Association of Win-Loss Record With Neuropsychiatric Symptoms and Brain Health Among Professional Fighters.

OBJECTIVE: Repetitive head impacts in professional fighting commonly lead to head injuries. Increased exposure to repetitive head trauma, measured by the number of professional fights and years of fighting, has been associated with slower processing speed and smaller brain volumes. The impact of win-loss outcomes has been investigated in other sports, with several studies suggesting that individuals on losing teams experience more head injuries. Here, the authors hypothesized that fighters with a worse fight record would exhibit poorer brain health outcomes. METHODS: The Professional Fighters Brain Health Study examined changes in neuropsychiatric symptoms, regional brain volume, and cognition among professional boxers and mixed martial arts fighters. These data were used to evaluate the relationship between win-loss ratios and brain health outcomes among professional fighters (N=212) by using validated neuropsychiatric symptom and cognitive measures and MRI data. RESULTS: Retired fighters with a better record demonstrated more impulsiveness (B=0.21, df=48) and slower processing speed (B=-0.42, df=31). More successful fighters did not perform better than fighters with worse records on any neuropsychiatric or cognitive test. Retired fighters with better fight records had smaller brain volumes in the subcortical gray matter, anterior corpus callosum, left and right hippocampi, left and right amygdala, and left thalamus. More successful active fighters had a smaller left amygdala volume. CONCLUSIONS: These findings suggest that among retired fighters, a better fight record was associated with greater impulsiveness, slower processing speed, and smaller brain volume in certain regions. This study shows that even successful fighters experience adverse effects on brain health.

A systematic review of cognition in idiopathic intracranial hypertension.

Background: Cognitive disturbance is not pathognomonic of idiopathic intracranial hypertension (IIH), and therefore is not routinely assessed unless it presents as a major complaint. Consequently, cognition has been slow to gain substantial traction in IIH-related research, despite its notable impact on a subset of patients. We completed a systematic review of the literature examining the neurocognitive profile of patients with IIH. Methods: A PRISMA compliant literature search was conducted in Ovid Medline, PubMed, PsycInfo, Embase, Web of Science, Cochrane, Cinahl, and Scopus databases. The initial query yielded 1376 unique articles. These articles were narrowed to those including empirical analyses of cognitive assessment in adult patients with IIH. Results: A final cohort of nine articles resulted, comprising the findings from 309 patients with IIH and 153 healthy control subjects. Although there was considerable variability in methodology particularly with respect to cognitive assessment, fairly consistent deficits were observed across studies in the domains of processing speed, working memory, sustained and complex attention, set-shifting, and confrontation naming. Body mass index and body weight were not associated with cognitive performance. Pertinent limitations of the literature were identified, most notably failure to report trial-level cognitive testing data, the need for more comprehensive testing batteries with less reliance on screening tools, and not controlling for variables that may impact cognition. Conclusions: A more complete understanding of the cognitive profile in patients with idiopathic intracranial hypertension could lead to the increased -relevance of cognitive screening in disease management, and therefore more appropriate neuropsychological referral, earlier identification of functional limitations, and targeted neurorehabilitation.

Sparring and the Brain: The Associations between Sparring and Regional Brain Volumes in Professional Mixed Martial Arts Fighters.

BACKGROUND: Mixed martial arts (MMA) fighters, due to exposure to repetitive head impacts, are at risk for brain atrophy and neurodegenerative sequelae. Simultaneously, motor skills training and cognition-rich activities have been linked with larger regional brain volumes. The majority of an MMA fighter's sporting activity occurs during practice (e.g., sparring) rather than formal competition. This study, therefore, aims to be the first to explore regional brain volumes associated with sparring in MMA fighters. METHODS: Ninety-four active, professional MMA fighters from the Professional Fighters Brain Health Study met inclusion criteria for this cross-sectional analysis. Adjusted multivariable regression analyses were utilized to examine the relationship between the number of sparring practice rounds per week during typical training and a select number of regional brain volumes (i.e., caudate, thalamus, putamen, hippocampus, amygdala). RESULTS: A higher number of weekly sparring rounds during training was significantly associated with larger left (beta = 13.5 µL/round, 95% CI 2.26-24.8) and right (beta = 14.9 µL/round, 95% CI 3.64-26.2) caudate volumes. Sparring was not significantly associated with left or right thalamus, putamen, hippocampus, or amygdala volumes. CONCLUSIONS: More weekly rounds of sparring was not significantly associated with smaller volumes in any of the brain regions studied in active, professional MMA fighters. Sparring's significant association with larger caudate volume raises questions about whether fighters who spar more experience attenuated trauma-related decreases in caudate volume relative to fighters who spar less, whether fighters who spar more experience minimal or even positive changes to caudate volume, whether baseline differences in caudate size may have mediated results, or whether some other mechanism may be at play. Given limitations inherent to the cross-sectional study design, more research is needed to further explore the brain effects of sparring in MMA.

