Optimizing cutpoints for clinical interpretation of brain amyloid status using plasma p-tau217 immunoassays.

INTRODUCTION: We aimed to evaluate clinical interpretation cutpoints for two plasma phosphorylated tau (p-tau)217 assays (ALZpath and Lumipulse) as predictors of amyloid status for implementation in clinical practice. METHODS: Clinical performance of plasma p-tau217 against amyloid positron emission tomography status was evaluated in participants with mild cognitive impairment or mild dementia (n = 427). RESULTS: Using a one-cutpoint approach (negative/positive), neither assay achieved ≥ 90% in both sensitivity and specificity. A two-cutpoint approach yielding 92% sensitivity and 96% specificity provided the desired balance of false positives and false negatives, while categorizing 20% and 39% of results as indeterminate for the Lumipulse and ALZpath assays, respectively. DISCUSSION: This study provides a systematic framework for selection of assay-specific cutpoints for clinical use of plasma p-tau217 for determination of amyloid status. Our findings suggest that a two-cutpoint approach may have advantages in optimizing diagnostic accuracy while minimizing potential harm from false positive results. HIGHLIGHTS: Phosphorylated tau (p-tau)217 cutpoints for detection of amyloid pathology were established. A two-cutpoint approach exhibited the best performance for clinical laboratory use. p-tau217 assays differed in the percentage of results categorized as intermediate.

The effect of burosumab on intact and C-terminal FGF23 measurements.

OBJECTIVE: To investigate the effect of CRYSVITA® (burosumab-twza) on FGF23 measurements in an intact and a C-terminal immunoassay. METHODS: An intact serum FGF23 (MedFrontier) and a C-terminal plasma FGF23 assay (Immutopics) were used. Serum/plasma pools were spiked to span the burosumab therapeutic range (1.4-11.3 µg/ml) and FGF23 recovery was assessed. Patient serum and plasma samples obtained pre and post-burosumab treatment were evaluated on both assays and compared with corresponding phosphorus measurements RESULTS: Spiking burosumab (1.4-11.3 µg/ml) into sample pools resulted in a dose-dependent negative analytical interference on intact FGF23 measurements and no significant interference for C-terminal FGF23 measurements. However, more than a 500-fold median increase (post- vs. pre-burosumab administration) in in vivo FGF23 concentrations were observed by both assays. CONCLUSIONS: Therapeutic concentrations of burosumab result in a negative analytical interference of the intact, but not the C-terminal FGF23 immunoassay. Despite this in vitro analytical interference in the intact assay, relatively large elevations of both intact FGF23 and C-terminal FGF23 measurements were observed in vivo following burosumab administration. Following burosumab administration, FGF23 measurements must be interpreted within the clinical context of the patient and other relevant biomarker results. SUMMARY: This article describes a negative analytical interference by burosumab in an intact FGF23 immunoassay. The recovery of C-terminal FGF23 is not significantly affected by the presence of burosumab. In vivo, both assays demonstrate extreme FGF23 elevations in the presence of the drug. Furthermore, the measurement of FGF23 blocked by burosumab is not clinically useful regarding hypophosphataemia.

Intact Fibroblast Growth Factor 23 Concentrations in Hypophosphatemic Disorders.

OBJECTIVE: Evaluation of circulating fibroblast growth factor 23 (FGF23) concentrations plays a key role in the differential diagnosis of patients presenting with hypophosphatemia. FGF23 concentrations obtained by different immunoassays are not comparable and subsequently, differences in the clinical performance of the assays might arise. In this study, we evaluated the clinical performance of the Medfrontier FGF23 Intact immunoassay (MedFrontier, Minaris Medical Co, Ltd, Tokyo, Japan) in clinically relevant hypophosphatemic conditions. METHODS: Intact FGF23 (iFGF23) was measured in serum samples from 61 patients with FGF23-dependent hypophosphatemia (42-tumor induced osteomalacia [TIO] and 19-X-linked hypophosphatemia [XLH]); 8 patients with FGF23-independent hypophosphatemia (6-Fanconi Syndrome and 2-Vitamin D dependent rickets); 10 normophosphatemic patients; 15 chronic kidney disease (CKD) stage-2/3 and 20 CKD stage-4/5 patients; and a healthy control population. Disease-specific differences in measured iFGF23 concentrations and FGF23 concentration association with phosphate concentrations were reported. RESULTS: iFGF23 concentrations were significantly elevated in 90% and 84% of TIO and XLH hypophosphatemia patients as compared to healthy controls (both TIO and XLH, P = .0001). There was no significant correlation between iFGF23 and phosphate concentrations (P = .74 and P = .86) for TIO and XLH, respectively. Patients with CKD showed a significant increase in serum iFGF23 as the estimated glomerular filtration rate decreased (ρ = -0.79, P ≤ 0.0001). CONCLUSIONS: This study evaluated the clinical performance of the MedFrontier iFGF23 assay in a large cohort of XLH and TIO Caucasian and Asian patients. The clinical sensitivity of this iFGF23 assay is appropriate for clinical use.

