Strength of the Uninvolved Limb Following Return to Activity After ACL Injury: Implications for Symmetry as a Marker of Sufficient Strength.

Background: Muscular strength deficits are common after ACL injury. While the Limb Symmetry Index (LSI), using the uninvolved limb as a reference, is widely used, negative strength adaptations may affect both limbs post-injury. It is uncertain how the strength of the uninvolved limb in those with an ACL injury compares to uninjured individuals, making it unclear whether it is appropriate as a benchmark for determining sufficient strength. Purpose: To compare the strength of key lower extremity muscles of the uninvolved limb in those with history of ACL injury (ACL-I) to the dominant limb in individuals with no history of ACL injury (control). Study Design: Cross-sectional study. Methods: A total of 5,727 military cadets were examined, with 82 females and 126 males in the ACL-I group and 2,146 females and 3,373 males in the control group. Maximum isometric strength was assessed for six muscle groups measured with a hand-held dynamometer. Separate two-way ANOVAs with limb and sex were performed for each muscle group. Results: Significant main effects for limb were observed with the uninvolved limb in the ACL-I group displaying greater strength compared to the dominant limb in the control group for the quadriceps, hamstrings, and gluteus medius, but effect sizes were small (Cohen's d <0.25). Significant main effects for sex were observed with greater male muscular strength in all six muscle groups with small to large effect sizes (Cohen's d 0.49-1.46). No limb-by-sex interactions were observed. Conclusions: There was no evidence of reduced strength in the uninvolved limb in those with a history of ACL injury compared to the dominant limb in those with no prior ACL injury. This finding suggests that, after clearance to return to activities, the uninvolved limb can be used as a standard for comparison of sufficient strength, including when using the LSI. Level of Evidence: Level 3.

Association of Premorbid Anxiety and Depression Symptoms in Concussion Recovery in Collegiate Student-Athletes.

BACKGROUND: Mental health disorders are linked to prolonged concussion symptoms. However, the association of premorbid anxiety/depression symptoms with postconcussion return-to-play timelines and total symptom burden is unclear. OBJECTIVE: To examine the association of self-reported premorbid anxiety/depression symptoms in collegiate student-athletes with (1) recovery times until asymptomatic, (2) return-to-play, and (3) postconcussion symptom burden. STUDY DESIGN: Athletes in the Concussion Assessment, Research and Education Consortium completed baseline concussion assessments (Sport Concussion Assessment Tool [SCAT3] and Brief Symptom Inventory-18 [BSI-18]). Athletes were tested postinjury at <6 hours, 24 to 48 hours, time of asymptomatic and start of return-to-play protocol, unrestricted return-to-play, and 6 months after injury. Injured athletes were categorized into 4 groups based on BSI-18 scores: (1) B-ANX, elevated anxiety symptoms only; (2) B-DEP, elevated depression symptoms only; (3) B-ANX&DEP, elevated anxiety and depression symptoms; and (4) B-NEITHER, no elevated anxiety or depression symptoms. Relationship between age, sex, BSI-18 group, SCAT3 total symptom and severity scores, and time to asymptomatic status and return-to-play was assessed with Pearson's chi-squared test and robust analysis of variance. LEVEL OF EVIDENCE: Level 3. RESULTS: Among 1329 athletes with 1352 concussions, no respondents had a self-reported premorbid diagnosis of anxiety/depression. There was no difference in time until asymptomatic or time until return-to-play between BSI-18 groups (P = 0.15 and P = 0.11, respectively). B-ANX, B-DEP, and B-ANX&DEP groups did not have higher total symptom or severity scores postinjury compared with the B-NEITHER group. CONCLUSION: Baseline anxiety/depression symptoms in collegiate student-athletes without a mental health diagnosis are not associated with longer recovery times until asymptomatic, longer time to return-to-play, or higher postconcussion total symptom and severity scores compared with athletes without baseline symptoms. CLINICAL RELEVANCE: Anxiety and depression symptoms without a clear mental health diagnosis should be considered differently from other comorbidities when discussing prolonged recovery in collegiate student-athletes.

Latent Profiles of Acute Symptoms, Cognitive Performance, and Balance in Sport-Related Concussions.