Neuroimaging Correlates of Post-Traumatic Stress Disorder in Traumatic Brain Injury: A Systematic Review of the Literature.

Neuroimaging is widely utilized in studying traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). The risk for PTSD is greater after TBI than after non-TBI trauma, and PTSD is associated with worse outcomes after TBI. Studying the neuroimaging correlates of TBI-related PTSD may provide insights into the etiology of both conditions and help identify those TBI patients most at risk of developing persistent symptoms. The objectives of this systematic review were to examine the current literature on neuroimaging in TBI-related PTSD, summarize key findings, and highlight strengths and limitations to guide future research. A Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) compliant literature search was conducted in PubMed (MEDLINE®), PsycINFO, Embase, and Scopus databases prior to January 2022. The database query yielded 4486 articles, which were narrowed based on specified inclusion criteria to a final cohort of 16 studies, composed of 854 participants with TBI. There was no consensus regarding neuroimaging correlates of TBI-related PTSD among the included articles. A small number of studies suggest that TBI-related PTSD is associated with white matter tract changes, particularly in frontotemporal regions, as well as changes in whole-brain networks of resting-state connectivity. Future studies hoping to identify reliable neuroimaging correlates of TBI-related PTSD would benefit from ensuring consistent case definition, preferably with clinician-diagnosed TBI and PTSD, selection of comparable control groups, and attention to imaging timing post-injury. Prospective studies are needed and should aim to further differentiate predisposing factors from sequelae of TBI-related PTSD.

Effect of traumatic brain injury on mild behavioral impairment domains prior to all-cause dementia diagnosis and throughout disease progression.

Introduction: Traumatic brain injury (TBI) may alter dementia progression, although co-occurring neuropsychiatric symptoms (NPS) have received less attention. Originally designed to evaluate behavioral disruption prior to dementia diagnosis, the mild behavioral impairment (MBI) construct relates NPS to underlying neural circuit disruptions, with probable relevance across the progression of neurodegenerative disease. Therefore, the MBI construct may represent a valuable tool to identify and evaluate related NPS both preceding diagnosis of all-cause dementia throughout the progression of disease, representing an important area of inquiry regarding TBI and dementia. This investigation sought to evaluate the effect of TBI on NPS related by the MBI construct in participants progressing from normal cognitive status to all-cause dementia. Methods: Using National Alzheimer's Coordinating Center data, individuals progressing from normal cognition to all-cause dementia (clinician diagnosed) over 7.6 ± 3.0 years were studied to estimate prevalence of MBI domains in 124 participants with prior TBI history (57 with loss of consciousness [LOC] <5 minutes, 22 with LOC >5 min, 45 unknown severity) compared to 822 without. MBI domain prevalence was evaluated (1) prior to dementia onset (including only time points preceding time at dementia diagnosis, as per MBI's original definition) and (2) throughout dementia progression (evaluating all available time points, including both before and after dementia diagnosis). Results: More severe TBI (LOC >5 minutes) was associated with the social inappropriateness MBI domain (adjusted odds ratio = 4.034; P = 0.024) prior to dementia onset, and the abnormal perception/thought content domain looking across dementia progression (adjusted hazard ratio [HRadj] = 3.703; P = 0.005). TBI (all severities) was associated with the decreased motivation domain looking throughout dementia progression (HRadj. = 1.546; P = 0.014). Discussion: TBI history is associated with particular MBI profiles prior to onset and throughout progression of dementia. Understanding TBI's impact on inter-related NPS may help elucidate underlying neuropathology with implications for surveillance, detection, and treatment of behavioral concerns in aging TBI survivors. Highlights: The mild behavioral impairment (MBI) construct links related neuropsychiatric symptoms (NPS) by probable underlying neural network dysfunction.Traumatic brain injury (TBI) with loss of consciousness (LOC) > 5 minutes was associated with pre-dementia social inappropriateness.TBI was associated with decreased motivation looking across dementia progression.TBI with LOC > 5 minutes was associated with abnormal perception/thought content.The MBI construct may be useful for examining related NPS across dementia progression.

