Exposure to Head Impacts and Cognitive and Behavioral Outcomes in Youth Tackle Football Players Across 4 Seasons.

Importance: Repetitive head impacts have been posited to contribute to neurocognitive and behavioral difficulties in contact sport athletes. Objective: To identify associations between cognitive and behavioral outcomes and head impacts measured in youth tackle football players over 4 seasons of play. Design, Setting, and Participants: This prospective cohort study was conducted from July 2016 through January 2020, spanning 4 football seasons. The setting was a youth tackle football program and outpatient medical clinic. Players were recruited from 4 football teams composed of fifth and sixth graders, and all interested players who volunteered to participate were enrolled. Data analysis was performed from March 2020 to June 2021. Exposures: Impacts were measured using helmet-based sensors during practices and games throughout 4 consecutive seasons of play. Impacts were summed to yield cumulative head impact gravitational force equivalents per season. Main Outcomes and Measures: Ten cognitive and behavioral measures were completed before and after each football season. Results: There were 70 male participants aged 9 to 12 years (mean [SD] age, 10.6 [0.64] years), with 18 completing all 4 years of the study. At the post-season 1 time point, higher cumulative impacts were associated with lower self-reported symptom burden (ß = -0.6; 95% CI, -1.0 to -0.2; P = .004). After correcting for multiple comparisons, no other associations were found between impacts and outcome measures. At multiple times throughout the study, premorbid attention-deficit/hyperactivity disorder, anxiety, and depression were associated with worse cognitive or behavioral scores, whereas a premorbid headache disorder or history of concussion was less often associated with outcomes. Conclusions and Relevance: In this cohort of youth tackle football players, premorbid conditions, including attention-deficit/hyperactivity disorder, anxiety, and depression, were associated with cognitive and behavioral outcomes more often than cumulative impact.

Subconcussive Head Impacts and Neurocognitive Function Over 3 Seasons of Youth Football.

OBJECTIVE: To determine the association between repetitive subconcussive head impacts and neurobehavioral outcomes in youth tackle football players. METHODS: Using helmet-based sensors, we measured head impacts for 3 consecutive seasons of play in 29 male players age 9-11. Cumulative impact g's were calculated. Players completed a battery of outcome measures before and after each season, including neuropsychological testing, vestibular-ocular sensitivity, and self- and parent-reported measures of symptoms and attention-deficit hyperactivity disorder (ADHD). RESULTS: Average cumulative impact over 3 seasons was 13 900g. High-intensity hits predicted worse change for self-reported social adjustment (P = .001). Cumulative impact did not predict change in any of the outcome measures. History of ADHD, anxiety, and depression predicted worse change for self-reported symptoms and social adjustment, independent of head impacts. When players were stratified into 3 groups based on cumulative impact across all 3 seasons, differences in outcome measures existed prior to the start of the first season. These differences did not further increase over the course of the 3 seasons. CONCLUSION: Over 3 consecutive seasons of youth tackle football, we found no association between cumulative head impacts and neurobehavioral outcomes. Larger sample sizes and longer follow-up times would further assist in characterizing this relationship.

Use of a Mandatory Clinical Decision Unit Reduces Readmission Rates following Total Joint Arthroplasty.

Readmission penalties have encouraged the implementation of protocols to reduce readmission rates. We hypothesized that by keeping postoperative patients, who return to the emergency department (ED) in a clinical decision unit (CDU) until being evaluated by the orthopaedic team, there would be a reduction in the readmission rate after total joint arthroplasty (TJA) at our institution. Our institution mandated the use of the CDU for all potential orthopaedic TJA readmissions. A retrospective review of prospectively collected data was performed on 365 patients who presented to the ED after either total hip arthroplasty (THA) or total knee arthroplasty (TKA). Patients presenting in the year prior to the implementation of the CDU program were compared with patients presenting in the year after implementation. Demographics, length of stay, comorbidities, and 30-day readmission rates were recorded. Additionally, a financial analysis was performed. Overall, for THA and TKA, there were a combined 141 ED visits prior to the implementation of the CDU program and 224 afterward; of these, 40 were readmitted before the CDU program and only 13 were readmitted afterward (p < 0.01). The financial analysis found that the overall 90-day cost for patients in the postoperative period was nearly $800 lower on average (p = 0.027) post-CDU implementation.During the first year of the CDU project at our institution, we significantly reduced the readmission rates following TJA and demonstrated significant cost saving. This is a Level III, prognostic study.

