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N/A, letter to the editor

Background: Free triiodothyronine (fT3) testing is most useful when thyroid stimulating hormone (TSH) is suppressed, and free thyroxine (fT4) is normal or decreased. These laboratory values in a symptomatic patient are referred to as T3 thyrotoxicosis. Standards for fT3 reflex testing have not been established. Herein, we examined the clinical utility of fT3 with the goal of identifying a TSH cutoff in the context of normal/decreased fT4 that maximizes the utility of measuring fT3. Methods: TSH, fT4, and fT3 results between January 2016 and October 2021 were extracted from the laboratory information system and grouped if resulted on the same day for the same patient. Frequency of biochemical T3 thyrotoxicosis was evaluated at different TSH cutoffs and in outpatient vs inpatient settings. Results: Of the 4366 TSH-fT4-fT3 results, 70 (1.6%) were consistent with biochemical T3 thyrotoxicosis. The common reasons were previously diagnosed hyperthyroidism on antithyroid medication (n = 28) or hypothyroidism on thyroid medication (n = 18) and newly diagnosed hyperthyroidism (n = 20, 0.5%). The likelihood of detecting T3 thyrotoxicosis increased with lower TSH cutoff (<0.3 μIU/mL, 10.3% vs <0.0 1μIU/mL, 27.6%). All patients with newly diagnosed hyperthyroidism had TSH <0.01 μIU/mL. Higher frequency of T3 thyrotoxicosis was observed in the outpatient setting (34%) relative to the inpatient setting (14%, P < 0.001) when TSH < 0.01 μIU/mL. Conclusions: T3 thyrotoxicosis is a relatively rare diagnosis and fT3 measurement has limited utility in the vast majority of patients. A fT3 reflex for patients with TSH <0.01 μIU/mL and normal/low fT4 may improve clinical utility and reduce unnecessary testing, especially in the outpatient setting. [ABSTRACT FROM AUTHOR]

Background: The Freelite assay (The Binding Site) is utilized to quantify serum immunoglobulin free light chains (sFLC), which is crucial for diagnosing and monitoring plasma cell dyscrasias (PCDs). Using the Freelite test, we compared methods and evaluated workflow differences across two analyzer platforms. Methods: sFLC concentrations were measured in 306 fresh serum specimens (cohort A) and 48 frozen specimens with documented sFLC >20 mg/dL (cohort B). Specimens were analyzed on the Roche cobas 8000 and Optilite analyzers using the Freelite κ and λ assays. Performance was compared using Deming regression. Workflow was compared by assessing turnaround time (TAT) and reagent usage. Results: For cohort A specimens, Deming regression revealed a slope of 1.04 (95% CI, 0.88–1.02) and an intercept of −0.77 (95% CI, −0.57 to 1.85) for sFLCκ and a slope of 0.90 (95% CI, −0.04 to 1.83) and intercept of 1.59 (95% CI, −3.12 to 6.25) for sFLCλ. Regression of the κ/λ ratio revealed a slope of 2.44 (95% CI, 1.47–3.41) and intercept of −8.13 (95% CI, −16.82 to 0.58) with a concordance kappa of 0.80 (95% CI, 0.69–0.92). The proportion of specimens with TAT >60 min was 0.33% and 8% for the Optilite and cobas, respectively (P < 0.001). The Optilite required 49 (P < 0.001) and 12 (P = 0.016) fewer tests for sFLCκ and sFLCλ relative to the cobas. Cohort B specimens showed similar but more dramatic results. Conclusions: Analytical performance of the Freelite assays was comparable on the Optilite and cobas 8000 analyzers. In our study, the Optilite required less reagent, had a slightly reduced TAT, and eliminated manual dilutions for samples with sFLC concentrations >20 mg/dL. [ABSTRACT FROM AUTHOR]

Background: False-positive results for human chorionic gonadotropic (hCG) on point-of-care (POC) devices can occur for a variety of technical and biological reasons. It has been postulated that urinary tract infection can result in false-positive POC hCG assays, but the cause of this phenomenon remains elusive. Gram-positive bacteria have previously been reported to express an hCG-like molecule. We investigated whether urinary tract infection with Gram-positive bacteria can result in false-positive POC hCG. Methods: We utilized remnant clinical urine specimens that had been submitted for culture as part of evaluation for urinary tract infection. Urine specimens with >100,000 colony-forming units per milliliter of Gram-positive bacteria (n=95) were tested on ICON 20 POC hCG tests (Beckman Coulter). Specimens from adult patients that had been collected for clinical testing in the prior 48 hours were included in the study, and only 1 specimen per patient was included. Results: Of 95 patients with Gram-positive urine specimens, 42 (44%) were female, and the median age was 62 years. The most common bacteria identified during clinical urine culture of these patients' specimens were coagulase-negative Staphylococcus species (36/95, 38%), Enterococcus species (34/95, 36%), and Streptococcus aga-lactiae (9/95, 9%). Five of 95 (5.3%) urine specimens were positive for POC hCG. Chart review revealed that 3 specimens were from pregnant women and 2 were from patients with cancer diagnoses. Conclusions: Urine specimens from patients suspected to have urinary tract infection with Gram-positive organ- isms did not cause positive results on POC hCG test devices. [ABSTRACT FROM AUTHOR]

