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Importance: Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders., Objective: To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI., Design, Setting, and Participants: This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023., Exposure: Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI])., Main Outcomes and Measures: The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury., Results: A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI)., Conclusions and Relevance: This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.

Importance: Cognitive dysfunction is common after traumatic brain injury (TBI), with a well-established dose-response relationship between TBI severity and likelihood or magnitude of persistent cognitive impairment. However, patterns of cognitive dysfunction in the long-term (eg, 6-month) recovery period are less well known., Objective: To characterize the prevalence of cognitive dysfunction within and across cognitive domains (processing speed, memory, and executive functioning) 6 months after injury in patients with TBI seen at level I trauma centers., Design, Setting, and Participants: This prospective longitudinal cohort study used data from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) and included patients aged 17 years or older presenting at 18 US level I trauma center emergency departments or inpatient units within 24 hours of head injury, control individuals with orthopedic injury recruited from the same centers, and uninjured friend and family controls. Participants were enrolled between March 2, 2014, and July 27, 2018. Data were analyzed from March 5, 2020, through October 3, 2023., Exposures: Traumatic brain injury (Glasgow Coma Scale score of 3-15) or orthopedic injury., Main Outcomes and Measures: Performance on standard neuropsychological tests, including premorbid cognitive ability (National Institutes of Health Toolbox Picture Vocabulary Test), verbal memory (Rey Auditory Verbal Learning Test), processing speed (Wechsler Adult Intelligence Scale [4th edition] Processing Speed Index), and executive functioning (Trail Making Test)., Results: The sample included 1057 persons with TBI (mean [SD] age, 39.3 [16.4] years; 705 [67%] male) and 327 controls without TBI (mean [SD] age, 38.4 [15.1] years; 222 [68%] male). Most persons with TBI demonstrated performance within 1.5 SDs or better of the control group (49.3% [95% CI, 39.5%-59.2%] to 67.5% [95% CI, 63.7%-71.2%] showed no evidence of impairment). Similarly, 64.4% (95% CI, 54.5%-73.4%) to 78.8% (95% CI, 75.4%-81.9%) of participants demonstrated no evidence of cognitive decline (defined as performance within 1.5 SDs of estimated premorbid ability). For individuals with evidence of either cognitive impairment or decline, diverse profiles of impairment across memory, speed, and executive functioning domains were observed (ie, the prevalence was >0 in each of the 7 combinations of impairment across these 3 cognitive domains for most TBI subgroups)., Conclusions and Relevance: In this cohort study of patients seen at level I trauma centers 6 months after TBI, many patients with TBI demonstrated no cognitive impairment. Impairment was more prevalent in persons with more severe TBI and manifested in variable ways across individuals. The findings may guide future research and treatment recommendations.

Importance: Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known., Objective: To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological concerns of self-reported PTE in a large, prospectively collected TBI cohort., Design, Setting, and Participants: This multicenter, prospective cohort study was conducted as part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study and identified patients presenting with TBI to 1 of 18 participating level 1 US trauma centers from February 2014 to July 2018. Patients with TBI, extracranial orthopedic injuries (orthopedic controls), and individuals without reported injuries (eg, friends and family of participants; hereafter friend controls) were prospectively followed for 12 months. Data were analyzed from January 2020 to April 2021., Exposure: Demographic, imaging, and clinical information was collected according to TBI Common Data Elements. Incidence of self-reported PTE was assessed using the National Institute of Neurological Disorders and Stroke Epilepsy Screening Questionnaire (NINDS-ESQ)., Main Outcomes and Measures: Primary outcomes included Glasgow Outcome Scale Extended, Rivermead Cognitive Metric (RCM; derived from the Rivermead Post Concussion Symptoms Questionnaire), and the Brief Symptom Inventory-18 (BSI)., Results: Of 3296 participants identified as part of the study, 3044 met inclusion criteria, and 1885 participants (mean [SD] age, 41.3 [17.1] years; 1241 [65.8%] men and 644 [34.2%] women) had follow-up information at 12 months, including 1493 patients with TBI; 182 orthopedic controls, 210 uninjured friend controls; 41 patients with TBI (2.8%) and no controls had positive screening results for PTE. Compared with a negative screening result for PTE, having a positive screening result for PTE was associated with presenting Glasgow Coma Scale score (8.1 [4.8] vs.13.5 [3.3]; P < .001) as well as with anomalous acute head imaging findings (risk ratio, 6.42 [95% CI, 2.71-15.22]). After controlling for age, initial Glasgow Coma Scale score, and imaging findings, compared with patients with TBI and without PTE, patients with TBI and with positive PTE screening results had significantly lower Glasgow Outcome Scale Extended scores (mean [SD], 6.1 [1.7] vs 4.7 [1.5]; P < .001), higher BSI scores (mean [SD], 50.2 [10.7] vs 58.6 [10.8]; P = .02), and higher RCM scores (mean [SD], 3.1 [2.6] vs 5.3 [1.9]; P = .002) at 12 months., Conclusions and Relevance: In this cohort study, the incidence of self-reported PTE after TBI was found to be 2.8% and was independently associated with unfavorable outcomes. These findings highlight the need for effective antiepileptogenic therapies after TBI.

