Pediatric sport and nonsport concussions presenting to emergency departments: injury circumstances, characteristics, and clinical management.

OBJECTIVE: The aim of this study was to compare injury circumstances, characteristics, and clinical management of emergency department (ED) presentations for sports-related concussion (SRC) and non-SRC. METHODS: This multicenter prospective observational study identified patients 5-17 years old who presented to EDs within 24 hours of head injury, with one or more signs or symptoms of concussion. Participants had a Glasgow Coma Scale score of 13-15 and no abnormalities on CT (if performed). Data were stratified by age: young children (5-8 years), older children (9-12 years), and adolescents (13-17 years). RESULTS: Of 4709 patients meeting the concussion criteria, non-SRC accounted for 56.3% of overall concussions, including 80.9% of younger child, 51.1% of older child, and 37.0% of adolescent concussions. The most common mechanism of non-SRC was falls for all ages. The most common activity accounting for SRC was bike riding for younger children, and rugby for older children and adolescents. Concussions occurring in sports areas, home, and educational settings accounted for 26.2%, 21.8%, and 19.0% of overall concussions. Concussions occurring in a sports area increased with age, while occurrences in home and educational settings decreased with age. The presence of amnesia significantly differed for SRC and non-SRC for all age groups, while vomiting and disorientation differed for older children and adolescents. Adolescents with non-SRC were admitted to a ward and underwent CT at higher proportions than those with SRC. CONCLUSIONS: Non-SRC more commonly presented to EDs overall, with SRC more common with increasing age. These data provide important information to inform public health policies, guidelines, and prevention efforts.

SARM1 regulates pro-inflammatory cytokine expression in human monocytes by NADase-dependent and -independent mechanisms.

SARM1 is a Toll-IL-1 receptor (TIR) domain-containing protein with roles in innate immunity and neuronal death in diverse organisms. Unlike other innate immune TIR proteins that function as adaptors for Toll-like receptors (TLRs), SARM1 has NADase activity, and this activity regulates murine neuronal cell death. However, whether human SARM1, and its NADase activity, are involved in innate immune regulation remains unclear. Here, we show that human SARM1 regulates proinflammatory cytokine expression in both an NADase-dependent and -independent manner in monocytes. SARM1 negatively regulated TLR4-dependent TNF mRNA induction independently of its NADase activity. In contrast, SARM1 inhibited IL-1ß secretion through both NADase-dependent inhibition of pro-IL-1ß expression, and NADase-independent suppression of the NLRP3 inflammasome and hence processing of pro-IL-1ß to mature IL-1ß. Our study reveals multiple mechanisms whereby SARM1 regulates pro-inflammatory cytokines in human monocytes and shows, compared to other mammalian TIR proteins, a distinct NADase-dependent role for SARM1 in innate immunity.

Influence of distal insertion technique, valve selection, and patient demographics on shunt survival in ventriculoperitoneal shunt insertion: A retrospective analysis of an Australian case series.

BACKGROUND: Ventriculoperitoneal (VP) shunt insertion is a means of diverting cerebrospinal fluid (CSF) for management of hydrocephalus. Revision rates, operating time, and length of stay (LOS) following laparoscopic insertion of the distal catheter have been mixed. There are limited data on the role of adhesiolysis during VP shunt insertion. Valve characteristics have also been shown to influence patient outcomes. There is a paucity of Australian data reporting on the effect of these variables on shunt outcomes. We aimed to study patient demographics, indications, and surgical and instrument variables in the Australian context. METHODS: We performed a retrospective, multi-surgeon, single-centre analysis of VP shunts inserted in adults via an open or laparoscopic technique. Data on patient demographics and surgery characteristics were collected from the hospital medical records and the Australasian Shunt Registry. The primary outcome was shunt revision rate and secondary outcomes were postoperative complications, operating time and LOS, and shunt survivability. RESULTS: Fifty-six participants were eligible for analysis. The overall revision rate was 14.3 %, which was lower than the national average. The distal catheter revision rate was 0 %. Laparoscopic insertion of the distal catheter was shown to significantly reduce operating time (70.4 min in the open group and 50.7 min in the laparoscopic group, p < 0.001). This was demonstrated across different aetiologies, and when controlling for age and valve-type (p < 0.05). The revision rate of non-programmable was higher than programmable valves (42.9 % versus 2.9 %, respectively). There were no differences between previous abdominal surgery, LOS, complication, or revision rate between open and laparoscopic insertion. VP shunt survivability was greater in the laparoscopic group (90-day shunt survival of 96.7 % and 92 % in the laparoscopy and open groups, respectively; p > 0.05). We did not find any significant difference in operating time or length of stay for age, sex, or previous abdominal surgery, even when accounting for surgical technique. Indication and shunt survivability varied widely between age groups. The use of laparoscopic insertion increased over time, though surgeons did not crossover techniques. CONCLUSIONS: The overall distal revision rate of VP shunts is low. Laparoscopic insertion of the distal catheter reduces operating time and may improve shunt survivability. Larger studies are needed to confirm differences in shunt survivability in open versus laparoscopic distal catheter insertion, between age groups, clinical indications, and valve type on patient outcomes.

