Return to play after head injury in adolescent sports: evaluating football versus other sports.

OBJECTIVE: Increased adolescent sports participation has raised concerns about higher rates of concussions, a prevalent injury among young athletes with potential long-term effects. Discrepancies in concussion recovery and management protocols across various sports underscore a critical issue in youth athletics. This study aimed to examine the relationship between sport type and the number of games missed following a concussion to inform targeted management strategies. METHODS: Data from 7445 postinjury ImPACT tests for athletes aged 12-22 years, collected from 2009 to 2019, were analyzed across different sports: baseball, basketball, cheerleading, football, ice hockey, lacrosse, soccer, softball, swimming, track and field, volleyball, and wrestling. The number of days and normalized missed games (NMG), a metric accounting for the different number of games in a season for different sports, were used to evaluate the effect of concussions across different sports. ANOVA, t-tests, and linear regression analyses were performed to model the effect of sport type on games missed in a season while controlling for sex, age, concussion history, diagnosed learning disability (DLD), and attention-deficit/hyperactivity disorder (ADHD). RESULTS: Multivariable linear regression analysis demonstrated that football participation significantly increased NMG (ß 1.681, 95% CI 0.807-2.554; p < 0.001) and days missed (ß 1.637, 95% CI 1.044-2.231; p < 0.001) after head injury. Concussion diagnoses were also found to significantly increase NMG (ß 2.344, 95% CI 1.629-3.059; p < 0.001) and days missed (ß 1.560, 95% CI 1.074-2.045; p < 0.001), as well as history of prior concussion (NMG: ß 7.791, 95% CI 7.368-8.215; p < 0.001; days missed: ß 5.232, 95% CI 4.945-5.520; p < 0.001). In contrast, factors such as age, sex, DLD, ADHD, and concussions causing loss of consciousness did not significantly affect NMG or days missed. ANOVA with Tukey Honest Significant Difference indicated that compared with football, ice hockey (mean difference [MD] 5.4 days, p = 0.011) and track and field (MD 4.1 days, p = 0.006) were associated with significantly more days being missed after head injury. Conversely, basketball (MD -3.0, p < 0.001) and volleyball (MD -2.6, p = 0.005) were associated with fewer missed games. CONCLUSIONS: Adolescents playing football missed fewer days and games after concussion than other contact and noncontact sports, including ice hockey and track and field, raising questions about variations in return-to-play protocols and cultural attitudes within sports. Further research is needed to determine the factors affecting games missed across sport types in adolescent athletics and return-to-play protocols.

Effects of hours of sleep on ImPACT concussion testing: comparing baseline with postinjury scores.

OBJECTIVE: The influence of sleep on baseline and postconcussion neurocognitive performance prior to Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is poorly understood. Since ImPACT is widely used in youth sport to assess neurocognitive performance before and after head injury, it is important to delineate factors that affect testing performance. While some have reported correlations between fewer hours of sleep and lower scores on baseline tests, others have not observed any such associations. Therefore, the authors sought to compare the relationship between sleep and neurocognitive performance on ImPACT at both baseline and postinjury. METHODS: The authors queried a database of 25,815 ImPACT tests taken from 2009 to 2019 by athletes aged 12-22 years. There were 11,564 baseline concussion tests and 7446 postinjury concussion ImPACT tests used in the analysis. Linear regression was used to model the effect of sleep on baseline and postconcussion ImPACT scores adjusting for sex, age, learning disability, attention-deficit/hyperactivity disorder, number of prior concussions, number of games missed, and strenuous exercise before testing. RESULTS: Mean composite scores expectedly were all significantly lower in the post-head injury group compared with the baseline group. In the multivariable analysis, at baseline, hours of sleep significantly affected symptom scores (ß = -1.050, 95% CI -1.187 to -0.9138; p < 0.0001). In the postinjury multivariable analysis, verbal memory (ß = 0.4595, 95% CI 0.2080-0.7110; p = 0.0003), visual memory (ß = 0.3111, 95% CI 0.04463-0.5777; p = 0.0221), impulse control (ß = -0.2321, 95% CI -0.3581 to -0.1062; p = 0.0003), and symptom scores (ß = -0.9168, 95% CI -1.259 to -0.5750; p < 0.0001) were all affected by hours of sleep. CONCLUSIONS: Hours of sleep did not alter neurocognitive metrics at baseline but did have an impact on post-head injury metrics. These findings suggest that individuals may be able to compensate for lack of sleep at baseline but not immediately after concussion. Concussions may reduce cognitive reserve or detract from the brain's resources, making sleep even more important for proper neurocognitive functioning postconcussion. Future work will analyze the effects of sleep on postconcussion test performance.

The effect of age on baseline neurocognitive performance.

