FDG altered biodistribution in white adipose tissue, a rare entity: case report and review of the literature.

PURPOSE: Altered 18F-fluorodeoxyglucose (FDG) biodistribution due to patient factors such as exercise and inadequate fasting are well established causes of limited diagnostic efficacy. In addition, medications such as G-CSF are known to affect uptake of FDG by bone marrow and spleen. In this study, we present a case of increased white adipose uptake in a pediatric lymphoma patient who recently received high dose dexamethasone and review the relevant literature regarding this rare and poorly understood pattern of altered FDG biodistribution. METHODS: A 14-year-old male patient diagnosed with B-cell lymphoblastic lymphoma underwent FDG-PET/CT for restaging shortly after completing an induction chemotherapy regimen. Images revealed diffuse FDG uptake localizing to white adipose tissue, attributed to the 29-day course of dexamethasone which was completed two days prior. A diagnostically adequate study with relative normalization of FDG biodistribution was obtained seven days later. RESULTS: In our review of the literature, diffuse FDG uptake by white fat is a rare occurrence and has only been reported by a few case reports and early observational studies. In addition to patients receiving corticosteroids, other cases of medication-induced adipose remodeling such as patients receiving highly active antiretroviral therapy have been documented with similar patterns of increased white adipose tissue activity. CONCLUSION: Corticosteroid-induced white fat uptake of FDG is a rare phenomenon that can limit diagnostic accuracy of FDG-PET/CT and necessitate repeat imaging. Current evidence suggests that a wait period of at least one week after discontinuation of corticosteroids is sufficient to allow for decreased white fat uptake and increased diagnostic accuracy.

Acute inorganic nitrate ingestion does not impact oral microbial composition, cognitive function, or high-intensity exercise performance in female team-sport athletes.

The purpose of this study was to investigate the effects of acute nitrate (NO3-)-rich beetroot juice ingestion on explosive and high-intensity exercise performance, oral microbiota composition, and cognitive flexibility (i.e., function), before and after maximal intermittent running exercise. Fifteen women team-sport athletes were assigned in a randomized, double-blind, crossover design to consume concentrated NO3--depleted beetroot juice (PL; 0.1 mmol NO3-) and NO3--rich beetroot juice (BR; 12.0 mmol NO3-) 2.5 h prior to performing a battery of exercise performance tasks and cognitive testing before and after the Yo-Yo intermittent recovery level 1 (YYIR1) running test. Resting plasma [NO3-] and plasma nitrite ([NO2-]) were elevated following BR (P < 0.001). BR did not impact global composition or relative abundance of taxa in the oral microbiome (P > 0.05) or cognitive flexibility before or after exercise (P > 0.05). There was no significant difference in performance during 20-m (PRE, PL: 4.38 ± 0.27 vs. BR: 4.38 ± 0.32 s; POST, PL: 4.45 ± 0.29 vs. BR: 4.43 ± 0.35 s) and 10-m sprints (PRE, PL 2.78 ± 0.15 vs. BR 2.79 ± 0.18 s; POST, PL: 2.82 ± 0.16 vs. BR: 2.81 ± 0.19 s), isokinetic handgrip dynamometry, medicine ball throw, horizontal countermovement jump, or YYIR1 (PL: 355 ± 163 m vs. BR: 368 ± 184 m) between BR and PL (P > 0.05). These findings indicate that acute dietary NO3- may not influence the oral microbiome, explosive and high-intensity exercise performance, or cognitive function in women team-sport athletes.

Malaria in pregnancy: baby steps.

