Immunoassays are currently the methods of choice for the measurement of a large panel of complex and heterogenous molecules owing to full automation, short turnaround time, high specificity and sensitivity. Despite remarkable performances, immunoassays are prone to several types of interferences that may lead to harmful consequences for the patient (e.g., prescription of an inadequate treatment, delayed diagnosis, unnecessary invasive investigations). A systematic search is only performed for some interferences because of its impracticality in clinical laboratories as it would notably impact budget, turnaround time, and human resources. Therefore, a case-by-case approach is generally preferred when facing an aberrant result. Hereby, we review the current knowledge on immunoassay interferences and present an algorithm for interference workup in clinical laboratories, from suspecting their presence to using the appropriate tests to identify them. We propose an approach to rationalize the attitude of laboratory specialists when faced with a potential interference and emphasize the importance of their collaboration with clinicians and manufacturers to ensure future improvements.
Evidence about the long‐term persistence of the booster‐mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID‐19 naive and 51 with a history of SARS‐CoV‐2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2‐ and 11.5‐fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS‐CoV‐2 infection. A corresponding 2.5‐ and 2.9‐fold decrease in binding antibodies was observed. The estimated T
1/2
of neutralizing antibodies in participants with and without history of SARS‐CoV‐2 infection was 42 (95% confidence interval [CI]: 25–137) and 36 days (95% CI: 25–65). Estimated T
1/2
were longer for binding antibodies: 168 (95% CI: 116–303) and 139 days (95% CI: 113–180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE (
r
= 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era.
Highlights d 3-BrPA treatment induces MCT1 silencing through gene promoter hypermethylation d 3-BrPA-resistant cancer cells strictly rely on MCT4 for lactate release and glycolysis d Hypoxia and OXPHOS inhibition are favorable to 3BrPAresistant cancer cells d Combination of 3-BrPA treatment and MCT4 inhibition prevents resistance development
Background
Interpretation of thyroid function tests by means of biological variation (BV) data is essential to identify significant changes between serial measurements at an individual level. Data on thyroid parameters in adults are limited.
Objectives
We aimed at determining the BV of four thyroid function test (thyroid‐stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3) and thyroglobulin (Tg)) by applying recent recommendations to acquire BV data on a latest generation of immunoassay.
Methods
Nineteen healthy volunteers (8 males and 11 females) were drawn every week during 5 consecutive weeks. Samples were analysed in duplicate on the Cobas 602 analyzer (Roche Diagnostics). After normality assessment, outlier exclusion and homogeneity of variance analysis, analytical variation (CVA), within‐subject biological variation (CVI) and between‐subject biological variation (CVG) were determined using nested ANOVA.
Results
CVA, CVI and CVG were 0.9%, 19.7% and 37.6% for TSH; 3.6%, 4.6% and 10.8% for FT4; 2.2%, 6.0% and 8.6% for FT3; and 0.9%, 15.4% and 84.9% for Tg. Index of individuality (II) for all parameters was between 0.2 and 0.7. The percentage above which the change between two measures is truly significant (reference change value) was 54.7% for TSH, 16.2% for FT4, 17.7% for FT3 and 42.8% for Tg.
Conclusion
Based on recent international recommendations, our study provides updated BV data for four thyroid function tests in European healthy volunteers. Reliable BV characteristics, and especially RCV, can facilitate the interpretation of consecutive thyroid function tests in an individual and therefore have the potential to efficiently support clinical decisions regarding thyroid diseases.
Laboratory investigations of hypercalcemia involve testing of various biochemical parameters such as parathyroid hormone (PTH), 25-(OH) Vitamin D (25-(OH) VitD), 1,25-(OH)2 Vitamin D3 (calcitriol) and PTH related peptide (PTHrp). We herein present an atypical case of severe hypercalcemia in a patient with rheumatoid arthritis who has been treated for years by various biological
disease-modifying antirheumatic drugs (DMARDs) and suddenly presented with general state alteration, oedema and ulceration of her right ankle. We illustrate how tuberculosis (TB) can cause high calcitriol concentration and subsequently lead to potentially severe hypercalcemia. Moreover, we highlight the importance of TB testing and follow-up in patients treated with biological DMARDs.
Introduction Studies about the duration of the humoral and
cellular response following the bivalent booster administration are
still scarce. We aimed at assessing the humoral and cellular response in
a cohort of healthcare workers that received this booster.
Material and methods Blood samples were collected before the
administration of the bivalent booster from Pfizer-BioNTech and after
14, 28, 90, and 180 days. Neutralizing antibodies against either the
D614G strain, the delta variant, the BA.5 variant, or the XBB.1.5
subvariant were measured. The cellular response was assessed by
measurement of the release of interferon gamma (IFNγ) from T cells in
response to an in vitro SARS-CoV-2 stimulation. Results
A substantial waning of neutralizing antibodies was observed after 6
months (23.1‐fold decrease), especially considering the XBB.1.5
subvariant. The estimated T of neutralizing
antibodies was 16.1 days (95% CI=10.2–38.4 days). Although most
participants still present a robust cellular response after 6 months
(i.e., 95%), a significant decrease was also observed compared to the
peak response (0.41 versus 0.95 UI/L, p=0.0083). Conclusion A
significant waning of the humoral and cellular response was observed
after 6 months. These data can also help national competent authorities
in their recommendation regarding the administration of an additional
booster.
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