Rejuveinix Shows a Favorable Clinical Safety Profile in Human Subjects and Exhibits Potent Preclinical Protective Activity in the Lipopolysaccharide-Galactosamine Mouse Model of Acute Respiratory Distress Syndrome and Multi-Organ Failure.

Background: New treatment platforms that can prevent acute respiratory distress syndrome (ARDS) or reduce its mortality rate in high-risk coronavirus disease 2019 (COVID-19) patients, such as those with an underlying cancer, are urgently needed. Rejuveinix (RJX) is an intravenous formulation of anti-oxidants and anti-inflammatory agents. Its active ingredients include ascorbic acid, cyanocobalamin, thiamine hydrochloride, riboflavin 5' phosphate, niacinamide, pyridoxine hydrochloride, and calcium D-pantothenate. RJX is being developed as an anti-inflammatory and anti-oxidant treatment platform for patients with sepsis, including COVID-19 patients with viral sepsis and ARDS. Here, we report its clinical safety profile in a phase 1 clinical study (ClinicalTrials.gov Identifier: NCT03680105) and its potent protective activity in the lipopolysaccharide galactosamine (LPS-GalN) mouse model of ARDS. Methods: A phase 1, double-blind, placebo-controlled, randomized, two-part, ascending dose-escalation study was performed in participating 76 healthy volunteer human subjects in compliance with the ICH (E6) good clinical practice guidelines to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RJX (Protocol No. RPI003; ClinicalTrials.gov Identifier: NCT03680105). The ability of RJX to prevent fatal shock, ARDS, and multi-organ failure was examined in the well-established LPS-GalN mouse model of sepsis and ARDS. Standard methods were employed for the statistical analysis of data in both studies. Findings: In the phase 1 clinical study, no participant developed serious adverse events (SAEs) or Grade 3-Grade 4 adverse events (AEs) or prematurely discontinued participation in the study. In the non-clinical study, RJX exhibited potent and dose-dependent protective activity, decreased the inflammatory cytokine responses (interleukin-6, tumor necrosis factor alpha, transforming growth factor beta), and improved survival in the LPS-GalN mouse model of sepsis and ARDS. Histopathological examinations showed that RJX attenuated the LPS-GalN induced acute lung injury (ALI) and pulmonary edema as well as liver damage. Conclusion: RJX showed a very favorable safety profile and tolerability in human subjects. It shows potential to favorably affect the clinical course of high-risk COVID-19 by preventing ARDS and its complications.

Proposal of a Functional Impairment Symptom Scale for Concussion.

Clinicians currently administer patient-reported symptom scales to quantify and track concussion symptoms. These scales are based on subjective ratings without reference to the degree of functional impairment caused by the symptoms. Our objective was to develop a concussion symptom scale based on functional impairment and compare it to a widely used concussion symptom checklist. We conducted a retrospective chart review evaluating 133 patients age 9-22 with an acute concussion who completed 2 symptom checklists at their initial visit-the Sport Concussion Assessment Tool (SCAT-3) symptom evaluation (22 symptoms, 0-6 scale) and the proposed Functional Impairment Scale (22 symptoms, 0-3 scale related to degree of functional impairment). Mean total symptom score was 27.2±22.9 for Sport Concussion Assessment Tool-3 and 14.7±11.9 for the Functional Impairment Scale. Pearson correlation between the scales was 0.98 (P < .001). Mean time from concussion to first visit was 6.9±6.2 days, and median clearance time after injury was 19 (95% CI 16-21) days. After adjusting for patient and injury characteristics, an increased score on each scale was associated with longer time to clearance (5-point increase in Sport Concussion Assessment Tool-3 hazard ratio 0.885, 95% CI 0.835-0.938, P < .001; 2.5-point increase in Functional Impairment Scale hazard ratio 0.851, 95% CI 0.802-0.902, P < .001). We propose a concussion symptom scale based on functional impairment that correlates strongly with the Sport Concussion Assessment Tool-3 scale, demonstrates a similar association with time to clearance, and may provide a more intuitive approach to monitoring how symptoms are affecting patients recovering from concussion. Future research should aim to validate this scale through a prospective longitudinal study.

