Blood Biomarkers for the Management of Mild Traumatic Brain Injury in Clinical Practice.

BACKGROUND: Despite the use of validated guidelines in the management of mild traumatic brain injury (mTBI), processes to limit unnecessary brain scans are still not sufficient and need to be improved. The use of blood biomarkers represents a relevant adjunct to identify patients at risk for intracranial injury requiring computed tomography (CT) scan. CONTENT: Biomarkers currently recommended in the management of mTBI in adults and children are discussed in this review. Protein S100 beta (S100B) is the best-documented blood biomarker due to its validation in large observational and interventional studies. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyterminal hydrolase L-1 (UCH-L1) have also recently demonstrated their usefulness in patients with mTBI. Preanalytical, analytical, and postanalytical performance are presented to aid in their interpretation in clinical practice. Finally, new perspectives on biomarkers and mTBI are discussed. SUMMARY: In adults, the inclusion of S100B in Scandinavian and French guidelines has reduced the need for CT scans by at least 30%. S100B has significant potential as a diagnostic biomarker, but limitations include its rapid half-life, which requires blood collection within 3 h of trauma, and its lack of neurospecificity. In 2018, the FDA approved the use of combined determination of GFAP and UCH-L1 to aid in the assessment of mTBI. Since 2022, new French guidelines also recommend the determination of GFAP and UCH-L1 in order to target a larger number of patients (sampling within 12 h post-injury) and optimize the reduction of CT scans. In the future, new cut-offs related to age and promising new biomarkers are expected for both diagnostic and prognostic applications.

S100B vs. "GFAP and UCH-L1" assays in the management of mTBI patients.

OBJECTIVES: To compare for the first time the performance of "GFAP and UCH-L1" vs. S100B in a cohort of patients managed for mild traumatic brain injury (mTBI) according to actualized French guidelines. METHODS: A prospective study was recently carried at the Emergency Department of Clermont-Ferrand University Hospital in France. Patients with mTBI presenting a medium risk of complications were enrolled. Blood S100B and "GFAP and UCHL-1" were sampled and measured according to French guidelines. S100B was measured in patients with samples within 3 h of trauma (Cobas®, Roche Diagnostics), while GFAP and UCHL-1 were measured in all patients (samples <3 h and 3-12 h) using another automated assay (i-STAT® Alinity, Abbott). RESULTS: For sampling <3 h, serum S100B correctly identifies intracranial lesions with a specificity of 25.7 % (95 % CI; 19.5-32.6 %), a sensitivity of 100 % (95 % CI; 66.4-100 %), and a negative predictive value of 100 % (95 % CI; 92.5-100 %). For sampling <12 h, plasma "GFAP and UCH-L1" levels correctly identify intracranial lesions with a specificity of 31.7 % (95 % CI; 25.7-38.2 %), a sensitivity of 100 % (95 % CI; 73.5-100 %), and a negative predictive value of 100 % (95 % CI; 95-100 %). Comparison of specificities (25.7 vs. 31.7 %) did not reveal a statistically significant difference (p=0.16). CONCLUSIONS: We highlight the usefulness of measuring plasma "GFAP and UCH-L1" levels to target mTBI patients (sampling within 12 h post-injury) and optimize the reduction of CT scans.

Comparison of GFAP and UCH-L1 Measurements Using Two Automated Immunoassays (i-STAT® and Alinity®) for the Management of Patients with Mild Traumatic Brain Injury: Preliminary Results from a French Single-Center Approach.

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.

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.

Evaluation of serum neurofilament light in the early management of mTBI patients.

OBJECTIVES: Serum S100B allows a one-third reduction of computed tomography (CT) scans performed for mild traumatic brain injury (mTBI) patients. In this study, we evaluated the diagnostic performance of serum NF-L in the detection of intracranial lesions induced by mTBI. METHODS: One hundred seventy-nine adult mTBI patients presenting to the emergency department of Clermont-Ferrand University Hospital with a Glasgow Coma Scale (GCS) score of 14-15 were included. S100B assays were performed for clinical routine while NF-L samples were stored at -80 °C until analysis. CT scans were performed for patients with S100B levels above the decision threshold of 0.10 µg/L. Later, NF-L and S100B levels were compared to CT scan findings to evaluate the biomarkers' performances. RESULTS: The area under the ROC curve (AUC) evaluating the diagnostic ability in the prediction of intracranial lesions was 0.72 (95% CI; 0.58-0.87) for S100B and 0.58 (95% CI; 0.45-0.71) for NF-L, the specificities (at a threshold allowing a 100% sensitivity) were 35.7% for S100B, and 28% for NF-L (p=0.096). AUCs of NF-L and S100B for the identification of patients with neurological disorders were statistically different (p<0.001). The AUCs were 0.87 (95% CI; 0.82-0.93) for NF-L and 0.57 (95% CI; 0.48-0.66) for S100B. There was a poor correlation between NF-L and S100B, and NF-L levels were correlated to patients' age (Spearman coefficient of 0.79). CONCLUSIONS: NF-L showed poor performances in the early management of mTBI patients. NF-L levels are strongly correlated to neurodegeneration, whether physiological, age-related, or pathological.