PURPOSE OF REVIEW: Malaria threatens pregnant women and their babies, particularly in Africa. RECENT FINDINGS: This century, the number of women at risk of malaria in pregnancy has decreased globally, apart from in Africa, where it has increased. Low and sub microscopic infections are increasingly documented but remain hard to diagnose with current point-of-care tests, and their contribution to morbidity and transmission are unclear. Artemether-lumefantrine has been endorsed for treatment in first trimester, but many women attend antenatal clinics later in pregnancy, and reaching high-risk young, first-time mothers is particularly difficult. Small-for-gestational-age babies frequently result from malaria, which affects the placenta's development and its functions such as nutrient transport. Resistance to continues to increase to sulphadoxine-pyrimethamine, the mainstay of intermittent preventive treatment in pregnancy. The alternative, dihydroartemisinin-piperaquine controls malaria better, but does not improve pregnancy outcomes, suggesting that sulphadoxine-pyrimethamine may have nonmalarial effects including improving gut function or reducing dangerous inflammation. Understanding of how the malaria parasite uses the VAR2CSA protein to bind to its placental receptor is increasing, informing the search for a vaccine to prevent pregnancy malaria. SUMMARY: Progress in several areas increases optimism that improved prevention and control of malaria in pregnancy is possible, but obstacles remain.

Evaluating spectral performance for quantitative contrast-enhanced breast CT with a GaAs based photon counting detector: a simulation approach.

Quantitative contrast-enhanced breast computed tomography (CT) has the potential to improve the diagnosis and management of breast cancer. Traditional CT methods using energy-integrated detectors and dual-exposure images with different incident spectra for material discrimination can increase patient radiation dose and be susceptible to motion artifacts and spectral resolution loss. Photon Counting Detectors (PCDs) offer a promising alternative approach, enabling acquisition of multiple energy levels in a single exposure and potentially better energy resolution. Gallium arsenide (GaAs) is particularly promising for breast PCD-CT due to its high quantum efficiency and reduction of fluorescence x-rays escaping the pixel within the breast imaging energy range. In this study, the spectral performance of a GaAs PCD for quantitative iodine contrast-enhanced breast CT was evaluated. A GaAs detector with a pixel size of 100µm, a thickness of 500µm was simulated. Simulations were performed using cylindrical phantoms of varying diameters (10 cm, 12 cm, and 16 cm) with different concentrations and locations of iodine inserts, using incident spectra of 50, 55, and 60 kVp with 2 mm of added aluminum filtration and and a mean glandular dose of 10 mGy. We accounted for the effects of beam hardening and energy detector response using TIGRE CT open-source software and the publicly available Photon Counting Toolkit (PcTK). Material-specific images of the breast phantom were produced using both projection and image-based material decomposition methods, and iodine component images were used to estimate iodine intake. Accuracy and precision of the proposed methods for estimating iodine concentration in breast CT images were assessed for different material decomposition methods, incident spectra, and breast phantom thicknesses. The results showed that both the beam hardening effect and imperfection in the detector response had a significant impact on performance in terms of Root Mean Squared Error (RMSE), precision, and accuracy of estimating iodine intake in the breast. Furthermore, the study demonstrated the effectiveness of both material decomposition methods in making accurate and precise iodine concentration predictions using a GaAs-based photon counting breast CT system, with better performance when applying the projection-based material decomposition approach. The study highlights the potential of GaAs-based photon counting breast CT systems as viable alternatives to traditional imaging methods in terms of material decomposition and iodine concentration estimation, and proposes phantoms and figures of merit to assess their performance.

Deep Learning - Methods to Amplify Epidemiological Data Collection and Analyses.

Deep learning is a subfield of artificial intelligence and machine learning based mostly on neural networks and often combined with attention algorithms that has been used to detect and identify objects in text, audio, images, and video. Serghiou and Rough (Am J Epidemiol. 0000;000(00):0000-0000) present a primer for epidemiologists on deep learning models. These models provide substantial opportunities for epidemiologists to expand and amplify their research in both data collection and analyses by increasing the geographic reach of studies, including more research subjects, and working with large or high dimensional data. The tools for implementing deep learning methods are not quite yet as straightforward or ubiquitous for epidemiologists as traditional regression methods found in standard statistical software, but there are exciting opportunities for interdisciplinary collaboration with deep learning experts, just as epidemiologists have with statisticians, healthcare providers, urban planners, and other professionals. Despite the novelty of these methods, epidemiological principles of assessing bias, study design, interpretation and others still apply when implementing deep learning methods or assessing the findings of studies that have used them.