Behavioral and Emotional Dyscontrol Following Traumatic Brain Injury: A Systematic Review of Neuroimaging and Electrophysiological Correlates.

BACKGROUND: Behavioral and emotional dyscontrol commonly occur following traumatic brain injury (TBI). Neuroimaging and electrophysiological correlates of dyscontrol have not been systematically summarized in the literature to date. OBJECTIVE: To complete a systematic review of the literature examining neuroimaging and electrophysiological findings related to behavioral and emotional dyscontrol due to TBI. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature search was conducted in PubMed (MEDLINE), PsycINFO, EMBASE, and Scopus databases prior to May 2019. The database query yielded 4392 unique articles. These articles were narrowed based on specific inclusion criteria (e.g., clear TBI definition, statistical analysis of the relationship between neuroimaging and dyscontrol). RESULTS: A final cohort of 24 articles resulted, comprising findings from 1552 patients with TBI. Studies included civilian (n = 12), military (n = 10), and sport (n = 2) samples with significant variation in the severity of TBI incorporated. Global and region-based structural imaging was more frequently used to study dyscontrol than functional imaging or diffusion tensor imaging. The prefrontal cortex was the most common neuroanatomical region associated with behavioral and emotional dyscontrol, followed by other frontal and temporal lobe findings. CONCLUSIONS: Frontal and temporal lesions are most strongly implicated in the development of postinjury dyscontrol symptoms although they are also the most frequently investigated regions of the brain for these symptom categories. Future studies can make valuable contributions to the field by (1) emphasizing consistent definitions of behavioral and emotional dyscontrol, (2) assessing premorbid dyscontrol symptoms in subjects, (3) utilizing functional or structural connectivity-based imaging techniques, or (4) restricting analyses to more focused brain regions.

Neuroimaging Correlates of Syndromal Anxiety Following Traumatic Brain Injury: A Systematic Review of the Literature.

BACKGROUND: Traumatic brain injury (TBI) can precipitate new-onset psychiatric symptoms or worsen existing psychiatric conditions. To elucidate specific mechanisms for this interaction, neuroimaging is often used to study both psychiatric conditions and TBI. This systematic review aims to synthesize the existing literature of neuroimaging findings among patients with anxiety after TBI. METHODS: We conducted a Preferred Reporting Items for Systematic Review and Meta-Analyses-compliant literature search via PubMed (MEDLINE), PsychINFO, EMBASE, and Scopus databases before May, 2019. We included studies that clearly defined TBI, measured syndromal anxiety as a primary outcome, and statistically analyzed the relationship between neuroimaging findings and anxiety symptoms. RESULTS: A total of 5982 articles were retrieved from the systematic search, of which 65 studied anxiety and 13 met eligibility criteria. These studies were published between 2004 and 2017, collectively analyzing 764 participants comprised of 470 patients with TBI and 294 non-TBI controls. Imaging modalities used included magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, electroencephalogram, magnetic resonance spectrometry, and magnetoencephalography. Eight of 13 studies presented at least one significant finding and together reflect a complex set of changes that lead to anxiety in the setting of TBI. The left cingulate gyrus in particular was found to be significant in 2 studies using different imaging modalities. Two studies also revealed perturbances in functional connectivity within the default mode network. CONCLUSIONS: This is the first systemic review of neuroimaging changes associated with anxiety after TBI, which implicated multiple brain structures and circuits, such as the default mode network. Future research with consistent, rigorous measurements of TBI and syndromal anxiety, as well as attention to control groups, previous TBIs, and time interval between TBI and neuroimaging, are warranted. By understanding neuroimaging correlates of psychiatric symptoms, this work could inform future post-TBI screening and surveillance, preventative efforts, and early interventions to improve neuropsychiatric outcomes.