Neurologic Effects of Gadolinium Retention in the Brain after Gadolinium-based Contrast Agent Administration.

Background Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. Purpose To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. Materials and Methods From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. Results No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks (P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks (P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%-98% removal for CSF, 34%-94% removal for serum), and was nearly completely removed from urine (range: 96%-99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. Conclusion In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.

False Positives in Thyroglobulin Determinations Due to the Presence of Heterophile Antibodies: An Underrecognized and Consequential Clinical Problem.

OBJECTIVE: To report a case series of thyroid cancer patients in whom false positive results in immunometric assays for thyroglobulin (TgIMA) were caused by heterophilic antibody interference, describe the clinical scenario in which this interference should be suspected, and recommend methods to demonstrate the interference. METHODS: Three patients with unexpectedly elevated thyroglobulin results (range, 1.6-75 ng/mL) were studied. In the first patient, thyroglobulin was elevated despite the presence of Tg antibody. In the second patient, suppressed thyroglobulin was higher than a recent stimulated thyroglobulin. In the third patient, thyroglobulin became detectable years after treatment and did not change after thyroid-stimulating hormone stimulation. TgIMA concentration determination was compared to determination by a mass spectrometry method (TgMS). Thyroglobulin was also remeasured after preabsorption with heterophile antibody blocking reagents and after serial dilutions. RESULTS: In all cases, thyroglobulin was undetectable by TgMS. In 2 of 3 patients, dilutions provided nonlinear thyroglobulin results. After blocking agent preabsorption, thyroglobulin dropped by 35%, 45%, and 91% in the 3 samples. CONCLUSION: False positive thyroglobulin concentrations from heterophilic antibody interference have significant impact on the management of thyroid cancer. Here we show that TgMS assays can be used to rule out heterophilic antibody interference. This interference should be suspected when a detectable thyroglobulin by TgIMA does not respond to thyroid-stimulating hormone or is discordant from the clinical assessment.

The Effect of Early Feeding on Initial Glucose Concentrations in Term Newborns.

OBJECTIVE: To evaluate the influence of early feeding on initial glucose concentrations in healthy term newborns who were not at risk for hypoglycemia. STUDY DESIGN: This retrospective observational study was conducted at the University of Arkansas for Medical Sciences where universal early glucose screening was standard of care for newborn infants. Plasma glucose concentrations were compared in term infants born in 2008 who were not at risk for neonatal hypoglycemia and who were fed before (early feeders) and after (late feeders) their initial glucose screens. Multiple linear regression models were built to determine whether glucose concentrations differed significantly between early vs late feeders. RESULTS: In the 315 early and 572 late feeders, the mean (SD) age of first feeding was 0.9 (0.6) and 3.8 (2.0) hours, respectively. The age at initial glucose specimen collection was 2.2 (1.1) and 1.8 (0.8) hours, respectively. The initial glucose concentration was not higher in early vs late feeders (51.8 ± 11.9 vs 55.5 ± 13.3 mg/dL; P < .001). In linear regression analyses of all infants, the mean initial glucose concentration was 3.61 (95% CI 1.75-5.48) mg/dL lower in early vs late feeders. CONCLUSIONS: Early feeding in otherwise healthy term newborns did not increase initial glucose concentrations compared with newborns who fed later (ie, fasted). Before direct evidence is available, these observations may be instructive for managing early asymptomatic hypoglycemia in at-risk newborns.

Evaluation of polypropylene CSF low-bind collection tubes for trace metal contamination.