Longitudinal neurocognitive trajectories and risk factors in the first three months following pediatric concussion.

OBJECTIVE: To identify differential trajectories of neurocognitive outcomes following pediatric concussion and investigate predictors associated with patterns of recovery up to 3 months. METHODS: 74 participants aged 8-17 years completed attention/working memory, processing speed, and executive function measures at 2 weeks, 1 month, and 3 months post-injury. We used principal component analysis to generate a composite of information processing. Group-based trajectory modeling identified latent trajectories. Multinominal logistic regression was used to examine associations between risk factors and trajectory groups. RESULTS: We identified three trajectories of neurocognitive outcomes. The medium (54.6%) and high improving groups (35.8%) showed ongoing increase in information processing, while the low persistent group showed limited change 3 months post-injury. This group recorded below average scores on Digit Span Forward and Backward at 3 months. History of pre-injury headache was significantly associated with the persistent low scoring group, relative to the medium improving (p = 0.03) but not the high improving group (p = 0.09). CONCLUSIONS: This study indicates variability in neurocognitive outcomes according to three differential trajectories, with groups partially distinguished by preexisting child factors (history of frequent headaches). Modelling that accounts for heterogeneity in individual outcomes is essential to identify clinically meaningful indices that are indicative of children requiring intervention.

Psychological Predictors of Mental Health Difficulties After Pediatric Concussion.

Children often experience mental health difficulties after a concussion. Yet, the extent to which a concussion precipitates or exacerbates mental health difficulties remains unclear. This study aimed to examine psychological predictors of mental health difficulties after pediatric concussion. Children (5 to <18 years of age, M = 11.7, SD = 3.3) with concussion were recruited in a single-site longitudinal prospective cohort study conducted at a tertiary children's hospital (n = 115, 73.9% male). The primary outcomes included internalizing (anxious, depressed, withdrawn behaviors), externalizing (risk-taking, aggression, attention difficulties), and total mental health problems, as measured by the Child Behavior Checklist at 2 weeks (acute) and 3 months (post-acute) after concussion. Predictors included parents' retrospective reports of premorbid concussive symptoms (Post-Concussion Symptom Inventory; PCSI), the child and their family's psychiatric history, child-rated perfectionism (Adaptive-Maladaptive Perfectionism Scale), and child-rated resilience (Youth Resilience Measure). Higher premorbid PCSI ratings consistently predicted acute and post-acute mental health difficulties. This relationship was significantly moderated by child psychiatric history. Furthermore, pre-injury learning difficulties, child psychiatric diagnoses, family psychiatric history, lower resilience, previous concussions, female sex, and older age at injury were associated with greater mental health difficulties after concussion. Pre-injury factors accounted for 23.4-39.9% of acute mental health outcomes, and 32.3-37.8% of post-acute mental health outcomes. When acute mental health was factored into the model, a total of 47.0-68.8% of variance was explained by the model. Overall, in this sample of children, several pre-injury demographic and psychological factors were observed to predict mental health difficulties after a concussion. These findings need to be validated in future research involving larger, multi-site studies that include a broader cohort of children after concussion.

Continuous white noise exposure during sleep and childhood development: A scoping review.