Design, Synthesis, and Evaluation of a New Chemotype Fluorescent Ligand for the P2Y2 Receptor.

The P2Y2 receptor (P2Y2R) is a target for diseases including cancer, idiopathic pulmonary fibrosis, and atherosclerosis. However, there are insufficient P2Y2R antagonists available for validating P2Y2R function and future drug development. Evaluation of how (R)-5-(7-chloro-2-((2-ethoxyethyl)amino)-4H-benzo[5,6]cyclohepta[1,2-d]thiazol-4-yl)-1-methyl-4-thioxo-3,4-dihydropyrimidin-2(1H)-one, a previously published thiazole-based analogue of AR-C118925, binds in a P2Y2R homology model was used to design new P2Y2R antagonist scaffolds. One P2Y2R antagonist scaffold retained millimolar affinity for the P2Y2R and upon further functionalization with terminal carboxylic acid groups affinity was improved over 100-fold. This functionalized P2Y2R antagonist scaffold was employed to develop new chemotype P2Y2R fluorescent ligands, that were attainable in a convergent five-step synthesis. One of these fluorescent ligands demonstrated micromolar affinity (pK d = 6.02 ± 0.12, n = 5) for the P2Y2R in isolated cell membranes and distinct pharmacology from an existing P2Y2R fluorescent antagonist, suggesting it may occupy a different binding site on the P2Y2R.

The Role of DNA Methylation in Gastrointestinal Disease: An Expanded Review of Malignant and Non-Malignant Gastrointestinal Diseases.

Esophageal, colorectal, pancreatic, hepatocellular, and gastric cancer together impact millions of patients worldwide each year, with high overall mortality rates and are increasing in incidence. Additionally, premalignant gastrointestinal diseases such as Barrett's esophagus and inflammatory bowel disease are also increasing in incidence. However, involvement of aberrant DNA methylation in these diseases is incompletely understood, especially given recent research advancements in this field. Here, we review knowledge of this epigenetic mechanism in gastrointestinal preneoplasia and neoplasia, considering mechanisms of action, genetic and environmental factors, and CpG island methylator phenotype. We also highlight developments in translational research, focusing on genomic-wide database data, methylation-based biomarkers and diagnostic tests, machine learning, and therapeutic epigenetic strategies.

The Association Between Autism Symptomatology and Adaptive Functioning Over Six Months: Findings from the Pilot Phase of the PARC Study.

PURPOSE: In the context of developmental trajectories, the association between adaptive functioning and core autism symptomatology remains unclear. The current study examines the associations of adaptive behavior with autism symptom sub-domains and with different facets of symptom expression. METHODS: Participants include 36 children with a recent diagnosis of autism (33 males; mean age = 56.4 months; SD = 9 months). Families were recruited in the context of the Pediatric Autism Research Cohort (PARC) project. Parents filled out questionnaires at two time points, six months apart, regarding their child's autism symptoms and adaptive functioning. The longitudinal relationship between adaptive functioning and autism symptoms was investigated using Mixed Linear Model analyses: one assessing the relationship between general symptom levels and adaptive functioning, and another examining the associations between symptom frequency and impact with adaptive functioning. We conducted Pearson correlation tests at both time points to assess the associations between symptom sub-domains and adaptive functioning. RESULTS: Findings showed that higher autism symptoms associated with lower adaptive behavior skills, and that this association remained stable over time. Autism impact scores did not significantly relate to adaptive skills, as opposed to frequency scores. Associations between adaptive functioning and autism symptom sub-domains strengthened over time. CONCLUSION: These findings suggest that adaptive functioning is associated with parent-report autism symptomatology, and that this association changes and, on average, becomes stronger over time. Findings may indicate that frequency and impact of symptoms have differential roles in the development of adaptive skills and are worthy of further exploration.

Tropine exacerbates the ventilatory depressant actions of fentanyl in freely-moving rats.