OBJECTIVE: Evaluate the independent effect of age on baseline neurocognitive performance. STUDY DESIGN: Baseline ImPACT scores from tests taken by 7454 athletes aged 12-22 from 2009 to 2019 were split into three age cohorts: 12-14 years (3244), 15-17 years (3732), and 18-22 years (477). Linear regression analyses were used to evaluate the effect of age on ImPACT composite scores while controlling for demographic differences, medication-use, and symptom burden. Significance values have been set at p < 0.05. RESULTS: Linear regression analyses demonstrated that increased age does not significantly affect symptom score (ß = 0.06, p = 0.54) but does improve impulse control (ß = -0.45, p < 0.0001), verbal memory (ß = 0.23, p = 0.03), visualmotor (ß = 0.77, p < 0.0001), and reaction time (ß = -0.008, p < 0.0001) scores.  However, age did not have an effect on visual memory scores (ß = -0.25, p = 0.07). CONCLUSIONS: Age was shown to be an independent modifier of impulse control, verbal memory, visual motor, and reaction time scores but not visual memory or symptom scores.  This underscores the previous literature showing developmental differences as age increases among the adolescent athlete population.  This data also indicates the need for repeat neurocognitive baseline testing every other year as baseline scoring is likely to change as athletes become older.

Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases.

BACKGROUND: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children. METHODS: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls. RESULTS: GDF15 levels compared to controls were mildly elevated in patients with α1-antitrypsin deficiency, Alagille syndrome, and biliary atresia-young subgroup, but markedly elevated in MH (p<0.001). FGF21 levels were mildly elevated in NASH and markedly elevated in MH (p<0.001). Both biomarkers were higher in patients with MH with a known genetic cause but were similar in acute and chronic presentations. Both markers had a strong performance to identify MH with a molecular diagnosis with the AUC for GDF15 0.93±0.04 and for FGF21 0.90±0.06. Simultaneous elevation of both markers >98th percentile of controls identified genetically confirmed MH with a sensitivity of 88% and specificity of 96%. In MH, independent predictors of survival without requiring liver transplantation were international normalized ratio and either GDF15 or FGF21 levels, with levels <2000 ng/L predicting survival without liver transplantation (p<0.01). CONCLUSIONS: GDF15 and FGF21 are significantly higher in children with MH compared to other childhood liver diseases and controls and, when combined, were predictive of MH and had prognostic implications.

Mapping and identifying service models for community-based services for children with intellectual disabilities and behaviours that challenge in England.

BACKGROUND: One in five children with an intellectual disability in the UK display behaviours that challenge. Despite associated impacts on the children themselves, their families, and services, little research has been published about how best to design, organise, and deliver health and care services to these children. The purpose of this study was to describe how services are structured and organised ("service models") in England for community-based health and care services for children with intellectual disability who display behaviours that challenge. METHODS: Survey data about services were collected from 161 eligible community-based services in England. Staff from 60 of these services were also interviewed. A combination of latent class and descriptive analysis, coupled with consultation with family carers and professionals was used to identify and describe groupings of similar services (i.e., "service models"). RESULTS: The latent class analysis, completed as a first step in the process, supported a distinction between specialist services and non-specialist services for children who display behaviours that challenge. Planned descriptive analyses incorporating additional study variables were undertaken to further refine the service models. Five service models were identified: Child and Adolescent Mental Health Services (CAMHS) (n = 69 services), Intellectual Disability CAMHS (n = 28 services), Children and Young People Disability services (n = 25 services), Specialist services for children who display behaviours that challenge (n = 27 services), and broader age range services for children and/or adolescents and adults (n= 12 services). CONCLUSIONS: Our analysis led to a typology of five service models for community health and care services for children with intellectual disabilities and behaviours that challenge in England. Identification of a typology of service models is a first step in building evidence about the best provision of services for children with intellectual disabilities who display behaviours that challenge. The methods used in the current study may be useful in research developing service typologies in other specialist fields of health and care. STUDY REGISTRATION: Trial Registration: Current Controlled Trials ISRCTN88920546, Date assigned 05/07/2022.