Patient-reported outcomes after operative versus nonoperative treatment of pediatric lateral humeral condyle fractures.

ABSTRACT: Lateral humeral condyle fractures in children are treated with several approaches, yet it is unclear which has the best treatment outcomes. We hypothesized that functional outcomes would be equivalent between treatment types, reduction approaches, and fixation types. Our purpose was to assess patient-reported outcomes and complications by treatment type (operative versus nonoperative), reduction approach (open versus percutaneous), and fixation type (cannulated screws versus Kirschner wires).We retrospectively reviewed data from acute lateral humeral condyle fractures treated at our level-1 pediatric trauma center from 2008 to 2017. Patients were included if they were 8 years or older and had completed clinical follow-up. Fractures were categorized by fracture severity as mild (<2-mm displacement), moderate (isolated, 2- to 5-mm displacement), or severe (isolated, >5-mm displacement or >2-mm displacement with concomitant elbow dislocation or other elbow fracture). We extracted data on patient age, sex, treatment type, reduction approach, fixation type, patient-reported outcomes (shortened Disabilities of the Arm, Shoulder, and Hand and Patient Reported Outcome Measurement Information System upper extremity), treatment complications, and follow-up duration. Patients in the operative versus nonoperative group and across fracture severity subgroups did not differ significantly by age, sex, or follow-up duration. Bivariate analysis was performed to determine whether outcomes differed by intervention. Alpha = 0.05.No differences were observed in patient-reported outcomes between operative versus nonoperative groups for the mild and severe fracture subgroups. No differences were observed between approach (open versus percutaneous) or instrumentation (cannulated screw versus Kirschner wire fixation) for any outcome measure within the operative group. Patients whose fractures were stabilized with screws versus wires had significantly higher rates of return to the operating room (94% versus 8.3%, P < .001). The overall complication rate for our cohort was low, with no differences by treatment type or fracture severity.In our cohort, patient-reported outcomes were similar across fracture severity categories, irrespective of treatment or fixation type. Patients who underwent internal fixation with cannulated screws experienced significantly higher rates of return to the operating room compared with those treated with Kirschner wires but otherwise had similar complication rates and patient-reported outcomes.Level of Evidence: 3.

Effect of Weight Class on Regional Brain Volume, Cognition, and Other Neuropsychiatric Outcomes among Professional Fighters.

Traumatic brain injury (TBI) is a common source of functional impairment among athletes, military personnel, and the general population. Professional fighters in both boxing and mixed martial arts (MMA) are at particular risk for repetitive TBI and may provide valuable insight into both the pathophysiology of TBI and its consequences. Currently, effects of fighter weight class on brain volumetrics (regional and total) and functional outcomes are unknown. Fifty-three boxers and 103 MMA fighters participating in the Professional Fighters Brain Health Study (PRBHS) underwent volumetric magnetic resonance imaging (MRI) and neuropsychological testing. Fighters were divided into lightweight (≤139.9 lb), middleweight (140.0-178.5 lb), and heavyweight (>178.5 lb). Compared with lightweight fighters, heavyweights displayed greater yearly reductions in regional brain volume (boxers: bilateral thalami; MMA: left thalamus, right putamen) and functional performance (boxers: processing speed, simple and choice reaction; MMA: Trails A and B tests). Lightweights suffered greater reductions in regional brain volume on a per-fight basis (boxers: left thalamus; MMA: right putamen). Heavyweight fighters bore greater yearly burden of regional brain volume and functional decrements, possibly related to differing fight dynamics and force of strikes in this division. Lightweights demonstrated greater volumetric decrements on a per-fight basis. Although more research is needed, greater per-fight decrements in lightweights may be related to practices of weight-cutting, which may increase vulnerability to neurodegeneration post-TBI. Observed decrements associated with weight class may result in progressive impairments in fighter performance, suggesting interventions mitigating the burden of TBI in professional fighters may both improve brain health and increase professional longevity.

Neurology trial registrations on ClinicalTrials.gov between 2007 and 2018: A cross-sectional analysis of characteristics, early discontinuation, and results reporting.

