% of all positive workorders annually from 2019-2023. There were no statistically significant differences in the cannabinoid positivity rates between 2019-2023. Of note, cannabinoid-only (delta-9-carboxy THC) workorders accounted for 28% of all positive workorders (n=25962) during that time frame. This was followed by methamphetamine-only (n=2485 workorders) and buprenorphine-only (n=1765 workorders). The combination of cannabinoids and methamphetamine, the most common drug combination found in UCT testing, had a range of positive results from 2019 - 2023 of 2.9 - 3.6% (n=1327 workorders). Cannabinoids and cocaine, the second most prevalent drug combination, ranged in positivity from 1.3 - 1.6% from 2019-2023 (n=616 workorders).

Conclusions
Cannabinoid exposure is prevalent in pregnant individuals undergoing UCT testing. Physicians should take care to keep informed on the impacts of cannabis exposure on the developing fetus and educating clients on the effects of cannabis exposure during pregnancy.
B-262 Validation of a point-of-care lateral flow immunoassay for urine drug testing prior to application in an outpatient rapid access addiction medicine clinic
Authors: Bohn M , Delaney S , Jung B , Lamb W , Leung F 
Published: October 2024

Abstract

Background
Point-of-care (POC) urine drug testing is a useful adjunct to self-reporting in rapid access addiction medicine settings to immediately guide patient management. However, available POC immunoassays have limitations including cross-reactivity with unrelated compounds or low sensitivity that may cause false results. Here, we assessed the performance of a multi-drug test panel by comparing against gold-standard liquid chromatography tandem mass spectrometry (LC-MS/MS) testing.

Methods
102 residual urine specimens were assayed using a competitive lateral flow immunoassay (LFA) for 10 drugs: 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP, methadone metabolite), buprenorphine, morphine, hydromorphone, oxycodone, fentanyl, cocaine, methamphetamine, amphetamine, and benzodiazepines (BTNX Rapid ResponseTM Multi-Drug Panel). Results were compared to those obtained by LC-MS/MS (n=67, 66%) or kinetic interaction of microparticles in solution automated immunoassay (KIMS) (Roche Diagnostics, n=35, 33%). Broad spectrum LC-MS/MS results were reviewed in entirety for discordant cases, particularly in false positives to identify the presence of any known cross-reacting compounds.

Results
Of 10 drugs evaluated, four demonstrated ≥95% agreement with LC-MS/MS or KIMS immunoassay (EDDP, buprenorphine, oxycodone, methamphetamine). Fentanyl demonstrated the highest false negative rate of 44% (LFA cut-off: 10 ng/mL) followed by amphetamines (22%, cut-off: 1000 ng/mL). Morphine and hydromorphone demonstrated false positive rates of 14% and 18%, respectively, with most cases likely due to cross-reacting opiate or opioid metabolites. Benzodiazepines (target: Oxazepam) demonstrated false positive and negative rates of 13% and 24%, respectively.

Conclusions
To our knowledge, this is the first study to evaluate the performance of the BTNX multi-drug test panel against definitive testing in urine samples. While good concordance was observed for most drugs, high rates of discordant results for fentanyl and others emphasize the need for confirmatory testing by methods with higher sensitivity and specificity. Careful consideration prior to implementation would be essential, including physician education, interpretative comments, and training resources.
B-263 Analytical Performance Evaluation of Eleven Drug of Abuse Assays on the Atellica CI Analyzer
Authors: Lewisch S , Gupta P , Varhue W , Arrode-Bruses G , 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 CH Amphetamines (Amp), Barbiturates (Brb), Benzodiazepine (Bnz), Cannabinoids THC (Thc), Cocaine Metabolite (Coc), Ecstasy (Xtc), Methadone (Mdn), Opiates (Op), Oxycodone (OXY), Phencyclidine (Pcp), and Propoxyphene (Ppx) Assays on the Atellica CI Analyzer.

Methods
Precision and method comparison (MC) studies were used as performance indicators. Precision studies were performed according to CLSI EP05-A3 using quality control (QC) samples consisting of contrived human urine samples. One aliquot of each QC was tested in duplicate in two runs per day ≥2 hours apart on each analyzer for ≥ 20 days. Precision for each assay was evaluated with one reagent lot on one system. Method comparison studies were performed with three reagent lots according to CLSI EP12-A2. Individual native and contrived human urine samples were analyzed using the Atellica CH Amp, Barb, Bnz, Thc, Coc, Xtc, Mdn, Op, OXY, Pcp, and Ppx Assays on both the Atellica CH and Atellica CI Analyzers. The results were assessed based on analyte values used for distinguishing positive (value ≥cutoff) and negative (value &lt;cutoff) specimens.

Results
As shown in table below, repeatability and within-lab %CVs based on manufacturer arbitrary units (mAU) were &lt;0.8% and &lt;3.2%, respectively or qualitative interpretation for each replicate remained unchanged for all 80 precision testing measurements (OXY, PcP). Qualitative accuracy assessed by concordance analysis demonstrated ≥95% agreement between the Atellica CI Analyzer and Atellica CH Analyzer.

