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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.

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.

In amyotrophic lateral sclerosis (ALS), motor neuron degeneration occurs simultaneously with systemic metabolic dysfunction and neuro-inflammation. The fibroblast growth factor 21 (FGF21) plays an important role in the regulation of both phenomena and is a major hormone of energetic homeostasis. In this study, we aimed to determine the relevance of FGF21 pathway stimulation in a male mouse model of ALS (mutated SOD1-G93A mice) by using a pharmacological agonist of FGF21, R1Mab1. Mice (SOD1-WT and mutant SOD1-G93A) were treated with R1Mab1 or vehicle. Longitudinal data about clinical status (motor function, body weight) and biological parameters (including hormonal, immunological, and metabolomics profiles) were collected from the first symptoms to euthanasia at week 20. Multivariate models were performed to identify the main parameters associated with R1Mab1 treatment and to link them with clinical status, and metabolic pathways involving the discriminant metabolites were also determined. A beneficial clinical effect of R1Mab1 was revealed on slow rotarod (p = 0.032), despite a significant decrease in body weight of ALS mice (p

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

International audience; 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, Aβ 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.

Converging evidence highlights that lipid metabolism plays a key role in ALS pathophysiology. Dyslipidemia has been described in ALS patients and may be protective but peripheral lipoprotein subclasses have never been studied.We collected sera from 30 ALS patients and 30 gender and age-matched controls. We analyzed 11 distinct lipoprotein subclasses by linear polyacrylamide gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA). We also measured lipoprotein (a), apolipoprotein B, and apolipoprotein E levels.ALS patients had significant higher total cholesterol, HDL-cholesterol, and LDL-cholesterol levels than controls (p0.0001, p=0.0007, and p=0.0065, respectively). The LDL-1 subfraction concentration was higher (1.03±0.41 vs. 0.71±0.28mmol/L; p=0.0006) and the IDL-B subfraction lower (6.5±2% vs. 8.0±2%; p=0.001) in ALS patients than controls.Our preliminary work confirmed the association between ALS and dyslipidemia. The low IDL-B levels may explain the hepatic steatosis frequently reported in ALS. The high levels of the cholesterol-rich LDL-1 subfraction is consistent with previously reported hypercholesterolemia.This study describes, for the first time, the distribution of serum lipoproteins in ALS patients, with low IDL-B and high LDL-1 subfraction level.