[Hormone anti-müllérienne (AMH) en pédiatrie : établissement de valeurs de référence avec le dosage de l'AMH Fujirebio® Lumipulse G et comparaison avec le dosage Roche® Elecsys sur les mêmes échantillons pédiatriques]. / Anti-müllerian hormone (AMH) in pediatrics: establishment of reference values with the Fujirebio® Lumipulse G AMH assay and comparison with Roche® Elecsys assay on the same pediatric samples.

We performed a method comparison between the Fujirebio® Lumipulse G AMH assay and the Roche® Elecsys AMH assay using the same pediatric samples. We described full pediatric gender and age-specific reference ranges for AMH using the Fujirebio® AMH assay on the Lumipulse G 600 II. The study was performed on 281 plasma samples collected in tubes with lithium heparin. The samples were from patients (135 males and 146 females) aged from 3 days to 22 years collected at the University Hospital Center of Tours. The Fujirebio® Lumipulse method showed excellent correlation with Roche® Elecsys but had a significant proportional positive bias. The data were used to propose pediatric reference values adapted to the Fujirebio® method. Our study described full pediatric gender and age-related reference ranges for AMH using the Fujirebio® AMH assay on the Lumipulse G600II. The delineation between normal male and female AMH concentrations make them valuable clinical tools for the monitoring of pediatric sexual and reproductive development from early childhood through the pubertal transition into adulthood.

3-Month Post-Operative Increase in FGF21 is Predictive of One-Year Weight Loss After Bariatric Surgery.

PURPOSE: The association between bariatric surgery outcome and blood levels of fibroblast growth factor 21 (FGF21) remains controversial. Many patients displayed stable or decreased FGF21 one year after bariatric surgery. Nevertheless, there is often an early increase FGF21 concentration in the post-surgery period. The aim of this study was to investigate the relationship between 3-month FGF21 response and percentage total weight loss at one year after bariatric surgery. MATERIALS AND METHODS: In this prospective monocentric study, a total of 144 patients with obesity grade 2-3 were included; 61% of them underwent a sleeve gastrectomy and 39% a Roux-en-Y gastric bypass. Data analysis was carried out to determine the relation between 3-month plasma FGF21 response and weight loss one year after bariatric surgery. Multiple adjustments were done including degree of weight loss after 3 months. RESULTS: FGF21 significantly increased between baseline and Month 3 (n = 144, p < 10-3), then decreased between Month 3 and Month 6 (n = 142, p = 0.047) and was not different from baseline at Month 12 (n = 142, p = 0.86). The 3-month-FGF21 response adjusted to body weight loss was not different between types of bariatric surgery. The 3-month-FGF21 response was associated to body weight loss at Month 6 (r = -0.19, p = 0.02) and Month 12 (r = -0.34, p < 10-4). After multiple regression analysis, only Month 12 body weight loss remained associated to 3-month FGF21 response (r = -0.3, p = 0.02). CONCLUSION: This study showed that the magnitude of changes in FGF21 at 3 months after bariatric surgery emerged as an independent predictor of one-year body weight loss irrespective of the type of surgery.

Assessment of the Safety and Efficacy of an Oral Probiotic-Based Vaccine Against Aspergillus Infection in Captive-Bred Humboldt Penguins (Spheniscus humboldti).

Aspergillosis is a fungal infection caused mainly by Aspergillus fumigatus that often results in respiratory disease in birds. Aspergillosis is a major cause of morbidity and mortality in captive-bred penguin species. Currently, there is no registered vaccine to prevent aspergillosis. Recent research demonstrated that oral administration of gram-negative bacteria expressing high levels of galactose-α-1,3-galactose (α-Gal) modulates anti-α-Gal immunity and protects turkeys from clinical aspergillosis caused by experimental A. fumigatus infection. The role of anti-α-Gal immunity in penguins has not been studied. Here, we tested the distribution of α-1,3-galactosyltransferase (α1,3GT) genes in the fecal microbiome of Humboldt penguins (Spheniscus humboldti). The occurrence of natural anti-α-Gal antibodies (Abs) in sera and eggs of healthy Humboldt penguins was also assessed. A trial was then conducted to test whether oral administration of Escherichia coli Nissle, expressing high α-Gal levels, modulates anti-α-Gal immunity in a colony of Humboldt penguins. Animals in the vaccination and placebo groups were evaluated before the trial and followed for one year for aspergillosis detection using a diagnostic panel including computed tomography scans, capillary zone electrophoresis, 3-hydroxybutyrate levels, and anti-A. fumigatus Abs. Anti-α-Gal Abs were detected in sera (IgM and IgY) and eggs (IgY) of healthy penguins. Microbiota analysis and functional predictions revealed the presence of α1,3GT genes in the microbiota of Humboldt penguins and other penguin species. A strong decrease in anti-α-Gal IgM levels was observed in all animals in the placebo group three months after vaccination protocol. This decrease was not observed in E. coli Nissle-treated penguins. After the vaccination protocol, we found a positive correlation between anti-E. coli IgY and anti-α-Gal IgY in the E. coli Nissle group, suggesting a correlation between the presence of the bacteria and these Abs. During the study period, three penguins exhibited respiratory signs consistent with aspergillosis. Two were from the placebo group whose symptoms resolved with specific treatments, while a single vaccinated individual developed fatal respiratory aspergillosis eight months after the trial. We conclude that E. coli Nissle represents a safe potential probiotic with a protective effect against aspergillosis in Humboldt penguins that deserves to be further explored for therapeutic uses in these animals.