Conclusions
Evaluation of the Atellica CH Amp, Barb, Bnz, Thc, Coc, Xtc, Mdn, Op, OXY, Pcp, and Ppx Assays using the Atellica CI Analyzer demonstrated acceptable precision and equivalent performance compared to the same assays on the Atellica CH Analyzer.
B-277 Detectable Levels of Toxic Metals in Children's Playgrounds
Authors: Oyelakin-Ogunbileje J O , Oyelakin S T , Sadagopa R V 
Published: October 2024

Abstract

Background
Metal-contaminated soil poses significant health risks to kids because they are more sensitive to heavy metal exposure in the environment. Studies have shown that continuous exposure to metals can increase the risk of metal accumulation in blood and various body organs. This study determines the levels of some toxic metals in various playgrounds in our community.

Methods
We determined the levels of lead (Pb), chromium (Cr), cadmium (Cd), and copper (Cu) in six playgrounds (parks) (T-RP, T-GP, T-TX, L-HH, L-WH, L-SPLX) using graphite furnace atomic absorption spectrophotometry (GF-AAS) technique. Soil samples were collected at least one foot below the soil surface, and metal was extracted using ultra-pure nitric before analysis using GF-AAS. Data were analyzed using analysis of variance (ANOVA).

Results
The results showed significant detectable levels of the metals in all playgrounds evaluated in this study. L-WH Park in League City has the highest detectable levels of Pb (12.43 ± 46 mg/Kg, P&lt;0.05) compared to other children playgrounds examined in this study (T-RP (3.93 ± 3.97 mg/Kg), T-GP (7.09 ± 2.79 mg/Kg), T-TX (6.05 ± 1.92 mg/Kg), L-HH (4.68 ± 0.76 mg/Kg), L-SPLX (2.64 ± 1.63 mg/Kg). The concentration of detectable cadmium in T-RP park (0.16 ± 0.11 mg/Kg) was significantly higher than all the other five children's playgrounds studied L-WH (0.02 ± 0.01 ), T-GP (0.05 ± 0.04 mg/Kg), T-TX (0.02 ± 0.01 mg/Kg), L-HH (0.04 ± 0.01 mg/Kg), L-SPLX (0.09 ± 0.04 mg/Kg) (P&lt;0.05).

Conclusions
The playgrounds contain detectable toxic metals that might pose health risks to children in the community. Though the lead levels are below the CDC-recommended lead soil concentration in urban areas, they still pose health risks to children in the environment when continuously exposed to the playground. The concentrations of Cu and Cr were not statistically different among the playgrounds. The detection of Pb and Cd highlights the potential health risks to children. Overall, this study shows that metal levels in playgrounds should be public information available to parents.
B-280 Nmr-based biomaker measurement determines high-dose methotrexate elimination rates in lymphoma and leukemia treatment
Authors: Robertson A , Einhell S , Schwäble Santamaría A , Grassi M , Pukrop T , Schiffer E 
Published: October 2024

Abstract

Background
The cytotoxic methotrexate (MTX) is used in high doses in lymphoma and acute lymphocytic leukemia (ALL) treatment. A therapeutic plasma dose range is crucial to minimize MTX accumulation and prolonged exposure, which can lead to myelosuppression and other adverse effects. Determining MTX elimination prior to drug administration is difficult, given its non-linear clearance. Here we present a model to predict MTX elimination rates based on metabolite measurement in patients receiving high-dose methotrexate, using nuclear-magnetic resonance (NMR) spectroscopy.

Methods
A series of 26 residual sera from patients receiving MTX infusions as per treatment protocols for CNS lymphoma (MATRIX protocol, 3.5 g/m2 over four hours) and ALL (GMALL protocol, 1.5 g/m2 over 24 hours) were collected from patients at the University Hospital Regensburg at four timepoints (t0, t24, t42, and t48). Serum was NMR-measured in five replicates. NMR spectra for each sample were characterized and relevant parameters extracted. First order elimination constants were modeled for two MTX dosage regimes (&lt;4 g, ≥4 g) using characterized NMR features from samples measured at t0.

Results
Metabolomic and lipidomic biomarkers measured at baseline (t0) were able to accurately predict MTX elimination rate constant k, determined by fitting MTX levels at a t24, t42, and t48, using first order c(t)∼c0*e(-kt) kinetic function (&gt;4 g: R2 = 0.475, p-value &lt; 0.05; ≤4 g: R2 = 0.918, p-value &lt; 0.01) (Fig. A). Results were cross-validated with five-time repeated three-fold cross-validation. Performance values are given as means of the folds.