BACKGROUND: White noise machines are widely used as a sleep aid for young children and may lead to poor hearing, speech, and learning outcomes if used incorrectly. OBJECTIVE: Characterize the potential impact of chronic white noise exposure on early childhood development. METHODS: Embase, Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science were searched from inception through June 2022 for publications addressing the effects of chronic noise exposure during sleep on early development in animals and children. PRISMA-ScR guidelines were followed. Among 644 retrieved publications, 20 met inclusion criteria after review by multiple authors. Seven studies evaluated animal models and 13 studies examined pediatric subjects, including 83 animal and 9428 human subjects. RESULTS: White noise machines can exceed 91 dB on maximum volume, which exceeds the National Institute for Occupational Safety and Health noise exposure guidelines for a 2-h work shift in adults. Evidence suggests deleterious effects of continuous moderate-intensity white noise exposure on early development in animal models. Human subject data generally corroborates these models; however, studies also suggest low-intensity noise exposure may be beneficial during sleep. CONCLUSIONS: Existing data support the limitation of maximal sound intensity and duration on commercially available white noise devices. Further research into the optimal intensity and duration of white noise exposure in children is needed.

Discovery of Alpha-1-Antichymotrypsin as a Marker of Delayed Recovery from Concussion in Children.

Of the four million children who experience a concussion each year, 30-50% of children will experience delayed recovery, where they will continue to experience symptoms more than two weeks after their injury. Delayed recovery from concussion encompasses emotional, behavioral, physical, and cognitive symptoms, and as such, there is an increased focus on developing an objective tool to determine risk of delayed recovery. This study aimed to identify a blood protein signature predictive of delayed recovery from concussion in children. Plasma samples were collected from children who presented to the Emergency Department at the Royal Children's Hospital, Melbourne, within 48h post-concussion. This study involved a discovery and validation phase. For the discovery phase, untargeted proteomics analysis was performed using single window acquisition of all theoretical mass spectra to identify blood proteins differentially abundant in samples from children with and without delayed recovery from concussion. A subset of these proteins was then validated in a separate participant cohort using multiple reaction monitoring and enzyme linked immunosorbent assay. A blood protein signature predictive of delayed recovery from concussion was modeled using a Support Vector Machine, a machine learning approach. In the discovery phase, 22 blood proteins were differentially abundant in age- and sex-matched samples from children with (n = 9) and without (n = 9) delayed recovery from concussion, six of whom were chosen for validation. In the validation phase, alpha-1-ACT was shown to be significantly lower in children with delayed recovery (n = 12) compared with those without delayed recovery (n = 28), those with orthopedic injuries (n = 7) and healthy controls (n = 33). A model consisting of alpha-1-ACT concentration stratified children based on recovery from concussion with an 0.88 area under the curve. We have identified that alpha-1-ACT differentiates between children at risk of delayed recovery from those without delayed recovery from concussion. To our knowledge, this is the first study to identify alpha-1-ACT as a potential marker of delayed recovery from concussion in children. Multi-site studies are required to further validate this finding before use in a clinical setting.

Capillary blood protein markers of posttraumatic headache in children after concussion.

OBJECTIVE: Posttraumatic headache (PTH) represents the most common acute and persistent symptom in children after concussion, yet there is no blood protein signature to stratify the risk of PTH after concussion to facilitate early intervention. This discovery study aimed to identify capillary blood protein markers, at emergency department (ED) presentation within 48 hours of concussion, to predict children at risk of persisting PTH at 2 weeks postinjury. METHODS: Capillary blood was collected using the Mitra Clamshell device from children aged 8-17 years who presented to the ED of the Royal Children's Hospital, Melbourne, Australia, within 48 hours of sustaining a concussion. Participants were followed up at 2 weeks postinjury to determine PTH status. PTH was defined per clinical guidelines as a new or worsened headache compared with preinjury. An untargeted proteomics analysis using data-independent acquisition (DIA) was performed. Principal component analysis and hierarchical clustering were used to reduce the dimensionality of the protein dataset. RESULTS: A total of 907 proteins were reproducibly identified from 82 children within 48 hours of concussion. The mean participant age was 12.78 years (SD 2.54 years, range 8-17 years); 70% of patients were male. Eighty percent met criteria for acute PTH in the ED, while one-third of participants with follow-up experienced PTH at 2 weeks postinjury (range 8-16 days). Hemoglobin subunit zeta (HBZ), cystatin B (CSTB), beta-ala-his dipeptidase (CNDP1), hemoglobin subunit gamma-1 (HBG1), and zyxin (ZYX) were weakly associated with PTH at 2 weeks postinjury based on up to a 7% increase in the PTH group despite nonsignificant Benjamini-Hochberg adjusted p values. CONCLUSIONS: This discovery study determined that no capillary blood protein markers, measured at ED presentation within 48 hours of concussion, can predict children at risk of persisting PTH at 2 weeks postinjury. While HBZ, CSTB, CNDP1, HBG1, and ZYX were weakly associated with PTH at 2 weeks postinjury, there was no specific blood protein signature predictor of PTH in children after concussion. There is an urgent need to discover new blood biomarkers associated with PTH to facilitate risk stratification and improve clinical management of pediatric concussion.

