Two-site evaluation of the Roche Elecsys Vitamin D total III assay.

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)2D3 and 3-epi-25(OH)D3, 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)2D3 and 3-epi-25(OH)D3 was weak or modest in available patient samples. However, using SRM972a with a high level of 3-epi-25(OH)D3 (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)D3 is still problematic in high titer samples.

The effect of serum vitamin D levels on ovarian reserve markers: a prospective cross-sectional study.

STUDY QUESTION: Is there any association between serum 25-OH vitamin D levels and ovarian reserve markers in infertile women? SUMMARY ANSWER: Vitamin D is not associated with the ovarian reserve markers, anti-mullerian hormone (AMH) and antral follicle count (AFC), in infertile women. WHAT IS KNOWN ALREADY: The mechanism underlying the relationship between vitamin D deficiency and reproduction is still unclear; however, evidence indicates a potential direct negative impact on ovarian function. This is mainly due to the fact that gonadal function may be altered by vitamin D deficiency, as observed by the expression of vitamin D receptor mRNA in human ovaries, mixed ovarian cell cultures and granulosa cell cultures. On the other hand, results from clinical studies are conflicting, with some suggesting that vitamin D status is associated with ovarian reserve, whereas other cross-sectional studies have not found any significant correlation between vitamin D and AMH levels. STUDY DESIGN, SIZE, DURATION: This study was a prospective cross-sectional study from the Centre for Reproductive Medicine at the University Hospital of Brussels. The duration of the study was one year. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, the study included 283 consecutive infertile women younger than 42 years old and undergoing their first treatment cycle in our institution. All patients were recruited within a time interval of 12 months from the initiation of the study, before undergoing infertility treatment. Women consuming vitamin D supplements or taking medication for systematic disease or women who had undergone ovarian surgery were excluded from the study. All infertile women had serum AMH and vitamin D sampled on the same day. AFC was measured on the second or third day of the first cycle following the blood sampling for the determination of AMH and 25-OH vitamin D levels. MAIN RESULTS AND THE ROLE OF CHANCE: Among all patients, 30.7% (n = 87) were vitamin D deficient (<20 ng/mL) whereas 69.3% (n = 196) had normal vitamin D levels (≥20 ng/mL). The mean AMH and AFC levels did not differ significantly between the two groups: AMH 3.9 µ/L (±3.8) versus 4.3 µ/L (±4.8), (P value = 0.5) and AFC 13.9 (±13.3) versus 12.7 (±11.4), (P = 0.7), respectively. No correlation was observed between 25-O H vitamin D and AMH (spearman's r = 0.02, P value = 0.7) or AFC (spearman's r = -0.02, P value = 0.7). In multiple linear regression analysis, after adjusting for potential confounders (age, BMI, smoking status, infertility cause and season of blood sampling), the regression slope in all participants for total 25OH-D predicting log10 AMH was 0.006 [standard error (SE) = 0.07, P value = 0.9]. Similarly, no significant association was observed between AFC and vitamin D levels, even after controlling for relevant co-variants (regression coefficient -0.09. SE 0.08, P value = 0.2). LIMITATIONS, REASONS FOR CAUTION: Although this is the first prospective study to evaluate the relationship between vitamin D and the most important ovarian reserve markers (AMH and AFC), we need to acknowledge that the data used to generate the study findings are cross-sectional in nature. In this regard, we cannot generate or exclude any causal effect hypothesis. Nevertheless, our data support that an association between vitamin D and ovarian reserve markers is highly unlikely to exist. WIDER IMPLICATIONS OF THE FINDINGS: Although data from basic research indicate that vitamin D deficiency may have an effect on steroidogenesis and follicular development, our study, by prospectively recruiting a large number of infertile women, clearly demonstrates that vitamin D deficiency is highly unlikely to have a detrimental effect on ovarian reserve. Ongoing prospective and translational research projects are currently being conducted in order to evaluate the potential effect of vitamin D deficiency on reproductive outcome mediated through either an effect on the oocyte quality or on endometrial receptivity and embryo implantation. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. No conflicts of interest are declared. TRIAL REGISTRATION NUMBER: N/A.

Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI.

STUDY QUESTION: What is the influence of vitamin D deficiency on pregnancy rates among women undergoing IVF/ICSI and Day 5 (blastocyst stage) single embryo transfer (SET)? SUMMARY ANSWER: Vitamin D deficiency results in significantly lower pregnancy rates in women undergoing single blastocyst transfer. WHAT IS KNOWN ALREADY: Preliminary experiments have identified the presence of vitamin D receptors in the female reproductive system. However, results regarding the effect of vitamin D deficiency on clinical outcomes are conflicting. None of the previous studies adopted a SET strategy. STUDY DESIGN, SIZE, DURATION: Serum vitamin D concentration was measured retrospectively in patients who underwent SET on Day 5. Overall 368 consecutive infertile women treated within a period of 15 months were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent ovarian stimulation for IVF/ICSI and Day 5 SET. Serum samples were obtained 7 days prior to embryo transfer and stored frozen at -20°C. Samples were collectively analyzed for their 25-OH vitamin D content. Vitamin D deficiency was defined as serum 25-OH vitamin D levels <20 ng/ml in accordance with the Institute of Medicine and the Endocrine Society clinical practice guidelines. MAIN RESULTS AND THE ROLE OF CHANCE: Clinical pregnancy rates were significantly lower in women with vitamin D deficiency compared with those with higher vitamin D values (41 versus 54%, P = 0.015).Logistic regression analysis was performed to identify whether vitamin D deficiency is independently associated with clinical pregnancy rates after controlling for 16 potential confounding factors. According to our results vitamin D deficiency was independently associated with lower clinical pregnancy rates, odds ratios [ORs (95% confidence interval (CI) 0.61 (0.39-0.95)] for vitamin D deficiency (deficient versus non-deficient women), P = 0.030. Finally, even when restricting our analysis to women undergoing elective SET (274 patients), vitamin D deficiency was again independently associated with pregnancy rates [OR (95% CI) 0.56 (0.33-0.93), P = 0.024]. LIMITATIONS, REASONS FOR CAUTION: Our results refer only to patients undergoing Day 5 SET. Although vitamin D deficiency appears to compromise pregnancy rates in this population, no guidance can be provided regarding a potential relationship between vitamin D deficiency and ovarian reserve or response to ovarian stimulation. WIDER IMPLICATIONS OF THE FINDINGS: Vitamin D deficiency impairs pregnancy rates in women undergoing single blastocyst transfer. Future prospective confirmatory studies are needed to validate our results and examine the exact underlying mechanism by which vitamin D levels may impair pregnancy rates in infertile women undergoing IVF/ICSI. STUDY FUNDING/COMPETING INTERESTS: None declared.

Serum S100B protein could help to detect cerebral complications associated with extracorporeal membrane oxygenation (ECMO).

BACKGROUND: To investigate if serum S100B protein levels could early detect cerebral complications under treatment extracorporeal membrane oxygenation (ECMO). METHODS: Serum S100B levels were measured over 5 days in 32 patients with cardiogenic and septic shock, including 15 patients who treated by ECMO and 17 who did not. Cerebral complications included hemorrhage, stroke, encephalopathy with myoclonus, and brain death. Delirium was identified by the positive Confusion Assessment Method in the ICU. RESULTS: S100B levels were elevated in 24/32 patients (75 %) at ICU admission. Five patients developed cerebral complications (2 hemorrhages with 1 brain death, 1 encephalopathy with myoclonus in the ECMO group and 2 strokes in the non-ECMO group). At day 5, S100B levels were higher in the 5 patients with cerebral complications than in the 27 without cerebral complications, regardless of ECMO (0.426 [0.421, 0.652] vs. 0.102 [0.085, 0.135] µg/L, p = 0.011). S100B levels were also more elevated in 3 patients with than in 12 without cerebral complications associated with ECMO (0.799 [0.325, 0.965] vs. 0.102 [0.09, 0.607] µg/L, p = 0.033). S100B levels were not associated with delirium after sedation withdrawal. CONCLUSIONS: Measurement serum S100B could be useful to detect cerebral complications in deeply sedated patients associated with ECMO but not for monitoring delirium after sedation withdrawal.