BACKGROUND: A sport-related concussion (SRC) is a common injury that affects multiple clinical domains such as cognition, balance, and nonspecific neurobehavioral symptoms. Although multidimensional clinical assessments of concussion are widely accepted, there remain limited empirical data on the nature and clinical utility of distinct clinical profiles identified by multimodal assessments. PURPOSE: Our objectives were to (1) identify distinct clinical profiles discernible from acute postinjury scores on the Sport Concussion Assessment Tool (SCAT), composed of a symptom checklist, a cognitive assessment (Standardized Assessment of Concussion), and a balance assessment (Balance Error Scoring System), and (2) evaluate the clinical utility of the identified profiles by examining their association with injury characteristics, neuropsychological outcomes, and clinical management-related outcomes. STUDY DESIGN: Cohort study (Prognosis); Level of evidence, 2. METHODS: Up to 7 latent profiles were modeled for 1885 collegiate athletes and/or military cadets who completed the SCAT at 0 to 12 hours after an injury. Chi-square tests and general linear models were used to compare identified profiles on outcomes at 12 to 72 hours after the injury. Kaplan-Meier analysis was used to investigate associations between clinical profiles and time to return to being asymptomatic and to return to play. RESULTS: There were 5 latent profiles retained: low impairment (65.8%), high cognitive impairment (5.4%), high balance impairment (5.8%), high symptom severity (16.4%), and global impairment (6.5%). The latent profile predicted outcomes at 12 to 72 hours in expectable ways (eg, the high balance impairment profile demonstrated worse balance at 12 to 72 hours after the injury). Time to return to being asymptomatic and to return to play were different across profiles, with the high symptom severity and global impairment profiles experiencing the longest recovery and the high balance impairment profile experiencing an intermediate-length recovery (vs low impairment profile). CONCLUSION: An SRC is a heterogeneous injury that presents in varying ways clinically in the acute injury period and results in different recovery patterns. These data support the clinical prognostic value of diverse profiles of impairment across symptom, cognitive, and balance domains. By identifying distinct profiles of an SRC and connecting them to differing outcomes, the findings support more evidence-based use of accepted multimodal clinical assessment strategies for SRCs.

The Prevalence and Influence of New or Worsened Neck Pain After a Sport-Related Concussion in Collegiate Athletes: A Study From the CARE Consortium.

BACKGROUND: Neck pain in a concussion population is an emerging area of study that has been shown to have a negative influence on recovery. This effect has not yet been studied in collegiate athletes. HYPOTHESIS: New or worsened neck pain is common after a concussion (>30%), negatively influences recovery, and is associated with patient sex and level of contact in sport. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Varsity-level athletes from 29 National Collegiate Athletic Association member institutions as well as nonvarsity sport athletes at military service academies were eligible for enrollment. Participants completed a preseason baseline assessment and follow-up assessments at 6 and 24 to 48 hours after a concussion, when they were symptom-free, and when they returned to unrestricted play. Data collection occurred between January 2014 and September 2018. RESULTS: A total of 2163 injuries were studied. New or worsened neck pain was reported with 47.0% of injuries. New or worsened neck pain was associated with patient sex (higher in female athletes), an altered mental status after the injury, the mechanism of injury, and what the athlete collided with. The presence of new/worsened neck pain was associated with delayed recovery. Those with new or worsened neck pain had 11.1 days of symptoms versus 8.8 days in those without (P < .001). They were also less likely to have a resolution of self-reported symptoms in ≤7 days (P < .001). However, the mean duration of the return-to-play protocol was not significantly different for those with new or worsened neck pain (7.5 ± 7.7 days) than those without (7.4 ± 8.3 days) (P = .592). CONCLUSION: This novel study shows that neck pain was common in collegiate athletes sustaining a concussion, was influenced by many factors, and negatively affected recovery.

Psychological Factors Are Related to Neuromuscular Asymmetries After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: After an anterior cruciate ligament reconstruction (ACLR), only 47% of military members return to full duty, possibly due to persistent neuromuscular asymmetries. Psychological factors may also contribute to reduced return to duty in military members. HYPOTHESIS: Psychological factors and time since surgery would be associated negatively with neuromuscular asymmetries, asymmetries would be greater in cadets postsurgery when compared with healthy controls, and asymmetries would be greater at earlier timepoints after ACLR. STUDY DESIGN: Case control. LEVEL OF EVIDENCE: Level 4. METHODS: This study examined the relationship between psychological factors and time since surgery with neuromuscular asymmetry, compared neuromuscular asymmetries between cadets with and without a history of ACLR, and explored differences in neuromuscular asymmetries at different timepoints in cadets with a history of ACLR. A total of 37 cadets post-ACLR (18.3 ± 9 months) and 28 controls participated. Psychological factors were assessed using the Tampa Scale of Kinesiophobia and Anterior Cruciate Ligament-Return to Sport after Injury scale (ACL-RSI). Participants performed a drop-jump landing, joint positioning sense (JPS), and isometric quadriceps strength testing. Peak vertical ground-reaction forces (vGRF), absolute angle of replication, peak quadriceps torque, rate of torque development (RTD), and RTD time torque interval 200 ms (TTI200) were analyzed. RESULTS: The ACL-RSI score was significantly related to limb symmetry index (LSI) peak quadriceps torque (r = 0.617, P < 0.01), LSI RTD (r = 0.367, P = 0.05), and LSI TTI200 (r = 0.0489, P < 0.01), but not time since surgery, JPS, or LSI peak vGRF. Cadets with a history of ACLR had significantly lesser ACL-RSI scores and greater asymmetries compared with controls. CONCLUSION: Reduced psychological readiness was associated with increased neuromuscular asymmetries after ACLR. CLINICAL RELEVANCE: Clinicians should assess psychological readiness during rehabilitation after ACLR.