BACKGROUND: Due to the ability of metal ions to cross the blood-brain barrier, there has been interest in analyzing cerebrospinal fluid (CSF) for trace element concentrations to investigate possible correlations with neurodegenerative diseases. In this study, Sarstedt polypropylene CSF collection tubes were analyzed to determine the contamination levels of aluminum, titanium, chromium, manganese, cobalt, nickel, molybdenum, gadolinium, vanadium, arsenic, cadmium, mercury, lead, thallium, selenium, copper, zinc, and iron. METHODS: Sarstedt polypropylene CSF collection tubes from 2 separate lots (n = 10 per lot) were filled with a 2 mL aliquot of a CSF pool with known element concentrations. After 24 hours of leaching at room temperature, all 18 elements were analyzed via inductively coupled plasma mass spectrometry (ICP-MS). Results were subtracted from the initial pool concentration to determine contamination levels. RESULTS: No detectable contamination above the assay limit of detection was found in 11 analytes. Molybdenum and selenium contamination was measured in all tubes, and aluminum, titanium, manganese, thallium, and zinc had minimal levels of sporadic detectable contamination in 25% or fewer of the tubes tested. CONCLUSIONS: Sarstedt polypropylene CSF tubes are an acceptable collection tube for the analysis of most assessed metals in CSF.

Circulating Chromogranin A as Surveillance Biomarker in Patients with Carcinoids - The CASPAR Study.

PURPOSE: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively indolent but can be more aggressive. The current recommendations for the use of serum CgA for GEP-NET patients are equivocal. This study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in GEP-NET patients. PATIENTS AND METHODS: A prospective, multi-center blinded observational study was designed to validate an automated chromogranin A (CgA) immunofluorescence assay for monitoring disease progression in GEP-NET patients. Tumor progression was evaluated with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by CT/MRI. An increase ≥ 50% above the prior CgA concentration to a value > 100 ng/mL in the following CgA concentration was considered positive. RESULTS: 153 GEP-NET patients were enrolled. Using the pre-specified cut-off of CgA change for tumor progression, specificity was 93·4% (95%-CI: 90·4%-95·5%, p < 0·001), sensitivity 34·4% (25·6%-44·3%), positive predictive value 57·9% (45·0-69·8), negative predictive value (NPV) 84·3% (80·5-87·6), and area under the curve 0·73 (0·67-0·79). CONCLUSIONS: Changes in serial measurements of serum CgA had a favorable specificity and NPV, making this test a useful adjunct to routine radiographic monitoring.

Total Copper and Labile Bound Copper Fraction as a Selective and Sensitive Tool in the Evaluation of Wilson Disease.

BACKGROUND: A dual filtration-based method for determination of serum labile bound copper (LBC) and LBC fraction (LBC/total copper) was developed. Reduced total copper, elevated LBC, and elevated LBC fraction have been reported in Wilson disease (WD). METHODS: To evaluate the diagnostic performance of these markers, samples were obtained from 21 WD treatment-naïve (WD-TN, no WD treatment or <28 days of treatment) patients, 46 WD standard-of-care-treated (WD-SOC) patients, along with 246 patients representing other potential disorders of copper status. These were then compared to 213 reference interval population patients. RESULTS: Receiver operating characteristic curves for the reference population vs WD-TN yielded areas under the curve for total copper, LBC, and LBC fraction, of 0.99, 0.81, and 0.98, respectively. Using Youden cutoffs, sensitivity/specificity for WD-TN was 95%/97% for total copper, 71%/85% for LBC, and 95%/94% for LBC fraction. LBC values, but not total copper and LBC fraction, differed substantially between WD-TN and WD-SOC cohorts.We propose a dual model wherein total copper and LBC fraction results must agree to be classified as a "positive" or "negative" result for WD. This correctly classified 19/21 WD-TN patients as positive, and 194/213 reference interval patients as negative. The remaining "indeterminate" patients (representing approximately 9% of the reference and the WD-TN populations) exhibited conflicting total copper and LBC fraction results. When indeterminate results are excluded, this model exhibited apparent 100% sensitivity/specificity. CONCLUSIONS: Agreement of total serum copper and LBC fraction classification may constitute an effective "rule-in" and "rule-out" assessment for WD-TN patients.

Performance of the Lumipulse plasma Aß42/40 and pTau181 immunoassays in the detection of amyloid pathology.