Echocardiographic integrated backscatter for detecting progression and regression of aortic valve calcifications in rats.

BACKGROUND: Calcification is an independent predictor of mortality in calcific aortic valve disease (CAVD). The aim of this study was to evaluate the use of non-invasive, non-ionizing echocardiographic calibrated integrated backscatter (cIB) for monitoring progression and subsequent regression of aortic valvular calcifications in a rat model of reversible renal failure with CAVD, compared to histology. METHODS: 28 male Wistar rats were prospectively followed during 21 weeks. Group 1 (N=14) was fed with a 0.5% adenine diet for 9 weeks to induce renal failure and CAVD. Group 2 (N=14) received a standard diet. At week 9, six animals of each group were killed. The remaining animals of group 1 (N=8) and group 2 (N=8) were kept on a standard diet for an additional 12 weeks. cIB of the aortic valve was calculated at baseline, 9 and 21 weeks, followed by measurement of the calcified area (Ca Area) on histology. RESULTS: At week 9, cIB values and Ca Area of the aortic valve were significantly increased in the adenine-fed rats compared to baseline and controls. After 12 weeks of adenine diet cessation, cIB values and Ca Area of group 1 decreased compared to week 9, while there was no longer a significant difference compared to age-matched controls of group 2. CONCLUSIONS: cIB is a non-invasive tool allowing quantitative monitoring of CAVD progression and regression in a rat model of reversible renal failure, as validated by comparison with histology. This technique might become useful for assessing CAVD during targeted therapy.

The value of anti-Mullerian hormone measurement in the long GnRH agonist protocol: association with ovarian response and gonadotrophin-dose adjustments.

BACKGROUND: This study evaluated the predictive value of serum and follicular fluid (FF) concentrations of anti-Müllerian hormone (AMH) with respect to treatment outcome variables in an IVF cycle. METHODS: A retrospective analysis was performed with data from 731 normogonadotrophic women undergoing controlled ovarian stimulation after stimulation with highly purified menotrophin (HP-hMG) or rFSH following a long GnRH agonist protocol. RESULTS: In both treatment groups, the serum AMH concentration at the start of the stimulation was significantly (P < 0.001) positively correlated with the serum levels of estradiol (HP-hMG: r = 0.45; rFSH: r = 0.55), androstenedione (HP-hMG: r = 0.50; rFSH: 0.49) and total testosterone (HP-hMG: r = 0.40; rFSH: r = 0.36) at the end of the stimulation as well as the number of oocytes retrieved (HP-hMG: r = 0.48; rFSH: r = 0.62), the AMH concentration in FF (HP-hMG: r = 0.55; rFSH: 0.61) and the serum progesterone concentration (HP-hMG: r = 0.39; rFSH: r = 0.50) at oocyte retrieval. For both treatments, serum AMH at the start of the stimulation was a good predictor of the need to increase or decrease the gonadotrophin dose on stimulation day 6 and of ovarian response below (<7 oocytes) or above (>15 oocytes) the target. No significant relationships were observed between serum AMH and embryo quality or ongoing pregnancy. CONCLUSION: The serum AMH concentration at the start of the stimulation in IVF patients down-regulated with GnRH agonist in the long protocol revealed a positive relationship with ovarian response to gonadotrophins in terms of oocytes retrieved and accompanying endocrine response. AMH is a good predictor of the need for gonadotrophin-dose adjustment on stimulation day 6 for patients with a fixed starting dose, but a poor predictor of embryo quality and pregnancy chances in individual patients.

Enzymatic pyruvate measurement by Cobas 6000 open channel assay.