Histological transitional zone pull-through in Hirschsprung disease. Postoperative functional results and current recommendations / Descenso en zona de transición histológica en la enfermedad de Hirschsprung. Resultados funcionales postoperatorios y recomendaciones actuales

Abstract Background: Surgeons create a neorectum to repair patients with Hirschsprung´s disease (HD), which should be formed from a normoganglionic bowel. However, the neorectum is occasionally created with a transition zone (TZ) bowel. A neorectum created with a TZ has been postulated as a cause of postoperative enterocolitis or constipation. This study compares the incidence of enterocolitis and constipation in patients with TZ neorectum and normoganglionic bowel. Methods: We conducted a retrospective review of patients with rectosigmoid HD who underwent primary pull-through. Patients were divided into normoganglionic neorectum (NNR) and TZ neorectum. The diagnosis was based on the final histopathologic report of the proximal margin. The incidence of enterocolitis and constipation was compared between these two groups. Results: A total of 98 HD patients were analyzed. Seventy-one patients fulfilled the inclusion criteria. 65 (92%) had a NNR, and six patients (8%) had a TZ neorectum. From these patients, 42 (59%) presented with enterocolitis or constipation. However, there was no significant difference between both groups. Conclusion: The present study showed no difference in the incidence of enterocolitis or postoperative constipation in HD patients with normoganglionic or TZ neorectum. These results suggest that TZ neorectum does not cause postoperative obstructive symptoms.

Resumen Introducción: Los cirujanos crean un neo-recto para tratar a los pacientes con enfermedad de Hirschsprung (EH), que debe formarse con intestino normogangliónico; sin embargo, en ocasiones el neo-recto se forma con intestino de la zona de transición. Se ha postulado que un neo-recto en zona de transición causa enterocolitis o estreñimiento postoperatorio. El objetivo de este estudio fue comparar la frecuencia de enterocolitis y estreñimiento en pacientes con neo-recto en zona de transición y con neo-recto normogangliónico. Métodos: Se llevó a cabo una revisión retrospectiva de pacientes con EH recto sigmoideo que se sometieron a descenso primario. Los pacientes se dividieron en el grupo neo-recto normogangliónico y el grupo con neo-recto en zona de transición. El diagnóstico del neo-recto se estableció con el informe histopatológico definitivo del margen proximal. Se comparó la frecuencia de enterocolitis y estreñimiento entre estos dos grupos. Resultados: Se analizó un total de 98 pacientes con EH, de los cuales 71 pacientes cumplieron los criterios de inclusión; 65 (92%) con neo-recto normogangliónico y seis (8%) con neo-recto en zona de transición. Posteriormente, 42 (59%) pacientes presentaron enterocolitis asociada a Hirschsprung (HAEC) o estreñimiento; sin embargo, no hubo diferencia significativa entre ambos grupos. Conclusiones: El presente estudio no demostró una diferencia en la frecuencia de HAEC o estreñimiento postoperatorio en pacientes con EH con neo-recto normogangliónico o en zona de transición. Estos resultados sugieren que un neo-recto en zona de transición no causa síntomas obstructivos postoperatorios.

Histological transitional zone pull-through in Hirschsprung disease. Postoperative functional results and current recommendations.

BACKGROUND: Surgeons create a neorectum to repair patients with Hirschsprung's disease (HD), which should be formed from a normoganglionic bowel. However, the neorectum is occasionally created with a transition zone (TZ) bowel. A neorectum created with a TZ has been postulated as a cause of postoperative enterocolitis or constipation. This study compares the incidence of enterocolitis and constipation in patients with TZ neorectum and normoganglionic bowel. METHODS: We conducted a retrospective review of patients with rectosigmoid HD who underwent primary pull-through. Patients were divided into normoganglionic neorectum (NNR) and TZ neorectum. The diagnosis was based on the final histopathologic report of the proximal margin. The incidence of enterocolitis and constipation was compared between these two groups. RESULTS: A total of 98 HD patients were analyzed. Seventy-one patients fulfilled the inclusion criteria. 65 (92%) had a NNR, and six patients (8%) had a TZ neorectum. From these patients, 42 (59%) presented with enterocolitis or constipation. However, there was no significant difference between both groups. CONCLUSION: The present study showed no difference in the incidence of enterocolitis or postoperative constipation in HD patients with normoganglionic or TZ neorectum. These results suggest that TZ neorectum does not cause postoperative obstructive symptoms.

INTRODUCCIÓN: Los cirujanos crean un neo-recto para tratar a los pacientes con enfermedad de Hirschsprung (EH), que debe formarse con intestino normogangliónico; sin embargo, en ocasiones el neo-recto se forma con intestino de la zona de transición. Se ha postulado que un neo-recto en zona de transición causa enterocolitis o estreñimiento postoperatorio. El objetivo de este estudio fue comparar la frecuencia de enterocolitis y estreñimiento en pacientes con neo-recto en zona de transición y con neo-recto normogangliónico. MÉTODOS: Se llevó a cabo una revisión retrospectiva de pacientes con EH recto sigmoideo que se sometieron a descenso primario. Los pacientes se dividieron en el grupo neo-recto normogangliónico y el grupo con neo-recto en zona de transición. El diagnóstico del neo-recto se estableció con el informe histopatológico definitivo del margen proximal. Se comparó la frecuencia de enterocolitis y estreñimiento entre estos dos grupos. RESULTADOS: Se analizó un total de 98 pacientes con EH, de los cuales 71 pacientes cumplieron los criterios de inclusión; 65 (92%) con neo-recto normogangliónico y seis (8%) con neo-recto en zona de transición. Posteriormente, 42 (59%) pacientes presentaron enterocolitis asociada a Hirschsprung (HAEC) o estreñimiento; sin embargo, no hubo diferencia significativa entre ambos grupos. CONCLUSIONES: El presente estudio no demostró una diferencia en la frecuencia de HAEC o estreñimiento postoperatorio en pacientes con EH con neo-recto normogangliónico o en zona de transición. Estos resultados sugieren que un neo-recto en zona de transición no causa síntomas obstructivos postoperatorios.