Our lab is investigating the efficacy profiles of tropine analogs against opioid-induced respiratory depression. The companion manuscript reports that the cell-permeant tropeine, tropine ester (Ibutropin), produces a rapid and sustained reversal of the deleterious actions of fentanyl on breathing, alveolar-arterial (A-a) gradient (i.e., index of alveolar gas exchange), and arterial blood-gas (ABG) chemistry in freely-moving male Sprague Dawley rats, while not compromising fentanyl analgesia. We report here that in contrast to Ibutropin, the injection of the parent molecule, tropine (200 µmol/kg, IV), worsens the adverse actions of fentanyl (75 µg/kg, IV) on ventilatory parameters (e.g., frequency of breathing, tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives), A-a gradient, ABG chemistry (e.g., pH, pCO2, pO2, and sO2), and sedation (i.e., the righting reflex), while not affecting fentanyl antinociception (i.e., the tail-flick latency) in freely-moving male Sprague Dawley rats. These data suggest that tropine augments opioid receptor-induced signaling events that mediate the actions of fentanyl on breathing and alveolar gas exchange. The opposite effects of Ibutropin and tropine may result from the ability of Ibutropin to readily enter peripheral and central cells. Of direct relevance is that tropine, resulting from the hydrolysis of Ibutropin, would combat the Ibutropin-induced reversal of the adverse effects of fentanyl. Because numerous drug classes, such as cocaine, atropine, and neuromuscular blocking drugs contain a tropine moiety, it is possible that their hydrolysis to tropine has unexpected/unintended consequences. Indeed, others have found that tropine exerts the same behavioral profile as cocaine upon central administration. Together, these data add valuable information about the pharmacological properties of tropine.

Oral Hedgehog Inhibitor, Vismodegib, for Locally Advanced Periorbital and Orbital Basal Cell Carcinoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the efficacy and safety of oral vismodegib (Erivedge; Genentech) in the management of locally advanced orbital and periorbital basal cell carcinoma (BCC). METHODS: A literature search was conducted last in September 2023 in the PubMed database for English language original research that evaluated the effect of oral vismodegib on orbital and periorbital BCC. Sixty articles were identified and 16 met the inclusion criteria. RESULTS: Most studies demonstrated high response rates, with up to 100% of patients responding to the medication in individual studies and initial complete regression occurring in up to 88% of patients. Vismodegib treatment resulted in significant reductions in tumor volume, resulting in globe preservation for most patients. However, in 12% of patients, the response was partial. Recurrences also occurred with substantial frequency, even after an initial complete response. As such, up to 79.4% of patients required surgical intervention, and up to 23% of patients still required exenteration. Use of these agents resulted in reductions in tumor volume that may delay or prevent the need for exenteration in some, but not all, patients. Importantly, molecular analysis of tissue excised after vismodegib therapy revealed persistent tumor in all patients, with frequent accumulation of mutations that may confer resistance to further hedgehog inhibitor therapy. Although most adverse events were rated as level I or II, side effects were common, with up to 100% of patients in studies experiencing at least 1 event. Muscle cramps, alopecia, weight loss, fatigue, and dysgeusia were the most common adverse events, and several patients discontinued therapy because of them. Furthermore, 1 patient died of sepsis that may have resulted from the therapy. CONCLUSIONS: Although level I and II evidence are lacking, most studies indicate a benefit from the use of oral vismodegib to treat orbital and periorbital BCC tumor volume. However, patients should be cautioned about the adverse side effects of treatment and the persistence of tumor cells with mutations that may cause long-term resistance. Use of vismodegib as short-term neoadjuvant therapy may be effective in shrinking tumor volume to reduce surgical morbidity while reducing the frequency and severity of side effects. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Method for B Cell Receptor Enrichment in Malignant B Cells.

