Use of Cotton Balls in Diapers for Collection of Urine Samples Impacts the Analysis of Routine Chemistry Tests: An Evaluation of Cotton Balls, Diapers, and Chemistry Analyzers.

OBJECTIVE: To evaluate the suitability of urine samples collected with cotton balls placed into diapers for routine laboratory chemistry analyses. STUDY DESIGN: Twenty pools of residual unpreserved urine samples were separated into control and treated aliquots. The treated samples were absorbed into 2 different brands of cotton balls, wrapped in 3 different brands of diapers, and incubated at 37°C for 1 hour. The urine-soaked cotton balls were placed into a syringe and expressed via plunger depression. Urine sodium, potassium, creatinine, urea, calcium, magnesium, inorganic phosphorus, albumin, and total protein were measured on all samples on 5 automated clinical chemistry platforms: Ortho Vitros 4600, Siemens Dimension Vista 500, Beckman Coulter AU5822, Roche Cobas 6000, and Abbott Architect c8000 at 5 separate hospital laboratories. Criteria used to exclude the presence of significant effects of urine from presoaked cotton balls in a diaper on the measurement of chemistry laboratory tests were R2 >0.95, slope of 0.9-1.1, and mean bias within ±10%. RESULTS: Albumin and total protein measurements demonstrated significant negative bias in urine from both brands of presoaked cotton balls with all brands of diapers on all 5 chemistry platforms compared with the control urine. We did not observe a significant effect of presoaking urine in cotton balls in a diaper on the measurement of sodium, inorganic phosphorus, and urea. The remaining tests demonstrated significant effects when measured in urine from presoaked cotton balls and/or diapers that were specific to the chemistry analyzer platform or diaper. CONCLUSIONS: Diaper and cotton ball-based urine collection significantly impacts the measurement of several common chemistry assays.

The 2021 PhD Board-Certified Clinical Chemist Compensation Survey.

INTRODUCTION: Doctoral-level clinical chemists work in various settings including academia, healthcare systems, reference laboratories, and industry. Information regarding compensation and benefits for PhD board-certified clinical chemists is limited. The American Association for Clinical Chemistry's (AACC) Society for Young Clinical Laboratorians (SYCL) Core Committee completed a compensation survey in February 2021 and compared that to previous survey results. METHODS: The 2021 salary survey was made available to all doctoral-level AACC members working in the United States and Canada. Respondents provided information on type of degree and board certification, years of experience, employment sector, geographic location, and gender. The survey collected confidential self-reported data from 208 respondents, with 187 (90%) respondents residing in the United States. RESULTS: The 25th percentile, median and 75th percentile total compensation range for 113 PhDrespondents who are certified by the American Board of Clinical Chemistry (ABCC) and residing in the United States was $150 000 to $159 000, $180 000 to $189 000, and $230 000 to $239 000, respectively. Most of the respondents worked in either an academic, hospital, or healthcare system setting, with 47% of respondents working at academic medical centers. CONCLUSIONS: In this 2021 compensation survey, we continue to see an upward trend in compensation ranges for board certified PhD clinical chemists. This report is important in allowing individuals to actively advocate with prospective and current employers for equal and fair compensation as well as other benefits that impact career development and growth.

The 2018 AACC/SYCL PhD Clinical Chemist Compensation Survey.

BACKGROUND: Doctoral level board-certified clinical chemists play an invaluable role in many facets of laboratory medicine and healthcare. However, information concerning their total compensation is sparse. CONTENT: A confidential self-reported compensation survey was conducted by the American Association for Clinical Chemistry's Society for Young Clinical Laboratorians (AACC SYCL) Core Committee from April 1 to April 17, 2018. Respondents provided information on geographic location, employment sector, gender, and years of experience to account for the influence of these variables on compensation. There were 199 respondents in total from the United States and Canada, however, only respondents employed in the United States with an earned doctoral degree and certification by the American Board of Clinical Chemistry (n = 133), were included in the full analysis. In comparison to compensation reported in AACC SYCL salary surveys conducted in 2010 and 2013, early career median salaries are trending upwards after correction for inflation. SUMMARY: This survey is the first to collect the gender of respondents, and identify a pay gap for some geographic groups. However, this gap could be due in part to a difference in the years of experience, since males were highly represented in the group with >20 years of experience (25 out of 35, 71%). Future studies on compensation trends within clinical chemistry that do not rely on self-report are needed to ensure accuracy and completeness of the dataset.

