Interest of blood biomarkers to predict lesions in medical imaging in the context of mild traumatic brain injury

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S100B, Actor and Biomarker of Mild Traumatic Brain Injury

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

Assessment of the advantage of the serum S100B protein biomonitoring in the management of paediatric mild traumatic brain injury—PROS100B: protocol of a multicentre unblinded stepped wedge cluster randomised trial

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Measurement of S100B protein: evaluation of a new prototype on a bioMérieux Vidas® 3 analyzer.

International audienceBackground The addition of S100B protein to guidelines for the management of mild traumatic brain injury (mTBI) decreases the amount of unnecessary computed tomography (CT) scans with a significant decrease in radiation exposure and an increase in cost savings. Both DiaSorin and Roche Diagnostics have developed automated assays for S100B determination. Recently, bioMérieux developed a prototype immunoassay for serum S100B determination. For the first time, we present the evaluation of the S100B measurement using a bioMérieux Vidas® 3 analyzer. Methods We evaluated the matrix effects of serum and plasma, and their stability after storage at 2-8 °C, -20 °C and -80 °C. The new measurement prototype (bioMérieux) was compared with an established one (Roche Diagnostics), and a precision study was also conducted. Lastly, clinical diagnostics performance of the bioMérieux and Roche Diagnostics methods were compared for 80 patients referred to the Emergency Department for mTBI. Results Stability after storage at 2-8 °C, -20 °C, and -80 °C and validation of the serum matrix were demonstrated. The bioMérieux analyzer was compared to the Roche Diagnostics system, and the analytical precision was found to be efficient. Clinical diagnosis performance evaluation confirmed the predictive negative value of S100B in the management of mTBI. Conclusions The study's data are useful for interpreting serum S100B results on a bioMérieux Vidas® 3 analyzer

Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes

International audienceContext: Sterile inflammation has been shown to play a key role in the rupture of the fetal membranes (FMs). Moreover, an early and exacerbated runaway inflammation can evolve into a preterm premature rupture of membranes and lead to potential preterm birth. In this context, we investigated the receptor for advanced glycation end products (RAGE), an axis implied in physiological sterile inflammation, in conjunction with two major ligands: AGEs and High-Mobility Group Box 1 (HMGB1). Our first objective was to determine the spatiotemporal expression profiles of the different actors of the RAGE-signaling axis in human FMs, including its intracellular adaptors Diaphanous-1 and Myd88. Our second goal was to evaluate the functionality of RAGE signaling in terms of FMs inflammation. Methods The presence of the actors (RAGE, HMGB1, Myd88, and Diaphanous-1) at the mRNA level was investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the human amnion and choriodecidua at the three trimesters and at term. Measurements were conducted at two distinct zones: the zone of intact morphology (ZIM) and the zone of altered morphology (ZAM). Then, proteins were quantified using Western blot analysis, and their localization was evaluated by immunofluorescence in term tissues. In addition, pro-inflammatory cytokine secretion was quantified using a Multiplex assay after the treatment of amnion and choriodecidua explants with two RAGE ligands (AGEs and HMGB1) in the absence or presence of a RAGE inhibitor (SAGEs). Results The FMs expressed the RAGE-signaling actors throughout pregnancy. At term, RNA and protein overexpression of the RAGE, HMGB1, and Diaphanous-1 were found in the amnion when compared to the choriodecidua, and the RAGE was overexpressed in the ZAM when compared to the ZIM. The two RAGE ligands (AGEs and HMGB1) induced differential cytokine production (IL1β and TNFα) in the amnion and choriodecidua. Conclusion Considered together, these results indicate that RAGE signaling is present and functional in human FMs. Our work opens the way to a better understanding of FMs weakening dependent on a RAGE-based sterile inflammation

The Biomarker S100B and Mild Traumatic Brain Injury: A Meta-analysis

The usefulness of S100B has been noted as a biomarker in the management of mild traumatic brain injury (mTBI) in adults. However, S100B efficacy as a biomarker in children has previously been relatively unclear

S100B Blood Level Determination for Early Management of Ski-Related Mild Traumatic Brain Injury: A Pilot Study

