Disparities in Screening for Substance Use Among Injured Adolescents.

This cohort study compares rates of biochemical substance use screening among injured adolescents by sociodemographic characteristics including sex, race, ethnicity, and insurance status.

Pediatric Trauma Mortality Differs by Neighborhood Opportunity Level.

OBJECTIVE: Traumatic injuries are a leading cause of death in children and a child's neighborhood characteristics can be a risk factor. Our objective was to describe the association between pediatric trauma mortality and Child Opportunity Index (COI). METHODS: A multicenter, retrospective cross-sectional study was conducted across 15 trauma centers from 2010 to 2021 within a large metropolitan county to evaluate trauma activation mortalities involving children <18 years-old. We examined clinical and demographic data from the county trauma registry and linked home zip code to COI, a measure of neighborhood level resources critical for children's development. Proportion of mortalities were compared to the proportion of children within each COI quintile and injury mechanism was evaluated across COI quintile. Analysis was performed using Kruskal-Wallis and chi-square tests (α = 0.05). RESULTS: Of 31,702 pediatric trauma activations, 513 (1.6%) mortalities occurred. Mortalities mostly resulted from assaults (37.0%), pedestrian injuries (26.7%), and motor-vehicle collisions (18.7%). Of all mortalities, 32.6% were firearm related, either from an assault or self-inflicted. A greater proportion of mortalities were children from very low (47.6%) and low (20.9%) COI neighborhoods with fewer from higher (8.8.% and 7.6%) COI-neighborhoods compared to the county's proportion of children within these quintiles (p < 0.001). The injury mechanisms were different, with mortalities of lower COI neighborhoods being associated with assaults (p = 0.005), while mortalities of higher COI neighborhoods were self-inflicted (p = 0.003). CONCLUSION: Lower opportunity neighborhoods had a higher incidence of pediatric trauma mortality. Mortality mechanism varied across neighborhoods with assault greater in lower opportunity neighborhoods and self-inflicted among higher opportunity neighborhoods. LEVEL OF EVIDENCE: Level III.

The Gastrointestinal Symptom Rating Scale has a Good Test-Retest Reliability in Well-Trained Athletes With and Without Previously Self-Identified Gastrointestinal Complaints.

BACKGROUND: Athletes often report gastrointestinal (GI) complaints. Standardized validated tests validated in athletes are lacking. OBJECTIVE: The objective of the current study was to investigate the test-retest reliability of the gastrointestinal symptoms rating scale (GSRS), a disease-specific instrument of 15 items to quantify the severity of various GI symptoms. METHODS: For this purpose, a 3-week repeated measurements design was used. The mean difference (Wilcoxon signed rank test), associations (Spearman correlations), and systematic difference using Bland-Altman calculations for repeated measurements, as well as its internal consistency (Cronbach's alpha) on testing day 1 and day 2 were analyzed, with significance set at p ≤ 0.05. A total of n = 70 well-trained athletes (26.1 ± 5.4 years, of which 40% were female) were included. RESULTS: A high Cronbach's α for GSRS was found on testing day 1 (0.825), and day 2 (0.823), suggesting a good and comparable internal consistency of the questionnaire. When assessing the multilevel temporal stability for total GSRS scores (28.0, IQR 22.0-36.3 vs 26.5, IQR 18.0-35.0), there was a small but significant difference (Z = - 2.489, and p = 0.013), but a fair correlation between day scores (r = 0.68, p < 0.001), and a Bland-Altman reporting difference between questionnaires within 10% of the total GSRS score, without significant reporting bias (p = 0.38). In most cases, except for hunger, burping, and loose stools, the individual GSRS items were reported in line with total scores and similar for sex. CONCLUSION: In conclusion, the GSRS is reliable when used with athletes, with good internal consistency for most symptoms independently of sex, except for hunger, burping, and loose stools.

Sex and the facilitation of cued fear by prior contextual fear conditioning in rats.