INTRODUCTION: This study evaluated the performance of the Lumipulse plasma beta-amyloid (Aß) 42/40 and pTau181 compared to other assays to detect an abnormal amyloid-positron emission tomography (PET). METHODS: Plasma samples from cognitively unimpaired (N = 179) and MCI/AD dementia (N = 36) individuals were retrospectively evaluated. Plasma Aß42/40 and pTau181 were measured using the Lumipulse and Simoa immunoassays. An immunoprecipitation mass spectrometry (IP-MS) assay for plasma Aß42/40 was also evaluated. Amyloid-PET status was the outcome measure. RESULTS: Lumipulse and IP-MS Aß42/40 exhibited the highest diagnostic accuracy for detecting an abnormal amyloid-PET (areas under the curve [AUCs] of 0.81 and 0.84, respectively). The Lumipulse and Simoa pTau181 assays exhibited lower performance (AUCs of 0.74 and 0.72, respectively). The Simoa Aß42/40 assay demonstrated the lowest diagnostic accuracy (AUC 0.57). Combining Aß42/40 and pTau181 did not significantly improve performance over Aß42/40 alone for Lumipulse (AUC 0.83) or over pTau181 alone for Simoa (AUC 0.71). DISCUSSION: The Lumipulse Aß42/40 assay showed similar performance to the IP-MS Aß42/40 assay for detection of an abnormal amyloid-PET; and both assays performed better than the two p-tau181 immunoassays. The Simoa Aß42/Aß40 assay was the least accurate at predicting an abnormal amyloid-PET status. Highlights: Lumipulse plasma Aß42/Aß40 AUC for abnormal amyloid-PET detection was 0.81.This performance was comparable to previously reported IP-MS and higher than Simoa.Performance of Alzheimer's disease blood biomarkers varies between assays.

Alzheimer Disease Cerebrospinal Fluid Biomarkers in a Tertiary Neurology Practice.

OBJECTIVE: To evaluate the performance of Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers in a tertiary neurology clinic setting with high frequency of non-AD cases, including normal pressure hydrocephalus (NPH). METHODS: There were 534 patients who underwent AD CSF biomarkers (Roche Elecsys Aß42, p-Tau181, total-Tau) from April 1, 2020, through April 23, 2021. A behavioral neurologist blinded to CSF results assigned a clinical diagnosis retrospectively on the basis of consensus criteria, and a neuroradiologist blinded to the diagnosis and CSF studies graded brain magnetic resonance images for indicators of CSF dynamics disorders. Associations between biomarkers, diagnoses, and imaging were assessed by χ2, analysis of covariance, and linear regression methods. RESULTS: Median age at time of testing was 67 years (range, 19 to 96 years), median symptom duration was 2 years (range, 0.4 to 28 years), and median Short Test of Mental Status score was 30 (range, 0 to 38). Clinical diagnoses significantly correlated with different CSF biomarker values (χ2=208.3; P=10e-4). p-Tau181/Aß42 ratios above 0.023 positively correlated with Alzheimer dementia (more than individual measures). This ratio also had the best performance for differentiating Alzheimer dementia from NPH (area under the curve, 0.869). Imaging markers supportive of CSF dynamics disorders correlated with low Aß42, p-Tau181, and total-Tau. CONCLUSION: In a heterogeneous clinical population, abnormal p-Tau181/Aß42 ratios (>0.023) have the strongest association with Alzheimer dementia and probably represent a comorbid AD pathologic component in persons clearly matching non-AD neurodegenerative syndromes. Altered CSF dynamics were associated with lower concentrations of AD CSF biomarkers regardless of clinical diagnosis, but the ratio compensates for these changes. In the appropriate clinical setting, an isolated abnormal Aß42 should prompt consideration of NPH.

Detection of Cadmium and Lead in Kidney Stones. Associations with Patient Demographics, Stone Composition, and Smoking.

BACKGROUND: Kidney stones are a highly prevalent disease worldwide. Additionally, both environmental and occupational exposure to Pb and Cd continue to be prevalent globally and can result in renal toxicity. The objective of this study was to examine the potential presence of Pb and Cd in kidney stones, and to assess for correlation with demographic factors including smoking, gender, age, and kidney stone matrix composition. METHODS: Patient kidney stones (n = 96) were analyzed using Fourier transform infrared spectroscopy to identify the stone constituents. Cd and Pb concentrations (µg/g) were determined by inductively coupled plasma mass spectrometry. Cd and Pb concentrations were correlated using bivariable and multivariable statistical analysis with demographic factors (age, gender, smoking status), and kidney stone composition. RESULTS: Kidney stone Cd (median 0.092 µg/g, range 0.014 to 2.46) and Pb concentrations (median 0.95 µg/g, range 0.060 to 15.4) were moderately correlated (r = 0.56, P < 0.0001). Cd concentrations were positively associated with patient history of smoking, patient age, and calcium oxalate monohydrate levels while negatively associated with struvite and uric acid/uric acid dihydrate. Pb concentrations were positively associated with females and apatite levels while negatively associated with uric acid/uric acid dihydrate. After holding constant other stone type composition levels, smoking status, and age, both Pb and Cd were positively associated with apatite and negatively associated with uric acid/uric acid dihydrate, struvite, and calcium carbonate. CONCLUSIONS: Cd and Pb kidney stone concentrations are associated with specific kidney stone types. Cd and Pb kidney stone concentrations are both associated with smoking.

