The pathogenesis of delirium in critically ill patients is multifactorial. How hypotension and hypoxemia affect brain function and whether they can promote delirium remains unclear. A high cumulative ...positive fluid balance may also have a negative effect on brain function and promote delirium. We hypothesized that delirium would be more likely to develop in patients with low systemic arterial pressure, hypoxemia and a higher positive fluid balance, and investigated these associations in a prospective observational cohort study in patients with shock. After initial resuscitation, episodes of hypotension, defined as a mean arterial pressure (MAP) <65 mmHg or diastolic pressure <60 mmHg, and hypoxemia, defined as peripheral oxygen saturation (SpO2) <90% for more than one minute or any arterial oxygen concentration (PaO2) <90 mmHg, were recorded during the first 5 days of the ICU stay. Fluid balance was evaluated daily and the 5-day cumulative fluid balance recorded. Delirium was assessed using the Confusion Assessment Method for the ICU. A total of 252 patients were admitted with shock during the study period; 185 (73%) developed delirium. Patients who developed delirium also had more episodes of hypotension with a low MAP (p = 0.013) or diastolic pressure (p = 0.018) during the first five days of the ICU stay than those who did not. Patients with a higher cumulative fluid balance during the same period were also more likely to develop delirium (p = 0.01); there was no significant difference in the occurrence of hypoxemia between groups. Joint modeling, combining a linear-mixed model and an adjusted Cox survival model showed that low diastolic pressure (alpha effect = -0.058±0.0013, p = 0.043) and a positive cumulative fluid balance (alpha effect = 0.04±0.003, p = 0.021) were independently associated with delirium. In conclusion, low diastolic pressure and a cumulative positive fluid balance but not hypoxemia were independently associated with development of delirium in patients with shock.
To evaluate the diagnostic performances of four SARS-CoV-2 IgG antibody immunoassays.
Following immunoassays were studied: Abbott's SARS-CoV-2 IgG assay, Diasorin's Liaison SARS-CoV-2 S2/S2 IgG ...assay, Euroimmun's Anti-SARS-CoV-2 IgG ELISA, and Roche's Elecsys Anti-SARS-CoV-2 assay. Specificity was retrospectively evaluated with 38 samples from 2019. Sensitivity samples (n = 147) were taken from SARS-CoV-2 real-time PCR-positive patients who developed COVID-19 symptoms ten days earlier.
Mean specificity was 96.6%. Mean sensitivity was 62.7% from ten days after onset of symptoms, 84.4% from 15 days after onset of symptoms, and 87.5% from 20 days after onset of symptoms.
Specificity was high, while Abbott and Roche were 100% specific. Sensitivity increased over time, with Abbott and Roche having the highest sensitivity at all time points with ≥90% from 20 days after symptoms' onset. These findings may assist in selecting SARS-CoV-2 IgG antibody immunoassays for additional diagnostics, epidemiological research, and vaccine development.
Over the last years, individualization of repetitive Transcranial Magnetic Stimulation (rTMS) parameters has been a focus of attention in the field of non-invasive stimulation. It has been proposed ...that in stress-related disorders personality characteristics may influence the clinical outcome of rTMS. However, the underlying physiological mechanisms as to how personality may affect the rTMS response to stress remains to be clarified. In this sham-controlled crossover study, after being stressed by the Trier Social Stress Test, 38 healthy females received two sessions of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex. To take possible personality influences into account, they also completed the Temperament and Character Inventory. Mood and salivary cortisol were assessed throughout the experimental protocol. Overall, two iTBS sessions did not significantly alter mood or influenced cortisol secretion. When taking into account personality features, higher scores on the character dimension Cooperativeness was related to decreased cortisol output, only when active iTBS was administered after the social stressor. In line with other studies, personality features such as the character dimension Cooperativeness may be of particular interest to explain individual neurobiological responses to neurostimulation.
Abrupt osmotic changes during rapid correction of chronic hyponatremia result in demyelinative brain lesions, but the sequence of events linking rapid osmotic changes to myelin loss is not yet ...understood. Here, in a rat model of osmotic demyelination syndrome, we found that massive astrocyte death occurred after rapid correction of hyponatremia, delineating the regions of future myelin loss. Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network, rapidly upregulated inflammatory cytokines genes, and increased serum S100B, which predicted clinical manifestations and outcome of osmotic demyelination. These results support a model for the pathophysiology of osmotic brain injury in which rapid correction of hyponatremia triggers apoptosis in astrocytes followed by a loss of trophic communication between astrocytes and oligodendrocytes, secondary inflammation, microglial activation, and finally demyelination.