Previous studies have shown that the formation of new memories can be influenced by prior experience. This includes work using Pavlovian fear conditioning in rodents that has shown that an initial fear conditioning experience can become associated with and facilitate the acquisition of new fear memories, especially when they occur close together in time. However, most of the prior studies used only males as subjects, resulting in questions about the generalizability of the findings from this work. Here we tested whether prior contextual fear conditioning would facilitate later learning of cued fear conditioning in both male and female rats, and if there were differences based on the interval between the two conditioning episodes. Our results showed that levels of cued fear were not influenced by prior contextual fear conditioning or by the interval between training; however, females showed lower levels of cued fear. Freezing behavior in the initial training context differed by sex, with females showing lower levels of contextual fear, and by the type of initial training, with rats given delayed shock showing higher levels of fear than rats given immediate shock during contextual fear conditioning. These results indicate that contextual fear conditioning does not prime subsequent cued fear conditioning and that female rats express lower levels of cued and contextual fear conditioning than males.

Adaptive optical third-harmonic generation microscopy for in vivo imaging of tissues.

Third-harmonic generation microscopy is a powerful label-free nonlinear imaging technique, providing essential information about structural characteristics of cells and tissues without requiring external labelling agents. In this work, we integrated a recently developed compact adaptive optics module into a third-harmonic generation microscope, to measure and correct for optical aberrations in complex tissues. Taking advantage of the high sensitivity of the third-harmonic generation process to material interfaces and thin membranes, along with the 1,300-nm excitation wavelength used here, our adaptive optical third-harmonic generation microscope enabled high-resolution in vivo imaging within highly scattering biological model systems. Examples include imaging of myelinated axons and vascular structures within the mouse spinal cord and deep cortical layers of the mouse brain, along with imaging of key anatomical features in the roots of the model plant Brachypodium distachyon. In all instances, aberration correction led to enhancements in image quality.

Operative Management of Charcot Neuropathy of the Foot and Ankle: A Retrospective Cohort Study of Long-Term Outcomes.

Treatment of Charcot neuroarthropathy (CN) of the foot and ankle remains challenging for both patients and surgeons. Nonoperative treatment with cast/orthosis immobilization has long been the main treatment, but surgical intervention has gained interest to improve poor long-term outcomes. Few long-term outcome studies exist on operative management of CN. A retrospective chart review was performed to analyze demographics, comorbidities, complications, and outcomes of operative management of CN. Patients were divided into two cohorts for analysis: limited surgical intervention (LSI) and reconstructive surgery (RS). Fifty-eight patients with CN treated surgically over 11 years were identified. Average follow-up was 46 months (range, 1 to 173 months). The mean age was 60.2 (range, 29 to 81) years, and the average body mass index was 34.3. Diabetes caused CN in 72.4% (42/58) of patients. The LSI cohort (n = 32) had significantly higher rates of presenting infection (59.4%; 19/32) and ulceration (87.5%; 28/32) compared with the RS cohort (n = 26; 23.1% [6/26] and 50% [13/26], respectively). Rates of postoperative infection and ulceration were lower in the LSI group (25% [8/32] and 34.4% [11/32], respectively) than the RS group (42.3% [11/26] and 42.3% [11/26], respectively). The amputation rate for the LSI cohort was 21.9% (7/32) compared with 23.1% (6/26) for RS. This large, single-center study of operatively treated CN patients showed no significant difference between LSI and RS. This study provides data to help surgeons counsel patients on expected outcomes.

Artificial targeting of the NEIL1 DNA glycosylase to the mitochondria.

The human NEIL1 DNA glycosylase is one of 11 mammalian glycosylases that initiate base excision repair. While substrate preference, catalytic mechanism, and structural information of NEIL1's ordered residues are available, limited information on its subcellular localization, compounded by relatively low endogenous expression levels, have impeded our understanding of NEIL1. Here, we employed a previously developed computational framework to optimize the mitochondrial localization signal of NEIL1, enabling the visualization of its specific targeting to the mitochondrion via confocal microscopy. While we observed clear mitochondrial localization and increased glycosylase/lyase activity in mitochondrial extracts from low-moderate NEIL1 expression, high NEIL1 mitochondrial expression levels proved harmful, potentially leading to cell death.