Core outcomes in nerve surgery: development of a core outcome set for brachial plexus and upper extremity nerve injuries.

OBJECTIVE: When considering traumatic brachial plexus and upper extremity nerve injuries, iatrogenic nerve injuries, and nontraumatic nerve injuries, brachial plexus and upper extremity nerve injuries are commonly encountered in clinical practice. Despite this, data synthesis and comparison of available studies are difficult. This is at least in part due to the lack of standardization in reporting and a lack of a core outcome set (COS). Thus, there is a need for a COS for adult brachial plexus and upper extremity nerve injuries (COS-BPUE). The objective of this study was to develop a COS-BPUE using a modified Delphi approach. METHODS: A 5-stage approach was used to develop the COS-BPUE: 1) consortium development, 2) literature review to identify potential outcome measures, 3) Delphi survey to develop consensus on outcomes for inclusion, 4) Delphi survey to develop definitions, and 5) consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-BPUE consisted of 36 data points/outcomes covering demographic, diagnostic, patient-reported outcome, motor/sensory outcome, and complication domains. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 24 months, with the consensus optimal time points for assessment being preoperatively and 3, 6, 12, and 24 months postoperatively. CONCLUSIONS: The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-BPUE should serve as a minimum set of data that should be collected in all future neurosurgical studies on adult brachial plexus and upper extremity nerve injuries. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.

Concussion incidence and mechanisms differ between elite females and males in Australian Football.

OBJECTIVES: To investigate the incidence and the game circumstances of concussion in the professional female (AFLW) and male (AFL) competitions of Australian Football, to identify potential targets for risk reduction. DESIGN: Retrospective cohort. METHODS: Concussion data were obtained from the AFL injury database, which included all concussions sustained by AFL (Male) players from 2015 to 18 and AFLW (Female) players from 2017 to 19. Concussions were diagnosed by experienced clinicians utilising standardised concussion assessment tools and injury definitions, as well as video review. Video footage was analysed to determine the circumstances each concussion occurred, which included the action and the contact-point of impact. RESULTS: The incidence of concussion was higher in the AFLW (Female) compared to the AFL (Male) (IRR = 2.12, 95 %CI 1.54 to 2.92). Video footage was available for 194/252 (77 %) concussions in the AFL and 35/44 (80 %) concussions in the AFLW. Male players were most frequently concussed during marking contests (28 %) with primary impact from the upper limb (22 %) or the shoulder (19 %). Conversely, being bumped (23 %) or tackled (20 %) were the main actions associated with concussion in female players, with the head (29 %) or the ground (23 %) the most common contact-points of impact. CONCLUSIONS: In elite Australian Football a higher incidence of concussion was demonstrated in female compared to male players. The mechanisms associated with concussion were also found to differ between male and female competitions, suggesting that different injury prevention interventions may be beneficial. In particular, a review of tackling and bumping skills training and education in the AFLW may reduce the risk of concussion.

SARM1 regulates NAD+-linked metabolism and select immune genes in macrophages.

Sterile alpha and HEAT/armadillo motif-containing protein (SARM1) was recently described as a NAD+-consuming enzyme and has previously been shown to regulate immune responses in macrophages. Neuronal SARM1 is known to contribute to axon degeneration due to its NADase activity. However, how SARM1 affects macrophage metabolism has not been explored. Here, we show that macrophages from Sarm1-/- mice display elevated NAD+ concentrations and lower cyclic ADP-ribose, a known product of SARM1-dependent NAD+ catabolism. Further, SARM1-deficient macrophages showed an increase in the reserve capacity of oxidative phosphorylation and glycolysis compared to WT cells. Stimulation of macrophages to a proinflammatory state by lipopolysaccharide (LPS) revealed that SARM1 restricts the ability of macrophages to upregulate glycolysis and limits the expression of the proinflammatory gene interleukin (Il) 1b, but boosts expression of anti-inflammatory Il10. In contrast, we show macrophages lacking SARM1 induced to an anti-inflammatory state by IL-4 stimulation display increased oxidative phosphorylation and glycolysis, and reduced expression of the anti-inflammatory gene, Fizz1. Overall, these data show that SARM1 fine-tunes immune gene transcription in macrophages via consumption of NAD+ and altered macrophage metabolism.

