The free cortisol calculated: correlation with the free cortisol concentrations measured with liquid chromatography-tandem mass spectrometry after equilibrium dialysis and establishment of reference intervals.

BACKGROUND: Changes in cortisol binding globulin (CBG) impact the total serum cortisol concentration and affect the accurate assessment of adrenal function. Free biologically cortisol can be calculated using different equations or directly measured after complicated procedures. METHODS: The free cortisol index (FCI) obtained using the Bonte formula as well as the free cortisol concentration calculated (Coolens equation) were first estimated for 45 healthy workers. The CBG level was determined by a competitive radioimmunoassay and the total cortisol concentration, was measured with an electrochemiluminescent assay. The correlations between FCI, the free cortisol concentrations calculated and the free cortisol levels measured with liquid chromatography-tandem mass spectrometry after equilibrium dialysis were studied for those 45 samples. Reference limits were established on 158 healthy hospital workers and patients with serum samples collected between 7:30 am and 10 am. RESULTS: The FCI as well as the free cortisol concentrations calculated obtained for the 45 samples correlated significantly with the free cortisol levels measured. Although the cortisol and CBG levels were statistically higher in women using contraceptives compared with women not taking them as well as men, the calculated FCI and free cortisol concentrations did not differ between these groups. The medians (P2.5-P97.5) obtained for the 158 healthy workers were respectively 26.4% (12.3-51.6%) and 10.6 nmol/L (4.3-26.7 nmol/L). CONCLUSIONS: This study highlighted a significant correlation between the FCI, the free cortisol concentrations calculated and the free cortisol levels measured with LC-MS/MS, it has also allowed the establishment of reference intervals for calculated FCI and free cortisol.

Cascadion™ SM Clinical Analyzer: Evaluation of the whole blood immunosuppressants quantification and routine usability.

BACKGROUND: Liquid chromatography coupled with tandem mass spectrometry (LC- MS/MS) tends to overcome other methods for therapeutic drugs monitoring (TDM) due to its very good analytical performances. Nevertheless, the lack of automation still limits its use in laboratory medicine. The Cascadion SM Clinical Analyzer (Thermo Fisher Scientific) is the first fully automated LC-MS/MS instrument available. We evaluated its immunosuppressant drugs (ISD) assay and the incorporation of such instrument into a core-laboratory. METHODS: An extended analytical verification of the Cascadion ISD panel including cyclosporin A, tacrolimus, everolimus and sirolimus was performed. It was compared to the MassTox ISD assay (Chromsystems). Different preanalytical and analytical conditions were tested. Finally, a turnaround-time evaluation and a satisfaction survey of users after 11 months of use in a core-laboratory were performed. RESULTS: Precision and linearity results were within the analytical goals fixed. The comparison with the MassTox ISD assay showed results in agreement except for cyclosporin A where a bias of -11.6% was observed, probably due to a greater trueness of the Cascadion method. Additional experiments showed good performances. The random accessibility and the ease of use by non-specialized staff members allowed a wider working time range and a reduction of the turnaround-time of 55%. CONCLUSION: The Cascadion ISD Panel held its promises in term of analytical performances, workflow aspects and ease of use by non-specialized staff.

Severity of COVID-19 among Hospitalized Patients: Omicron Remains a Severe Threat for Immunocompromised Hosts.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the general population in the context of a relatively high immunity gained through the early waves of coronavirus disease 19 (COVID-19), and vaccination campaigns. Despite this context, a significant number of patients were hospitalized, and identifying the risk factors associated with severe disease in the Omicron era is critical for targeting further preventive, and curative interventions. We retrospectively analyzed the individual medical records of 1501 SARS-CoV-2 positive hospitalized patients between 13 December 2021, and 13 February 2022, in Belgium, of which 187 (12.5%) were infected with Delta, and 1036 (69.0%) with Omicron. Unvaccinated adults showed an increased risk of moderate/severe/critical/fatal COVID-19 (crude OR 1.54; 95% CI 1.09-2.16) compared to vaccinated patients, whether infected with Omicron or Delta. In adults infected with Omicron and moderate/severe/critical/fatal COVID-19 (n = 323), immunocompromised patients showed an increased risk of in-hospital mortality related to COVID-19 (adjusted OR 2.42; 95% CI 1.39-4.22), compared to non-immunocompromised patients. The upcoming impact of the pandemic will be defined by evolving viral variants, and the immune system status of the population. The observations support that, in the context of an intrinsically less virulent variant, vaccination and underlying patient immunity remain the main drivers of severe disease.

Two-day low-dose dexamethasone suppression test more accurate than overnight 1-mg in women taking oral contraceptives.

INTRODUCTION: Late-night salivary cortisol (LSaC) and 24-h urinary free cortisol measurement, and overnight 1-mg dexamethasone suppression test (1 mg-DST) are the first-line screening tests recommended for Cushing's syndrome. Through elevations in the level of cortisol-binding globulin, oral contraceptive agents lead to increases in the total plasma cortisol concentration, yielding false-positive 1 mg-DST results. OBJECTIVE: To compare the accuracy of the overnight 1-mg DST and two-day low-dose DST (2d-DST) in female volunteers taking combined oestrogen-progestin oral contraceptives (COCs). METHODS: This prospective study enrolled 30 healthy participants. Their plasma cortisol response levels were compared after the 1-mg DST and 2d-DST and classified into three categories: normal (≤50 nmol/L), doubtful (51-138 nmol/L) and abnormal (>138 nmol/L). Salivary cortisol was also measured at late night and after the DSTs. RESULTS: Following the 1-mg DST and 2d-DST, the plasma cortisol concentrations decreased to a median of 69 nmol/L and 37 nmol/L, respectively (p < 0.001). A statistically significant higher proportion of unclear or abnormal results were observed after the 1-mg DST (63%) than after the 2d-DST (27%) (p = 0.004). None of the values were >138 nmol/L after the 2d-DST, while 11% of them were abnormal after the 1-mg DST (p = 0.25). No LSaC value was abnormal. CONCLUSION: Our results suggest that, when late-night salivary cortisol is not available, the 2d-DST could be a better screening option than the 1-mg DST for women taking oral contraceptive agents who are reluctant to stop them. This finding requires confirmation in those with a suspicion of hypercortisolism.

Matching visual induction effects on screens of different size.

In the film industry, the same movie is expected to be watched on displays of vastly different sizes, from cinema screens to mobile phones. But visual induction, the perceptual phenomenon by which the appearance of a scene region is affected by its surroundings, will be different for the same image shown on two displays of different dimensions. This phenomenon presents a practical challenge for the preservation of the artistic intentions of filmmakers, because it can lead to shifts in image appearance between viewing destinations. In this work, we show that a neural field model based on the efficient representation principle is able to predict induction effects and how, by regularizing its associated energy functional, the model is still able to represent induction but is now invertible. From this finding, we propose a method to preprocess an image in a screen-size dependent way so that its perception, in terms of visual induction, may remain constant across displays of different size. The potential of the method is demonstrated through psychophysical experiments on synthetic images and qualitative examples on natural images.