Establishment of a Labile Bound Copper Reference Interval in a Healthy Population via an Inductively Coupled Plasma Mass Spectrometry Dual Filtration-Based Assay.

CONTEXT.­: Clinical testing for Wilson disease (WD) is potentially challenging. Measuring the fraction of labile bound copper (LBC) to total copper may be a promising alternative diagnostic tool with better sensitivity and specificity than some current biomarker approaches. A dual filtration-based inductively coupled mass spectrometry (ICP-MS) assay to measure LBC in serum was developed. OBJECTIVE.­: To establish a reference interval for LBC and LBC to total copper (LBC fraction) in a healthy adult population, and to examine associations between total copper, LBC, and LBC fraction with age, sex, menopausal status, hormone replacement therapy, and supplement use. DESIGN.­: Serum samples were collected from healthy male (n = 110) and female (n = 104) patients between the ages of 19 and 80 years. Total copper and LBC were analyzed using ICP-MS. Results were used to calculate the LBC fraction. Reference intervals were calculated for the 2.5th and 97.5th percentiles for both LBC and LBC fraction. RESULTS.­: The reference intervals for LBC were determined to be 13 to 105 ng/mL and 12 to 107 ng/mL for female and male patients, respectively. The reference intervals for the LBC fraction were 1.0% to 8.1% and 1.2% to 10.5% for female and male patients, respectively. No significant associations were found regarding age, menopausal status, hormone replacement therapy, or vitamin and supplement use. CONCLUSIONS.­: Sex-specific reference intervals have now been established for LBC and LBC fraction. These data in conjunction with further testing of WD populations can be used to assess the sensitivity and specificity of LBC fraction in screening, monitoring, and diagnosis.

Lack of observed interference by therapeutic monoclonal antibodies in select commonly utilized immunoassays.

BACKGROUND: Therapeutic monoclonal antibodies (tmabs) have been hypothesized to interfere with immunoassay measurements, although studies investigating this potential new class of interference are lacking. This study evaluated the effects of tmabs used in cancers ipilimumab (Bristol Myers Squibb), nivolumab (Bristol Myers Squibb), pembrolizumab (Merck) and autoimmune disorders adalimumab (AbbVie), infliximab (Janssen) and vedolizumab (Takeda) in common immunoassays used in the clinical laboratory. METHODS: Residual sera from 10 randomly chosen patients were split into two tubes and spiked with same volume (approximately 5 % final volume) of either saline (control) or 6 tmabs (final concentration of 100 µg/mL each). Concentrations from sixteen analytes in 19 different assays were assessed: TSH (Roche and Beckman), free thyroxine (Roche and Siemens), cortisol (Beckman), Cancer Antigens (CA): CA19-9 (Beckman), CA15-3 (Roche), CA125 (Roche), and CA27.29 (Siemens), carcinoembryonic antigen (Beckman), alpha-fetoprotein (Beckman), thyroglobulin (Beckman) and thyroglobulin antibodies (Beckman), thyroid peroxidase antibody (Beckman), beta-human chorionic gonadotropin (Roche and Beckman), total prostate-specific antigen (Roche), parathyroid hormone (Roche) and antinuclear antibodies IgG (Werfen). The tmab spiked residual sera were compared with matched saline spiked sera and percent error was assessed against allowable total error defined from biological variation or CLIA limits. RESULTS: None of the tested immunoassays were affected by the presence of the tmabs, in samples within or outside assay reference intervals. The median % error among all immunoassays ranged between -2.0% (for TSH) to 2.7% (for TPO Ab assay). CONCLUSION: These findings demonstrate no detectable tmab interference for the assessed immunoassays using spiked preparations of the tmabs in residual human sera. The findings are limited to the tmabs and immunoassays studied here.

Different glucose analyzers report different glucose concentration values in term newborns.