Mild Traumatic Brain Injury Characteristics and Symptoms in Preschool Children: How Do They Differ to School Age Children? A Multicenter Prospective Observational Study.

OBJECTIVE: To investigate if preschool children differ to school age children with mild traumatic brain injury (TBI) with respect to injury causes, clinical presentation, and medical management. DESIGN: A secondary analysis of a dataset from a large, prospective and multisite cohort study on TBI in children aged 0-18 years, the Australian Paediatric Head Injury Rules Study. SETTING: Nine pediatric emergency departments (ED) and 1 combined adult and pediatric ED located across Australia and New Zealand. PARTICIPANTS: 7080 preschool aged children (2-5 years) were compared with 5251 school-age children (6-12 years) with mild TBI (N= (N=12,331) MAIN OUTCOME MEASURES: Clinical report form on medical symptoms, injury causes, and management. RESULTS: Preschool children were less likely to be injured with a projectile than school age children (P<.001). Preschool children presented with less: loss of consciousness (P<.001), vomiting (P<.001), drowsiness (P=.002), and headache (P<.001), and more irritability and agitation (P=.003), than school-age children in the acute period after mild TBI. Preschool children were less likely to have neuroimaging of any kind (P<.001) or to be admitted for observation than school age children (P<.001). CONCLUSIONS: Our large prospective study has demonstrated that preschool children with mild TBI experience a different acute symptom profile to older children. There are significant clinical implications with symptoms post-TBI used in medical management to aid decisions on neuroimaging and post-acute intervention.

Fatigue recovery and connected factors following paediatric concussion.

OBJECTIVE: Using a biopsychosocial framework and the three-factor fatigue model, we aimed to (1) plot recovery of fatigue over the 3 months following paediatric concussion and (2) explore factors associated with persisting fatigue during the first 3 months postconcussion. METHODS: 240 children and adolescents aged 5-18 years (M=11.64, SD=3.16) completed assessments from time of injury to 3 months postinjury. Separate linear mixed effects models were conducted for child and parent ratings on the PedsQL-Multidimensional Fatigue Scale to plot recovery across domains (General, Cognitive, Sleep/Rest) and Total fatigue, from 1 week to 3 months postinjury. Two-block hierarchical regression analyses were then conducted for parent and child ratings of fatigue at each time point, with age, sex and acute symptoms in block 1 and child and parent mental health variables added to block 2. RESULTS: There was a significant reduction in both child and parent ratings across the 3 months postinjury for all fatigue domains (all p<0.001). For both child and parent fatigue ratings, child mental health was the most significant factor associated with fatigue at all time points. Adding child and parent mental health variables in the second block of the regression substantially increased the variance explained for both child and parent ratings of fatigue. CONCLUSION: Our findings confirm that fatigue improves during the first 3 months postconcussion and highlights the importance of considering child and parent mental health screening when assessing patients with persisting postconcussive symptoms.

Pediatric Sport-Related Concussion: Recommendations From the Amsterdam Consensus Statement 2023.

The 6th International Consensus Conference on Concussion in Sport, Amsterdam 2022, addressed sport-related concussion (SRC) in adults, adolescents, and children. We highlight the updated evidence-base and recommendations regarding SRC in children (5-12 years) and adolescents (13-18 years). Prevention strategies demonstrate lower SRC rates with mouthguard use, policy disallowing bodychecking in ice hockey, and neuromuscular training in adolescent rugby. The Sport Concussion Assessment Tools (SCAT) demonstrate robustness with the parent and child symptom scales, with the best diagnostic discrimination within the first 72 hours postinjury. Subacute evaluation (>72 hours) requires a multimodal tool incorporating symptom scales, balance measures, cognitive, oculomotor and vestibular, mental health, and sleep assessment, to which end the Sport Concussion Office Assessment Tools (SCOAT6 [13+] and Child SCOAT6 [8-12]) were developed. Rather than strict rest, early return to light physical activity and reduced screen time facilitate recovery. Cervicovestibular rehabilitation is recommended for adolescents with dizziness, neck pain, and/or headaches for greater than 10 days. Active rehabilitation and collaborative care for adolescents with persisting symptoms for more than 30 days may decrease symptoms. No tests and measures other than standardized and validated symptom rating scales are valid for diagnosing persisting symptoms after concussion. Fluid and imaging biomarkers currently have limited clinical utility in diagnosing or assessing recovery from SRC. Improved paradigms for return to school were developed. The variable nature of disability and differences in evaluating para athletes and those of diverse ethnicity, sex, and gender are discussed, as are ethical considerations and future directions in pediatric SRC research.

