Charlotte Oris

Introduction : Chez l’adulte, la protéine S100B représente un biomarqueur de choix pour exclure l’existence de lésions cérébrales, au cours de la prise en charge du TCL (traumatisme crânien léger), permettant de diminuer l’exposition inutile aux radiations et les coûts liés au diagnostic. Au CHU de Clermont-Ferrand, son dosage est réalisé en routine à partir de la technique de référence, Cobas e411®. Objectifs : Etudier le seuil optimal de la S100B en fonction de l’âge et de la pratique d’une activité physique. Evaluer les performances d’une nouvelle méthode de dosage de la S100B (Vidas®) installée en avant-première au CHU de Clermont-Ferrand. Etudier l’intérêt de nouveaux biomarqueurs cérébraux dans la prise en charge du TCL. Matériels et Méthodes : Chez la population pédiatrique, une méta-analyse individuelle (n = 373 patients) a été réalisée à partir des données publiées sur l’intérêt de la S100B dans la prise en charge du TCL. Une étude rétrospective (n = 1172 patients) a également été menée chez la personne âgée en cas de TCL. Chez le rugbyman, une étude multicentrique a été conduite chez 496 joueurs professionnels. Les performances pré-analytiques, analytiques et post-analytiques du test Vidas® ont été évaluées par des études de stabilité, de précision et de comparaison à la technique de référence (Cobas e411®). L’intérêt du dosage d’autres biomarqueurs cérébraux a été étudié à travers la rédaction d’une revue bibliographique, la mise en place d’une collecte d’échantillons biologiques BIOTRAUMAP et la réalisation d’une étude multicentrique menée chez 496 rugbymen professionnels dont les biomarqueurs (GFAP glial fibrillary acidic protein, UCH-L1 ubiquitin carboxy-terminal hydrolase L1, NFL neurofilament light chain, Tau, SBDP spectrin breakdown products, NSE neuron specific enolase) ont été dosés durant la saison et 36 heures après la suspicion d’une commotion.Résultats : Notre méta-analyse souligne l’importance d’appliquer des valeurs de référence adaptées à l’âge de l’enfant et de respecter un délai de prélèvement inférieur à 3 h après le TCL. Pour la première fois, nous avons validé un nouveau seuil décisionnel (0,15 µg/L) adapté à la prise en charge du TCL chez les patients > 80 ans, permettant une réduction de la réalisation des scanners cérébraux similaire à celle rapportée chez l’adulte (~ 30%). Chez le rugbyman, il est nécessaire pour chaque joueur de disposer d’une concentration basale mesurée à distance d’un exercice physique, afin de gagner en spécificité et d’interpréter correctement la concentration obtenue à 36 h de la commotion. L’étude menée sur le Vidas® a montré des performances conformes et adaptées à une utilisation en routine de la S100B en cas de TCL. Enfin, la littérature souligne l’intérêt de nouveaux biomarqueurs cérébraux dans la prise en charge du TCL. Dans ce sens, 536 patients ont pu être inclus dans la collecte BIOTRAUMAP entre octobre 2019 et août 2021. Dans nos travaux menés chez le rugbyman, la S100B et le NFL sont les plus prometteurs pour différencier les commotions résolutives à 36 h des commotions non résolutives. Conclusion : La S100B, intégrée dans un algorithme de décision clinique, pourrait éviter la réalisation d’au moins un tiers des scanners cérébraux de l’enfant et de la personne âgée pris en charge pour TCL ; à la condition d’une interprétation standardisée du test (délai de 3h, valeurs de références adaptées). Chez le sportif professionnel, l’interprétation des concentrations de la S100B est basée sur une médecine personnalisée et non sur un seuil décisionnel unique. Concernant le test Vidas®, ses performances sont comparables à celles de la méthode de référence utilisée en routine au CHU de Clermont-Ferrand. Enfin, de futures études seront conduites à partir de la collecte BIOTRAUMAP pour évaluer l’intérêt de nouveaux biomarqueurs cérébraux dans la prise en charge du TCL.