Baseline ImPACT Composite Scores in Student-Athletes With Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Athletes who are diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of concussion compared to other athletes. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is a widely used concussion tool, but it relies on pre-injury baseline testing that can be affected by psychiatric conditions. This research aims to determine if there are differences in pre-injury testing composite scores in student-athletes with ADHD compared to those without ADHD diagnosis. METHODS: We obtained 11,563 pre-season ImPACT assessments of 7,454 student-athletes (ages: 12-22) from 2009 to 2019. After exclusions, there were 6,920 control and 276 ADHD subjects. Multivariable linear regression analyses compared the independent effect of ADHD on the six ImPACT composite score metrics with Bonferroni correction for multiple comparisons with a = 0.008. RESULTS: Univariate analyses indicated ADHD is associated with more symptoms as measured by the Post-Concussion Symptom Scale (PCSS) (ß = 2.67, 95% CI: 1.47-3.87, p < .0001) and worse Impulse Control scores (ß = 0.93, 95% CI: 0.33-1.53, p = .002). In multivariate analysis, this association was the same for symptom score (ß = 2.48, 95% CI: 1.22-3.74, p < .0001), but Impulse Control was not significantly different after multiple comparison adjustment (ß = 0.87, 95% CI: 0.22-1.15, p = .009). CONCLUSIONS: The ADHD subjects reported worse symptoms at baseline and had worse Impulse Control in univariate analysis, but not multivariate analysis. These results can further guide clinicians in concussion diagnosis and test interpretations for student-athletes with ADHD, considering the symptom burden at baseline.

Glycerol as a precursor for hepatic de novo glutathione synthesis in human liver.

BACKGROUND: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components of glutathione, the major antioxidant in the liver. In principle, glycerol could be incorporated into glutathione via the TCA cycle or 3-phosphoglycerate, but it is unknown whether glycerol contributes to hepatic de novo glutathione biosynthesis. METHODS: Glycerol metabolism to hepatic metabolic products including glutathione was examined in the liver from adolescents undergoing bariatric surgery. Participants received oral [U-13C3]glycerol (50 mg/kg) prior to surgery and liver tissue (0.2-0.7g) was obtained during surgery. Glutathione, amino acids, and other water-soluble metabolites were extracted from the liver tissue and isotopomers were quantified with nuclear magnetic resonance spectroscopy. RESULTS: Data were collected from 8 participants (2 male, 6 female; age 17.1 years [range 14-19]; BMI 47.4 kg/m2 [range 41.3-63.3]). The concentrations of free glutamate, cysteine, and glycine were similar among participants, and so were the fractions of 13C-labeled glutamate and glycine derived from [U-13C3]glycerol. The signals from all component amino acids of glutathione - glutamate, cysteine and glycine - were strong and analyzed to obtain the relative concentrations of the antioxidant in the liver. The signals from glutathione containing [13C2]glycine or [13C2]glutamate derived from the [U-13C3]glycerol drink were readily detected, and 13C-labelling patterns in the moieties were consistent with the patterns in corresponding free amino acids from the de novo glutathione synthesis pathway. The newly synthesized glutathione with [U-13C3]glycerol trended to be lower in obese adolescents with liver pathology. CONCLUSIONS: This is the first report of glycerol incorporation into glutathione through glycine or glutamate metabolism in human liver. This could represent a compensatory mechanism to increase glutathione in the setting of excess glycerol delivery to the liver.

Effects of repetitive head trauma on symptomatology of subsequent sport-related concussion.