BACKGROUND: Increasing neurological disease burden and advancing treatment options require clinical trials to expand the evidence base of clinical care. We aimed to characterize neurology clinical trials registered between October 2007 and April 2018 and identify features associated with early discontinuation and results reporting. METHODS: We compared 16,994 neurology (9.4%) and 163,714 non-neurology comparison trials registered to ClinicalTrials.gov. Trials therapeutic focus within neurology was assigned via combination programmatic and manual review. We performed descriptive analyses of trial characteristics, cox regression of early discontinuation, and multivariable logistic regression for results reporting within 3 years of completion. RESULTS: Most neurology trials were academic-funded (58.5%) followed by industry (31.9%) and US-government (9.6%). Neurology trials focused more on treatment than prevention compared to non-neurology studies. Of neurology trials, 11.3% discontinued early, and 32.2% of completed trials reported results by April 30, 2018. In multivariable analysis accounting for time-to-event, neurology trials were at lower risk of discontinuation than non-neurology trials (adjusted hazard 0.83, p < 0.0001). Both academic and government-funded trials had greater risk of discontinuation than industry (adjusted hazard 0.57 and 0.46, respectively). Among completed trials, government-funded studies (adjusted odds ratio 2.12, p < 0.0001) had highest odds of results reporting while academic trials reported less (adjusted odds ratio 0.51, p < 0.0001). CONCLUSIONS: Funding source is associated with trial characteristics and outcomes in neurology. Improvements in trial completion and timely dissemination of results remain urgent goals for the field.

Why the Hips Remain Stable When the Spine Strays: A Deeper Analysis of the Relationship Between Hip Displacement and Severe Scoliosis in Patients With Cerebral Palsy.

BACKGROUND: Many patients with spastic quadriplegic cerebral palsy (CP) and severe scoliosis develop hip displacement, whereas others do not. We investigated demographic characteristics, risk factors for CP, and imaging findings associated with nondisplaced hips in patients with CP and severe scoliosis. METHODS: We retrospectively analyzed records of 229 patients with spastic quadriplegic CP and severe scoliosis who presented for treatment at our US academic tertiary care hospital between August 2005 and September 2015. Demographic characteristics, risk factors for CP, and brain magnetic resonance imaging (MRI) findings were documented. Patients were classified as Gross Motor Function Classification System (GMFCS) level 4 or higher, with 58% at GMFCS level 5.3. Displaced hips (n=181 patients) were defined as a migration percentage of ≥30% or previous surgery for hip displacement/adductor contractures. Patients who did not meet these criteria were classified as nondisplaced (n=48 patients). We used univariate analysis and multivariate logistic regression to determine associations between patient factors and hip displacement (alpha=0.05). RESULTS: Patients born at term (≥37 wk) had 2.5 times the odds [95% confidence interval (CI): 1.3-5.0] of having nondisplaced hips compared with patients born prematurely. Females had 2.0 times the odds (95% CI: 1.0-3.9) of having nondisplaced hips compared with males. Patients with normal brain MRI findings had 9.6 times the odds (95% CI: 2.3-41) of having nondisplaced hips compared with patients with abnormal findings. Hip displacement was not associated with race (P>0.05). CONCLUSIONS: Gestational age 37 weeks or above, female sex, and normal brain MRI findings are independently associated with nondisplaced hips in patients with spastic quadriplegic CP and severe scoliosis. These findings direct attention to characteristics that may place patients at greater risk of displacement. Future work may influence preventative screening practices and improve patient counseling regarding the risk of hip displacement. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Traumatic brain injury alters neuropsychiatric symptomatology in all-cause dementia.

INTRODUCTION: Traumatic brain injury (TBI) may alter the course of neuropsychiatric symptom (NPS) onset during dementia development. The connection among TBI, NPS, and dementia progression is of increasing interest to researchers and clinicians. METHODS: Incidence of NPS was examined in participants with normal cognition who progressed to all-cause dementia based on whether TBI history was present (n = 130) or absent (n = 849). Survival analyses were used to examine NPS incidence across 7.6 ± 3.0 years of follow-up. RESULTS: Participants with TBI history had increased prevalence and incidence of apathy (44.7% vs 29.9%, P = .0062; HRadj. = 1.708, P = .0018) and motor disturbances (17.2% vs 9.5%, P = .0458; HRadj. = 2.023, P = .0168), controlling for demographics and type of dementia diagnosis. Earlier anxiety onset was associated with TBI (692 days prior to dementia diagnosis vs 161 days, P = .0265). DISCUSSION: History of TBI is associated with increased risk for and earlier onset of NPS in the trajectory of dementia development.