Sex differences in contextual fear expression are associated with altered medial prefrontal cortex activity.

Understanding the neural basis of fear expression in rodents has implications for understanding pathological fear responses that characterize posttraumatic stress disorder. Even though posttraumatic stress disorder is more common in females, little is known about the neural circuit interactions supporting fear expression in female rodents. In this study, we were interested in determining whether neural activity associated with the expression of contextual fear differed between males and females within the projections from the medial prefrontal cortex to the ventrolateral periaqueductal gray, and in the medial prefrontal cortex in neurons that do not project to the periaqueductal gray. We infused a viral retrograde tracer into the ventrolateral periaqueductal gray in male and female rats and trained them in a contextual fear conditioning task. The following day rats were re-exposed to the conditioning context and were sacrificed shortly thereafter. Neural activity was measured using EGR1 immunofluorescence. The behavioral results showed that males exhibited higher levels of freezing during the context test than females. Male rats that underwent training and testing showed an increase in the proportion of viral infected cells that express EGR1 in the PL compared to rats that had only received context exposure. Trained female rats were not different than controls, however a direct comparison between sexes was not different. In cells not labeled by the tracer, males showed higher levels of fear-induced EGR1 expression in the prelimbic cortex than females. Conversely, females showed higher levels of EGR1 expression in the infralimbic cortex following testing as compared to males. These results suggest that sex differences in the expression of contextual fear may involve differences in the relative activity levels of the prelimbic and infralimbic cortex.

Engineering ethanologenicity into the extremely thermophilic bacterium Anaerocellum (f. Caldicellulosiriuptor) bescii.

The anaerobic bacterium Anaerocellum (f. Caldicellulosiruptor) bescii natively ferments the carbohydrate content of plant biomass (including microcrystalline cellulose) into predominantly acetate, H2, and CO2, and smaller amounts of lactate, alanine and valine. While this extreme thermophile (growth Topt 78 °C) is not natively ethanologenic, it has been previously metabolically engineered with this property, albeit initially yielding low solvent titers (∼15 mM). Herein we report significant progress on improving ethanologenicity in A. bescii, such that titers above 130 mM have now been achieved, while concomitantly improving selectivity by minimizing acetate formation. Metabolic engineering progress has benefited from improved molecular genetic tools and better understanding of A. bescii growth physiology. Heterologous expression of a mutated thermophilic alcohol dehydrogenase (AdhE) modified for co-factor requirement, coupled with bioreactor operation strategies related to pH control, have been key to enhanced ethanol generation and fermentation product specificity. Insights gained from metabolic modeling of A. bescii set the stage for its further improvement as a metabolic engineering platform.

Bipolar Ablation From the Anterior Interventricular Vein to the Left Ventricle.

Ventricular tachycardia from the left ventricular summit can be challenging for catheter ablation due to difficult accessibility and proximity to coronary arteries. This paper presents a case of premature ventricular contraction-induced ventricular tachycardia from the left ventricular summit that was ablated using bipolar radiofrequency ablation from the anterior interventricular vein and adjacent left ventricular endocardium.

A latent profile analysis of relationship satisfaction and self-regulation among low-income participants who attended relationship education with a partner.