OBJECTIVE: Adolescent participation in athletics continues to grow, leading to an increasing incidence of sports-related concussion (SRC). The current literature suggests that a greater number of prior concussions positively correlates with a greater number of total symptoms, but the specific concussion-related symptoms are not as well defined. The current study investigated the effects of prior recurrent head injury on the symptom profiles of student-athletes after another suspected concussion. METHODS: A multicenter database consisting of 25,815 Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) results was filtered for student-athletes aged 12-22 years old who competed in 21 different sports. Patients were separated into 2 cohorts: athletes reporting a single prior concussion (SRC1) and athletes reporting 2 or more prior concussions (SRC2+). Comparisons were assessed for differences in 22 symptoms and 4 symptom clusters at baseline, first postinjury test (PI1), and second postinjury test (PI2) by using univariate and multivariate analyses. RESULTS: No differences were seen between SRC1 (n = 2253) and SRC2+ (n = 976) at baseline. At PI1, the SRC2+ group (n = 286) had lower severity of headaches (p = 0.04) but increased nervousness (p = 0.042), irritability (p = 0.028), sadness (p = 0.028), visual problems (p = 0.04), and neuropsychiatric symptoms (p = 0.009) compared with SRC1 (n = 529). Multivariate analysis revealed decreased headache severity with increased prior concussion (ß = -0.27,95% CI -0.45 to -0.09, p = 0.003). Multivariate analysis at PI2 demonstrated the SRC2+ cohort (n = 130) had increased cognitive (ß = 1.22, 95% CI 0.27-2.18, p = 0.012), sleep (ß = 0.63, 95% CI 0.17-1.08, p = 0.007), and neuropsychiatric (ß = 0.67,95% CI 0.14-1.2,0.014) symptoms compared with SRC1 (n = 292). CONCLUSIONS: At longitudinal follow-up, patients with a history of recurrent concussions reported greater symptom burden in cognitive, sleep, and neuropsychiatric symptom clusters but not migraine symptoms. This is an important distinction because migraine symptoms are often more easily distinguishable to patients, parents, and physicians. Careful assessment of specific symptoms should be considered in patients with a history of recurrent head injury prior to return to play.

Why so low? An unusual case of myositis in a child.

BACKGROUND: Sarcoidosis is characterized by non-caseating epithelioid granulomas in various tissues throughout the body, most commonly the lung. Non-caseating granulomas may be seen in skeletal muscle, though typically asymptomatic and under-recognized. While rare in children, there is a need to better characterize the disease and its management. Here we present a 12-year-old female with bilateral calf pain who was ultimately found to have sarcoid myositis. CASE PRESENTATION: A 12-year-old female presented to rheumatology with significantly elevated inflammatory markers and isolated lower leg pain. MRI of the distal lower extremities demonstrated extensive bilateral myositis with active inflammation, atrophy, and to a lesser extent fasciitis. This distribution of myositis in a child garnered a broad differential requiring a systematic evaluation. Ultimately, muscle biopsy revealed non-caseating granulomatous myositis with perivascular inflammation, extensive muscle fibrosis, and fatty replacement of the muscle with a CD4+ T cell predominant, lymphohistiocytic infiltrate consistent with sarcoidosis. Review of histopathology from age 6 of an extraconal mass resected from her right superior rectus muscle further confirmed the diagnosis. She had no other clinical symptoms or findings of sarcoidosis. The patient improved significantly with methotrexate and prednisone, though flared again after self-discontinuation of medications and was subsequently lost to follow-up. CONCLUSION: This is the second reported case of granulomatous myositis associated with sarcoidosis in a pediatric patient, and the first to present with a chief complaint of leg pain. Increased knowledge of pediatric sarcoid myositis within the medical community will enhance recognition of the disease, improve the evaluation of lower leg myositis, and advance outcomes for this vulnerable population.

A multicenter, longitudinal survey of headaches and concussions among youth athletes in the United States from 2009 to 2019.

