Neurologic Statistical Prognostication and Risk Assessment for Kids on Extracorporeal Membrane Oxygenation-Neuro SPARK.

This study presents Neuro-SPARK, the first scoring system developed to assess the risk of neurologic injury in pediatric and neonatal patients on extracorporeal membrane oxygenation (ECMO). Using the extracorporeal life support organization (ELSO) registry, we applied robust machine learning methodologies and clinical expertise to a 10 years dataset. We produced separate models for veno-venous (V-V ECMO) and veno-arterial (V-A ECMO) configurations due to their different risk factors and prevalence of neurologic injury. Our models identified 14 predictor variables for V-V ECMO and 20 for V-A ECMO, which demonstrated moderate accuracy in predicting neurologic injury as defined by the area under the receiver operating characteristic (AUROC) (V-V = 0.63, V-A = 0.64) and good calibration as measured by the Brier score (V-V = 0.1, V-A = 0.15). Furthermore, our post-hoc analysis identified high- and low-risk groups that may aid clinicians in targeted neuromonitoring and guide future research on ECMO-associated neurologic injury. Despite the inherent limitations, Neuro-SPARK lays the foundation for a risk-assessment tool for neurologic injury in ECMO patients, with potential implications for improved patient outcomes.

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.

Early Changes in Arterial Partial Pressure of Carbon Dioxide and Blood Pressure After Starting Extracorporeal Membrane Oxygenation in Children: Extracorporeal Life Support Organization Database Study of Neurologic Complications.

OBJECTIVE: Neurologic complications in pediatric patients supported by extracorporeal membrane oxygenation (ECMO) are common and lead to morbidity and mortality; however, few modifiable factors are known. DESIGN: Retrospective study of the Extracorporeal Life Support Organization registry (2010-2019). SETTING: Multicenter international database. PATIENTS: Pediatric patients receiving ECMO (2010-2019) for all indications and any mode of support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We investigated if early relative change in Pa co2 or mean arterial blood pressure (MAP) soon after starting ECMO was associated with neurologic complications. The primary outcome of neurologic complications was defined as a report of seizures, central nervous system infarction or hemorrhage, or brain death. All-cause mortality (including brain death) was used as a secondary outcome.Out of 7,270 patients, 15.6% had neurologic complications. Neurologic complications increased when the relative Pa co2 decreased by greater than 50% (18.4%) or 30-50% (16.5%) versus those who had a minimal change (13.9%, p < 0.01 and p = 0.046). When the relative MAP increased greater than 50%, the rate of neurologic complications was 16.9% versus 13.1% those with minimal change ( p = 0.007). In a multivariable model adjusting for confounders, a relative decrease in Pa co2 greater than 30% was independently associated with greater odds of neurologic complication (odds ratio [OR], 1.25; 95% CI, 1.07-1.46; p = 0.005). Within this group, with a relative decrease in Pa co2 greater than 30%, the effects of increased relative MAP increased neurologic complications (0.05% per BP Percentile; 95% CI, 0.001-0.11; p = 0.05). CONCLUSIONS: In pediatric patients, a large decrease in Pa co2 and increase in MAP following ECMO initiation are both associated with neurologic complications. Future research focusing on managing these issues carefully soon after ECMO deployment can potentially help to reduce neurologic complications.

Adiponectin resistance and proinflammatory changes in the visceral adipose tissue induced by fructose consumption via ketohexokinase-dependent pathway.

An epidemic of obesity and type 2 diabetes is linked with the increase in consumption of fructose-containing sugars, such as sucrose and high-fructose corn syrup. In mammalian cells, fructose is metabolized predominantly via phosphorylation to fructose-1 phosphate by ketohexokinase (KHK) or by alternative pathways. Here we demonstrate that a KHK-dependent pathway mediates insulin resistance and inflammatory changes in the visceral fat in response to high fructose. We used mice (males, C57BL/6 background) including littermate wild-type control and mice lacking both isoforms of KHK (KHK-null). Fructose diet induced metabolic syndrome, including visceral obesity, insulin resistance, proinflammatory changes in the visceral fat (production of proinflammatory adipokines and macrophage infiltration), the endoplasmic reticulum stress signaling, and decrease of the high-molecular weight adiponectin followed by decrease in the downstream signaling. KHK-KO mice consuming the same high-fructose diet remained lean, with normal insulin sensitivity and healthy visceral adipose tissue with normal adiponectin function not distinguishable from the control by any of the tested parameters. This study demonstrates that blocking KHK and redirecting fructose metabolism to alternative pathways is an effective way to prevent visceral obesity and insulin resistance induced by high fructose, a widespread component of Western diets.