BACKGROUND: Blood pyruvate measurement in conjunction with lactic acid is useful for differentiating pyruvate dehydrogenase deficiencies from primary or secondary disorders of mitochondrial electron transport. METHODS: We evaluated the analytical performance of pyruvate measurement by an enzymatic open channel assay on a Roche Cobas 6000. RESULTS: The assay was linear from 0.07 to 0.50 mmol/L pyruvate. Total imprecision ranged from 15.7% to 7.1% at pyruvate levels of 0.08 to 0.31 mmol/L, respectively. Functional sensitivity was 0.07 mmol/L. The assay showed no interference by lipids or bilirubin, whereas haemolysis influenced pyruvate concentrations in a hemoglobin concentration-independent manner. Method comparison with patient samples (n = 41) showed that the Cobas 6000 enzymatic method correlated well (r2 = 0.930) with a similar enzymatic assay on a Cobas Mira platform and showed better accuracy in external control schemes. CONCLUSIONS: Enzymatic pyruvate measurement by a Cobas 6000 open channel shows satisfactory analytical performance. The assay can be integrated in the automated laboratory workflow and is always ready for use thanks to its on-board reagents.

Astrocytes are an early target in osmotic demyelination syndrome.

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.

Evaluation of four laboratory-based SARS-CoV-2 IgG antibody immunoassays.

OBJECTIVES: To evaluate the diagnostic performances of four SARS-CoV-2 IgG antibody immunoassays. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Extensive monitoring of the natural menstrual cycle using the serum biomarkers estradiol, luteinizing hormone and progesterone.

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 â€‹pmol/L (114-332), 757 â€‹pmol/L (222-1959) and 412 â€‹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 â€‹nmol/L (0.159-0.616), 1.81 â€‹nmol/L (0.175-13.2) and 28.8 â€‹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.

Drotrecogin alfa (activated) may attenuate severe sepsis-associated encephalopathy in clinical septic shock.

INTRODUCTION: Sepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction induced by the immuno-inflammatory response to infection. Elevated levels of the brain-specific S100B protein are present in many septic patients and reflect the severity of SAE. Adjunctive treatment with drotrecogin alfa (activated) (DrotAA), the human recombinant form of activated protein C, has been shown to improve mortality in patients with severe sepsis-induced organ failure. We studied the effect of DrotAA on S100B levels in patients with acute septic shock who presented with increased baseline values of this biomarker. METHODS: All patients received standard goal-directed resuscitation treatment. Patients with pre-existing or acute neurological disorders were excluded. Based on the Glasgow coma scale (GCS), patients were classified into two groups: GCS >or= 13 and GCS <13. DrotAA was given as a continuous infusion of 24 microg/kg/h for 96 h. S100B was measured before sedation and the start of DrotAA (0 h) and at 32 h, 64 h and 96 h and at corresponding time points in patients not treated with DrotAA. The lower limit of normal was < 0.5 microg/L. RESULTS: Fifty-four patients completed the study. S100B was increased in 29 (54%) patients. Twenty-four patients (9 with GCS >or= 13 and 15 with GCS <13) received DrotAA. S100B levels in DrotAA-treated patients with a GCS <13, though higher at baseline than in untreated subjects (1.21 +/- 0.22 microg/L vs. 0.95 +/- 0.12 microg/L; P = 0.07), progressively and significantly decreased during infusion (0.96 +/- 0.22 microg/L at 32 h, P = 0.3; 0.73 +/- 0.12 microg/L at 64 h, P < 0.05; and 0.70 +/- 0.13 microg/L at 96 h, P < 0.05 vs. baseline). This patient group had also significantly lower S100B values at 64 h and at 96 h than their untreated counterparts. In the patients with a GCS >or= 13, S100B levels were not influenced by DrotAA treatment. CONCLUSIONS: S100B-positivity is present in more than half of the patients with septic shock. When increased S100B levels are used as a surrogate for SAE, adjunctive DrotAA treatment seems to beneficially affect the evolution of severe SAE as discriminated by an admission GCS <13.