B cells are central to the adaptive immune response and provide long-lasting immunity after infection. B cell activation is mediated by the surface membrane-bound B cell receptor (BCR) following recognition of a specific antigen. The BCR has been challenging to analyse using mass spectrometry (MS) due to the difficulty of isolating and enriching this membrane-bound protein complex. There are approximately 120,000 BCRs on the B cell surface; however, depending on the B cell activation state, there may be hundreds-of-millions to billions of proteins in a B cell. Consequently, advanced proteomic techniques such as MS workflows that use purified proteins to yield structural and protein-interaction information have not been published for the BCR complex. This paper describes a method for enriching the BCR complex that is MS-compatible. The method involves a Protein G pull down on agarose beads using an intermediary antibody to each of the BCR complex subcomponents (CD79a, CD79b, and membrane immunoglobulin). The enrichment process is shown to pull down the entire BCR complex and has the advantage of being readily compatible with further proteomic study including MS analysis. Using intermediary antibodies has the potential to enrich all isotypes of the BCR, unlike previous methods described in the literature that use protein G-coated beads to directly pull down the membrane IgG (mIgG) but cannot be used for other mIg isotypes.

Sources of nutrients fuelling post-flood phytoplankton biomass in a subtropical bay.

Extreme rainfall from an ex-tropical cyclone caused a major flood event in the Logan River system in southeast Queensland, Australia. This resulted in a significant flood plume, containing nutrients and sediment, being discharged into the adjacent estuary/Bay system. The spatial extent of higher phytoplankton biomass (Chl a) matched the distribution of higher nutrient and sediment concentrations post-flood, suggesting nutrients fuelled phytoplankton production. Particulate nitrogen (PN) constituted over 50 % of total nitrogen in floodwaters, with lower proportions of dissolved inorganic nitrogen (DIN) and phosphate (PO4-P). Phytoplankton utilised DIN rapidly but may have maintained growth due to the release of ammonia from suspended sediments and microbial mineralisation of particulate organic nitrogen. Ammonia release from intertidal sediments contributed minimally (0.85 %) to daily phytoplankton nitrogen demands. Our study highlights the need to understand the fate of particulate nitrogen in coastal systems and its role in stimulating phytoplankton growth.

Prevalence of preexisting articular bone pathology in patients with osteoarthritis screened for fasinumab clinical trials identified by X-ray or magnetic resonance imaging.

OBJECTIVE: To examine the prevalence of preexisting articular bone pathology in patients with hip or knee pain due to osteoarthritis (OA) screened for fasinumab clinical trials. METHOD: This post-hoc analysis included patients with OA screened for three phase 3 fasinumab studies (NCT02683239, NCT03161093, NCT03304379). During screening, participants who met other clinical inclusion/exclusion criteria underwent radiography of knees, hips, and shoulders. Those with Kellgren-Lawrence grade (KLG) ≥2 for index joint and without an exclusionary finding proceeded to magnetic resonance imaging (MRI) of index, contralateral, and KLG ≥3 joints. Exclusionary findings included bone fragmentation/collapse, bone loss/resorption, osteonecrosis, and fracture, by either X-ray or MRI. Participants with extensive subchondral cysts were also excluded. Prevalence of abnormalities on radiographs and MRIs are reported. RESULTS: Of 27,633 participants screened, 21,997 proceeded to imaging. Of these, 1203 (5.5%) were excluded due to the presence of ≥1 joint with severe articular bone pathology (X-ray or MRI): bone fragmentation/collapse (2.61%), subchondral insufficiency fracture (SIF; 1.67%), osteonecrosis (1.11%), and significant bone loss (0.32%). Additionally, 3.14% screen-failed due to extensive subchondral cysts. More than half of the exclusions due to bone fragmentation/collapse (386/572), osteonecrosis (141/245) and significant bone loss (59/71), and approximately one third of SIF (133/367) and extensive subchondral cysts (229/689) were evident on X-rays. CONCLUSIONS: Approximately one in 20 participants with OA who met the clinical screening criteria for fasinumab phase 3 trials were later excluded due to preexisting severe articular bone pathology findings by X-ray or MRI.

Questionable evidence and argumentation regarding alleged misuse of Medicare.

What is known about this topic? We discuss a recently published paper that alleges clinicians are causal agents of non-compliant billing of Medicare. What does this paper add? The paper's arguments are partially supported by unreferenced assertions, potential logical fallacies, inaccurate reporting of referenced material and unsubstantiated rhetoric. What are the implications for practitioners? Due to the lack of substantive evidence, it cannot be concluded that clinicians are the causal agents of non-compliant billing of Medicare.