Jump Landing Kinematics: Establishing Normative Ranges For Male And Female Athletes.

CONTEXT: Lower extremity joint (LE) kinematics during landing tasks are important predictors of injury risk and performance outcomes in athletes. OBJECTIVE: To establish sex-related differences and normative ranges for LE kinematics during the jump-landing task in a large cohort of healthy military service academy cadets. DESIGN: Cross-Sectional Study. SETTING: US Air Force, Naval, and Military Academies. PARTICIPANTS: 5308 cadets (2062 females [38.8%]). MAIN OUTCOME MEASURE(S): Sex-related differences in LE kinematics were analyzed using independent samples t-tests. Mean differences (MD) and effect sizes (d) were reported for interpretability. Normative ranges for hip and knee joint angles were established separately for males and females at initial contact (IC) and 50% of the stance phase. RESULTS: Compared to males, moderate effect sizes (d ≥ .5) were observed for knee external rotation (negative value) where females displayed greater motion at IC and at 50% stance (MD: - 3.9˚ and -5.0˚, respectively, p < .001). The following findings were of small effect size (.2 ≥ d > .5). Females exhibited less knee and hip flexion at IC (MD: -1.8˚ and -0.5˚, respectively, p < .001) and at 50% stance (MD: -4.1˚ and -4.6˚, respectfully, p < .001). This was accompanied by females having greater knee valgus (negative value) and hip adduction at IC (MD: -2.2˚ and 1.06˚, respectively, p < .001) and at 50% stance (MD: -3.2˚ and 1.8˚, respectfully, p < .001). CONCLUSION: This study establishes normative ranges for LE kinematics during the jump-landing task in a large cohort of healthy military service academy cadets entering their first year. Sex- related differences in LE kinematics were observed, highlighting the importance of considering sex as a factor in the evaluation of lower extremity movement quality and management of injury risk.

Mechanisms of Injury Leading to Concussions in Collegiate Soccer Players: A CARE Consortium Study.

BACKGROUND: Few previous studies have investigated how different injury mechanisms leading to sport-related concussion (SRC) in soccer may affect outcomes. PURPOSE: To describe injury mechanisms and evaluate injury mechanisms as predictors of symptom severity, return to play (RTP) initiation, and unrestricted RTP (URTP) in a cohort of collegiate soccer players. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The Concussion Assessment, Research and Education (CARE) Consortium database was used. The mechanism of injury was categorized into head-to-ball, head-to-head, head-to-body, and head-to-ground/equipment. Baseline/acute injury characteristics-including Sports Concussion Assessment Tool-3 total symptom severity (TSS), loss of consciousness (LOC), and altered mental status (AMS); descriptive data; and recovery (RTP and URTP)-were compared. Multivariable regression and Weibull models were used to assess the predictive value of the mechanism of injury on TSS and RTP/URTP, respectively. RESULTS: Among 391 soccer SRCs, 32.7% were attributed to a head-to-ball mechanism, 27.9% to a head-to-body mechanism, 21.7% to a head-to-head mechanism, and 17.6% to a head-to-ground/equipment mechanism. Event type was significantly associated with injury mechanism [χ2(3) = 63; P < .001), such that more head-to-ball concussions occurred in practice sessions (n = 92 [51.1%] vs n = 36 [17.1%]) and more head-to-head (n = 65 [30.8%] vs n = 20 [11.1]) and head-to-body (n = 76 [36%] vs n = 33 [18.3%]) concussions occurred in competition. The primary position was significantly associated with injury mechanism [χ2(3) = 24; P < .004], with goalkeepers having no SRCs from the head-to-head mechanism (n = 0 [0%]) and forward players having the least head-to-body mechanism (n = 15 [19.2%]). LOC was also associated with injury mechanism (P = .034), with LOC being most prevalent in head-to-ground/equipment. Finally, AMS was most prevalent in head-to-ball (n = 54 [34.2%]) and head-to-body (n = 48 [30.4%]) mechanisms [χ2(3) = 9; P = .029]. In our multivariable models, the mechanism was not a predictor of TSS or RTP; however, it was associated with URTP (P = .044), with head-to-equipment/ground injuries resulting in the shortest mean number of days (14 ± 9.1 days) to URTP and the head-to-ball mechanism the longest (18.6 ± 21.6 days). CONCLUSION: The mechanism of injury differed by event type and primary position, and LOC and AMS were different across mechanisms. Even though the mechanism of injury was not a significant predictor of acute symptom burden or time until RTP initiation, those with head-to-equipment/ground injuries spent the shortest time until URTP, and those with head-to-ball injuries had the longest time until URTP.