Relationship education has shown promising effects for low-income couples on outcomes such as promoting positive communication, improving global relationship satisfaction, parenting, and individual psychological distress. Studies also indicate that couples' baseline distress (e.g., relational and individual) moderates outcomes. Yet, few studies implemented a person-centered approach to analyzing data for those who participate in relationship education. In a sample of 488 low-income opposite-gendered couples, we identified latent profile groups for men and women based on self-reported relationship satisfaction and behavioral self-regulation scores, thus incorporating both relational and individual factors. Results yielded a three-class solution for men and a four-class solution for women. We then examined group profile differences in individual psychological distress and relationship satisfaction change scores after completing the relationship education intervention (12 h of PREP's Within Our Reach). Results indicated significant differences, suggesting that group membership can predict overall improvements in both psychological and relationship distress. Thus, RE programmers and policymakers may consider flexible delivery (e.g., more or less content; more or less intense coaching) that considers overall baseline relational and/or individual functioning as opposed to a one-size-fits-all method.

Hamstring Muscle-Tendon Geometric Adaptations to Resistance Training Using the Hip Extension and Nordic Hamstring Exercises.

Targeted resistance training stimulates hamstring muscle hypertrophy, but its effect on tendon-aponeurosis geometry is unknown. This study examined changes in hamstring muscle, free tendon, and aponeurosis geometry following a 10 week Nordic or hip extension exercise intervention. Thirty recreationally active males were randomly allocated (n = 10 per group) to a Nordic, hip extension, or control group. Magnetic resonance imaging of both thighs was acquired pre- and post-intervention. Changes in free tendon and aponeurosis volume for each hamstring muscle, biceps femoris long head (BFlh) aponeurosis interface area and muscle volume-to-interface area ratio were compared between groups. Regional changes in muscle CSA were examined via statistical parametric mapping. The change in semimembranosus free tendon volume was greater for the Nordic than control group (mean difference = 0.06 cm3, 95% CI = 0.02-0.11 cm3). No significant between-group differences existed for other hamstring free tendons or aponeuroses. There were no between-group differences in change in BFlh interface area. Change in BFlh muscle volume-to-interface area ratio was greater in the hip extension than Nordic (mean difference = 0.10, 95% CI = 0.007-0.19, p = 0.03) and control (mean difference = 0.12, 95% CI = 0.03-0.22, p = 0.009) groups. Change in muscle CSA following training was greatest in the mid-portion of semitendinosus for both intervention groups, and the mid-portion of BFlh for the hip extension group. There was limited evidence for tendon-aponeurosis hypertrophy after 10 weeks of training with the Nordic or hip extension exercises. For the BFlh, neither intervention altered the interface area although hip extension training stimulated an increase in the muscle volume-to-interface area ratio, which may have implications for localized tissue strains. Alternative muscle-tendon loading strategies appear necessary to stimulate hamstring tendon adaptations.

A scoping review of machine learning applied to peripheral nerve interfaces.

Peripheral nerve interfaces (PNIs) can enable communication with the peripheral nervous system and have a broad range of applications including in bioelectronic medicine and neuroprostheses. They can modulate neural activity through stimulation or monitor conditions by recording from the peripheral nerves. The recent growth of Machine Learning (ML) has led to the application of a wide variety of ML techniques to PNIs, especially in circumstances where the goal is classification or regression. However, the extent to which ML has been applied to PNIs or the range of suitable ML techniques has not been documented. Therefore, a scoping review was conducted to determine and understand the state of ML in the PNI field. The review searched five databases and included 63 studies after full-text review. Most studies incorporated a supervised learning approach to classify activity, with the most common algorithms being some form of neural network (artificial neural network, convolutional neural network or recurrent neural network). Unsupervised, semi-supervised and reinforcement learning approaches are currently underutilized and could be better leveraged to improve performance in this domain.

Automated Insulin Delivery for Young People with Type 1 Diabetes and Elevated A1c.