Evaluation of the Immunomodulatory Effects of Radiation for Chimeric Antigen Receptor T Cell Therapy in Glioblastoma Multiforme.

Standard-of-care treatment for Glioblastoma Multiforme (GBM) is comprised of surgery and adjuvant chemoradiation. Chimeric Antigen Receptor (CAR) T cell therapy has demonstrated disease-modifying activity in GBM and holds great promise. Radiation, a standard-of-care treatment for GBM, has well-known immunomodulatory properties and may overcome the immunosuppressive tumor microenvironment (TME); however, radiation dose optimization and integration with CAR T cell therapy is not well defined. Murine immunocompetent models of GBM were treated with titrated doses of stereotactic radiosurgery (SRS) of 5, 10, and 20 Gray (Gy), and the TME was analyzed using Nanostring. A conditioning dose of 10 Gy was determined based on tumor growth kinetics and gene expression changes in the TME. We demonstrate that a conditioning dose of 10 Gy activates innate and adaptive immune cells in the TME. Mice treated with 10 Gy in combination with mCAR T cells demonstrated enhanced antitumor activity and superior memory responses to rechallenge with IL13Rα2-positive tumors. Furthermore, 10 Gy plus mCAR T cells also protected against IL13Rα2-negative tumors through a mechanism that was, in part, c-GAS-STING pathway-dependent. Together, these findings support combination conditioning with low-dose 10 Gy radiation in combination with mCAR T cells as a therapeutic strategy for GBM.

Inflammatory Changes after Medical Suppression of Suspected Endometriosis for Implantation Failure: Preliminary Results.

Unexplained euploid embryo transfer failure (UEETF) is a frustrating and unanswered conundrum accounting for 30 to 50% of failures in in vitro fertilization using preimplantation genetic testing for aneuploidy (PGT-A). Endometriosis is thought by many to account for most of such losses and menstrual suppression or surgery prior to the next transfer has been reported to be beneficial. In this study, we performed endometrial biopsy in a subset of women with UEETF, testing for the oncogene BCL6 and the histone deacetylase SIRT1. We compared 205 PGT-A cycles outcomes and provide those results following treatment with GnRH agonist versus controls (no treatment). Based on these and previous promising results, we next performed a pilot randomized controlled trial comparing the orally active GnRH antagonist, elagolix, to oral contraceptive pill (OCP) suppression for 2 months before the next euploid embryo transfer, and monitored inflammation and miRNA expression in blood, before and after treatment. These studies support a role for endometriosis in UEETF and suggest that medical suppression of suspected disease with GnRH antagonist prior to the next transfer could improve success rates and address underlying inflammatory and epigenetic changes associated with UEETF.

Cardiovascular Clinical Trials in the Asia-Pacific Region.

This Viewpoint discusses the potential challenges to the operational conduct of clinical trials in the Asia-Pacific region, where there is a high rate of cardiovascular disease, and provides possible solutions.

Epidemiology, treatment patterns, and clinical outcomes in de novo oligometastatic hormone-sensitive prostate cancer.

BACKGROUND: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone-sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. METHODS: In this observational retrospective cohort study, 400 de novo metastatic hormone-sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow-up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan-Meier methods estimated overall survival (OS) and castration-resistant prostate cancer (CRPC)-free survival from mHSPC diagnosis date and a log-rank test compared these outcomes by oligometastatic status. RESULTS: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non-omHSPC had higher median prostate-specific antigen at diagnosis (151.7) than omHSPC (44.1). First-line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non-omHSPC (14%). More omHSPC patients received metastasis-directed therapy/prostate radiation therapy (14%) versus non-omHSPC (2%). Median OS and CRPC-free survival (in months) were higher in omHSPC versus non-omHSPC (44.4; 95% confidence interval [CI], 33.9-not estimated vs. 26.2; 95% CI, 20.5-32.5, p = .0089 and 27.6; 95% CI, 22.1-37.2 vs. 15.3; 95% CI, 12.8-17.9, p = .0049), respectively. CONCLUSIONS: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non-omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non-omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies.

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.