Conclusions
NMR-measured biomarkers can predict dose-dependent MTX elimination rates in patients receiving high-dose MTX, presenting a novel method to predict MTX clearance, allowing for personalized dose-monitoring and minimization of adverse events. Validation with a larger cohort is required.
B-287 Comparing a Recently FDA-Cleared Free Phenytoin Assay to a Laboratory Developed Test
Authors: Zakrajsek J A , Zakrajsek J T , McShane A J 
Published: October 2024

Abstract

Background
Phenytoin is an anti-convulsant drug that is commonly prescribed to epileptic patients to control seizures. The drug circulates in two forms: protein-bound (90%), and the free, biologically active form (10%). In certain circumstances, such as protein-binding disruption, hypoalbuminemia, and drug-drug interactions, the total phenytoin serum concentration may not accurately reflect active phenytoin levels. Therefore, a free phenytoin level (i.e. non-protein bound) may be indicated. Until recent FDA-clearance, we utilized an in-house, laboratory-development test (LDT) to deliver these needed results. The purpose of this study was to validate the FDA-cleared assay and compare its performance characteristics to a free phenytoin LDT.

Methods
Validation of the FDA-cleared assay was performed on an automated chemistry analyzer (Roche Diagnostics, cobas c502), utilizing a kinetic interaction of microparticles in a solution (KIMS) method. Both the FDA and LDT assay used the same free phenytoin reagent, however the calibrators and pipetting parameters for each assay were different. FDA assay used a six-point calibration at concentrations of: 0, 2.5, 5, 10, 20, 40 µg/mL (Preciset TDM I Calibrators), whereas the LDT assay used a six-point calibration at concentrations of: 0.0, 0.5, 1.0, 2.0, 3.0, 4.0 µg/mL (cobas FP Free Phenytoin Calibrators). The following performance characteristics were determined for the FDA-cleared assay and compared to the current LDT: analytical measurement range, precision, accuracy, and maximum dilution. Free forms of the drug were obtained as a filtrate through centrifugation using a molecular weight cut-off filter (30 kDa, Millipore), spun at 3600 rpm for twenty minutes.

Results

Conclusions
The FDA-cleared free phenytoin assay is suitable for use in the clinical laboratory producing similar results to our LDT. Switching to the FDA-cleared assay reduces the regulatory burden and eliminates the need for transferring reagent into open channel cassettes and manual dilutions.
B-295 Sensitive and Rapid Homogeneous Immunoassay for the Detection of Zolpidem and its Major Metabolite in Urine
Authors: Hennessey V , Chung K , Singh R , Houts T , O’Malley R 
Published: October 2024

Abstract

Background
Zolpidem, a schedule IV controlled substance under the Controlled Substances Act, is commonly known as Ambien and Ambien CR, a prescription only treatment for insomnia. Zolpidem is one of the most common prescribed sleep aids in the U.S. due to its rapid sedative effects. The recommended duration of treatment is between two days and four weeks, as long-term use of zolpidem increases the risk of habit formation. Addiction to zolpidem can cause severe side effects, including memory loss, delusion, and in extreme cases, fatal overdose. From 2005-2010, Zolpidem-related emergency room visits doubled, underscoring the need for accurate testing as zolpidem testing plays an important role in cases of misuse, diversion, and forensics. The sole commercially available homogeneous immunoassay for the detection of zolpidem in urine has a relatively high cutoff at 20 ng/mL and poor cross-reactivity (0.02%) to major metabolite zolpidem 4-carboxylic acid. ARK Diagnostics has developed the ARK™ Zolpidem Assay to detect zolpidem at a cutoff concentration of 10 ng/mL with high cross-reactivity to its metabolite, Zolpidem phenyl 4-carboxylic acid and no cross-reactivity to zaleplon and zopiclone at concentrations below 100,000 ng/mL.

Methods
The ARK™ Zolpidem Assay is a liquid stable homogeneous enzyme immunoassay, consisting of two reagents, with a cutoff concentration of 10 ng/mL and semi-quantitative range up to 40 ng/mL. Preliminary performance characterization for this assay was evaluated on the Beckman Coulter AU680 Automated Clinical Chemistry Analyzer. Precision, analytical recovery, specificity, Histogram Overlap Analysis of ±50% controls and the cutoff, and method comparison with LC-MS/MS were evaluated.

Results
In semi-quantitative mode, total precision ranged from 2.6 to 3.1% CV. Spiked recovery of zolpidem ranged from 88.6% (2.5 ng/mL) to 96.8% (10 ng/mL). The major metabolite, zolpidem phenyl-4-carboxylic acid, showed an approximate equivalence to the 10 ng/mL zolpidem cutoff at 30 ng/mL (33.3% cross-reactivity). Histogram overlap analysis showed no overlap between cutoff and control levels. Method correlation with LC-MS/MS using authentic urine samples showed an excellent agreement with a specificity of 100% and sensitivity of 100% (15 positives and 100 negatives).

Conclusions
The ARK™ Zolpidem Assay measures zolpidem and its major metabolite zolpidem phenyl-4-carboxylic acid in human urine with acceptable performance. The assay is sensitive, rapid, and applicable to a wide range of clinical chemistry analyzers.