Unrecognized Elevations of Toxic Elements in Urine and Blood Highlight the Potential Need for a Broader Approach to Exposure Assessment.

Heavy metals testing remains an ongoing challenge for diagnosing acute or chronic exposure to heavy metals. In this study, we determined the positivity rates of single element and panel testing for toxic elements, and evaluated the potential utility of an expanded detection protocol for screening of toxic element exposures. The retrospective analysis included data from urine (n = 19,343) and blood (n = 196,019) specimens tested using inductively coupled plasma-mass spectrometry (ICP-MS) for arsenic, cadmium, lead and mercury (blood), and arsenic, cadmium, copper, lead, mercury and zinc (urine). Lead industrial monitoring in blood and cadmium exposure in blood and urine were included to represent directed single element ordering. The percent of positive results, defined as results greater than the upper limit of the reference interval was determined. For blood, the highest positivity was observed for lead occupational exposure monitoring (26.2%) whereas for urine, the highest positivity was observed for zinc testing (28.1%). Remarkably, reanalysis using an expanded panel, of 120 blood and 174 urine specimens originally negative identified 42% (50 of 120) of the blood specimens with at least one elevated result and 48% (83 of 174) of the urine specimens with at least one elevated result. Our results indicate that a broad elemental screening panel may help ensure easier identification of elemental exposure and may eliminate the need for additional follow-up sample collections.

Reference Intervals for Intestinal Disaccharidase Activities Determined from a Non-Reference Population.

BACKGROUND: Cutoff activities for diagnosing disaccharidase deficiencies are historical and are difficult to verify from a reference population. The objectives of this study were to validate the utility of historical disaccharidase cutoffs using data from clinical samples and to evaluate the demographics of individuals for whom intestinal disaccharidase testing was performed. METHODS: Results from 14,827 disaccharidase test samples were extracted from the laboratory information system. Data were analyzed by the Hoffman method to calculate a reference interval for each enzyme, and the lower limits were compared to historical cutoffs. The observed frequencies of disaccharidase deficiencies were determined using historic and calculated cutoffs. RESULTS: The median patient age of the entire data set was 13 years (range <1-88 years), and 45% were male. The cutoffs for lactase, maltase, palatinase, and sucrase were determined to be 10, 100, 9, and 25 U/g protein, respectively. Applying these cutoffs to the data set, 61% had no enzyme deficiencies, 35% were lactase deficient, 11% were maltase deficient, 13% were palatinase deficient, and 13% were sucrase deficient. Pandisaccharidase deficiency was present in 8%. CONCLUSIONS: Disaccharidase testing is most commonly performed in patients <18 years. Lactase deficiency is the most frequently observed single-disaccharidase deficiency. The historical cutoffs for maltase and sucrase were validated. To align with calculated reference intervals, the palatinase cutoff should increase from 5 to 9 U/g protein, and the lactase cutoff should decrease from 15 to 10 U/g protein.

Pathology consultation on urine compliance testing and drug abuse screening.

OBJECTIVES: Compliance testing in pain management requires a distinct approach compared with classic clinical toxicology testing. Differences in the patient populations and clinical expectations require modifications to established reporting cutoffs, assay performance expectations, and critical review of how best to apply the available testing methods. Although other approaches to testing are emerging, immunoassay screening followed by mass spectrometry confirmation remains the most common testing workflow for pain management compliance and drug abuse testing. METHODS: A case-based approach was used to illustrate the complexities inherent to and uniqueness of pain management compliance testing for both clinicians and laboratories. RESULTS: A basic understanding of the inherent strengths and weaknesses of immunoassays and mass spectrometry provides the clinician a better understanding of how best to approach pain management compliance testing. CONCLUSIONS: Pain management compliance testing is a textbook example of an emerging field requiring open communication between physician and performing laboratory to fully optimize patient care.

Total arsenic screening prior to fractionation enhances clinical utility and test utilization in the assessment of arsenic toxicity.