Modeling Risk for Lower Extremity Musculoskeletal Injury in U.S. Military Academy Cadet Basic Training.

INTRODUCTION: Sport and tactical populations are often impacted by musculoskeletal injury. Many publications have highlighted that risk is correlated with multiple variables. There do not appear to be existing studies that have evaluated a predetermined combination of risk factors that provide a pragmatic model for application in tactical and/or sports settings. PURPOSE: To develop and test the predictive capability of multivariable risk models of lower extremity musculoskeletal injury during cadet basic training at the U.S.Military Academy. MATERIALS AND METHODS: Cadets from the class of 2022 served as the study population. Sex and injury history were collected by questionnaire. Body Mass Index (BMI) and aerobic fitness were calculated during testing in the first week of training. Movement screening was performed using the Landing Error Scoring System during week 1 and cadence was collected using an accelerometer worn throughout initial training. Kaplan-Meier survival curves estimated group differences in time to the first musculoskeletal injury during training. Cox regression was used to estimate hazard ratios (HRs) and Akaike Information Criterion (AIC) was used to compare model fit. RESULTS: Cox modeling using HRs indicated that the following variables were associated with injury risk : Sex, history of injury, Landing Error Scoring System Score Category, and Physical Fitness Test (PT) Run Score. When controlling for sex and history of injury, amodel including aerobic fitness and BMI outperformed the model including movement screening risk and cadence (AIC: 1068.56 vs. 1074.11) and a model containing all variables that were significant in the univariable analysis was the most precise (AIC: 1063.68). CONCLUSIONS: In addition to variables typically collected in this tactical setting (Injury History, BMI, and aerobic fitness), the inclusion of kinematic testing appears to enhance the precision of the risk identification model and will likely continue to be included in screening cadets at greater risk.

Optimizing Concussion Care Seeking: Connecting Care-Seeking Behaviors and Neurophysiological States Through Blood Biomarkers.

BACKGROUND: Timely and appropriate medical care after concussion presents a difficult public health problem. Concussion identification and treatment rely heavily on self-report, but more than half of concussions go unreported or are reported after a delay. If incomplete self-report increases exposure to harm, blood biomarkers may objectively indicate this neurobiological dysfunction. PURPOSE/HYPOTHESIS: The purpose of this study was to compare postconcussion biomarker levels between individuals with different previous concussion diagnosis statuses and care-seeking statuses. It was hypothesized that individuals with undiagnosed concussions and poorer care seeking would show altered biomarker profiles. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Blood samples were collected from 287 military academy cadets and collegiate athletes diagnosed with concussion in the Advanced Research Core of the Concussion Assessment, Research and Education Consortium. The authors extracted each participant's self-reported previous concussion diagnosis status (no history, all diagnosed, ≥1 undiagnosed) and whether they had delayed or immediate symptom onset, symptom reporting, and removal from activity after the incident concussion. The authors compared the following blood biomarkers associated with neural injury between previous concussion diagnosis status groups and care-seeking groups: glial fibrillary acidic protein, ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light chain (NF-L), and tau protein, captured at baseline, 24 to 48 hours, asymptomatic, and 7 days after unrestricted return to activity using tests of parallel profiles. RESULTS: The undiagnosed previous concussion group (n = 21) had higher levels of NF-L at 24- to 48-hour and asymptomatic time points relative to all diagnosed (n = 72) or no previous concussion (n = 194) groups. For those with delayed removal from activity (n = 127), UCH-L1 was lower at 7 days after return to activity than that for athletes immediately removed from activity (n = 131). No other biomarker differences were observed. CONCLUSION: Individuals with previous undiagnosed concussions or delayed removal from activity showed some different biomarker levels after concussion and after clinical recovery, despite a lack of baseline differences. This may indicate that poorer care seeking can create neurobiological differences in the concussed brain.

Species delimitation in Amana (Liliaceae): transcriptomes battle with evolutionary complexity.

