Induction of erythroferrone in healthy humans by micro-dose recombinant erythropoietin or high-altitude exposure.

The erythropoietin (Epo)-erythroferrone (ERFE)-hepcidin axis coordinates erythropoiesis and iron homeostasis. While mouse studies have established that Epo-induced ERFE production represses hepcidin synthesis by inhibiting hepatic BMP/SMAD signaling, evidence for the role of ERFE in humans is limited. To investigate the role of ERFE as a physiological erythroid regulator in humans, we conducted two studies: first, 24 males received six injections of saline (placebo), recombinant Epo (rhEpo) 20 UI kg-1 (micro-dose) or 50 UI kg-1 (low-dose). Second, we quantified ERFE in 22 subjects exposed to high altitude (3800 m) for 15 hours. In the first study, total hemoglobin mass (Hbmass) increased after low- but not after micro-dose injections, when compared to placebo. Serum ERFE levels were enhanced by rhEpo, remaining higher than after placebo for 48 (micro-dose) or 72 hours (low-dose) post-injections. Conversely, hepcidin levels decreased when Epo and ERFE arose, before any changes in serum iron parameters occurred. In the second study, serum Epo and ERFE increased at high altitude. The present results demonstrate that in healthy humans ERFE responds to slightly increased Epo levels not associated with Hbmass expansion and down-regulates hepcidin in an apparently iron-independent way. Notably, ERFE flags micro-dose Epo, thus holding promise as novel anti-doping biomarker.

Prediction of neurocritical care intensity through automated infrared pupillometry and transcranial doppler in blunt traumatic brain injury: the NOPE study.

PURPOSE: This pilot study aimed to determine the capacity of automated infrared pupillometry (AIP) alone and in combination with transcranial doppler (TCD) on admission to rule out need for intense neuroAQ2 critical care (INCC) in severe traumatic brain injury (TBI). METHODS: In this observational pilot study clinicians performed AIP and TCD measurements on admission in blunt TBI patients with a Glasgow Coma Score (GCS) < 9 and/or motor score < 6. A Neurological Pupil index (NPi) < 3, Pulsatility Index (PI) > 1,4 or diastolic blood flow velocity (dV) of < 20 cm/s were used to rule out the need for INCC (exceeding the tier 0 Seattle Consensus Conference). The primary outcome was the negative likelihood ratio (nLR) of NPi < 3 alone or in combination with TCD to detect need for INCC. RESULTS: A total of 69 TBI patients were included from May 2019 to September 2020. Of those, 52/69 (75%) median age was 45 [28-67], median prehospital GCS of 7 [5-8], median Injury Severity Scale of 13.0 [6.5-25.5], median Marshall Score of 4 [3-5], the median Glasgow Outcome Scale at discharge was 3 [1-5]. NPi < 3 was an independent predictor of INCC. NPi demonstrated a nLR of 0,6 (95%CI 0.4-0.9; AUROC, 0.65, 95% CI 0.51-0.79), a combination of NPi and TCD showed a nLR of 0.6 (95% CI 0.4-1.0; AUROC 0.67 95% CI 0.52-0.83) to predict INCC. CONCLUSION: This pilot study suggests a possible useful contribution of NPi to determine the need for INCC in severe blunt TBI patients on admission.

Early Pupillometry Assessment in Traumatic Brain Injury Patients: A Retrospective Study.

BACKGROUND: The aim of this study was to evaluate whether the early assessment of neurological pupil index (NPi) values derived from automated pupillometry could predict neurological outcome after traumatic brain injury (TBI). METHODS: Retrospective observational study including adult (>18 years) TBI patients admitted from January 2018 to December 2020, with available NPi on admission. Abnormal NPi was considered if <3. Unfavorable neurological outcome (UO) at hospital discharge was considered for a Glasgow Outcome Scale of 1-3. RESULTS: 100 patients were included over the study period (median age 48 (34-69) years and median GCS on admission 11 (6-15)); 49 (49%) patients had UO. On admission, 20 (20%) patients had an abnormal NPi (NPi < 3); median worst (i.e., from both eyes) NPi was 4.2 (3.2-4.5). Median worst and mean NPi on admission were significantly lower in the UO group than others (3.9 (1.7-4.4) vs. 4.4 (3.7-4.6); p = 0.005-4.0 (2.6-4.5) vs. 4.5 (3.9-4.7); p = 0.002, respectively). The ROC curve for the worst and mean NPi showed a moderate accuracy to predict UO (AUC 0.66 (0.56-0.77); p = 0.005 and 0.68 (0.57-0.78); p = 0.002). However, in a generalized linear model, the prognostic role of NPi on admission was limited. CONCLUSIONS: Low NPi on admission has limited prognostic value in TBI.