Specific changes of erythroid regulators and hepcidin in patients infected by SARS-COV-2.

Iron metabolism is tightly linked to infectious and inflammatory signals through hepcidin synthesis. To date, iron homeostasis during SARS-CoV-2 infection has not yet been described. The aim of this study is to characterize the hepcidin and erythroid regulators (growth differentiation factor 15 (GDF-15) and erythroferrone (ERFE)) by measuring concentrations in plasma in context of COVID-19 disease.We performed a single-center observational study of patients with COVID-19 to evaluate concentrations of main regulatory proteins involved in iron homeostasis, namely: hepcidin, ERFE and GDF-15. SARS-CoV-2 infection (COVID-19+) was defined by a positive RT-PCR. Sixteen patients with COVID-19+ were gender-matched and age-matched to 16 patients with a sepsis unrelated to SARS-CoV-2 (COVID-19-) and were compared with non-parametric statistic test.Clinical and hematological parameters, plasma iron, transferrin, transferrin saturation, ferritin, soluble transferrin receptor and C reactive protein were not statistically different between both groups. Median plasma hepcidin concentrations were higher in the COVID-19+ group (44.1 (IQR 16.55-70.48) vs 14.2 (IQR 5.95-18.98) nmol/L, p=0.003), while median ERFE and GDF-15 concentrations were lower in the COVID-19+ group (0.16 (IQR 0.01-0.73) vs 0.89 (IQR 0.19-3.82) ng/mL, p=0.035; 2003 (IQR 1355-2447) vs 4713 (IQR 2082-7774) pg/mL, p=0015), respectively) compared with the COVID-19- group.This is the first study reporting lower ERFE and GDF-15 median concentrations in patients with COVID-19+ compared with patients with COVID-19-, associated with an increased median concentration of hepcidin in the COVID-19+ group compared with COVID19- group.

Megaloblastic anemia-related iron overload and erythroid regulators: a case report.

BACKGROUND: In ineffective erythropoiesis, hepcidin synthesis is suppressed by erythroid regulators, namely erythroferrone and growth differentiation factor-15. For the first time, the hypothesis that iron overload in megaloblastic anemia may be related to ineffective erythropoiesis is explored by describing the kinetics of hepcidin, erythroferrone, and growth differentiation factor-15 levels in a patient diagnosed with megaloblastic anemia associated with iron overload. CASE PRESENTATION: An 81-year-old Caucasian male was admitted for fatigue. He had type-2 diabetes previously treated with metformin, ischemic cardiac insufficiency, and stage-3 chronic kidney disease. Vitiligo was observed on both hands. Biological tests revealed normocytic non-regenerative anemia associated with hemolysis, thrombocytopenia, and elevated sideremia, ferritin, and transferrin saturation levels. Megaloblastic anemia was confirmed with undetectable blood vitamin B12 and typical cytological findings like hyper-segmented neutrophils in blood and megaloblasts in bone marrow. The patient received vitamin B12 supplementation. At 3 months, biological parameters reached normal values. Hepcidin kinetics from diagnosis to 3 months inversely correlated with those of erythroferrone and growth differentiation factor-15. CONCLUSIONS: This case suggests that iron-overload mechanisms of dyserythropoietic anemias may apply to megaloblastic anemias.

An automated alert system based on the p-Tau/Tau ratio to quickly inform health professionals upon a suspected case of sporadic Creutzfeldt-Jakob disease.