The effect of neurostimulation applied to the left dorsolateral prefrontal cortex on post-stress adaptation as a function of depressive brooding.

Depressive brooding following a stressful event predicts negative affect and neuroendocrine responses related to psychological stress. The dorsolateral prefrontal cortex (DLPFC) has been associated with the top-down regulation of thoughts and emotions, and abnormal neural activity within this region has been associated with increased psychological stress and ruminative thinking. The aim of this study was to investigate whether the modulation of the DLPFC could have beneficial effects on ruminative thoughts and the endocrine response following a self-relevant stressor. Using a sham-controlled within-subjects crossover-design, two sessions of intermittent theta-burst stimulation (iTBS) were administered over the left DLPFC to thirty-eight healthy-volunteers after they were confronted with a social-evaluative stressor, the Trier Social Stress Test. To assess stress recovery, momentary rumination was measured before and after a resting period subsequent to the encounter with the stressor. In addition, cortisol levels were measured between and after the two iTBS sessions that were applied during the stress recovery phase. Overall, iTBS did not significantly influence ruminative thinking and cortisol secretion during the stress recovery phase. However, taking into account participants ruminative tendencies, our results revealed that for participants with higher levels of brooding ruminative thinking remained stable after iTBS, whereas in the sham condition there was a marginal significant increase in ruminative thinking. Moreover, only after iTBS, there was a significant reduction in cortisol secretion (i.e. a faster return to baseline as compared to sham) for high brooders during the recovery from the stressor. These results show that the prefrontal cortex plays a role in stress recovery mechanisms in individuals who are more vulnerable for psychopathology.

Testicular growth and tubular function in prepubertal boys conceived by intracytoplasmic sperm injection.

OBJECTIVE: Little is known about the gonadal function of boys conceived by intracytoplasmic sperm injection (ICSI) from fathers with compromised spermatogenesis. To evaluate the potential risk of tubular dysfunction in these boys, we assessed morphological and functional gonadal parameters and their correlation with paternal sperm characteristics. STUDY DESIGN: In a group of 88 eight-year-old ICSI boys, we measured testicular and penile size. Serum concentrations of anti-mullerian hormone (AMH) and inhibin B were analyzed in 59 of them. RESULTS: Except for two boys with micropenis, penis length and mean testicular length were normal in all boys. In 7 boys inhibin B concentrations were below the lower limit for age, while all AMH results were within normal limits. Serum Sertoli cell markers correlated significantly with each other (p < 0.005), but were independent of paternal sperm parameters. CONCLUSION: Our data suggest that penile and testicular growth as well as Sertoli cell function are normal in the majority of prepubertal ICSI boys. Serum AMH and inhibin B levels were found to be independent of sperm quality of the father. Further follow-up of these prepubertal children is needed to examine whether normal Sertoli cell markers will be followed by a normal spermatogenesis in puberty.

The influence of personality on the effect of iTBS after being stressed on cortisol secretion.

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.

Serum Anti-Müllerian Hormone Is Significantly Altered by Downregulation With Daily Gonadotropin-Releasing Hormone Agonist: A Prospective Cohort Study.

Research Question: What is the effect of gonadotropin-releasing hormone (GnRH)-agonist treatment on serum anti-Müllerian hormone (AMH)? Design: This prospective cohort study conducted in a tertiary university hospital comprised patients (n = 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. Results: 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; p < 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; p < 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%; p < 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%. Conclusions: 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.

Hypotension and a positive fluid balance are associated with delirium in patients with shock.

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.

Multicenter evaluation of a rapid electrochemiluminescent adrenocorticotropic hormone (ACTH) immunoassay.

BACKGROUND: Measuring plasma adrenocorticotropic hormone (ACTH) is a key step in the differential diagnosis of hypothalamic-pituitary-adrenal disorders. METHODS: The recently developed electrochemiluminescence Elecsys ACTH immunoassay (Roche Diagnostics, Mannheim, Germany) was evaluated at six clinical laboratories on the Modular E170 and/or the Elecsys 2010 (Roche Diagnostics) immunoanalysers. RESULTS: The within-run and between-run imprecision was

Liver cirrhosis and thyroid function: Friend or foe?