Serum free thyroxine (FT4) testing in pregnancy is known to be challenging for immunoassays (IAs). We verified the reliability of FT4 results by 3 commercial IAs throughout pregnancy, by comparison ...of the pattern to that obtained with an equilibrium dialysis isotope dilution–mass spectrometry (ED ID–MS) candidate reference measurement procedure.
Pregnant females (107) and age-matched non-pregnant controls (26) were enrolled. The IAs tested were those performed on the Cobas 6000 (Roche Diagnostics), ARCHITECT i2000SR (Abbott Diagnostics) and Immulite 2000 (Siemens Healthcare) platforms.
Compared to the controls (mean FT4: 18.2
pmol/L), ED ID–MS gave in the late first trimester pregnancy an 8.8% lower (
p
<
0.05) mean; in the second trimester it was 29.1% lower (
p
<
0.001), to stabilize in the third trimester (
p
=
0.99). Similar observations were made for the Cobas and Immulite IAs. The ARCHITECT IA showed no significant decrease in the late first trimester (mean 13.5
pmol/L versus 13.6
pmol/L in controls), but a significant, less pronounced, decrease in the second and third trimesters (15% and 14.4%, respectively). All IAs were susceptible towards alterations in T4 binding proteins during pregnancy.
We proved that IAs may give a FT4 pattern during pregnancy similar to that obtained by ED ID–MS.
Expected values for estradiol (E2), luteinizing hormone (LH), and progesterone determined in serum allow accurate assessment of menstrual cycle phase. Automated immunoassays demonstrate variable ...degrees of bias, emphasizing the need to establish method-specific reference values. We therefore established method-specific reference intervals for the Elecsys® LH assay and new generation Elecsys Estradiol III and Progesterone III assays (cobas e 801 analyzer) in 85 apparently healthy women aged 22–37 (US)/18–37 (EU) years over one natural menstrual cycle. Cycle length and day of ovulation were standardized; phases were defined by LH surge and/or progesterone/E2 levels. Median (5th–95th percentile) concentrations (follicular/ovulation/luteal) were E2: 198 pmol/L (114–332), 757 pmol/L (222–1959) and 412 pmol/L (222–854); LH: 7.14 IU/L (4.78–13.2), 22.6 IU/L (8.11–72.7) and 6.24 IU/L (2.73–13.1); progesterone: 0.212 nmol/L (0.159–0.616), 1.81 nmol/L (0.175–13.2) and 28.8 nmol/L (13.1–46.3). Sub-phase (early/intermediate/late) reference values were also determined for follicular and luteal phases. This multicenter study established reliable, method-specific E2, LH and progesterone reference values that could assist clinical decision-making in women with fertility disorders and monitoring of natural cycles in assisted reproductive treatment.
•E2, LH and progesterone are biomarkers for assessing natural menstrual cycle phase.•These biomarkers support diagnosis, monitoring and treatment of fertility disorders.•E2, LH and progesterone profiles were derived using new generation Elecsys® assays.•Expected serum values are presented for each menstrual cycle phase and sub-phase.•Data will inform clinical decision-making for women with fertility disorders.
What is the effect of gonadotropin-releasing hormone (GnRH)-agonist treatment on serum anti-Müllerian hormone (AMH)?
This prospective cohort study conducted in a tertiary university hospital ...comprised patients (
= 52) who self-administered daily triptorelin (0.1 mg/0.1 mL) subcutaneously for 14 days from menstrual cycle day 21 ± 3, between July 2015 and March 2016. Enrolled women were 18-43 years old, considered normal ovarian responders, with a planned GnRH agonist controlled ovarian stimulation protocol. The primary endpoint was to evaluate the effect of GnRH agonist on serum AMH levels after 7 and 14 days of treatment.
Under GnRH agonist treatment, serum AMH was significantly decreased vs. baseline on day 7 (mean change from baseline: -0.265 ng/mL; 95% confidence interval CI, -0.395 to -0.135 ng/mL;
< 0.001). On day 14, serum AMH was significantly increased (mean change from baseline: 0.289 ng/mL; 95% CI, 0.140-0.439 ng/mL;
< 0.001). Although the median change in AMH from baseline was only -14.9% on day 7 and +17.4% on day 14, from day 7 to 14 AMH significantly increased by 0.55 ng/mL (43.8%;
< 0.001), which is of paramount clinical importance. A linear, mixed-effect model demonstrated that GnRH agonist treatment for 7 and 14 days had a highly significant effect on serum AMH concentration after adjustment for confounding factors (age, body mass index, baseline antral follicle count, and visit). AMH assay precision was excellent (four aliquots/sample); coefficient of variation was 1.2-1.4%.