Head Impact Burden Differs Between Seasons in Youth and High School US Football Players.

Retrospective estimates of head impact burden in contact sports are often used in studies assessing for correlation of head impact exposure with neurocognitive outcomes later in life. These estimations assume a consistent impact burden from year to year. We monitored head impacts in youth tackle football players in the 6th-8th grades and high school varsity players using helmet-based sensors during two consecutive seasons. Helmet-based pressure sensors were used to measure head impacts, and estimates of peak linear acceleration (g's) were then grouped and summed for cumulative impact. After each season, players estimated whether they experienced an average, below average, or above average head impact burden in relation to their teammates. Of the 98 players who participated, 54 played in both seasons and sustained a median of 102.5 impacts (2206 cumulative g's) in season 1 and 161 impacts (3682 cumulative g's) in season 2. Using pairwise comparisons, number of impacts and cumulative g's increased in the youth players from season 1 to season 2 (p = 0.0021 and p = 0.0018, respectively), but there was a trend towards a decrease in number of impacts and g's at the high school level. In an exploratory analysis, perceived cumulative head impact and measured cumulative g's weakly correlated (Pearson's correlation coefficient = 0.26 for season 1 and 0.02 for season 2). In conclusion, cumulative head impacts differ significantly from one season to the next, and players have difficulty estimating their cumulative head impacts in relation to their team mates, especially at the youth level. Retrospective estimations of head impact burden should account for this variability.

Characterization of Pulmonary Emboli in Total Joint Arthroplasty Patients Compared to General Medical Patients.

Pulmonary emboli (PEs) occur in medical and postoperative total joint arthroplasty (TJA) patients. These are different patient populations, yet both undergo identical diagnosis and treatment regardless of PEs size and quantity. To date, there has been no analysis of the location, size, and quantity of emboli that occur postoperatively in TJA compared with general medical patients. We hypothesized TJA patients would have different size and distribution of PEs per event compared with medical patients. A retrospective chart review was conducted of patients who underwent total hip or knee arthroplasty in comparison to general medical patients at our institution from 2006 to 2011 with a PE diagnosis. Medical co-morbidities, sex, age, procedure, postoperative day, size, and location of PE using spiral computed tomography were recorded using a novel mapping scheme. Embolus size was defined based on blockage level in the pulmonary arterial tree. Of the 4,178 TJA patients reviewed, 51 were diagnosed with a PE. A total of 67% of TJA patients were women, yet women represented 90% (n = 46) of TJA PE patients (p < 0.0001). Medical patients had an equal distribution of men and women with PEs. Orthopaedic patients averaged more (4.0 vs. 2.2, p < 0.0001) and smaller PEs compared with medical patients (p < 0.0001). In conclusion, women undergoing TJA had significantly higher risk of developing PE compared with male arthroplasty or medical patients. Differences were observed in size and distribution of PEs between medical and TJA patients, which suggest a different nature of embolic phenomenon.

Early Results of a Modern Uncemented Total Knee Arthroplasty System.

Historically, cementless total knees were associated with early failure, which made cemented total knee arthroplasty the gold standard. Manufacturers have introduced newer uncemented technologies that provide good initial stability and use highly porous substrates for bony in-growth. The authors hypothesized that the implants would have equivalent 90-day clinical and economic outcomes. Prospectively collected data on 252 uncemented knees in the Michigan Arthroplasty Registry Collaborative Quality Initiative database were reviewed. Ninety-day outcomes, demographics, length of stay, complications, emergency department visits, readmissions, and financial data were compared with those of an age-matched group of cemented knees. Uncemented knees had shorter length of stay (1.58 vs 1.87 days; P<.01), were more frequently discharged home (90.48% vs 68.75%; P<.0001), and used less home care (6.35% vs 19.14%; P<.0001) or extended care facilities (2.78% vs 11.72%; P=.0001). More uncemented knees had "no complications." Moreover, there were no re-operations in uncemented knees, compared with 19 reoperations in cemented knees. Uncemented knees were better than age-matched counterparts for Knee injury and Osteoarthritis Outcome Score (63.69 vs 47.10, n=85 and n=43, P<.0001) and Patient-Reported Outcomes Measurement Information System (PROMIS) T-Physical and T-Mental scores (44.12 vs 39.45, P<.0001; 51.84 vs 47.82, P=.0018). Cemented cases were more expensive overall, and surgical ($6806.43 vs $5710.78; P<.01) and total hospital ($8347.65 vs $7016.11; P<.01) costs were higher. The 90-day readmission and hospital outpatient costs were not significantly different between designs. Uncemented total knee arthroplasty, when using modern technologies, is successful and economically viable for an at-risk bundle. The results of this study should alleviate fears of increased cost, early failure, complications, or poor outcomes with the use of a modern uncemented total knee arthroplasty. [Orthopedics. 2019; 42(6):355-360.].