INTRODUCTION: The liver plays a central role in thyroid hormone metabolism, transport, and clearance. A normal function of both the thyroid gland and the liver is therefore necessary to maintain normal thyroid hormone levels and action. Data regarding thyroid function in patients with liver cirrhosis are scarce and variable. The most consistent finding is a decreased free triiodothyronine (fT3) level, which correlates with the severity of liver disease and has been proposed as a prognostic factor for liver-related complications. AIM OF THE STUDY: To evaluate thyroid hormone values in patients with stable liver cirrhosis and to compare them with healthy controls without liver disease. We also assessed the prevalence of thyroid autoimmunity and whether liver function tests correlated with thyroid function. MATERIAL AND METHODS: We performed a prospective case-control study in an endocrinological setting. Twenty-nine patients with stable cirrhosis (20 males and 9 females, mean age 60.97 ± 7.17 years) were included in the case group and 50 healthy subjects (22 males and 28 females, mean age 61.70 ± 13.00 years) in the control group. We excluded patients with confounding factors known to influence thyroid function. Levels of serum thyroid-stimulating hormone (TSH), fT3, free thyroxine (fT4) and anti-TPO-antibodies (TPO-Ab) were measured. These thyroid hormone values were compared in both groups. Biochemical indices of liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [AP], gamma-glutamyl transpeptidase [GGT], INR, total bilirubin, and albumin levels) were correlated with thyroid function tests. RESULTS: fT3 en fT4 levels were significantly lower in patients with cirrhosis than in healthy subjects (p = 0.001 and 0.002, respectively). TSH levels were not statistically significantly different in the two groups. The level of TPO-Ab was not increased in patients with cirrhosis compared to healthy controls. fT3 correlated negatively with the Child-Pugh score. DISCUSSION: These results indicate that, compared to healthy controls, patients with cirrhosis have decreased fT3 and fT4 levels and comparable TSH levels and may be consistent with findings of limited acquired central hypothyroidism as observed in the non-thyroidal illness syndrome (NTIS). fT3 levels correlated negatively with Child-Pugh score, a measure of severity of liver dysfunction. We did not find an increased prevalence of thyroid autoimmunity in these patients.

Serum reproductive hormone levels and ultrasound findings in female offspring after intracytoplasmic sperm injection: first results.

OBJECTIVE: To compare reproductive hormone levels and antral follicle count in intracytoplasmic sperm injection (ICSI)-conceived offspring and peers born after spontaneous conception. DESIGN: Single-center study of the reproductive health at the age of 18-22 years in the worldwide oldest cohort of female ICSI offspring. SETTING: University hospital. PATIENT(S): A longitudinally followed cohort of singleton women (n = 71) conceived by means of ICSI because of male infertility and a cross-sectionally recruited group of spontaneously conceived women of the same age (n = 81). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Differences in serum reproductive hormone levels and ultrasound findings. RESULT(S): Median levels of antimüllerian hormone (AMH), FSH, LH, and DHEAS were similar between ICSI women and their spontaneously conceived counterparts. Median E2 levels in ICSI women taking hormonal contraceptives were higher compared with control women. A minority of ICSI women had AMH levels below the 5th or above the 95th percentile, and ICSI women were not more likely to have AMH levels below the 5th percentile or above the 95th percentile compared with control women. Mean follicle count per ovary was similar between the ICSI and control groups. Furthermore, a similar proportion of women had >19 follicles per ovary (ICSI: 20.9%; control: 20.0%). A strong positive correlation between AMH level and mean follicle count per ovary was found. CONCLUSION(S): In this cohort of 71 young adult women conceived by means of ICSI because of male infertility in their parents, antral follicle count and circulating reproductive hormone levels, including AMH, FSH, LH, and DHEAS, were found to be similar to results from peers born after spontaneous conception.