Species delimitation has long been a subject of controversy, and there are many alternative concepts and approaches used to define species in plants. The genus Amana (Liliaceae), known as "East Asian tulips" has a number of cryptic species and a huge genome size (1C = 21.48-57.35 pg). It also is intriguing how such a spring ephemeral genus thrives in subtropical areas. However, phylogenetic relationships and species delimitation within Amana are challenging. Here we included all species and 84 populations of Amana, which are collected throughout its distribution range. A variety of methods were used to clarify its species relationships based on a combination of morphological, ecological, genetic, evolutionary and phylogenetic species concepts. This evidence supports the recognition of at least 12 species in Amana. Moreover, we explored the complex evolutionary history within the genus and detected several historical hybridization and introgression events based on phylogenetic trees (transcriptomic and plastid), phylonetworks, admixture and ABBA-BABA analyses. Morphological traits have undergone parallel evolution in the genus. This spring ephemeral genus might have originated from a temperate region, yet finally thrives in subtropical areas, and three hypotheses about its adaptive evolution are proposed for future testing. In addition, we propose a new species, Amana polymorpha, from eastern Zhejiang Province, China. This research also demonstrates that molecular evidence at the genome level (such as transcriptomes) has greatly improved the accuracy and reasonability of species delimitation and taxon classification.

Timing of Outcomes and Expectations After Knee Surgery in the US Military: A Systematic Review.

CONTEXT: Knee injury and subsequent surgery are widespread in the military setting. Associations between knee surgery and expected outcomes over time have not been consolidated and characterized systematically by procedure type across the body of literature, and the temporal expectations of these outcomes remain unclear. OBJECTIVE: To summarize common postoperative follow-up times and associated outcomes that determine clinical or surgical failure in US service members after elective knee surgery. DATA SOURCES: A systematic search was conducted with 3 bibliographic databases of published research reports from 2010 through 2021. STUDY SELECTION: Studies in US military service members undergoing elective knee surgery, with a minimum of 1-year follow-up, and reporting on a functional/occupational outcome were included. Three reviewers screened all abstracts and full-text articles to determine eligibility. STUDY DESIGN: Systematic review of longitudinal cohort studies. LEVEL OF EVIDENCE: Level 2a. DATA EXTRACTION: Extracted data included military demographics, surgical procedure variables, surveillance period, and outcome measures. The Newcastle-Ottawa Scale and the Grading of Recommendations Assessment, Development, and Evaluation approach were used to determine study quality and risk of bias. RESULTS: A total of 22 studies (mean follow-up time of 40.7 months) met the inclusion criteria. For cruciate ligament repair, approximately one-third of patients required a second surgery or were medically separated from military service by 2 years from surgery; 100% were reinjured by 4 years, and 85% sustained a new injury within 5 years of surgery. For meniscal repair, nearly one-third of patients were medically separated, and half were placed on activity restrictions within 3 years of surgery. For articular cartilage repair, within 5 years, 39% of patients required a second surgery, 30% were placed on activity restrictions, and 36% were medically separated. For patellar repair, 37% of patients were medically separated and over half were placed on activity restrictions within 5 years. CONCLUSION: Common knee surgeries can have long-term implications for military careers that may not become apparent with shorter follow-up periods (<2 years). When longer surveillance periods are used (eg, up to 5 years), additional surgical procedures are more common and the likelihood of being injured or medically separated from military service is higher.

Efficacy of a Novel Telehealth Application in Health Behavior Modification and Symptomology in Military Service Members at Risk for Post-traumatic Osteoarthritis.

INTRODUCTION: Mobile applications (apps) may be beneficial to promote self-management strategies to mitigate the risk of developing post-traumatic osteoarthritis in military members following a traumatic knee injury. This study investigated the efficacy of a mobile app in facilitating behavior modification to improve function and symptomology among military members. MATERIALS AND METHODS: This is a preliminary pre and post hoc analysis of a randomized control trial. The MARX scale, Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire, and the Knee Injury and Osteoarthritic Outcome Score Readiness to Manage Osteoarthritis Questionnaire were completed at baseline, 6-week, 6-month, and 12-month follow-up. Participants in the treatment arm completed the System Usability Scale. Data were analyzed using descriptive statistics, the Wilcoxon sum of ranks test, the Wilcoxon signed-rank test, and Cohen's d effect size. RESULTS: A total of 28 participants were included. Between-group differences for baseline and 6-week follow-up were significantly improved in the injured knee ICOAP constant pain score for the treatment group (treatment: -4.2 ± 12, 95% CI: -11.5, 3.1; control: 5.5 ± 9.9, 95% CI: 0.9, 10.1; P = .035, effect size = 0.905). Within-group differences for baseline and 6-week follow-up demonstrated a significant decline in the injured knee ICOAP constant pain score among the control group (signed-rank: 16.0, P = .031, Cohen's d = 0.339). No other significant differences were observed. A good System Usability Scale score for usability was found (76.6 ± 8.8). CONCLUSIONS: These results indicate that the mobile app is easy to use and may contribute to improved constant pain symptomology for patients at risk for post-traumatic osteoarthritis.

