Prognostic and Diagnostic Utility of Serum Biomarkers in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0-18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9-15) and severe (GCS 3-8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6-9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0-48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.

Utility of Brain Injury Biomarkers in Children With Congenital Heart Disease Undergoing Cardiac Surgery.

BACKGROUND: Congenital heart disease (CHD) affects roughly 40,000 children annually. Despite advancements, children undergoing surgery for CHD are at an increased risk for adverse neurological outcomes. At present, there is no gold standard for the diagnosis of cerebral injury during the perioperative period. OBJECTIVE: To determine the utility of brain injury biomarkers in children undergoing cardiac surgery. METHODS: We searched PUBMED, EMBASE, LILACS, EBSCO, ClinicalTrials.gov, Cochrane Databases, and OVID interface to search MEDLINE through July 2021 and assessed the literature following the snowball method. The search terms used were "congenital heart disease," "cardiopulmonary bypass," "biomarkers," "diagnosis," "prognosis," and "children." No language or publication date restrictions were used. Papers studying inflammatory and imaging biomarkers were excluded. The risk of bias, strengths, and limitations of the study were reported. Study was registered in PROSPERO ID: CRD42021258385. RESULTS: A total of 1449 articles were retrieved, and 27 were included. Eight neurological biomarkers were examined. Outcomes assessed included prognosis of poor neurological outcome, mortality, readmission, and diagnosis of brain injury. Results from these studies support that significant perioperative elevations in brain injury biomarkers in cerebrospinal fluid and serum, including S100B, GFAP, NSE, and activin A, may be diagnostic of real-time brain injury and serve as an independent predictor of adverse neurological outcomes in patients with CHD undergoing cardiopulmonary bypass. CONCLUSIONS: There are limited homogeneous data in the field, limiting the generalizability and comparability of the results. Further large-scale longitudinal studies addressing neurological biomarkers in children undergoing CHD corrective surgery are required to support the routine use of neuronal biomarkers in this population.

Association between erectile dysfunction and the severity of obstruction to airflow in patients with chronic obstructive pulmonary disease / Asociación entre disfunción eréctil y la severidad de la obstrucción al flujo aéreo en pacientes con enfermedad pulmonar obstructiva crónica

Objectives: The objective of this study was to explore a possible association between ED and the severity of airflow obstruction in patients with COPD. Materials and methods: A cross-sectional study was conducted using the International Index Erectile Function (IIEF), a scale validated and translated to Spanish. Bivariate analyses between subgroups were made for quantitative variables using a t-test for means and Mann­Whitney U for medians; qualitative variables were compared using the χ2 test or Fisher's test, depending on distribution. Confusion bias in the association between ED and airflow obstruction was controlled using a logistic regression model. Results: The Spanish version of the IIEF-15 scale was valid and applicable to the Colombian population. The prevalence of ED in COPD patients living at high altitudes was similar to that found at sea level. Such prevalence is higher than in general population. Beta-blockers increased 7 times the risk of ED, but we found no association between the degree of airflow obstruction and ED. Conclusion: Although the severity of COPD is not associated with ED, the prevalence of ED in COPD is higher than in general population. Therefore, ED screening in COPD patients using the IIEF could be justified. The strong association between beta-blockers and ED had not been previously described in patients with COPD but must be considered in their clinical management.

Objetivos: Explorar una posible asociación entre DE y severidad de la obstrucción al flujo aéreo en pacientes con EPOC. Materiales y métodos: Estudio de corte transversal aplicando el Índice Internacional de Función Eréctil (IIFE), validado y traducido al español. Se realizó análisis bivariado para variables cuantitativas usando prueba-t para medias y U de Mann Whitney para medianas; las variables cualitativas fueron comparadas usando prueba de Chi2 o test de Fisher, según distribución. Los sesgos de confusión en la asociación entre DE y obstrucción al flujo aéreo fueron controlados usando un modelo de regresión logística. Resultados: La versión en español de la escala IIFE-15 fue aplicable en población colombiana. La prevalencia de DE en pacientes con EPOC viviendo a gran altura fue similar a lo encontrado a nivel del mar. Esta prevalencia es mayor que en población general. El uso de beta-bloqueadores aumentó hasta siete veces el riesgo de DE, pero no se encontró asociación entre el grado de obstrucción y la DE. Conclusiones: Aunque la severidad de la EPOC no está asociada con DE, la prevalencia de DE en EPOC es mayor que en población general. Está justificada la realización de tamizaje usando el IIFE. La asociación fuerte entre beta-bloqueadores y DE no se ha descrito previamente en pacientes con EPOC, pero debe considerarse en su manejo.

Blood-based traumatic brain injury biomarkers - Clinical utilities and regulatory pathways in the United States, Europe and Canada.

INTRODUCTION: Traumatic brain injury (TBI) is a major global health issue, resulting in debilitating consequences to families, communities, and health-care systems. Prior research has found that biomarkers aid in the pathophysiological characterization and diagnosis of TBI. Significantly, the FDA has recently cleared both a bench-top assay and a rapid point-of-care assays of tandem biomarker (UCH-L1/GFAP)-based blood test to aid in the diagnosis mTBI patients. With the global necessity of TBI biomarkers research, several major consortium multicenter observational studies with biosample collection and biomarker analysis have been created in the USA, Europe, and Canada. As each geographical region regulates its data and findings, the International Initiative for Traumatic Brain Injury Research (InTBIR) was formed to facilitate data integration and dissemination across these consortia. AREAS COVERED: This paper covers heavily investigated TBI biomarkers and emerging non-protein markers. Finally, we analyze the regulatory pathways for converting promising TBI biomarkers into approved in-vitro diagnostic tests in the United States, European Union, and Canada. EXPERT OPINION: TBI biomarker research has significantly advanced in the last decade. The recent approval of an iSTAT point of care test to detect mild TBI has paved the way for future biomarker clearance and appropriate clinical use across the globe.