Impact of disease activity and treatments on ovarian reserve in patients with rheumatoid arthritis in the ESPOIR cohort.

OBJECTIVES: Patients with RA have a higher prevalence of infertility than the general population. This study sought to examine the impact of RA disease activity and treatments on ovarian reserve measured by serum anti-Müllerian hormone (AMH) levels in the ESPOIR cohort. We sought to better define the indications for fertility preservation. METHODS: Patients and serum analysis data were derived from the French national cohort ESPOIR. Enrolled patients (n = 102; 18-37-year-olds) fulfilled ACR/EULAR 2010 criteria for RA. Serum AMH levels were measured at T0, T6, T12, T24 and T36 months post-diagnosis. The impacts of RA activity (DAS28 and CRP level) and treatments (MTX only or with other medications) were evaluated at each study visit. RESULTS: A gradual decrease in patients' serum AMH levels was observed over time, in line with the descending curve described for healthy women. Serum AMH levels of RA patients in comparison with the values considered normal for age did not reveal any significant differences (P > 0.05). We did not observe any impact of RA treatments. We demonstrated an inverse correlation between AMH variation and disease activity (DAS28: r = -0.27, P = 0.003; CRP: r = -0.16, P = 0.06). CONCLUSION: This is the first study to determine serum AMH levels of a large cohort of RA patients over 36 months. Rapid disease activity control appears to be required to limit changes in the ovarian reserve. Fertility preservation is not likely to be necessary if inflammation is promptly controlled. CLINICALTRIALS.GOV IDENTIFIER: NCT03666091.

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

Background 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.

Prevalence of FGF23 elevation in patients with hypophosphatemia.

BACKGROUND AND AIMS: To investigate the contribution of FGF23 in explaining the cases of hypophosphatemia observed in clinical practice, we aimed to determine for the first time the prevalence of FGF23 elevation in patients with hypophosphatemia and to describe the different mechanisms of FGF23-related hypophosphatemic disorders. MATERIALS AND METHODS: We performed a prospective, observational, multicenter, cohort study of 260 patients with hypophosphatemia. Blood measurements (PTH, 1,25-dihydroxyvitamin D, bone alkaline phosphatase, 25-hydroxyvitamin D, and FGF23) were performed on a Liaison XL® (DiaSorin) analyzer. RESULTS: Primary elevation of FGF23 (>95.4 pg/mL) was reported in 10.4% (95CI: 7.0-14.7) of patients (n = 27) with hypophosphatemia, suggesting that at least 1 in 10 cases of hypophosphatemia was erroneously attributed to an etiology other than FGF23 elevation. Patients with elevated blood FGF23 were grouped according to the etiology of the FGF23 elevation. Thus, 10 patients had a renal pathology, chronic kidney disease or post-renal transplantation condition. The remaining patients (n = 17) had the following etiologies: malignancies (n = 9), benign pancreatic tumor (n = 1), post-cardiac surgery (n = 4), cirrhosis (n = 2), and chronic obstructive pulmonary disease (n = 1). CONCLUSION: In order to improve patient management, it seems essential to better integrate plasma FGF23 measurement into the routine evaluation of hypophosphatemia.

Periostin in Osteoporosis and Cardiovascular Disease.