Measurement of Head Kinematics Using Instrumented Mouthguards During Introductory Boxing Courses in U.S. Military Academy Cadets.

INTRODUCTION: Use of wearable impact sensor devices to quantitatively measure head impact exposure remains largely unstudied in military-style martial arts training and combat sports, particularly at the beginner levels. The baseline frequency and severity of head impact exposure during introductory military-style martial arts trainings, such as combatives training, is valuable information for developing future programs of instruction and exposure monitoring programs. The purpose of this study was to describe head impact exposures experienced during introductory combatives training (a boxing course) at U.S. Military Academy. METHODS: This study used instrumented mouthguards to measure head impact exposure in U.S. Military Academy cadets during a compulsory boxing course. Summary exposures from a preliminary dataset are presented. RESULTS: Twenty-two male subjects (19.9 ± 1.1 years, 86.6 ± 11.7 kg) participated in 205 analyzed player-bouts (full contact sparring sessions) with 809 video verified impacts (average 3.9 impacts per player-bout). The mean peak linear acceleration was 16.5 ±7.1 G, with a maximum of 70.8 G. There was a right-skewed distribution, with 640/809 (79.1%) events falling between 10 and 20 G. The mean peak angular acceleration was 1.52 ± 0.96 krad/s2, with a maximum of 8.85 krad/s2. CONCLUSIONS: Compared to other high-risk sports at Service Academies, head impacts from beginner boxing were of similar magnitude to those reported for Service Academy football and slightly lower than those reported for Service Academy rugby. Based on these preliminary data, the risk profile for introductory military-style martial arts training, such as boxing or combatives, may be similar to other contact sports like football and rugby, but further research is required to confirm these findings and understand the effects of the exposures in a shorter duration.

Gene Expression Alterations in Peripheral Blood Following Sport-Related Concussion in a Prospective Cohort of Collegiate Athletes: A Concussion Assessment, Research and Education (CARE) Consortium Study.

BACKGROUND: Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury. OBJECTIVE: The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery. METHODS: We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline. RESULTS: Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion. CONCLUSIONS: Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.

Beach-Chair Versus Lateral Decubitus Positioning for Primary Arthroscopic Anterior Shoulder Stabilization: A Consecutive Series of 641 Shoulders.

BACKGROUND: There are limited data comparing the beach-chair (BC) versus lateral decubitus (LD) position for arthroscopic anterior shoulder stabilization. PURPOSE: To identify predictors of instability recurrence and revision after anterior shoulder stabilization and evaluate surgical position and glenoid bone loss as independent predictors of recurrence and revision at short- and midterm follow-ups. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A consecutive series of 641 arthroscopic anterior stabilization procedures were performed from 2005 to 2019. All shoulders were evaluated for glenohumeral bone loss on magnetic resonance imaging. The primary outcomes of interest were recurrence and revision. Multivariable logistic regression models were used to assess the relationships of outcomes with age, position, glenoid bone loss group, and track. RESULTS: A total of 641 shoulders with a mean age of 22.3 years (SD, 4.45 years) underwent stabilization and were followed for a mean of 6 years. The overall 1-year recurrent instability rate was 3.3% (21/641) and the revision rate was 2.8% (18/641). At 1 year, recurrence was observed in 2.3% (11/487) and 6.5% (10/154) of BC and LD shoulders, respectively. The 5-year recurrence and revision rates were 15.7% (60/383) and 12.8% (49/383), respectively. At 5 years, recurrence was observed in 16.4% (48/293) and 13.3% (12/90) of BC and LD shoulders, respectively. Multivariable modeling demonstrated that surgical position was not associated with a risk of recurrence after 1 year (odds ratio [OR] for LD vs BC, 1.39; P = .56) and 5 years (OR for LD vs BC, 1.32; P = .43), although younger age at index surgery was associated with a higher risk of instability recurrence (OR, 1.73 per SD [4.1 years] decrease in age; P < .03). After 1 and 5 years, surgical position results were similar in a separate multivariable logistic regression model of revision surgery as the dependent variable, when adjusted for age, surgical position, bone loss group, and track. At 5 years, younger age was an independent risk factor for revision: OR 1.68 per SD (4.1 years) decrease in age (P < .05). CONCLUSION: Among fellowship-trained orthopaedic surgeons, there was no difference in rates of recurrence and revision surgery after performing arthroscopic anterior stabilization in either the BC or the LD position at 1- and 5-year follow-ups. In multivariable analysis, younger age, but not surgical position, was an independent risk factor for recurrence.