OBJECTIVE/ BACKGROUND: Chronic headaches and sports-related concussions are among the most common neurological morbidities in adolescents and young adults. Given that the two can overlap in presentation, studying the effects of one on another has proven difficult. In this longitudinal study, we sought to assess the relationship between chronic headaches and concussions, analyzing the role of historic concussions on chronic headaches, as well as that of premorbid headaches on future concussion incidence, severity, and recovery. METHODS: This multi-center, longitudinal cohort study followed 7,453 youth athletes who were administered demographic and clinical surveys as well as a total of 25,815 Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) assessments between 2009 and 2019. ImPACT was administered at baseline. Throughout the season concussions were examined by physicians and athletic trainers, followed by re-administration of ImPACT post-injury (PI), and at follow-up (FU), a median of 7 days post-concussion. Concussion incidence was calculated as the total number of concussions per patient years. Concussion severity and recovery were calculated as standardized deviations from baseline to PI and then FU in Symptom Score and the four neurocognitive composite ImPACT scores: Verbal Memory, Visual Memory, Processing Speed, and Reaction Time. Data were collected prospectively in a well-organized electronic format supervised by a national research-oriented organization with rigorous quality assurance. Analysis was preformed retrospectively. RESULTS: Of the eligible athletes, 1,147 reported chronic headaches (CH) at the start of the season and 6,306 reported no such history (NH). Median age of the cohort was 15.4 ± 1.6 years, and students were followed for an average of 1.3 ± 0.6 years. A history of concussions (OR 2.31, P < 0.0001) was associated with CH. Specifically, a greater number of past concussions (r2 = 0.95) as well as concussions characterized by a loss of consciousness (P < 0.0001) were associated with more severe headache burden. The CH cohort had a greater future incidence of concussion than the NH cohort (55.6 vs. 43.0 per 100 patient-years, P < 0.0001). However, multivariate analysis controlling for demographic, clinical, academic, and sports-related variables yielded no such effect (OR 0.99, P = 0.85). On multivariable analysis the CH cohort did have greater deviations from baseline to PI and FU in Symptom Score (PI OR per point 1.05, P = 0.01, FU OR per point 1.11, P = 0.04) and Processing Speed (OR per point 1.08, P = 0.04), suggesting greater concussion severity and impaired symptomatic recovery as compared to the NH cohort. CONCLUSION: A history of concussions was a significant contributor to headache burden among American adolescents and young adults. However, those with chronic headaches were not more likely to be diagnosed with a concussion, despite presenting with more severe concussions that had protracted recovery. Our findings not only suggest the need for conservative management among youth athletes with chronic headaches, they also indicate a potential health care gap in this population, in that those with chronic headaches may be referred for concussion diagnosis and management at lower rates than those with no such comorbidity.

Maternal Western diet is associated with distinct preclinical pediatric NAFLD phenotypes in juvenile nonhuman primate offspring.

Pediatric NAFLD has distinct and variable pathology, yet causation remains unclear. We have shown that maternal Western-style diet (mWSD) compared with maternal chow diet (CD) consumption in nonhuman primates produces hepatic injury and steatosis in fetal offspring. Here, we define the role of mWSD and postweaning Western-style diet (pwWSD) exposures on molecular mechanisms linked to NAFLD development in a cohort of 3-year-old juvenile nonhuman primates offspring exposed to maternal CD or mWSD followed by CD or Western-style diet after weaning. We used histologic, transcriptomic, and metabolomic analyses to identify hepatic pathways regulating NAFLD. Offspring exposed to mWSD showed increased hepatic periportal collagen deposition but unchanged hepatic triglyceride levels and body weight. mWSD was associated with a downregulation of gene expression pathways underlying HNF4α activity and protein, and downregulation of antioxidant signaling, mitochondrial biogenesis, and PPAR signaling pathways. In offspring exposed to both mWSD and pwWSD, liver RNA profiles showed upregulation of pathways promoting fibrosis and endoplasmic reticulum stress and increased BiP protein expression with pwWSD. pwWSD increased acylcarnitines and decreased anti-inflammatory fatty acids, which was more pronounced when coupled with mWSD exposure. Further, mWSD shifted liver metabolites towards decreased purine catabolism in favor of synthesis, suggesting a mitochondrial DNA repair response. Our findings demonstrate that 3-year-old offspring exposed to mWSD but weaned to a CD have periportal collagen deposition, with transcriptional and metabolic pathways underlying hepatic oxidative stress, compromised mitochondrial lipid sensing, and decreased antioxidant response. Exposure to pwWSD worsens these phenotypes, triggers endoplasmic reticulum stress, and increases fibrosis. Overall, mWSD exposure is associated with altered expression of candidate genes and metabolites related to NAFLD that persist in juvenile offspring preceding clinical presentation of NAFLD.

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p < 0.001) and MMP-7 ( p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2 = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated ( p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 ( p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. CONCLUSIONS: Endoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.

Rosai-Dorfman-Destombes Disease in the Pediatric Head and Neck.

BACKGROUND: Rosai-Dorfman-Destombes disease (RDD), or sinus histiocytosis with massive lymphadenopathy, is a rare form of non-Langerhans cells histiocytosis. It has a wide-ranging variability in presentation since first described in 1969 but much of its characteristics in children remain unknown. METHODS: A retrospective chart review of children diagnosed with RDD at a tertiary care children's hospital was conducted from 2000 to 2021. RESULTS: Twelve RDD patients were identified, with an average age of 7 years (SD 4.3). Males comprised 58% of the cohort, and African American ethnicity was most common (42%). Nodal RDD was found in 7 patients (58%). Nine patients (75%) presented RDD within the head and neck, 6 of whom had nodal RDD. The most common presentation was cervical lymphadenopathy, which most often involved levels V (67%), II (56%), III (44%), and I (11%), in order of frequency. Recurrence and persistence of disease after initial treatment was common, with 5 (42%) being disease free at the time of the last follow up. Fifty-eight percent (7/12) developed recurrence or had persistent disease and 4 required adjuvant systemic treatment with corticosteroids and/or chemotherapy. One patient succumbed after developing treatment related acute myelodysplastic leukemia (t-AML) from chemotherapy used to treat recurrent RDD. CONCLUSION: Pediatric RDD presents at a young age and most commonly involving cervical lymphadenopathy. Ongoing surveillance in the setting of persistence or recurrence without clearly defined prognostic risk factors is important.