Response profiles of circulating leukocytes and metal ions in patients with a modular dual-mobility hip implant.

INTRODUCTION: The purpose of this study was to retrospectively evaluate blood metal ion levels and leukocyte profiles in patients with modular dual-mobility hip implant (MDM) during a postoperative follow-up up to 2 years. METHODS: We recruited 49 patients in a retrospective cohort study and had postoperative follow-up up to 2 years. Blood concentrations of chromium (Cr), cobalt (Co) and serum cytokines were measured. Flow cytometry was used to quantify the subpopulations of leukocytes, including CD14+ and CD16+ monocytes, CD3+ T lymphocytes, CD19+ B lymphocytes, CD4+ Helper T-cells and CD45+RA memory vs. naïve T-cells. RESULTS: Clinical performances of implants were good during 2 years of follow-up. Cr levels were normal in all patients and only detectable in 1 patient (1.4µg/L, ref < 5.0µg/L). Co levels were mildly elevated in 4 patients at 1 year (mean 1.375µg/L, range 1.2-1.7µg/L, ref < 1.0µg/L) and in 2 patients at 2-year follow-up (both 1.2µg/L). Interestingly, Co level observed in 3 patients at 1 year converted to undetectable at their 2-year follow-up. Percentages of B cells, T cells and their subpopulations were within normal levels. There was no increase of CD16+ inflammatory monocytes. DISCUSSION: With the recent introduction of MDM systems there is potential for metal ion release from the interface between the acetabular shell and CoCr liner. Clinical results have been good and metal levels undetectable or within acceptable ranges at 1-2 years. There was no evidence of activated immune response, as manifested by constant circulating leukocyte profiles and no increase of CD16+ inflammatory monocytes.

Neurocognitive Function and Head Impact Burden over Two Seasons of Youth Tackle Football.

This prospective cohort study sought to determine the association of repetitive sub-concussive head impacts with neurocognitive outcomes in youth tackle football players. The study sample included 166 youth tackle football players over two seasons: 70 primary school players ages 9-12 and 96 high school players ages 15-18. Helmet-based sensors recorded head impacts during practices and games, and impacts were summed to provide a cumulative measure of impact for each season. Participants also were stratified by "high intensity" and "low intensity" groups based on whether they sustained high or low g-force impacts. Participants completed assessments on a variety of neurologic, cognitive, and behavioral outcomes before and after each football season. In the subgroup of 55 players who participated in both seasons, the average combined cumulative impact for primary school and high school players was 7127 (standard deviation [SD] 4670) and 6558 (SD 4438) g-forces, respectively. Neither cumulative impact nor impact intensity predicted change scores from pre-season 1 to post-season 2 on any outcome measures. Instead, younger age group and history of attention deficit hyperactivity disorder (ADHD) predicted worse change scores on several cognitive measures and an ADHD symptom reporting scale. In the full 166-player cohort, a computerized test of processing speed declined over time, while the remaining 22 outcome measures either did not change or improved over time. Minimal changes were observed in neurocognitive outcomes associated with participation in youth tackle football over the course of two seasons, and there was no correlation with the number and severity of head impacts sustained over that time. However, longer prospective follow-up times will be beneficial.

Comparing the Acute Presentation of Sport-Related Concussion in the Pediatric and Adult Populations.