Initial Mild Traumatic Brain Injury Characteristics and Recovery Patterns Among Females Across the United States Military Service Academies: A Report from the NCAA-DoD CARE Consortium.

Mild traumatic brain injury (mTBI) has been described in the United States (US) military service academy cadet population, but female-specific characteristics and recovery outcomes are poorly characterized despite sex being a confounder. Our objective was to describe female cadets' initial characteristics, assessment performance, and return-to-activity outcomes post-mTBI. Female cadets (n = 472) from the four US military service academies who experienced a mTBI completed standardized mTBI assessments from pre-injury to acute initial injury and unrestricted return-to-duty (uRTD). Initial injury presentation characteristics (e.g., delayed symptoms, retrograde amnesia) and return-to-activity outcomes [i.e., return-to-learn, initiate return-to-duty protocol (iRTD), uRTD] were documented. Descriptive statistics summarized female cadets' injury characteristics, return-to-activity outcomes, and post-mTBI assessment performance change categorization (worsened, unchanged, improved) relative to pre-injury baseline using established change score confidence rank criteria for each assessment score. The median (interquartile range) days to return-to-learn (n = 157) was 7.0 (3.0-14.0), to iRTD (n = 412) was 14.7 (8.6-25.8), and to uRTD (n = 431) was 26.0 (17.7-41.8). The majority experienced worse SCAT total symptom severity (77.8%) and ImPACT reaction time (97.0%) acutely < 24-h versus baseline, but unchanged BESS total errors (75.2%), SAC total score (72%), BSI-18 total score (69.6%), and ImPACT verbal memory (62.3%), visual memory (58.4%), and visual motor speed (52.5%). We observed similar return-to-activity times in the present female cadet cohort relative to the existing female-specific literature. Confidence ranks categorizing post-mTBI performance were heterogenous and indicate multimodal assessments are necessary. Our findings provide clinically relevant insights to female cadets experiencing mTBI across the US service academies for stakeholders providing healthcare.

Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts.

Objective: The aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes. Methods: This pilot study comprised two independent cohorts. The first cohort-part of a Traumatic Head Injury Neuroimaging Classification (THINC) study-with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort-with a mean age of 19 years-comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay. Results: Concentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690-0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT-/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT-/MRI-, n = 111) findings and UIC (P-values < 0.05). Conclusion: These findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions.

Association Between Symptom Cluster Endorsement at Initiation of a Graduated Return-to-Activity Protocol and Time to Return to Unrestricted Activity After Concussion in United States Service Academy Cadets.

BACKGROUND: The endorsement of symptoms upon initiation of a graduated return-to-activity (GRTA) protocol has been associated with prolonged protocols. It is unclear whether there are specific symptom clusters affecting protocol durations. PURPOSE: To describe the endorsement of specific concussion symptom clusters at GRTA protocol initiation and examine the association between symptom cluster endorsement and GRTA protocol duration. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This study was conducted among cadets enrolled at 3 US service academies. Participants completed an evaluation upon GRTA protocol initiation. Participants endorsing symptoms were binarized based on 6 symptom clusters (cognitive, emotional, insomnia, physical, sensitivity, and ungrouped). The primary outcome of interest was GRTA protocol duration based on symptom cluster endorsement severity. Prevalence rates were calculated to describe symptom cluster endorsement. Kaplan-Meier survival estimates and univariate and multivariable Cox proportional hazards regression models were calculated for all 6 symptom clusters to estimate GRTA protocol duration while controlling for significant covariates. RESULTS: Data from 961 concussed participants were analyzed. Of these, 636 participants were asymptomatic upon GRTA protocol initiation. Among the 325 symptomatic participants, the physical symptom cluster (80%) was most endorsed, followed by the cognitive (29%), insomnia (23%), ungrouped (19%), sensitivity (15%), and emotional (9%) clusters. Univariate results revealed a significant association between endorsing cognitive (hazard ratio [HR], 0.79; p = .001), physical (HR, 0.84; p < .001), insomnia (HR, 0.83; p = .013), sensitivity (HR, 0.70; p < .001), and ungrouped (HR, 0.75; p = .005) symptom clusters and GRTA protocol duration. Endorsing physical (HR, 0.84; p < .001) and sensitivity (HR, 0.81; p = .036) clusters maintained a significant association with GRTA protocol duration in the multivariable models. CONCLUSION: Participants endorsing physical or sensitivity symptom clusters displayed GRTA protocols prolonged by 16% to 19% compared with participants not endorsing that respective cluster after controlling for significant covariates.