Medical Student Research Productivity: Which Variables are Associated with Matching to a Highly Ranked Orthopaedic Residency Program?

OBJECTIVE: Little is known about the importance of an applicant's research productivity in terms of matching into a highly-ranked orthopaedic residency. We characterized the research of orthopaedic residents who matched in 2017 to determine whether 1) program tiers differed by their residents' research; and 2) discrete increases in applicants' research were associated with matching into higher-ranked programs. DESIGN: We searched Scopus for resident publications accepted before 2017 or published through January 2017. Using an established ranking system, programs were ranked (tier-1, highest; tier-5, lowest) by their department's number of citations from 2005 to 2015. We compared resident research productivity among these 5 tiers. We then categorized residents by discrete levels of research productivity (0, 1, or ≥2 publications) and compared the differences in matched program rank. SETTING: Data collection and analysis performed at Johns Hopkins Hospital, a tertiary care center in Baltimore, MD. PARTICIPANTS: We obtained our sample from allopathic orthopaedic program websites, excluding military programs and international students, for a total of 111 programs (565 of 726 matched residents [78%]). RESULTS: Tier-1 and tier-2 programs differed significantly in their residents' publications, h-index, and citations. Programs of other tiers did not differ significantly. Applicants with 1 publication matched to higher-ranked residency programs than those with 0 publications. When comparing residents with 1 publication versus residents with more than 1 publication, we found no significant differences in program rank matched. CONCLUSIONS: Our results suggest that higher-tier orthopaedic residency programs match residents with greater research productivity than do lower-tier programs. Having 1 publication was associated with matching into a higher-ranked program but no significant associations were observed beyond the first publication.

Bioengineering lungs - current status and future prospects.

INTRODUCTION: Once pulmonary disease progresses to end-stage pulmonary disease, treatment options are very limited. An important advance in the field is the development of a bioartificial lung derived from a generic matrix scaffold populated with patients' own cells. Significant progress has already been made in the engineering of bioartificial lungs. AREAS COVERED: This review explains how previous and current research contributes to the goal of creating a successful bioartificial lung, and the barriers faced in doing so. We will also highlight some of the design considerations being explored to optimize bioartificial lungs and considerations for clinical translation. EXPERT OPINION: While current bioartificial lungs are able to provide short-term gas exchange in large-animal studies, much work is still required to combine the disciplines of cell biology, materials science, and tissue engineering to create such clinically useful and functioning artificial lungs.

Opioid use after adult spinal deformity surgery: patterns of cessation and associations with preoperative use.

OBJECTIVE: The objectives of the study were to determine, among patients with adult spinal deformity (ASD), the following: 1) how preoperative opioid use, dose, and duration of use are associated with long-term opioid use and dose; 2) how preoperative opioid use is associated with rates of postoperative use from 6 weeks to 2 years; and 3) how postoperative opioid use at 6 months and 1 year is associated with use at 2 years. METHODS: Using a single-center, longitudinally maintained registry, the authors identified 87 patients who underwent ASD surgery from 2013 to 2017. Fifty-nine patients reported preoperative opioid use (37 high-dose [≥ 90 morphine milligram equivalents daily] and 22 low-dose use). The duration of preoperative use was long-term (≥ 6 months) for 44 patients and short-term for 15. The authors evaluated postoperative opioid use at 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery. Multivariate logistic regression was used to determine associations of preoperative opioid use, dose, and duration with use at each time point (alpha = 0.05). RESULTS: The following preoperative factors were associated with opioid use 2 years postoperatively: any opioid use (adjusted odds ratio [aOR] 14, 95% CI 2.5-82), high-dose use (aOR 7.3, 95% CI 1.1-48), and long-term use (aOR 17, 95% CI 2.2-123). All patients who reported high-dose opioid use at the 2-year follow-up examination had also reported preoperative opioid use. Preoperative high-dose use (aOR 247, 95% CI 5.8-10,546) but not long-term use (aOR 4.0, 95% CI 0.18-91) was associated with high-dose use at the 2-year follow-up visit. Compared with patients who reported no preoperative use, those who reported preoperative opioid use had higher rates of use at each postoperative time point (from 94% vs 62% at 6 weeks to 54% vs 7.1% at 2 years) (all p < 0.001). Opioid use at 2 years was independently associated with use at 1 year (aOR 33, 95% CI 6.8-261) but not at 6 months (aOR 4.3, 95% CI 0.95-24). CONCLUSIONS: Patients' preoperative opioid use, dose, and duration of use are associated with long-term use after ASD surgery, and a high preoperative dose is also associated with high-dose opioid use at the 2-year follow-up visit. Patients using opioids 1 year after ASD surgery may be at risk for long-term use.