Computed Tomographic Angiography Provides Reliable Coronary Artery Evaluation in Infants With Pulmonary Atresia Intact Ventricular Septum.

Evaluate the use of coronary CTA as an initial assessment for determining Right Ventricle Dependent Coronary Circulation (RVDCC) in neonates with Pulmonary Atresia with Intact Ventricular Septum (PA IVS). Retrospective review of cases with coronary CTA and compare with available catheter angiography, pathology, surgical reports, and outcomes from Mar 2015 to May 2022. In our cohort of 16 patients, 3 were positive for RVDCC, confirmed by pathologic evaluation, and there was concordance for presence or absence of RVDCC with catheter angiography in 5 patients (4 negatives for RVDCC, 1 positive). Clinical follow up for the 8 patients that underwent RV decompression had no clinical evidence of myocardial ischemia. Our findings suggest that coronary CTA is reliable as first-line imaging for determination of RVDCC in neonates with PA IVS. These findings, if supported by further prospective study, may reserve invasive coronary angiography for cases with diagnostic uncertainty or at the time of necessary transcatheter interventions.

Preliminary Evaluation of a Novel Point of Care Diagnostic Device for Sports-Related Concussion.

OBJECTIVE: Visinin-like protein 1 (VILIP-1) is a neuron-specific calcium sensor protein rapidly released into blood after mild traumatic brain injury (mTBI) and may be a suitable biomarker for identification of sports-related concussion (SRC). The objective of the study is to test if quantification of a specific post-translationally modified (ubiquitinated) form of VILIP-1 (ubVILIP-1) from a fingerstick blood sample using a point of care (POC) lateral flow device (LFD) can be used to rapidly identify athletes with SRC. DESIGN: Prospective cohort study. SETTING: Side-line blood collection at football, soccer, and volleyball games/practices. PARTICIPANTS: Division I athletes with/without SRC. MAIN OUTCOME MEASURES: Blood ubVILIP-1 concentrations. RESULTS: Data collected over 2 athletic seasons from non-SRC athletes (controls) show a small but statistically significant elevation of ubVILIP-1 over an individual season for male athletes (P = 0.02) dependent on sport (P = 0.014) and no significant changes in ubVILIP-1 levels between seasons. For SRC athletes, the data show ubVILIP-1 levels substantially increase above baseline as soon as 30 minutes postdiagnosis with peak concentrations and times postinjury that vary based on injury severity. CONCLUSION: Results of the study suggest quantification of blood ubVILIP-1 levels measured using an LFD may provide an objective identification of athletes with SRC, setting the stage for further study with a larger number of SRC patients.

The discriminatory ability of FibroScan liver stiffness measurement, controlled attenuation parameter, and FibroScan-aspartate aminotransferase to predict severity of liver disease in children.

Vibration controlled transient elastography (FibroScan) is used to predict the severity of liver fibrosis and steatosis. In pediatrics, few studies have been performed directly comparing liver histologic features with FibroScan liver stiffness measurements (LSMs) and controlled attenuation parameters (CAPs). The FibroScan-aspartate aminotransferase (FAST) score, which predicts liver disease severity in adult nonalcoholic fatty liver disease (NAFLD), has not been analyzed in children. The aims of this study were to determine if LSM and CAP correlated with liver histologic fibrosis stage and steatosis grade, respectively, and to determine the predictive capacity of FAST in pediatric NAFLD. Research participants (n = 216) included those with FibroScan within 90 days of a liver biopsy. The ability of LSM, CAP, and FAST to predict severity of liver disease was analyzed by Spearman correlation, linear regression, and receiver operating characteristic and C statistic. Significant correlations were identified between LSM and Ishak fibrosis stages, with the strongest correlation occurring in the non-NAFLD group (Spearman r = 0.47, p < 0.0001). LSM adequately predicted Ishak stages F0-2 versus F3-F6 (area under the receiver operating characteristic curve [AUROC], 0.73 for all; 0.77 for non-NAFLD). CAP strongly predicted histologic steatosis grade (r = 0.84; p < 0.0001; AUROC, 0.98). FAST had acceptable discriminatory ability for significant liver disease (AUROC, 0.75). A FAST cutoff ≥0.67 had a sensitivity of 89% but a specificity of only 62% at determining significant liver disease. This study encompasses one of the largest pediatric cohorts describing the accuracy of FibroScan LSM and CAP to predict liver histologic fibrosis stage and steatosis grade, respectively. In order to determine specific LSM, CAP, and FAST cut-off values for fibrosis stages, steatosis grades, and significant liver disease, respectively, a much larger cohort is necessary and will likely entail the need for multicentered studies.