GnRH agonist treatment had a clinically significant effect on serum AMH, dependent on treatment duration. The clear V-shaped response of AMH level to daily GnRH agonist treatment has important clinical implications for assessing ovarian reserve and predicting ovarian response, thus AMH measurements under GnRH agonist downregulation should be interpreted with great caution.
A prospective study was undertaken in 438 women (ages, 32 +/- 5 years) with various causes of infertility, and in 100 age-matched (33 +/- 5 years) healthy parous controls with the aim of assessing ...the prevalence of autoimmune thyroid disease (AITD) and hitherto undisclosed alterations of thyroid function. Female origin of the infertility was diagnosed in 45% of the couples, with specific causes including endometriosis (11%), tubal disease (30%), and ovarian dysfunction (59%). Male infertility represented 38% and idiopathic infertility 17% of the couples. Overall, median thyrotropin (TSH) was significantly higher in patients with infertility compared to controls: 1.3 (0.9) versus 1.1 (0.8) mIU/L. Serum TSH above normal (>4.2 mIU/L) or suppressed TSH (<0.27 mIU/L) levels were not more prevalent in the infertile women than in controls. The prevalence of positive thyroid peroxidase antibody (TPO-Ab) was higher in all investigated women of infertile couples, compared to controls (14% vs. 8%), but the difference was not significant. However, in infertility of female origin, a significant higher prevalence of positive TPO-Ab was present, compared to controls: 18% versus 8%. Furthermore, among the female causes, the highest prevalence of positive antibodies was observed in women with endometriosis (29%). When thyroid antibodies were positive, both hypothyroidism and hyperthyroidism were more frequent in all women of infertile couples and in the women with a female infertility cause, compared to women in the same groups but without positive TPO-Ab. The present study shows that in infertile women, thyroid autoimmunity features are significantly more frequent than in healthy fertile controls and this was especially the case for the endometriosis subgroup.
We retrospectively compared the first trimester Down's syndrome serum screening markers free beta-hCG (fβhCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11–14 weeks of gestation in 4,088 ...women with naturally conceived pregnancies and in women pregnant after ICSI (n = 163), IVF (n = 59) and frozen–thawed embryo transfer (n = 31), and we searched for a potential relationship between infertility cause and marker levels. We found lower serum PAPP-A levels in pregnancies after IVF and ICSI compared with spontaneously conceived pregnancies and non-male factor infertility was associated with elevated serum fβhCG levels at 11–14 weeks of gestation.
Abstract
Objectives
The high request for vitamin D testing in the last decades has led manufacturers to develop assays on automated immunoassay platforms. The objective of this study was to evaluate ...the performance of the new Elecsys Vitamin D total III assay for the measurement of total 25(OH)D.
Methods
A total of 844 serum samples collected in two clinical laboratories were used to evaluate the new Roche Elecsys Vitamin D total III assay. Comparisons with Roche Elecsys Vitamin D total II and liquid chromatography tandem mass spectrometry (LC-MS/MS) were carried out. Additionally, assay imprecision, linearity, matrix effects, biotin interference, cross-reactivity with 24,25(OH)
2
D
3
and 3-epi-25(OH)D
3
, and outlier rate were evaluated for the Elecsys Vitamin D total III assay.
Results
Only the comparison between LC-MS/MS and Roche Elecsys Vitamin D total III achieved the optimal specification for bias (i.e., <3.4%). Imprecision, linearity and matrix effects showed acceptable results. The biotin interference threshold was increased up to 1,200 ng/mL and the outlier rate was low (0.26%). The cross-reactivity with 24,25(OH)
2
D
3
and 3-epi-25(OH)D
3
was weak or modest in available patient samples. However, using SRM972a with a high level of 3-epi-25(OH)D
3
(enriched) revealed an important cross-reactivity with both Roche Elecsys Vitamin D total II and III assays (+74.7% and +73.7%).
Conclusions
In conclusion, the Roche Elecsys Vitamin D total III assay presents several advantages compared to the previous assay generation: higher biotin interference threshold, broader measuring range, and better comparability with LC-MS/MS. However, the cross-reactivity toward 3-epi-25(OH)D
3
is still problematic in high titer samples.
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