Background: The American Academy of Pediatrics and Pediatric Endocrine Society neonatal hypoglycemia guidelines based their glucose concentration treatment thresholds on studies that predominantly used Beckman and Yellow Springs Glucose Oxidase Analyzers. Currently, a majority (76%) of U.S. hospital laboratories utilizing glucose oxidase methodology use Vitros® Glucose Analyzers. However, a bias of ~+5% between glucose concentrations from Beckman vs. Vitros Glucose Analyzers has been reported; this could have a clinically significant effect when using published guideline treatment thresholds. Methods: To determine if there is similar instrument bias between Beckman and Vitros Analyzers in reported glucose concentrations from term newborns, we compared plasma glucose concentrations measured within the first 3 h after birth by Beckman vs. Vitros Analyzers in a total of 1,987 newborns (Beckman n = 904, Vitros n = 1,083). Data were fit using nonlinear cubic spline models between collection time and glucose concentration. Results: The non-linear patterns of initial glucose concentrations (during the first 3 h after birth) as measured by Beckman and Vitros Analyzers paralleled each other with no overlap of the fit spline curve 95% confidence intervals, with an approximate +5 mg/dL constant bias. Additionally, in method comparison studies performed in the Chemistry Laboratory on adult samples, there was a +4.2-7.4 mg/dL measured glucose bias for the Beckman vs. Vitros Analyzer. Conclusion: Glucose concentrations from term, appropriate size for gestational age newborns were about 5 mg/dL higher when measured by Beckman vs. Vitros Analyzers. Perhaps, concentrations of 45 mg/dL reported from Beckman Analyzers may be equivalent to 40 mg/dL from Vitros Analyzers. When managing neonatal hypoglycemia, it is important to know which analyzer was used and whether adjusting for potential instrument bias is necessary when following published guidelines.

Performance characteristics of the BRAHMS KRYPTOR automated squamous cell carcinoma antigen assay.

BACKGROUND: Squamous cell carcinoma antigen (SCCA) is a glycoprotein biomarker for squamous cell carcinoma (SCC). SCCA elevations have also been noted in other conditions. The purpose of this study was to evaluate the analytical and clinical performance of an automated SCCA homogenous immunofluorescent assay (BRAHMS KRYPTOR). METHODS: Reference intervals were determined using 119 samples from healthy donors. To assess clinical performance, samples were collected from patients with cervical (n = 12), head and neck (n = 23), lung (n = 14), or cutaneous (n = 11) SCC in addition to hepatocellular carcinoma, psoriasis, or atopic dermatitis. RESULTS: Upper 95th percentile sex-specific reference intervals were 2.00 µg/L for males and 1.67 µg/L for females. Intra- and inter-assay CVs were less than 5%. Comparison of the BRAHMS KRYPTOR to an ELISA SCCA immunoassay exhibited a correlation coefficient of 0.8809. The mean sensitivity for all SCC positive patients was 23.3%. With the exception of psoriasis (58.6%) specificity exceeded 95% for the non-SCC populations. CONCLUSION: The BRAHMS KRYPTOR SCCA assay showed good analytical performance and acceptable overall clinical specificity. Consistent with previous studies, the sensitivity of SCCA for SCC was low. In the absence of other robust circulating markers, SCCA remains an imperfect yet useful tool in the evaluation of SCC.

Plasma neurofilament light chain (NfL) reference interval determination in an Age-stratified cognitively unimpaired cohort.

BACKGROUND AND AIMS: Neurofilament light chain (NfL) is an emerging biomarker of neurodegenerative disease progression. As plasma NfL increases with age, characterization of NfL concentrations in an age-stratified cognitively unimpaired population was assessed. MATERIALS AND METHODS: EDTA-plasma samples were measured using the Simoa® NF-light™ Advantage Kit assay. One-sided reference intervals were established from 1100 cognitive normal individuals (588 male, 512 female) aged 20 to 95 years. Of those, 927 samples were obtained from the Mayo Clinic Study of Aging cohort (age > 50 years), and the remainder (age < 50 years) were obtained from individuals without known neurological conditions. All samples were from individuals without known chronic kidney disease, stroke or myocardial infarction, and a body mass index < 30 kg/m2. RESULTS: The 97.5th percentile limits for the following age ranges (in years) were (pg/mL): 20 s: ≤8.4, 30 s: ≤11.4, 40 s: ≤15.4, 50 s: ≤20.8, 60 s: ≤28.0, 70 s: ≤37.9, 80+: ≤51.2. Sex had no significant effect on reference intervals. Observed NfL concentrations increased at a rate of 3.1 % per year of age. CONCLUSIONS: Characterization of the rate of NfL concentration increase and decade-wide reference intervals from a neurologically well-characterized patient population will aid in interpretation of NfL during the clinical evaluation of a potential neurodegenerative disease.