BACKGROUND: Automated insulin delivery is the treatment of choice in adults with type 1 diabetes. Data are needed on the efficacy and safety of automated insulin delivery for children and youth with diabetes and elevated glycated hemoglobin levels. METHODS: In this multicenter, open-label randomized controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio either to use an automated insulin delivery system (MiniMed 780G) or to receive usual diabetes care of multiple daily injections or non--automated pump therapy (control). The patients were children and youth (defined as 7 to 25 years of age) with elevated glycemia (glycated hemoglobin ≥8.5% with no upper limit). The primary outcome was the baseline-adjusted between-group difference in glycated hemoglobin at 13 weeks. RESULTS: A total of 80 patients underwent randomization (37 to automated insulin delivery and 43 to control) and all patients completed the trial. At 13 weeks, the mean (±SD) glycated hemoglobin decreased from 10.5±1.9% to 8.1±1.8% in the automated insulin delivery group but remained relatively consistent in the control group, changing from 10.4±1.6% to 10.6±1.8% (baseline-adjusted between-group difference, -2.5 percentage points; 95% confidence interval [CI], -3.1 to -1.8; P<0.001). Patients in the automated insulin delivery group spent on average 8.4 hours more in the target glucose range of 70 to 180 mg/dl than those in the control group. One severe hypoglycemia event and two diabetic ketoacidosis events occurred in the control group, with no such events in the automated insulin delivery group. CONCLUSIONS: In this trial of 80 children and youth with elevated glycated hemoglobin, automated insulin delivery significantly reduced glycated hemoglobin compared with usual diabetes care, without resulting in severe hypoglycemia or diabetic ketoacidosis events. (Funded by Lions Clubs New Zealand District 202F and others; Australian New Zealand Clinical Trials Registry number, ACTRN12622001454763.).

A Comparative Assessment of Outcomes Following Mandibular Distraction Osteogenesis and Tongue-Lip Adhesion in Pierre Robin Sequence.

The purpose of this study was to assess long-term outcomes of tongue-lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) to resolve upper airway obstruction in patients with Robin sequence (RS). A retrospective cohort study was performed of subjects presenting to a tertiary care pediatric center who underwent either primary MDO or TLA for the treatment of RS between 2004 and 2020. N=59 subjects met inclusion criteria (n=34 MDO, n=25 TLA), and there were no significant differences in preoperative patient characteristics other than age at surgery (MDO 31 d vs. TLA 17 d, P=0.049). Preoperative apnea-hypopnea index (AHI) was similar between cohorts (33.9 and 46.7, P=0.38). Subjects who underwent MDO demonstrated improved AHI on initial postoperative polysomnogram performed at 2 weeks (3.4 vs. 11.6, P=0.014), however AHI at the second postoperative timepoint (270 vs. 142 d, P=0.007) was no different between cohorts (2.8 vs. 2.6, P=0.89). No subject in either group required enteral nutrition or supplemental oxygen at last follow-up. In subjects undergoing MDO, 14.7% demonstrated temporary asymmetric marginal mandibular nerve dysfunction. Forty-seven percent of MDO patients had injury to first primary molars. MDO and TLA both ultimately achieved similar long-term resolution of upper airway obstruction and associated feeding difficulties in patients with Robin sequence. MDO offered a more immediate airway improvement, but the procedure carried a potential risk of neurosensory and dental injury when compared with TLA.

Infinity: A Prospective Trial for Safety and Accuracy of Navigated Posterior Cervical and Thoracic Instrumentation in long-segment Fusions.

