Adolescent females are at a higher risk of anterior cruciate ligament (ACL) injury than males. While prior studies have associated injury timing and menstrual cycle phase, these data are limited by indirect cycle tracking and lack of analysis on ACL structure, mechanics, or composition. Additionally, little is known about how female sex hormones influence the distinct ACL bundles. This exploratory study investigated associations between serum sex hormone concentrations and size, mechanics, and composition of the ACL and its bundles in a female adolescent pig model. Serum from nine adolescent female Yorkshire crossbreed pigs was collected pre-euthanasia and analyzed for levels of estradiol, progesterone, and testosterone. The ACL and its bundles were assessed for size via magnetic resonance imaging (MRI), mechanics via robotic testing, and composition via biochemical and histological analyses. While individual hormone levels and the estradiol-to-progesterone (E/P) ratio had no association with most metrics, the E/P ratio was significantly associated with ACL size and T2* relaxation time. Higher E/P ratios were negatively associated with anteromedial (AM) bundle cross-sectional area (CSA) (R2 = 0.44) and overall ACL volume (R2 = 0.49) and positively associated with posterolateral (PL) bundle T2* relaxation time (R2 = 0.69, p < 0.05). Serum E/P ratio was also positively associated with normalized ACL stiffness, but there were no associations observed for tissue composition. The results of this exploratory study indicate that the ACL may be responsive to exposure to the relative concentration of female sex hormone in a bundle-specific manner.

Aberrant gait biomechanics following ACL reconstruction (ACLR) are linked to knee osteoarthritis development in adult patients. However, limited research exists to characterize walking biomechanics profiles of pediatric ACLR patients. The study purpose was to determine (1) differences in biomechanical profiles between pediatric ACLR patients (Tanner Stage I-IV) and two comparison-control groups (i.e., uninjured, matched pediatrics, adult-matched ACLR); (2) associations between biomechanical and Knee Osteoarthritis Outcomes Score (KOOS)-Child outcomes in pediatric ACLR patients. Gait biomechanics were collected in pediatric ACLR (n = 25), pediatric controls (n = 25), and adult ACLR groups (n = 25). Pediatric patients completed the KOOS-Child at the same session. A functional mixed effects model determined between-group differences in biomechanical variables. Uncorrected partial correlations, controlling for gait speed, were utilized to determine the association between discrete biomechanics and KOOS-Child scores. Pediatric ACLR patients demonstrated lesser first and second peak vertical ground reaction force (vGRF) and greater midstance vGRF than pediatric controls. Pediatric ACLR patients exhibited lesser midstance and greater late stance vGRF compared to the adult ACLR group. Pediatric ACLR patients demonstrated lesser knee flexion angle, knee extension moment, and knee abduction moment profiles compared to pediatric controls and adult ACLR patients throughout the majority of the stance phase. Greater midstance vGRF was associated with greater KOOS-Child Quality of Life scores in the contralateral limb (r = 0.54, p = 0.006). Pediatric ACLR patients exhibit unique biomechanical profiles compared to pediatric controls and adult ACLR patients; however, the associations with patient-reported outcomes remain unclear. Pediatrics may experience an exaggerated response to ACLR that may impact knee joint health.