Despite growing research on concussion, there is minimal evidence comparing the acute presentation of concussion between pediatric and adult patients. This cross-sectional study compares injury characteristics, symptoms, and neurologic examination in sport-related concussion based on age. Patients presenting to an outpatient sports neurology clinic for initial assessment of concussion within 7 days of injury were divided into 2 groups, 18 and older (n = 28) and 17 and younger (n = 107). There were no significant differences between pediatric and adult patients in any score of the Sport Concussion Assessment Tool-3rd Edition symptom scale, neurologic examination category, pertinent elements of past medical history, or characteristics of the concussion. The pediatric group had higher average hours of sleep (8.1 ± 0.3 vs 7.1 ± 0.58; P = .03) and were less likely to wake refreshed (36.3% vs 65%; P = .02). The initial presentation of concussion within 7 days of injury will likely not differ by age, specifically 18 and older versus 17 and younger.

Head Impact Burden and Change in Neurocognitive Function During a Season of Youth Football.

OBJECTIVE: To determine the association of repetitive subconcussive head impacts with functional outcomes in primary and high school tackle football players. SETTING: Youth football fields and an outpatient sports neurology clinic. PARTICIPANTS: A total of 112 primary school (n = 55, age 9-12 years) and high school (n = 57, age 15-18 years) football players. DESIGN: A prospective cohort study. MAIN MEASURES: Helmet-based sensors were used to record head impacts during practices and games during the 2016 football season. Impact g-forces were summed to yield a measure of cumulative impact. History of self-reported premorbid medical diagnoses was obtained preseason. Players completed assessments of a variety of outcomes both pre- and postseason: neuropsychological test performance, symptoms, vestibular and ocular-motor screening, balance, parent-completed attention-deficit hyperactivity disorder (ADHD) symptoms, and self-reported behavioral adjustment. RESULTS: Average cumulative impact was 3700 (standard deviation = 2700) g-forces for the season and did not differ between age groups (P = .594). Cumulative impact did not predict pre- to postseason change scores on any outcome measures (all P > .05). Instead, younger age group and reported history of premorbid ADHD predicted change scores on several cognitive testing measures and parent-reported ADHD symptoms, while reported history of premorbid anxiety and depression predicted change scores on symptom reporting. CONCLUSIONS: In youth tackle football, subconcussive head impacts sustained over the course of a single season may not be associated with neurocognitive functional outcomes. The absence of a significant association may reflect the relatively short follow-up interval, and signals the need for studies across multiple seasons.

Selective inhibition of ATPase activity during contraction alters the activation of p38 MAP kinase isoforms in skeletal muscle.

Muscle contractions strongly activate p38 MAP kinases, but the precise contraction-associated sarcoplasmic event(s) (e.g., force production, energetic demands, and/or calcium cycling) that activate these kinases are still unclear. We tested the hypothesis that during contraction the phosphorylation of p38 isoforms is sensitive to the increase in ATP demand relative to ATP supply. Energetic demands were inhibited using N-benzyl-p-toluene sulphonamide (BTS, type II actomyosin) and cyclopiazonic acid (CPA, SERCA). Extensor digitorum longus muscles from Swiss Webster mice were incubated in Ringer's solution (37°C) with or without inhibitors and then stimulated at 10 Hz for 15 min. Muscles were immediately freeze-clamped for metabolite and Western blot analysis. BTS and BTS + CPA treatment decreased force production by 85%, as measured by the tension time integral, while CPA alone potentiated force by 310%. In control muscles, contractions resulted in a 73% loss of ATP content and a concomitant sevenfold increase in IMP content, a measure of sustained energetic imbalance. BTS or CPA treatment lessened the loss of ATP, but BTS + CPA treatment completely eliminated the energetic imbalance since ATP and IMP levels were nearly equal to those of non-stimulated muscles. The independent inhibition of cytosolic ATPase activities had no effect on contraction-induced p38 MAPK phosphorylation, but combined treatment prevented the increase in phosphorylation of the γ isoform while the α/ß isoforms unaffected. These observations suggest that an energetic signal may trigger phosphorylation of the p38γ isoform and also may explain how contractions differentially activate signaling pathways.