STUDY DESIGN: Unblinded single-arm prospective clinical trial. OBJECTIVE: Evaluate safety and accuracy of navigation for placement of posterior cervicothoracic instrumentation. SUMMARY OF BACKGROUND DATA: Computer assisted stereotactic navigation for placement of spinal instrumentation has been widely studied and implemented in the thoracic and lumbar spine. However less literature exists regarding the use of computer assisted navigation for posterior cervical instrumentation, particularly with lateral mass fixation. Here we present the first prospective study of navigated cervical lateral mass screw placement for cervicothoracic fusion. METHODS: Patients who met indications for posterior cervical fusion were screened, consented, and enrolled preoperatively for instrumentation with Medtronic Infinity Occipital-Cervical-Thoracic implants, with use of intraoperative O-arm and stereotactic Stealth navigation. Postoperative CTs of the instrumented levels were obtained during the same hospital admission. Primary outcome of the trial was safety. Secondary outcomes were screw accuracy assessed by Gertzbein-Robbins grade, neurologic exams, and patient reported outcomes on the PROMIS 29 questionnaire. RESULTS: A total of 50 patients underwent surgery, and 557 screws were placed. There were no adverse events related to the use of navigation or screw malposition. Gertzbein-Robbins grade A or B placement comprised 95% of navigated screws. There was a decrease in positive Hoffmann sign rate postoperatively, and sensory and motor exams remained stable. There was improvement in patient reported pain and sleep domains. CONCLUSIONS: Navigation for cervicothoracic instrumentation is safe overall and leads to high rates of accurately placed screws. Longer term follow up could provide more insight to whether the use of this technology results in durable improvement in spinal alignment parameters and patient reported outcomes. LEVEL OF EVIDENCE: 3.

Tumor-related epilepsy in high-grade glioma: a large series survival analysis.

PURPOSE: Seizures are a common clinical occurrence in high-grade glioma (HGG). While many studies have explored seizure incidence and prevalence in HGG, limited studies have examined the prognostic effect of seizures occurring in the post-diagnosis setting. This study aims to assess the impact of seizure presentation on HGG survival outcomes. METHODS: Single-center retrospective review identified 950 patients with histologically-confirmed high-grade glioma. Seizure presentation was determined by clinical history and classified as early onset (occurring within 30 days of HGG presentation) or late onset (first seizure occurring after beginning HGG treatment). The primary outcome, hazard ratios for overall survival and progression-free survival, was assessed with multivariable Cox proportional-hazards models. IDH1 mutation status (assessed through immunohistochemistry) was only consistently available beginning in 2015; subgroup analyses were performed in the subset of patients with known IDH1 status. RESULTS: Epileptic activity before (HR = 0.81, 95% CI = 0.68-0.96, P = 0.017) or after (HR = 0.74, 95% CI = 0.60-0.91, P = 0.005) HGG diagnosis associated with improved overall survival. Additionally, late seizure onset significantly associated with lower odds of achieving partial (OR = 0.25, 95% CI = 0.12-0.53, P = < 0.001) or complete (OR = 0.30, 95% CI = 0.18-0.50, P < 0.001) seizure control than patients with early seizure onset. CONCLUSIONS: Clinical seizures both at the time of diagnosis and later during the HGG treatment course are associated with improved overall survival. This association potentially persists for both IDH1-wildtype and IDH1-mutant patients, but further study is required.

Acute ocular hypertension in the living human eye: Model description and initial cellular responses to elevated intraocular pressure.

This initial methods study presents the initial immunohistochemical and transcriptomic changes in the optic nerve head and retina from three research-consented brain-dead organ donors following prolonged and transient intraocular pressure (IOP) elevation. In this initial study, research-consented brain-dead organ donors were exposed to unilateral elevation of IOP for 7.5 h (Donor 1), 30 h (Donor 2), and 1 h (Donor 3) prior to organ procurement. Optic nerve tissue and retinal tissue was obtained following organ procurement for immunohistological and transcriptomic analysis. Optic nerve sections in Donor 1 exposed to 7.5-hours of unilateral sub-ischemic IOP elevation demonstrated higher levels of protein expression of the astrocytic marker, glial fibrillary acidic protein (GFAP), within the lamina cribrosa with greatest expression inferior temporally in the treated eye compared to control. Spatial transcriptomic analysis performed on optic nerve head tissues from Donor 2 exposed to 30 h of unilateral IOP elevation demonstrated differential transcription of mRNA across laminar and scleral regions. Immunohistochemistry of retinal sections from Donor 2 exhibited higher GFAP and IBA1 expression in the treated eye compared with control, but this was not observed in Donor 3, which was exposed to only 1-hour of IOP elevation. While there were no differences in GFAP protein expression in the retina following the 1-hour IOP elevation in Donor 3, there were higher levels of transcription of GFAP in the inner nuclear layer, and CD44 in the retinal ganglion cell layer, indicative of astrocytic and Müller glial reactivity as well as an early inflammatory response, respectively. We found that transcriptomic differences can be observed across treated and control eyes following unilateral elevation of IOP in brain dead organ donors. The continued development of this model affords the unique opportunity to define the acute mechanotranscriptomic response of the optic nerve head, evaluate the injury and repair mechanisms in the retina in response to IOP elevation, and enable correlation of in vivo imaging and functional testing with ex vivo cellular responses for the first time in the living human eye.