Objectives: To compare the diagnostic performances of GFAP and UCH-L1 with S100B in detecting intracranial injury, while investigating the impact of confounding factors. Methods: In a large prospective cohort of 1,010 patients with mild traumatic brain injury, we first evaluated the clinical performances of S100B and the GFAP/UCH-L1 combination. To explore the impact of pre-analytical interferences on GFAP and UCH-L1 levels, HIL indices (hemolysis, icterus, lipemia) were measured using the Atellica ^® analyzer, and spiking experiments were performed with increasing concentrations of hemolysate, bilirubin, and Intralipid ^® . We then assessed the influence of four confounders on biomarker specificity: age over 80 years, hemolysis, neurodegenerative diseases, and extracranial fractures. Finally, we evaluated the ability of the biomarkers to predict clinical outcomes at one month. Results: S100B and the GFAP/UCH-L1 combination showed sensitivities of 96 and 100 %, and specificities of 25 and 27 %, respectively. False positives were significantly associated with age >80 and extracranial fractures for S100B; with age >80 and neurodegenerative diseases for GFAP; and with age >80, hemolysis, and extracranial fractures for UCH-L1. UCH-L1 levels were markedly increased by hemolysis, starting at 400 mg/L of hemoglobin. Age was the only confounding factor to significantly affect specificity. Using age-adjusted thresholds in patients over 80 increased specificity to 30 % for S100B and 33 % for GFAP/UCH-L1. Overall, the biomarkers exhibited limited predictive value and performed poorly for one-month clinical outcomes. Conclusions: S100B and the GFAP/UCH-L1 combination demonstrated very high sensitivities, close to 100 %, with specificities of approximately 30 % for the diagnosis of intracranial lesions. Age-adjusted thresholds improve specificity in older patients, supporting their clinical implementation. This study also provides the first evidence that hemolysis significantly elevates UCH-L1 concentrations from 400 mg/L of hemoglobin.

The measurement of blood glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) may assist in the management of mild traumatic brain injury (mTBI). This study aims to compare GFAP and UCH-L1 values measured using a handheld device with those measured using a core laboratory platform. We enrolled 230 mTBI patients at intermediate risk of complications. Following French guidelines, a negative S100B value permits the patient to be discharged without a computed tomography scan. Plasma GFAP and UCH-L1 levels were retrospectively measured using i-STAT^® and Alinity^® i analyzers in patients managed within 12 h post-trauma. Our analysis indicates a strong correlation of biomarker measurements between the two analyzers. Cohen’s kappa coefficients and Lin’s concordance coefficients were both ≥0.7, while Spearman’s correlation coefficient was 0.94 for GFAP and 0.90 for UCH-L1. Additionally, the diagnostic performance in identifying an intracranial lesion was not significantly different between the two analyzers, with a sensitivity of 100% and specificity of approximately 30%. GFAP and UCH-L1 levels measured using Abbott’s i-STAT^® and Alinity^® i platform assays are highly correlated both analytically and clinically in a cohort of 230 patients managed for mTBI according to French guidelines.

Mild traumatic brain injury (mTBI) accounts for approximately 80% of all TBI cases and is a growing source of morbidity and mortality worldwide. To improve the management of children and adults with mTBI, a series of candidate biomarkers have been investigated in recent years. In this context, the measurement of blood biomarkers in the acute phase after a traumatic event helps reduce unnecessary CT scans and hospitalizations. In athletes, improved management of sports-related concussions is also sought to ensure athletes’ safety. S100B protein has emerged as the most widely studied and used biomarker for clinical decision making in patients with mTBI. In addition to its use as a diagnostic biomarker, S100B plays an active role in the molecular pathogenic processes accompanying acute brain injury. This review describes S100B protein as a diagnostic tool as well as a potential therapeutic target in patients with mTBI.