Core outcomes in nerve surgery: development of a core outcome set for ulnar neuropathy at the elbow.

OBJECTIVE: Ulnar neuropathy at the elbow (UNE) is common, affecting 1%-6% of the population. Despite this, there remains a lack of consensus regarding optimal treatment. This is primarily due to the difficulty one encounters when trying to assess the literature. Outcomes are inconsistently reported, which makes comparing studies or developing meta-analyses difficult or even impossible. Thus, there is a need for a core outcome set (COS) for UNE (COS-UNE) to help address this problem. The objective of this study was to utilize a modified Delphi method to develop COS-UNE. METHODS: A 5-stage approach was utilized to develop COS-UNE: stage 1, consortium development; 2, literature review to identify potential outcome measures; 3, Delphi survey to develop consensus on outcomes for inclusion; 4, Delphi survey to develop definitions; and 5, consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 21 participants, all neurological surgeons representing 11 countries. The final COS-UNE consisted of 22 data points/outcomes covering the domains of demographic characteristics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 6 months, with the consensus optimal timepoints for assessment identified as preoperatively and 3, 6, and 12 months postoperatively. CONCLUSIONS: The authors identified consensus data points/outcomes and also provided definitions and specific scales to be utilized to help ensure that clinicians are consistent in their reporting across studies on UNE. This COS should serve as a minimum set of data to be collected in all future neurosurgical studies on UNE. The authors hope that clinicians evaluating ulnar neuropathy will incorporate this COS into routine practice and that future studies will consider this COS in the design phase.

Challenges of conducting a randomised placebo-controlled trial of spinal surgery: the SUcceSS trial of lumbar spine decompression.

Although placebo-controlled trials are considered the gold standard for evaluating the efficacy of healthcare interventions, they can be perceived to be controversial and challenging to conduct for surgical treatments. The SUcceSS trial is the first placebo-controlled trial of lumbar decompression surgery for symptomatic lumbar canal stenosis. The SUcceSS trial has experienced common issues affecting the implementation of randomised placebo-controlled surgery trials, accentuated by the COVID-19 pandemic. Using the SUcceSS trial as an example, we discuss key challenges and mitigation strategies specific to the conduct of a randomised placebo-controlled surgical trial. Overall, the key lessons learned were (i) involving key stakeholders early and throughout the trial design phase may increase clinician and patient willingness to participate in a placebo-controlled trial of surgical interventions, (ii) additional resources (e.g. budget, staff time) are likely required to successfully operationalise trials of this nature, (iii) the level of placebo fidelity, timing of randomisation relative to intervention delivery, and nuances of the surgical procedure under investigation should be considered carefully. Findings are based on one example of a placebo-controlled surgical trial; however, researchers may benefit from employing or building from the strategies described and lessons learned when designing or implementing future trials of this nature.

Examining post-concussion white matter change in a pediatric sample.

Diffusion-Weight Imaging (DWI) is increasingly used to explore a range of outcomes in pediatric concussion, particularly the neurobiological underpinnings of symptom recovery. However, the DWI findings within the broader pediatric concussion literature are mixed, which can largely be explained by methodological heterogeneity. To address some of these limitations, the aim of the present study was to utilize internationally- recognized criteria for concussion and a consistent imaging timepoint to conduct a comprehensive, multi-parametric survey of white matter microstructure after concussion. Forty-three children presenting with concussion to the emergency department of a tertiary level pediatric hospital underwent neuroimaging and were classified as either normally recovering (n = 27), or delayed recovering (n = 14) based on their post-concussion symptoms at 2 weeks post-injury.We combined multiple DWI metrics across four modeling approaches using Linked Independent Component Analysis (LICA) to extract several independent patterns of covariation in tissue microstructure present in the study cohort. Our analysis did not identify significant differences between the symptomatic and asymptomatic groups and no component significantly predicted delayed recovery. If white matter microstructure changes are implicated in delayed recovery from concussion, these findings, alongside previous work, suggest that current diffusion techniques are insufficient to detect those changes at this time.