INTRODUCTION: Knowing the risk of potential sporadic Creutzfeldt-Jakob disease (sCJD) instrument-contamination is essential in hospitals. We examined the relevance of the p-Tau/Tau ratio to exclude a probable case of sCJD in clinical practice, and we established an alert system to quickly inform health professionals in case of positivity. METHODS: This retrospective study was conducted on 143 cerebrospinal fluid samples from patients suspected for sCJD. The distinction between probable cases of sCJD and other patients was based on clinical, paraclinical and biological (14-3-3, Tau, p-Tau, Aß 1-42) data. From this experience, the health professionals developed an alert system to be implemented upon a suspected case of sCJD. RESULTS: A significant decrease in p-Tau/Tau ratio between sCJD and the other diseases was observed (p < 0 .001). The combined Tau test presented a sensitivity higher than 14-3-3 (100% versus 92.3%, p =0 .006) and an equivalent specificity (90% versus 96.1%). The time required for obtaining results was higher for 14-3-3 due to the centralization of investigations in some laboratories (3 weeks versus 2 h). In the presence of these elements, the triggering of the alert system was based on the p-Tau/Tau ratio. This system involves sending an automatic mail to the hospital department involved in the patient's care and the hospital hygiene team, which oversees the application of the procedures. CONCLUSION: The p-Tau/Tau concentrations present the desired criteria for use in current medical practice to fight against iatrogenic transmission. The alert system confirms a probable case of sCJD instantly to health professionals. Hygiene and sterilization measures can be applied immediately.

Hypercalcemia is associated with a poor prognosis in lymphoma a retrospective monocentric matched-control study and extensive review of published reported cases.

The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that aimed to compare the outcome of patients diagnosed with any histological subtype of lymphoma associated with hypercalcemia, at diagnosis or relapse, with a group of controls matched for histological and prognostic factors. Sixty-two and 118 comparable patients treated between 2000 and 2016 were included in hypercalcemia and control cohorts, respectively. Hypercalcemia was found mainly at diagnosis (71%) in higher-risk patients (prognosis scores ≥ 3, 76%) and those with diffuse large B cell lymphoma (67.7%), stage III/IV disease (91.9%), and elevated LDH (90.3%). Two-year progression-free survival (PFS) was shorter in the hypercalcemia than control cohort [30.1% (95% confidence interval (95% CI) 18.3-41.9) vs 63.9% (95% CI 5.1-72.7), p < 0.001]. Two-year overall survival (OS) was 40.6% (95% CI 28.1-53.1) and 77.7% (95% CI 70.1-85.3) in the hypercalcemia and control cohorts, respectively (p < 0.001). Hypercalcemia was independently associated with poor PFS [HR = 2.5 (95% CI 1.4-3.5)] and OS [HR = 4.7 (95% CI 2.8-7.8)] in multivariate analysis. Among the 40 patients who received autologous stem cell transplantation (ASCT), hypercalcemia was still associated with shorter OS [2-year OS: 65% (95% CI 40.1-89.9) vs 88.0 (95% CI 75.3-100), p = 0.04]. Hypercalcemia may be associated with chemo-resistance, given its impact on PFS and OS. Hence, these data suggest that alternate strategies for lymphoma patients with hypercalcemia should be developed.

Post hoc analysis of plasma amino acid profiles: towards a specific pattern in autism spectrum disorder and intellectual disability.

Objectives Autism spectrum disorders and intellectual disability present a challenge for therapeutic and dietary management. We performed a re-analysis of plasma amino acid chromatography of children with autism spectrum disorders ( n = 22) or intellectual disability ( n = 29) to search for a metabolic signature that can distinguish individuals with these disorders from controls ( n = 30). Methods We performed univariate and multivariate analyses using different machine learning strategies, from the raw data of the amino acid chromatography. Finally, we analysed the metabolic pathways associated with discriminant biomarkers. Results Multivariate analysis revealed models to discriminate patients with autism spectrum disorders or intellectual disability and controls from plasma amino acid profiles ( P < 0.0003). Univariate analysis showed that autism spectrum disorder and intellectual disability patients shared similar differences relative to controls, including lower glutamate ( P < 0.0001 and P = 0.0002, respectively) and serine ( P = 0.002 for both) concentrations. The multivariate model ( P < 6.12.10-7) to discriminate between autism spectrum disorders and intellectual disability revealed the involvement of urea, 3-methyl-histidine and histidine metabolism. Biosigner analysis and univariate analysis confirmed the role of 3-methylhistidine ( P = 0.004), histidine ( P = 0.003), urea ( P = 0.0006) and lysine ( P = 0.002). Conclusions We revealed discriminant metabolic patterns between autism spectrum disorders, intellectual disability and controls. Amino acids known to play a role in neurotransmission were discriminant in the models comparing autism spectrum disorders or intellectual disability to controls, and histidine and b-alanine metabolism was specifically highlighted in the model.