Context: Osteoporosis (OP) and cardiovascular disease (CVD), prevalent disorders worldwide, often coexist and share common risk factors. The identification of common biomarkers could significantly improve patients' preventive care. Objectives: The objectives are 1, to review periostin (Postn) involvement in osteoporosis and in CVD, and 2, identify if Postn could be a common biomarker. Design: This is a scoping review on Postn in OP and CVD. Methods: Databases were searched, in vitro and in vivo, for publications in English on Postn, bone, and the cardiovascular system, with no limit regarding publication date. Results: Postn appears as a key factor in OP and CVD. Its role as a potential biomarker in both pathologies is described in recent studies, but a number of limitations have been identified. Conclusions: Current evidence provides fragmented views on Postn in OP and CVD and does not encapsulate Postn as a common pivotal thread linking these comorbidities. A number of gaps impede highlighting Postn as a common biomarker. There is room for future basic and clinical research with Postn as a marker and a target to provide new therapeutic options for aging patients with concomitant OP and CVD.

Tumor-Induced Osteomalacia in Patients With Malignancy: A Meta-analysis and Systematic Review of Case Reports.

CONTEXT: Tumor-induced osteomalacia (TIO) due to fibroblast growth factor 23 (FGF23) overexpression is becoming recognized in patients with malignancy. The condition may be underdiagnosed, with a scarce medical literature. OBJECTIVE: To perform a meta-analysis of case reports to allow a better understanding of malignant TIO and its clinical implications. METHODS: Full texts were selected according to strict inclusion criteria. All case reports were included where patients had hypophosphatemia, malignant TIO, and FGF23 blood levels. Thirty-two of 275 eligible studies (n = 34 patients) met inclusion criteria. A list of desired data was extracted and graded for methodological quality. RESULTS: Prostate adenocarcinoma (n = 9) were the most tumors reported. Twenty-five of 34 patients had a metastatic disease and a poor clinical outcome was reported for 15 of 28 patients. The median levels of blood phosphate and C-terminal FGF23 (cFGF23) were 0.40 mmol/L and 788.5 RU/mL, respectively. For most of patients, blood PTH was elevated or within range, and calcitriol levels were inappropriately low or normal. Alkaline phosphatase concentrations were increased for 20 of 22 patients. The cFGF23 values were significantly higher for patients with a poor clinical outcome when compared to other patients (1685 vs 357.5 RU/mL). In case of prostate cancer, cFGF23 levels were significantly lower (429.4 RU/mL) than for other malignancies (1007.5 RU/mL). CONCLUSION: We report for the first time a detailed description of the clinical and biological characteristics of malignant TIO. In this context, FGF23 blood measurement would be of value for the diagnostic workup, prognostication, and follow-up of patients.

[Calprotectin levels in meconium measured with an automated immunoassay (Liaison® XL)]. / Valeurs de référence de la calprotectine méconiale (immuno-dosage Liaison® XL).

A threshold of 50 µg fecal calprotectin per g stool sample (µg/g) is commonly used to diagnose chronic inflammatory bowel disease in adult patients and children over 4 years of age. In younger children, fecal calprotectin values are physiologically increased. For the first time, the objective of our study was to establish reference ranges in newborns for the measurement of meconium calprotectin with an automated assay (Liaison® XL, DiaSorin). A prospective study was conducted in 2022 in the Maternity Unit of the Clermont-Ferrand University Hospital, with the inclusion of full-term newborns without intestinal involvement. The quantitative automated Liaison® XL calprotectin assay was assessed on a panel of meconium samples. In our cohort of 132 term neonates, calprotectin values ranged from 21 to 855 µg/g of meconium (2,5th to 97.5th percentile) and the median value was 194 µg/g. In our cohort, only sex-related differences were observed for calprotectin values. No significant differences were found for the other factors studied (maternal or neonatal). Because of inter-individual variability, a sequential measurement of newborn calprotectin from meconium should be considered.

Influence of Perinatal Factors on Blood Tryptase and Fecal Calprotectin Levels in Newborns.

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.

Blood Biomarkers for Return to Play after Concussion in Professional Rugby Players.