The effect of age of first exposure to competitive fighting on cognitive and other neuropsychiatric symptoms and brain volume.

It has long been established that fighting sports such as boxing and mixed martial arts can lead to head injury. Prior work from this group on the Professional Fighters Brain Health Study found that exposure to repetitive head impacts is associated with lower brain volumes and decreased processing speed in fighters. Current and previously licensed professional fighters were recruited, divided into active and retired cohorts, and matched with a control group that had no prior experience in sports with likely head trauma. This study examined the relationship between age of first exposure (AFE) to fighting sports and brain structure (MRI regional volume), cognitive performance (CNS Vital Signs, iComet C3), and clinical neuropsychiatric symptoms (PHQ-9, Barratt Impulsiveness Scale). Brain MRI data showed significant correlations between earlier AFE and smaller bilateral hippocampal and posterior corpus callosum volumes for both retired and active fighters. Earlier AFE in active fighters was correlated with decreased processing speed and decreased psychomotor speed. Retired fighters showed a correlation between earlier AFE and higher measures of depression and impulsivity. Overall, the results help to inform clinicians, governing bodies, parents, and athletes of the risks associated with beginning to compete in fighting sports at a young age.

History of traumatic brain injury interferes with accurate diagnosis of Alzheimer's dementia: a nation-wide case-control study.

Traumatic brain injury (TBI) and Alzheimer's disease (AD) bear a complex relationship, potentially increasing risk of one another reciprocally. However, recent evidence suggests post-TBI dementia exists as a distinct neurodegenerative syndrome, confounding AD diagnostic accuracy in clinical settings. This investigation sought to evaluate TBI's impact on the accuracy of clinician-diagnosed AD using gold standard neuropathological criteria. In this preliminary analysis, data were acquired from the National Alzheimer's Coordinating Centre (NACC), which aggregates clinical and neuropathologic information from Alzheimer's disease centres across the United States. Modified National Institute on Aging-Reagan criteria were applied to confirm AD by neuropathology. Among participants with clinician-diagnosed AD, TBI history was associated with misdiagnosis (false positives) (OR = 1.351 [95% CI: 1.091-1.674], p = 0.006). Among participants without clinician-diagnosed AD, TBI history was not associated with false negatives. TBI moderates AD diagnostic accuracy. Possible AD misdiagnosis can mislead patients, influence treatment decisions, and confound research study designs. Further work examining the influence of TBI on dementia diagnosis is warranted.

Exosomes function in antigen presentation during an in vivo Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis-infected macrophages and dendritic cells are limited in their ability to present antigen to CD4+ T cells suggesting that other mechanism of antigen presentation are driving the robust T cell response observed during an M. tuberculosis infection. These mechanisms could include antigens present in apoptotic bodies, necrotic debris, exosomes or even release of non-vesicular antigen from infected cells. However, there is limited data to support any of these mechanisms as important in driving T cell activation in vivo. In the present study we use Rab27a-deficient mice which show diminished trafficking of mycobacterial components to exosomes as well as M. tuberculosis strains that express recombinant proteins which traffic or fail to traffic to exosomes. We observed that exosomes released during a mouse M. tuberculosis infection contribute significantly to its T cell response. These finding imply that exosomes function to promote T cell immunity during a bacterial infection and are an important source of extracellular antigen.