OBJECTIVES: The objective was to evaluate the utility of a screen with reflex-to-fractionation testing compared with direct-to-fractionation testing for suspected toxic exposure. METHODS: This study was based on a retrospective data analysis of urine arsenic results from previously tested samples (n=12,960). Total urine arsenic by inductively coupled plasma mass spectrometry was used as a screening method to identify elevated arsenic concentrations. Arsenic fractionation was the speciation assay to differentiate toxic and benign arsenic species. RESULTS: Screening samples based on total arsenic concentration resulted in less than 10% of samples requiring arsenic fractionation, with a final positivity rate of less than 1% for toxic arsenic. Samples with fractionation ordered directly had a positivity rate for toxic arsenic of 3.3%. The overall positivity rate for exposure to toxic arsenic was less than 1%. CONCLUSIONS: A total arsenic screen before fractionation reduces the number of samples requiring fractionation by more than 91%, supporting the use of a screen with a reflex-to-fractionation approach for urine arsenic.

THE SYNTHESIS OF 13C9-15N-LABELED 3,5-DIIODOTHYRONINE AND THYROXINE.

Thyroid hormones undergo extensive metabolism to regulate hormone activity. A labeled thyroid hormone would be useful to track hormone metabolism through various pathways. While radiolabeled thyroid hormones have been synthesized and used for in vivo studies, a stable isotope labeled form of thyroid hormone is required for studying thyroid hormone metabolism by LC-MS/MS, an analytical technique that has certain advantages without the complications of radioactivity. Here we report the synthesis of 13C9-15N-T2 and 13C9-15N-T4, two labeled thyroid hormone derivatives suitable for in vivo LC-MS/MS studies.

Biosynthesis of 3-iodothyronamine (T1AM) is dependent on the sodium-iodide symporter and thyroperoxidase but does not involve extrathyroidal metabolism of T4.

3-Iodothyronamine (T(1)AM) is an endogenous thyroid hormone derivative with unknown biosynthetic origins. Structural similarities have led to the hypothesis that T(1)AM is an extrathyroidal metabolite of T(4). This study uses an isotope-labeled T(4) [heavy-T(4) (H-T(4))] that can be distinguished from endogenous T(4) by mass spectrometry, which allows metabolites to be identified based on the presence of this unique isotope signature. Endogenous T(1)AM levels depend upon thyroid status and decrease upon induction of hypothyroidism. However, in hypothyroid mice replaced with H-T(4), the isotope-labeled H-T(3) metabolite is detected, but no isotope-labeled T(1)AM is detected. These data suggest that T(1)AM is not an extrathyroidal metabolite of T(4), yet is produced by a process that requires the same biosynthetic factors necessary for T(4) synthesis.

Identification and quantification of 3-iodothyronamine metabolites in mouse serum using liquid chromatography-tandem mass spectrometry.

3-Iodothyronamine (T(1)AM) is an endogenous derivative of thyroxine. Recently there have been numerous reports of analytical methods to quantify endogenous T(1)AM levels, but substantial discrepancies in concentration depending on the method of analysis (LC-MS/MS or immunoassay) suggest endogenous T(1)AM may be covalently modified in vivo. Using information dependent acquisition methods to perform unbiased scans for T(1)AM metabolites following a single IP injection in mice, we have identified O-sulfonate-T(1)AM, N-acetyl-T(1)AM and T(1)AM-glucuronide as conjugates occurring in vivo, as well as the oxidatively deaminated 3-iodothyroacetic acid and non-iodinated thyroacetic acid. 3-iodothyroacetic acid, O-sulfonate-T(1)AM and T(1)AM-glucuronide are present in serum at greater concentrations that unmodified T(1)AM and all metabolites are extensively distributed to tissues. These results suggest covalent modifications of T(1)AM may play a critical role in regulating distribution and biological activity of T(1)AM, and analytical methods to quantify endogenous T(1)AM should be able to account for these metabolites as well.

Validation of a liquid chromatography-tandem mass spectrometry method to enable quantification of 3-iodothyronamine from serum.

There is great interest lately in the availability of analytical methods for quantification of 3-iodothyronamine from blood and tissues. To date, no validated method for determination of 3-iodothyronamine from biological matrices has been described. Detailed in this report is an LC-MS/MS method that permits accurate and reproducible quantification of pharmacological concentrations of 3-iodothyronamine from rat serum, with a 0.0008 M lower limit of quantification. Endogenous 3-iodothyronamine was observed from rodent and human serum (0.2 mL) at the method limit of detection. In summary, the LC-MS/MS method enables quantification of circulating 3-iodothyronamine to allow examination of a relationship with biological activity.