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood., Objective: To identify pathological CT features associated with adverse outcomes after mTBI., Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021., Exposures: Acute nonpenetrating head trauma., Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months., Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study., Conclusions and Relevance: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.

Importance: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI., Objective: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI., Design, Setting, and Participants: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021., Exposures: Moderate or severe TBI., Main Outcomes and Measures: The Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed., Results: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months., Conclusions and Relevance: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.

Importance: Uveitic glaucoma is among the most common causes of irreversible visual loss in uveitis. However, glaucoma detection can be obscured by inflammatory changes., Objective: To determine whether retinal nerve fiber layer (RNFL) measurement can be used to detect glaucoma in uveitic eyes with elevated intraocular pressure (IOP)., Design, Setting, and Participants: Comparative case series of RNFL measurement using optical coherence tomography performed from May 1, 2010, through October 31, 2012, at a tertiary referral center. We assigned 536 eyes with uveitis (309 patients) in the following groups: normal contralateral eyes with unilateral uveitis (n = 72), normotensive uveitis (Uv-N) (n = 143), raised IOP and normal optic disc and/or visual field (Uv-H) (n = 233), and raised IOP and glaucomatous disc and/or visual field (Uv-G) (n = 88)., Exposures: Eyes with uveitis and elevated IOP (>21 mm Hg) on at least 2 occasions., Main Outcomes and Measures: Comparison of RNFL values between groups of eyes and correlation with clinical data; risk factors for raised IOP, glaucoma, and RNFL thinning., Results: Mean (SD) global RNFL was thicker in Uv-N (106.4 [21.4] µm) compared with control (96.0 [9.0] µm; P < .001) eyes and was thicker in Uv-N eyes with active (119.6 [23.2] µm) compared with quiescent (102.3 [20.8] µm; P = .001) uveitis, which in turn was not significantly different from control eyes (P = .07). Compared with Uv-N eyes, significant RNFL thinning was seen in all quadrants except the temporal in Uv-G eyes and significant thinning in the inferior quadrant of Uv-H eyes with no evidence of disc or visual field changes (P = .03). Risk factors for elevated IOP were male sex and anterior uveitis. Age, higher peak IOP, longer duration of follow-up, and uveitis-induced elevation of IOP were risk factors for glaucoma and RNFL defect., Conclusions and Relevance: Screening for glaucomatous RNFL changes in uveitis must be performed during quiescent periods. Thinning of the inferior quadrant suggests that glaucomatous damage, more than uveitic ocular hypertension, is in fact occurring. Measurement of RNFL may detect signs of damage before disc or visual field changes and therefore identifies a subgroup that should receive more aggressive treatment.