We prospectively evaluated a panel of seven blood biomarkers (S100 calcium-binding protein B [S100B], neuron specific enolase [NSE], spectrin breakdown products [SBDP], ubiquitin C-terminal hydrolase L1 [UCHL1], glial fibrillary acidic protein [GFAP], neurofilament light chain [NFL], and tubulin-associated unit [Tau]) for sport-related concussion (SRC) in a large multi-centric cohort of 496 professional rugby players from 14 French elite teams. Players were sampled twice during the season (beginning and end) away from any sport practice. From these two baseline samples, we evaluated the intra-individual variability to establish the effect of rugby on blood biomarkers over a season. Only S100B and GFAP remained stable over the course of a season. During the period of the study, a total of 45 SRC cases was reported for 42 players. In 45 SRCs, the head injury assessment (HIA) process was performed and blood collection was realized 36 h after the concussion (HIA-3 stage). For each biomarker, raw concentrations measured 36 h after SRC were not significantly different between players with a non-resolutive SRC (n = 28) and those with a resolutive SRC (n = 17; p between 0.06 and 0.92). In a second step, blood concentrations measured 36 h after SRC were expressed according to the basal concentrations as an individual percentage change (PCH36[%]), calculated as follows: PCH36 = 100 × (([Biomarker]36h - [Biomarker]basal)/[Biomarker]basal). S100B and NFL concentrations expressed as PCH36[%] were significantly different between non-resolutive and resolutive SRCs (p = 0.006 and 0.01 respectively), with a positive delta found in non-resolutive SRCs. Among the two biomarkers, it is important to note that only the S100B protein was stable during the season. In the context of our study, during HIA-3 assessment, S100B seems to perform better than NSE, SBDP, UCHL1, GFAP, NFL, and Tau as biomarker for SRC. From a clinical standpoint, the S100B modification over baseline may be valuable, at 36 h after concussion to distinguish non-resolutive SRC from resolutive SRC.

Hypophosphatemia related to a neuro-endocrine tumor of the pancreas: A case report.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by hypophosphatemia associated with elevated fibroblast growth factor 23 (FGF23). TIO is primarily caused by benign mesenchymal tumors of the soft tissue and skeleton. Rarely, it is associated with a solid tumor or hematological malignancy. To date, no case of osteomalacia related to pancreatic cancer has been reported in the literature. CASE REPORT: A 77-year-old woman was admitted to the rheumatology department (RD) of the Clermont-Ferrand University Hospital (France) for further evaluation of her hypophosphatemia. The patient reported bone pain, myalgia, and asthenia. Further laboratory tests revealed hyperphosphaturia, normocalcemia, low serum calcitriol, elevated serum alkaline phosphatase (ALP), and elevated plasma parathyroid hormone (PTH). A renal phosphate depletion disorder was suspected as an etiology for this hypophosphatemia. Finally, FGF23 levels were found to be significantly elevated, leading to a definitive diagnosis of pancreatic neuroendocrine tumor. CONCLUSION: This is the first report of hypophosphatemic osteomalacia related to pancreatic cancer. Therefore, in the setting of hypophosphatemia associated with renal phosphate wasting and low calcitriol level, plasma FGF23 measurement should be considered.

Waldenstrom's macroglobulinemia highlighted by turbidity interference: a case report / Découverte d'une maladie de Waldenström via une interférence de turbidité : à propos d'un cas

A 65-year-old female was admitted to the Emergency Department for a fall. Upon admission, a blood sample was drawn for routine laboratory tests. Blood glucose measurement using the hexokinase method was made impossible due to a high lipemia index measured by the instrument despite a clear plasma specimen. It is well known that hemolysis, icterus, and lipemia interferences disrupt spectrophotometric quantifications. However, in this case, the absence of lipemia was confirmed by plasma triglycerides measurement in the normal reference range. Protein electrophoresis along with an immunofixation were carried out to characterize a monoclonal gammopathy since the presence of a monoclonal gammopathy in very high concentrations generates turbidity and interferes with spectrophotometric assays. A gamma peak evoking a monoclonal gammopathy was found on the serum electrophoresis and the immunofixation was positive for a monoclonal IgM kappa. Myelogram showed plasmocytes, lymphoplasmacytic cells and mast cells infiltration which led to the diagnosis of Waldenstrom macroglobulinemia. Based on this case, we propose a course of action to be taken in the case of a high lipemia index and clear plasma.

Une femme de 65 ans est admise aux urgences pour une chute. À l'admission, un échantillon de sang a été prélevé pour réaliser un bilan biologique de routine. Sur ce bilan, la mesure spectrophotométrique de la glycémie par la méthode de l'hexokinase était impossible en raison d'un indice de lactescence trop élevé et ce malgré un plasma d'aspect clair. Il est bien connu que l'hémolyse, l'ictère et la lactescence interfèrent dans le dosage spectrophotométrique. Cependant, dans ce cas, il n'y a pas de perturbation du bilan lipidique chez la patiente. Une prestation de conseil a donc été réalisée par le service de biochimie afin de recommander la réalisation d'une électrophorèse des protéines sériques car la présence d'une gammapathie monoclonale à des concentrations très élevées génère de la turbidité et interfère avec les dosages spectrophotométriques. Un pic dans la fraction des gammaglobulines évoquant une gammapathie monoclonale a été retrouvé sur l'électrophorèse sérique, l'immunofixation confirme la présence d'une IgM kappa monoclonale. Le myélogramme montre une infiltration de plasmocytes, de lymphoplasmocytes et de mastocytes ce qui a conduit au diagnostic de maladie de Waldenström. Sur la base de ce cas, nous proposons une conduite à tenir en cas d'indice de lactescence élevé avec un plasma d'aspect clair.