Solid Pseudopapillary Neoplasm: A Single Institutional Case Series of a Rare Pancreatic Tumor.

Purpose: Solid pseudopapillary neoplasms (SPN) are rare pancreatic cystic neoplasms with low malignant potential that tend to occur in young women. Due to the rarity of this disease, there are few large case series in the literature, and the exact pathophysiology remains unknown. In this article, we aim to share our institutional experience. Methods: Retrospective clinical data collection and analysis was performed on all patients with a diagnosis of SPN at the University of Colorado Hospital and Children's Hospital of Colorado (n = 28). Results: Twenty-eight patients were diagnosed with SPN during the study period. The median age was 21.5 years, and the majority of patients were female (89.3%) and Caucasian (60.7%). Six patients were diagnosed incidentally (21.4%). The majority of tumors were in the pancreatic tail (46.4%), and most underwent distal pancreatectomy (64.3%). The mean tumor size was 5.4 cm, and R0 resection was achieved in 25 patients (89.3%). Ten patients underwent laparoscopic resection (35.7%). The median hospital length of stay was 8.5 days, and postoperative complication rate was 39.3%. Median follow-up was 41 months, with 78.6% of patients alive without evidence of disease, while 2 patients were lost to follow-up. Two patients developed recurrence/metastases, which were resected; both are alive without evidence of disease. Conclusion: SPN are rare pancreatic tumors diagnosed most frequently in young women. Surgical resection is the mainstay of treatment, and outcomes are excellent if complete resection is achieved. Predictors of malignant disease are inconsistent in current literature. Considerations should be made for a minimally invasive approach in patients with SPN. Multidisciplinary clinics may be helpful in the diagnosis, management, and surveillance of pancreatic cystic lesions, with major potential for the advanced practitioner role.

Evaluation of differences across age groups in the incidence, severity, and recovery of concussion in adolescent student-athletes from 2009 to 2019.

OBJECTIVE: Concussion incidence is known to be highest in children and adolescents; however, there is conflicting evidence about the effect of age on concussion risk and recovery within the adolescent age range. The heterogeneity of results may be partially due to the use of age groupings based on convenience, making comparisons across studies difficult. This study evaluated the independent effect of age on concussion incidence, severity, and recovery in student-athletes aged 12-18 years using cluster analysis to define groupings. METHODS: Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores of 11,403 baseline tests and 4922 postinjury tests were used to calculate the incidence rates for adolescent student-athletes grouped into 3 age bands (12-13, 14-15, and 16-18 years of age) on the basis of clustering analysis. The recently created Severity Index was used to compare concussion severity between groups. Follow-up tests for subjects who sustained a concussion were used to evaluate recovery time. The chi-square test and 1-way ANOVA were used to compare differences in demographic characteristics and concussion incidence, severity, and recovery. Multivariable logistic and linear regressions were used to evaluate the independent effects of age on concussion incidence and severity, respectively. Multivariable Cox hazard regression was used to evaluate differences in recovery time. Further analyses were conducted to directly compare findings across studies on the basis of the age groupings used in prior studies. RESULTS: Multivariable regression analyses demonstrated that the 14- to 15-year-old age group had a significantly higher concussion incidence than both the 12- to 13-year-old (14- to 15-year-old group vs 12- to 13-year-old group, OR 1.57, 95% CI 1.16-2.17, p = 0.005) and 16- to 18-year-old (16- to 18-year-old group vs 14- to 15-year-old group, OR 0.79, 95% CI 0.69-0.91, p = 0.0008) age groups. There was no difference in incidence between the 12- to 13-year-old and 16- to 18-year-old groups (16- to 18-year group vs 12- to 13-year group, OR 1.26, 95% CI 0.93-1.72, p = 0.15). There were also no differences in concussion severity or recovery between any groups. CONCLUSIONS: This study found that concussion incidence was higher during mid-adolescence than early and late adolescence, suggesting a U-shaped relationship between age and concussion risk over the course of adolescence. Age had no independent effect on concussion severity or recovery in the 12- to 13-, 14- to 15-, and 16- to 18-year-old groups. Further analysis of the various age groups revealed that results may vary significantly with minor changes to groupings, which may explain the divergent results in the current literature on this topic. Thus, caution should be taken when interpreting the results of this and all similar studies, especially when groupings are based on convenience.