Background: Serum free light chain (FLC) assays are used clinically to measure the concentration of ĸ and λ FLC in patients with suspected or diagnosed plasma cell proliferative disorders. Previous studies have demonstrated a loss of linearity in low concentration ranges of these assays. We hypothesized that this result could be caused by a matrix effect. Methods: Recovery studies were performed for ĸ and λ FLC in both serum and saline using the Freelite assay (Binding Site) on a Cobas c502 system (Roche). Samples were analyzed either at the recommended dilution or undiluted. Follow-up studies were performed in varying matrices ranging from 0% to 100% saline. Retrospective patient data were analyzed to assess the impact on reported ĸ FLC, λ FLC, and ĸ/λ ratio. Results: FLC in a serum matrix demonstrated underrecovery relative to samples diluted in saline for both ĸ and k FLC. Of 255 patient samples with λ FLC measured undiluted (λ FLC <6.0 mg/L), an unexpected gap was observed in patient results between 2.0 and 6.0 mg/L. In addition, 23 patients measured serially with λ FLC between 2.0 and 6.0 mg/L demonstrated dramatic changes in ĸ/λ ratio, with no changes in ĸ FLC, likely because of the matrix effect. Conclusions: The ĸ and λ Freelite assays exhibit a matrix effect when samples are tested undiluted, which has the potential to affect the ĸ/λ ratio. Consequently, our laboratory has stopped reporting λ FLC <6.0 mg/L. [ABSTRACT FROM AUTHOR]

Background: Homogeneous turbidimetric immunoassays are widely used in the clinical laboratory and offer short assay times, reduced reagent costs, and the potential for full automation. However, these assays have a limited analytical measurement range (AMR) above which antigen excess leads to falsely low estimates of the analyte concentration (i.e., the hook effect). Traditional methods for correction of antigen excess require sample dilution, compromising time and cost-efficiency. Therefore, novel methods that extend the AMR are needed. Methods: A kinetic model of a generic homogeneous turbidimetric immunoassay was built and then parameterized using a genetic algorithm. Kinetic features that could be used to extend the AMR were identified and subsequently validated with clinical data from consecutive measurements of 2 homogeneous turbidimetric immunoassays: κ serum free light chain and rheumatoid factor. Results: A novel kinetic parameter, the area under the curvature (AUCU), was derived that increases in proportion to the analyte concentration in a range beyond the AMR of conventional end point methods. When applied to clinical data, the AUCU method provided a log-linear calibration curve in the zone of antigen excess extending the AMR by >10-fold for 2 different immunoassays. Conclusions: The AUCU method detects and corrects antigen excess, extending the AMR in homogeneous turbidimetric immunoassays. The advantage of this method over conventional methods would be a reduction in the number of repeated samples, resulting in significant time and cost savings. [ABSTRACT FROM AUTHOR]

Background: Toxoplasmosis is routinely diagnosed through detection of Toxoplasma gondii--specific antibodies. However, the imperfect specificity of T. gondii serologic assays is a well-recognized limitation. The new BioPlex 2200 (Bio-Rad Laboratories) T. gondii, rubella, and cytomegalovirus (ToRC) IgM multiplex flow immunoassay (MFI) received FDA clearance in May 2017. We evaluated the clinical performance of the new T. gondii IgM and existing IgG portion of this MFI. Methods: Three hundred prospectively collected consecutive, residual sera, submitted for T. gondii serologic testing as part of routine clinical care, and an archived set of 52 residual sera previously positive for anti--T. gondii IgM and IgG with the predicate ADVIA Centaur Toxoplasma IgM and IgG assays (Siemens) were evaluated. Performance of the BioPlex 2200 T. gondii IgM and IgG MFIs was assessed by calculating positive (PPA) and negative percent agreement (NPA) compared to the Centaur tests. Results: Among prospective specimens, the BioPlex 2200 T. gondii IgM and IgG MFIs demonstrated a PPA of 0% (0/7) and 82.3% (28/34) and NPA of 99.3% (288/290) and 95.8% (251/262), respectively, with the Centaur assays. Chart review of the 7 Centaur T. gondii IgM-positive samples revealed that these were likely falsely positive. Among archived samples, the BioPlex 2200 T. gondii IgM and IgG MFIs showed PPAs of 90.4% (47/52) and 100% (52/52), respectively. Conclusions: The BioPlex 2200 T. gondii IgM and IgG MFIs demonstrated excellent concordance with the Centaur assays. The T. gondii IgM MFI may provide higher specificity in low-prevalence populations. [ABSTRACT FROM AUTHOR]

Background: Improving promotion and retention of women in pathology at major medical schools is important, especially in schools and departments that are below Association of American Medical College averages for these metrics. Our objective was to create a professional development program for women within the Department of Pathology at Washington University School of Medicine and to assess its perceived value. Methods: A forum for women faculty, residents, and fellows was created and has been in place for 5 years. The forum meets once per month; the content includes various topics, articles, books, and invited speakers and covers a broad range of professional development subjects. The success of the forum was assessed by surveying attendees. A survey was created with Surveymonkey.com and sent to 65 women who had been invited to the forum over the 5-year period. Results: Responses were received from 26/65 (40%) women surveyed. Junior faculty constituted 42% of attendees, with fellows, residents, midcareer faculty, and senior faculty attending in the descending order of frequency. All responders found the forum valuable. The most valuable content can be broken into 2 major themes: (a) issues facing women in medicine (such as unconscious bias) and (b) tools for improving professional development (such as negotiation skills for women). Conclusions: Survey responses and comments indicate that this forum is perceived as extremely valuable. This format and content could easily be replicated in any academic department. Knowledge of what topics women found the most valuable can help direct the content and enhance successful outcomes of this type of professional development program. [ABSTRACT FROM AUTHOR]

The author talks about the difficulty of reporting quantitative human chorionic gonadotropin (hCG) results. She discusses study findings on the different concentrations of hCG of men and women, indication of intermediate hCG concentrations, and recommendations to help improve the reporting of quantitative hCG results.