Association between proteinuria trajectories and outcomes in critically ill patients with sepsis or shock.

BACKGROUND: Proteinuria results from kidney damage and can be a predictor of illness severity and mortality in the intensive care unit (ICU). However, the optimal timing of proteinuria measurements and the reference values remain undetermined. Our objective was to identify the patterns of proteinuria change associated with mortality in ICU patients with sepsis or shock. METHODS: This monocentric retrospective cohort study performed from April 2010 to April 2018 involved all ICU patients with sepsis or shock and at least two measurements of proteinuria from a 24h-urine collection during the first 10 days of ICU stay, the first of which was made within 48h after ICU admission. We identified proteinuria trajectories by a semi-parametric mixture model and analysed the association between the trajectories and the mortality at day 28 by Cox proportional-hazards model. RESULTS: A total of 3,344 measurements of proteinuria from 659 patients were analysed. Four proteinuria trajectories were identified. Trajectories 1, 2, 3 and 4 comprised 127, 421, 60 and 51 patients, and were characterized by a first proteinuria of 1.14 [0.66-1.55], 0.52 [0.26-0.91], 2.92 [2.38-3.84] and 2.58 [1.75-3.32] g/24h (p<0.001) and a mortality of 24.4%, 38%, 20% and 43% (p = 0.002), respectively. Trajectories 3 and 4 had a high first proteinuria (>2g/24h). Only, the proteinuria of trajectory 4 increased within 3 days following the first measurement and was associated with increased mortality at day 28 (hazard ratio: 2.36 95%CI [1.07-5.19], p = 0.03), regardless of acute renal failure. The factors associated with trajectory 4 were cancer (relative risk: 8.91 95%CI [2.09-38.02], p = 0.003) and use of inotropic drugs (relative risk: 0.17 95%CI [0.04-0.69], p = 0.01). CONCLUSION: This exploratory study of ICU patients with sepsis or shock identified four proteinuria trajectories with distinct patterns of proteinuria change over time and mortality rates. These results provide novel insights into renal pathophysiology and may be helpful to investigate subphenotypes of kidney injury among ICU patients in future studies.

[Pre-analytical phase impact in the differences in natremia obtained by direct and indirect ion selective electrodes methods]. / Impact de la phase pré-analytique dans les différences de natrémies obtenues par techniques potentiométriques directe et indirecte.

Natremia is an important biological parameter providing information on the hydration state of patient's intracellular sector. Its measurement can be carried out either by multiparametric laboratory analyser (indirect potentiometry) or delocalized biology analyser (direct potentiometry). The main problem is that for a same patient, these two analysers can give quite different results, hence inducing interpretation problems for clinician. Two one-week study periods comparing the variations in blood sodium levels produced by these automatic analysers were carried out in two intensive care units of Clermont-Ferrand University Hospital. During the second study period, a protocol for collecting blood samples was applied in order to improve the pre-analytical conditions. Between the two weeks of studies, the median of the differences in natremia was significantly reduced, going from 4 mmol/L to 2 mmol/L (p < 0.001), as was the proportion of patients with large differences in sodium levels (strictly higher than 3 mmol/L) going from 51% to 24.8% (p < 0.001). The patients still presenting large variations in sodium had a median of proteins significantly lower than patients with deviations less than or equal to 3 mmol/L: 58.1 g/L against 62.25 g/L respectively (p < 0.001) leading to pseudo-hypernatremia (indirect potentiometry). Despite a significant reduction in differences linked to the application of good preanalytical practices, some patients nonetheless presented a major difference in natremia due to the difference of technique (variations in the lipidoprotein phase of the plasma of intensive care patients) and to the measurement uncertainties.

Ghrelin as a Biomarker of Stress: A Systematic Review and Meta-Analysis.

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.

Predictive Performance of Blood S100B in the Management of Patients Over 65 Years Old With Mild Traumatic Brain Injury.

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%).