International audienceBackground: Mild traumatic brain injury (mTBI) management in emergency departments is a complex process involving clinical evaluation, laboratory testing, and computerized tomography (CT) scanning. Protein S100B has proven to be a useful blood biomarker for early evaluation of mTBI, as it reduces the required CT scans by one-third. However, to date, the ability of S100B to identify positive abnormal findings in the CT scans of patients suffering from mTBI caused by ski practice has not been investigated. Thus, the primary aim of this study was to investigate the diagnostic performance of S100B as an mTBI management biomarker in patients with ski-related mTBI. Materials and Methods: One hundred and thirty adult mTBI patients presenting to the emergency department of Hôpital du Valais in Sion, Switzerland, with a Glasgow Coma Scale (GCS) score of 13-15 and clinical indication for a CT scan were included in the study. Blood samples for S100B measurement were collected from each patient and frozen in 3-hour post-injury intervals. CT scans were performed for all patients. Later, serum S100B levels were compared to CT scan findings in order to evaluate the biomarker's performance. Results: Of the 130 included cases of mTBI, 87 (70%) were related to ski practice. At the internationally established threshold of 0.1 μg/L, the receiver operating characteristic curve of S100B serum levels for prediction of abnormal CT scans showed 97% sensitivity, 11% specificity, and a 92% negative predictive value. Median S100B concentrations did not differ according to sex, age, or GCS score. Additionally, there was no significant difference between skiers and non-skiers. However, a statistically significant difference was found when comparing the median S100B concentrations of patients who suffered fractures or had polytrauma and those who did not suffer fractures. Conclusion: The performance of S100B in post-mTBI brain lesion screenings seems to be affected by peripheral lesions and/or ski practice. The lack of neurospecificity of the biomarker in this context does not allow unnecessary CT scans to be reduced by one-third as expected

Exploring Serum Biomarkers for Neuropathic Pain in Rat Models of Chemotherapy-Induced Peripheral Neuropathy: A Comparative Pilot Study with Oxaliplatin, Paclitaxel, Bortezomib, and Vincristine

International audienceBlood biomarkers, including neurofilament light chain (NfL), have garnered attention as potential indicators for chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting adverse effect of neurotoxic anticancer drugs. However, no blood biomarker has been established for routine application or translational research. This pilot study aimed to evaluate a limited panel of blood biomarkers in rat models of CIPN and their correlations with neuropathic pain. CIPN models were induced through repeated injections of oxaliplatin, paclitaxel, bortezomib, and vincristine. Electronic von Frey testing was used to assess tactile allodynia. Post anticancer injections, serum concentrations of 31 proteins were measured. Allodynia thresholds decreased in anticancer-treated animals compared to controls. No consistent modifications were observed in the biomarkers across CIPN models. The most noteworthy biomarkers with increased concentrations in at least two CIPN models were NfL (paclitaxel, vincristine), MCP-1, and RANTES (oxaliplatin, vincristine). Vincristine-treated animals exhibited strong correlations between LIX, MCP-1, NfL, and VEGF concentrations and tactile allodynia thresholds. No single biomarker can be recommended as a unique indicator of CIPN-related pain. Because of the study limitations (single dose of each anticancer drug, young animals, and single time measurement of biomarkers), further investigations are necessary to define the kinetics, specificities, and sensitivities of MCP-1, RANTES, and NfL

Inherited Metabolic Diseases and Cardiac Pathology in Adults: Diagnosis and Prevalence in a CardioMetabo Study

International audienceMany inherited metabolic diseases (IMD) have cardiac manifestations. The aim of this study was to estimate the prevalence of IMD in adult patients with hypertrophic cardiomyopathy (HCM) and cardiac rhythm abnormalities that require cardiac implantable electronic devices (CIEDs). The study included a review of the medical files of patients aged 18 to 65 years who were followed in our cardiology department during the period 2010-2017. Metabolic explorations for Fabry disease (FD), mitochondrial cytopathies, and fatty-acid metabolism disorders were carried out in patients with unexplained etiology. The prevalence of IMD in patients with HCM was 5.6% (confidence interval (CI): 2.6-11.6). Six cases of IMD were identified: 1 mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, 1 Hurler syndrome, 2 Friedreich's ataxia, 1 FD, and 1 short-chain acyl-CoA dehydrogenase deficiency. Three cases of IMD were identified in patients requiring CIEDs: 1 patient with Leber hereditary optic neuropathy, 1 FD, and 1 short chain acyl-CoA dehydrogenase (SCAD) deficiency. IMD prevalence in patients with CIEDs was 3.1% (CI: 1.1-8.8). IMD evaluation should be performed in unexplained HCM and cardiac rhythm abnormalities adult patients, since the prevalence of IMD is relatively important and they could benefit from specific treatment and family diagnosis