Meaning in life (but not life satisfaction) moderates the effects of battlefield experiences on suicidal ideation and anxiety.

OBJECTIVE: Although research has been conducted in the last decade distinguishing between meaning in life and life satisfaction, no research has examined whether their potential moderating role in mental health problems is distinct. Among military personnel, mental health is paramount, and suicide is one of the leading causes of death. METHOD: Data were collected to determine the potential moderating effects of meaning in life and/or life satisfaction of battlefield experiences on depression, anxiety, and thoughts about death (including suicidal ideation). Data were collected on 851 total military personnel, spanning two distinct survey administrations, who reported at least one combat deployment. RESULTS: Findings suggest that meaning in life has a significant moderating effect on the impact of life-threatening experiences on anxiety and thoughts about death (including suicidal ideation), but no moderating effect on depression. Life satisfaction had no significant moderating role for any mental health outcome. CONCLUSIONS: This research suggests that meaning in life is a significant buffer against certain negative mental health outcomes stemming from life-threatening experiences. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Establishing thresholds for shock index in children to identify major trauma.

BACKGROUND: An abnormal shock index (SI) is associated with greater injury severity among children with trauma. We sought to empirically-derive age-adjusted SI cutpoints associated with major trauma in children, and to compare the accuracy of these cutpoints to existing criteria for pediatric SI. METHODS: We performed a retrospective cohort study using the 2021 National Trauma Data Bank (NTDB) Participant Use File. We included injured children (<18 years), excluding patients with traumatic arrests, mechanical ventilation upon hospital presentation, and inter-facility transfers. Our outcome was major trauma defined by the standardized triage assessment tool (STAT) criteria. Our exposure of interest was the SI. We empirically-derived upper and lower cutpoints for the SI using age-adjusted Z-scores. We compared the performance of these to the SI, pediatric-adjusted (SIPA), and the Pediatric SI (PSI). We validated the performance of the cutpoints in the 2019 NTDB. RESULTS: We included 64,326 and 64,316 children in the derivation and validation samples, of whom 4.9 % (derivation) and 4.0 % (validation) experienced major trauma. The empirically-derived age-adjusted SI cutpoints had a sensitivity of 43.2 % and a specificity of 79.4 % for major trauma in the validation sample. The sensitivity of the PSI for major trauma was 33.9 %, with a specificity of 90.7 % among children 1-17 years of age. The sensitivity of the SIPA was 37.4 %, with a specificity of 87.8 % among children 4-16 years of age. Evaluated using logistic regression, patients with an elevated age-adjusted SI had 3.97 greater odds (95 % confidence interval [CI] 3.63-4.33) of major trauma compared to those with a normal age-adjusted SI. Patients with a depressed SI had 1.55 greater odds (95 % CI 1.36-1.78) of major trauma. The area under the receiver operator characteristic curve (AUROC) for the empirically-derived model (0.62, 95 % CI 0.61-0.63) was similar to the AUROC for PSI (0.62, 95 % CI 0.61-0.63); both of which were greater than the SIPA model (0.58, 95 % CI 0.57-0.59). CONCLUSION: Age-adjusted SI cutpoints demonstrated a mild gain in sensitivity compared to existing measures. However, our findings suggest that the SI alone has a limited role in the identification of major trauma in children.