Importance: Birdshot chorioretinopathy is a chronic intraocular inflammatory disease with no uniform method to document long-term disease progression or response to treatment., Objective: To examine the long-term visual, clinical, and anatomic outcomes of patients with birdshot chorioretinopathy., Design, Setting, and Participants: A retrospective evaluation of 46 patients with birdshot chorioretinopathy treated at Moorfields Eye Hospital, London, England, was conducted. Medical records for a 19-year period (1993-2012) were reviewed., Exposures: Patients received no treatment, short-term (≤1 year) treatment including local or systemic corticosteroids, or long-term (>1 year) treatment including systemic corticosteroids and second-line immunosuppressive agents., Main Outcomes and Measures: Details regarding clinical and anatomic outcome, including best-corrected visual acuity, and visual field indices were evaluated., Results: Ninety-two eyes of 46 patients were monitored for a mean (SE) of 57.2 (5.8) months (445 eye-years, 17% follow-up of ≥10 years). Patients maintained a steady best-corrected visual acuity throughout the follow-up period. Some clinical indices correlated with transient worse best-corrected visual acuity, including presence of cataract (P = .05), foveal leakage on fluorescein angiography (P = .04), and increased central retinal thickness (P = .02). Serial visual field studies demonstrated that patients who received only short-term treatment had a worsening of their pattern standard deviation with time (Spearman correlation, 0.57; P = .003); for those who received long-term treatment, the pattern standard deviation remained stable (Spearman correlation, -0.24; P = .26)., Conclusions and Relevance: Our results suggest that central visual acuity can be maintained long term in patients with birdshot chorioretinopathy. Those who receive long-term immunosuppression appear to maintain better peripheral visual fields compared with patients who receive short-term treatment.

Objective: To investigate the histologic and biomechanical properties of rabbit tissue-engineered cartilage exposed to insulinlike growth factor 1 and transforming growth factor beta., Design: Controlled study., Subjects: New Zealand white rabbits aged 3 to 4 weeks., Intervention: A mean of 3.42 million rabbit chondrocytes were placed onto 2 x 1-cm polyglycolic/poly-L-lactic acid mesh templates. One group (n = 21) was placed in complete medium for 4 days. The experimental group (n = 19) was placed into complete medium with insulinlike growth factor 1 (50 ng/mL) and transforming growth factor beta (1 ng/mL). After 96 hours the templates were removed and implanted into the dorsum of the donor rabbit. The templates were harvested after 8 weeks and subjected to gross, histologic, and biomechanical testing., Results: All samples showed histologic characteristics consistent with normal cartilage. No statistically significant differences were found with biomechanical testing between the control and experimental groups., Conclusion: In spite of more promising results from earlier studies, these results do not support improved histologic features or mechanical performance with the addition of insulinlike growth factor 1 and transforming growth factor beta to the chondrocyte/template complex.

The clinical and pathological features of 13 carotid body paragangliomas from 12 patients were examined and correlated with the DNA ploidy pattern as determined by image analysis. These tumors occurred in 7 women and 5 men aged 19 to 62 years (average, 42 years). All presented with a slowly enlarging, usually asymptomatic mass of 2 weeks' to 25 years' duration. Two patients were related and had a family history of paragangliomas. The tumors ranged from 2 to 6 cm. All contained scattered chief cells with pleomorphic nuclei, two exhibited mitoses, and three showed perineural and three vascular invasion. Follow-up was available in all 12 patients and ranged from 15 months to 28 years (average, 7.3 years). None of the tumors recurred locally, but one did metastasize to a single cervical lymph node that was apparent at the time of diagnosis. Of 13 carotid body paragangliomas examined for DNA, 4 were diploid, 3 diploid-tetraploid, 3 tetraploid, 2 aneuploid, and 1 polyploid. The only malignant tumor was polyploid. From these observations, we conclude that abnormalities in DNA content of carotid body paragangliomas are common and that tumor ploidy cannot be used to assess malignant potential. We also found no apparent relationship among nuclear pleomorphism, mitotic activity, perineural invasion, or vascular invasion and clinical behavior. Perineural and vascular invasion, however, were observed only in tumors with abnormal DNA histograms.