Quantifying Intubation Forces on Incisors and Tongue Base Across Exposure Difficulty and Experience in a Simulator.

OBJECTIVE: Laryngoscopy simulators quantifying forces on critical structures in progressively challenging airways and operator expertise are lacking. We aimed to quantify laryngoscopy forces across expertise and exposure difficulty. STUDY DESIGN: Prospective observational study Setting: Tertiary care medical center Methods: Force gauges were affixed to a difficult airway mannequin to quantify teeth and tongue forces across increasingly challenging airway exposure. Medical students (n=10), residents (n=11), and otolaryngology staff (n=10) performed direct laryngoscopy using a Miller size 3 laryngoscope with 1) normal neck/jaw mobility, 2) restricted neck extension, 3) restricted jaw opening, and 4) restricted neck/jaw mobility. Incisor and tongue pounds of force (lbf) were continuously measured. RESULTS: As the difficulty setting increased, forces exerted by the students, residents, and staff on the incisors and tongue base increased (p=0.01). Between normal and maximally restricted settings, force delivered to the incisors increased by 6.95 lbf (standard error (SE) 1.29), 5.93 lbf (SE 0.98), and 5.94 lbf (SE 0.70) for the students, residents, and staff, respectively. At the tongue base, force increased by 0.37 lbf (SE 0.18), 0.46 lbf (SE 0.14), and 0.73 lbf (SE 0.15) for the students, residents, and staff, respectively. Esophageal intubations occurred in 50% of the students, 23% of the residents, and 45% of the otolaryngology staff at maximal difficulty, with none at the easiest setting (p=0.33). Compared to the residents, the staff applied significantly increased pressure on the tongue base during laryngoscopy (p=0.02). CONCLUSION: Forces exerted on the incisors and tongue base varied across exposure difficulty and expertise levels, suggesting that they may be useful markers for training and competence assessment.

QUAS-R: An SLC1A5-mediated glutamine uptake assay with single-cell resolution reveals metabolic heterogeneity with immune populations.

System-level analysis of single-cell data is rapidly transforming the field of immunometabolism. Given the competitive demand for nutrients in immune microenvironments, there is a need to understand how and when immune cells access these nutrients. Here, we describe a new approach for single-cell analysis of nutrient uptake where we use in-cell biorthogonal labeling of a functionalized amino acid after transport into the cell. In this manner, the bona fide active uptake of glutamine via SLC1A5/ASCT2 could be quantified. We used this assay to interrogate the transport capacity of complex immune subpopulations, both in vitro and in vivo. Taken together, our findings provide an easy sensitive single-cell assay to assess which cells support their function via SLC1A5-mediated uptake. This is a significant addition to the single-cell metabolic toolbox required to decode the metabolic landscape of complex immune microenvironments.

When should an athlete retire or discontinue participating in contact or collision sports following sport-related concussion? A systematic review.

OBJECTIVE: To systematically review the scientific literature regarding factors to consider when providing advice or guidance to athletes about retirement from contact or collision sport following sport-related concussion (SRC), and to define contraindications to children/adolescent athletes entering or continuing with contact or collision sports after SRC. DATA SOURCES: Medline, Embase, SPORTSDiscus, APA PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials were searched systematically. STUDY ELIGIBILITY CRITERIA: Studies were included if they were (1) original research, (2) reported on SRC as the primary source of injury, (3) evaluated the history, clinical assessment and/or investigation of findings that may preclude participation in sport and (4) evaluated mood disturbance and/or neurocognitive deficits, evidence of structural brain injury or risk factors for increased risk of subsequent SRC or prolonged recovery. RESULTS: Of 4355 articles identified, 93 met the inclusion criteria. None of the included articles directly examined retirement and/or discontinuation from contact or collision sport. Included studies examined factors associated with increased risk of recurrent SRC or prolonged recovery following SRC. In general, these were low-quality cohort studies with heterogeneous results and moderate risk of bias. Higher number and/or severity of symptoms at presentation, sleep disturbance and symptom reproduction with Vestibular Ocular Motor Screen testing were associated with prolonged recovery and history of previous concussion was associated with a risk of further SRC. CONCLUSION: No evidence was identified to support the inclusion of any patient-specific, injury-specific or other factors (eg, imaging findings) as absolute indications for retirement or discontinued participation in contact or collision sport following SRC. PROSPERO REGISTRATION NUMBER: CRD42022155121.