Background: Blood tryptase and fecal calprotectin levels may serve as biomarkers of necrotizing enterocolitis. However, their interpretation may be hindered by the little-known effects of perinatal factors. The aim of this study was to compare the tryptase and calprotectin levels in newborns according to their term, trophicity, and sex. Method: One hundred and fifty-seven premature newborns and 157 full-term newborns were included. Blood tryptase and fecal calprotectin were assayed. Results: Blood tryptase levels were higher in premature than in full-term newborns (6.4 vs. 5.2 µg/L; p < 0.001). In situations of antenatal use of corticosteroids (p = 0.007) and non-exclusive use of human milk (p = 0.02), these levels were also higher. However, in multiple linear regression analyses, only prematurity significantly influenced tryptase levels. Fecal calprotectin levels were extremely wide-ranging and were much higher in female than in male newborns (300.5 vs. 110.5 µg/g; p < 0.001). Conclusions: The differences in tryptase levels according to term could be linked to early aggression of the still-immature digestive wall in premature newborns, in particular, by enteral feeding started early. The unexpected influence of sex on fecal calprotectin levels remains unexplained.

Background: We previously assessed the inclusion of S100B blood determination into clinical decision rules for mild traumatic brain injury (mTBI) management in the Emergency Department (ED) of Clermont-Ferrand Hospital. At the 0.10 µg/L threshold, S100B reduced the use of cranial computed tomography (CCT) scan in adults by at least 30% with a ~100% sensitivity. Older patients had higher serum S100B values, resulting in lower specificity (18.7%) and decreased CCT reduction. We conducted this study to confirm the age effect on S100B concentrations, and to propose new decisional thresholds for older patients.Methods: A total of 1172 mTBI patients aged 65 and over were included. They were divided into 3 age groups: 65–79, 80–89, and ≥ 90 years old. S100B’s performance to identify intracranial lesions (sensitivity [SE] and specificity [SP]) was assessed using the routine 0.10 µg/L threshold and also other more efficient thresholds established for each age group.Results: S100B concentration medians were 0.18, 0.26, and 0.32 µg/L for the 65–79, 80–89, and ≥ 90 years old age groups, respectively (p < .001). The most efficient thresholds were 0.11 µg/L for the 65–79 age group and 0.15 µg/L for the other groups. At these new thresholds, SP was respectively 28.4%, 34.3%, and 20.5% for each age group versus 24.9%, 18.2%, and 10.5% at the 0.10 µg/L threshold.Conclusions: Adjustment of the S100B threshold is necessary in older patients’ management. An increased threshold of 0.15 µg/L is particularly interesting for patients ≥ 80 years old, allowing a significant increase of CCT scan reduction (29.3%).

Introduction: Ghrelin is an orexigenic hormone which favors food-seeking behavior and has been postulated to be a biomarker of stress. We conducted a systematic review and meta-analysis on the evolution of ghrelin levels following acute stress. Methods: The PubMed, Cochrane Library, Embase, and ScienceDirect databases were searched for studies reporting ghrelin levels before and after acute stress in humans. Results: We included ten studies for a total of 348 patients. Acute stress (intervention) was always in a laboratory. Acute stress was psychological (Trier Social Stress Test), physical, or mixed (cold pressure test). The overall meta-analysis demonstrated an increase in ghrelin after the stress intervention (ES = 0.21, 95CI 0.09 to 0.34) compared with baseline levels. Stratification by time demonstrated an acute increase in ghrelin levels in the five minutes immediately following the initiation of stress (0.29, 0.10 to 0.48) but without any difference after. Obese individuals had a more significant (ES = 0.51, 95CI 0.18 to 0.84) and prolonged increase in ghrelin levels for up to 45 min compared with non-obese individuals who had a significant increase only five minutes after stress. Moreover, the ghrelin levels increased in response to stress with BMI (coefficient 0.028, 0.01 to 0.49; p = 0.013) and decreased with the time after the stress intervention (coefficient -0.007, −0.014 to −0.001; p = 0.025). Conclusion: Ghrelin is a biomarker of stress, with a short-term increase following acute stress. Obese individuals have both a higher and prolonged response, emphasizing the link between obesity and stress.