Predicting Postoperative Injury and Military Discharge Status After Knee Surgery in the US Army.

BACKGROUND: Researchers have assessed postoperative injury or disability predictors in the military setting but typically focused on 1 type of surgical procedure at a time, used relatively small sample sizes, or investigated mixed cohorts with civilian populations. PURPOSE: To identify the relationship between baseline variables and injury incidence or military discharge status in US Army soldiers after knee surgery. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Data were obtained from a repository containing personnel, performance, and medical records for all active-duty US Army soldiers. Multivariate logistic regressions were used to estimate the effects of numerous variables on postoperative injury or on medical discharge. Variable selection and model validation were conducted using the k-fold method. RESULTS: A total of 7567 soldiers underwent knee surgery between 2017 and 2019. Meniscal procedures were the most common type of surgery (39%), and approximately 71% of the cohort had a postoperative injury. Significant predictors for sustaining a postoperative injury included having a previous nonknee injury (odds ratio [OR], 1.5), female sex (OR, 1.3), and Black race (OR, 1.2). Within 4 years after surgery, 17% of soldiers were discharged from the military because of knee-related disability. Significant predictors for discharge from duty included enlisted rank (OR, 2.3), recent fitness test failure (OR, 1.9), number of previous knee surgeries (OR, 1.7), and having a previous nonknee injury (OR, 1.6). CONCLUSION: After knee surgery, nearly three-fourths of the soldiers in this cohort sustained a postoperative injury and almost one-fifth of soldiers were medically discharged from the military within 4 years. This study identified variables that indicate statistically increased risk for these postoperative outcomes and highlighted potentially modifiable factors.

Normative Values for Pupillary Light Reflex Metrics Among Healthy Service Academy Cadets.

INTRODUCTION: Assessments of the pupil's response to light have long been an integral part of neurologic examinations. More recently, the pupillary light reflex (PLR) has shown promise as a potential biomarker for the diagnosis of mild traumatic brain injury. However, to date, few large-scale normative data are available for comparison and reference, particularly, in military service members. The purpose of this study was to report normative values for eight PLR measurements among healthy service academy cadets based on sex, age, sleep, race, ethnicity, anisocoria, and concussion history. METHODS: Freshmen entering a U.S. Service Academy completed a quantitative pupillometric assessment in conjunction with baseline concussion testing. PLR measurements were conducted using a Neuroptics PLR-3000 with a 121 µW light stimulus. The device measured maximum and minimum pupil diameter (mm), latency (time to maximum pupil constriction post-light stimulus [s]), peak and average constriction velocity (mm/s), average dilation velocity (mm/s), percentage pupil constriction, and T75 (time for pupil re-dilation from minimum pupil diameter to 75% maximum diameter [s]). During baseline testing, cadets also reported concussion history (yes and no) and hours slept the night before (<5.5 and ≥5.5). Normative values for each PLR measurement were calculated as mean ± SD, percentiles, and interquartile range. Mann-Whitney U tests were used to assess differences based on sex, concussion history, ethnicity, and hours slept for each PLR measurement. Kruskall-Wallis testing was used to assess differences based on age, race, and anisocoria. Alpha was set at .05 and nonparametric effect sizes (r) were calculated for statistically significant results. Effect sizes were interpreted as no effect (r < .1), small (r ≥.1-<.3), medium (r ≥.3-<.5), or large (r ≥ .5). All procedures were reviewed and approved by the local institutional review board and the U.S. Army Human Research Protection Office before the study was conducted. Each subject provided informed consent to participate in the study before data collection. RESULTS: Of the 1,197 participants baselined, 514 cadets (131 female; 18.91 ± 0.96 years) consented and completed a valid baseline pupillometric assessment. Eighty participants reported at least one previous concussion and participants reported an average of 5.88 ± 1.63 h slept the previous night. Mann-Whitney U results suggest females had larger initial (z = -3.240; P = .001; r = .10) and end pupil diameter (z = -3.080; P = .002; r = .10), slower average dilation velocity (z = 3.254; P = .001; r = .11) and faster T75 values (z = -3.342; P = .001; r = .11). Age, sleep, and race stratified by sex, also displayed a significant impact on specific PLR metrics with effect sizes ranging from small to medium, while ethnicity, anisocoria, and concussion history did not display an impact on PLR metrics. CONCLUSION: This study provides the largest population-specific normative values for eight PLR measurements. Initial and end pupil diameter, dilation velocity, and the T75 metrics differed by sex; however, these differences may not be clinically significant as small effect size was detected for all metrics. Sex, age, sleep, and race may impact specific PLR metrics and are worth consideration when performing PLR assessments for mild traumatic brain injury management.