BACKGROUND:Incidence rates of pediatric anterior cruciate ligament (ACL) injuries and ACL reconstruction (ACLR) are increasing. In adult patients with ACLR, limb-level loading profiles are less dynamic compared with uninjured controls (ie, lesser peaks and minimal offloading during midstance) early post-ACLR, and less dynamic profiles are associated with deleterious knee tissue changes. However, joint-level loading magnitudes during gait in the pediatric ACLR population are unknown. PURPOSE/HYPOTHESIS:The purpose of this study was to compare medial and lateral tibiofemoral joint contact force profiles between pediatric patients with ACLR and pediatric matched controls. It was hypothesized that pediatric patients with ACLR would demonstrate less dynamic medial and lateral joint contact force profiles compared with matched uninjured pediatric controls. STUDY DESIGN:Cross-sectional study; Level of evidence, 2. METHODS:Pediatric patients 6 to 24 months post-ACLR (n = 25) and matched pediatric controls (n = 25; Tanner stage category, sex, Tegner activity score ±3) underwent a gait biomechanical assessment at a single time point, where ground-reaction forces and marker trajectories were collected. The concurrent optimization of muscle activation and kinematics algorithm was utilized to estimate medial and lateral compartment tibiofemoral joint contact forces in the ACLR limb and pediatric matched control limb. A functional linear model was utilized to determine differences in joint contact force profiles throughout stance phase (0%-100%). RESULTS:Pediatric patients with ACLR demonstrated a high occurrence of concomitant injuries (80% meniscal pathology; 13% chondral injuries) and walked with greater medial tibiofemoral joint contact forces in midstance (42%-63% of the stance phase; 339-N maximal difference) and greater lateral joint contact forces in the late stance compared with pediatric controls (69%-80%; 288 N). CONCLUSION:Pediatric patients with ACLR may demonstrate a less dynamic tibiofemoral joint contact force loading profile in the medial compartment, as evidenced by greater loading during midstance, compared with matched pediatric controls.

Purpose: Females with above-average anterior knee laxity values are at increased risk of anterior cruciate ligament (ACL) injury. The purpose of this study was to examine the effects of menarche age (MA) and menarche offset on anterior knee laxity in young, physically active women. Methods: Anterior knee laxity (KT-2000) and menstrual characteristics (per self-report) were recorded in 686 Slovenian sportswomen from team handball, volleyball and basketball club sports (average years sport participation: 7.3 +/- 3.6 years). Females were stratified into four groups based on their self-reported age at menarche: 9-11, 12, 13 and 14+ years. Anterior knee laxity was compared across MA groups using a univariate analysis of variance (ANOVA) with Bonferroni correction, with and without controlling for factors that could potentially differ between groups and influence anterior knee laxity. Females were then stratified into four groups based on the number of years they were away from their age at onset of menarche. Groups were compared using a univariate ANOVA with Bonferroni correction, with and without controlling for factors that differed between groups and could influence anterior knee laxity. Results: Anterior knee laxity was greater in females who attained menarche at 12 years of age (6.4 +/- 1.5 mm) or younger (6.6 +/- 1.6 mm) compared to 14 years of age or older (5.8 +/- 1.2 mm) (p < 0.001; partial eta(2) = 0.032). Anterior knee laxity was 0.7-1.4 mm greater in females who were 5 or more years away from menarche compared to those who were within 2 years of menarche (5.8 +/- 1.3 mm; p < 0.001). Conclusion: Anterior knee laxity is greater in females who attained menarche at a younger age and in females who are 5 or more years postmenarche. Age of menarche represents a critical pubertal event that is easy for women to recall and may provide important insights into factors that moderate anterior knee laxity, a risk factor for ACL injury in women.

Although higher anterior knee laxity (AKL) is an established risk factor of anterior cruciate ligament injury, underlying mechanisms are uncertain. While decreased proprioception and altered movement patterns in individuals with AKL have been identified, the potential impact of higher laxity on brain activity is not well understood. Thus, the purpose of this study is to identify the impact of different magnitudes of knee laxity on brain function during anterior knee joint loading. Twenty-seven healthy and active female college students without any previous severe lower leg injuries volunteered for this study. AKL was measured using a knee arthrometer KT-2000 to assign participants to a higher laxity (N = 15) or relatively lower laxity group (N = 12). Functional magnetic resonance images were obtained during passive anterior knee joint loading in a task-based design using a 3 T MRI scanner. Higher knee laxity individuals demonstrated diminished cortical activation in the left superior parietal lobe during passive anterior knee joint loading. Less brain activation in the regions associated with awareness of bodily movements in females with higher knee laxity may indicate a possible connection between brain activity and knee laxity. The results of this study may help researchers and clinicians develop effective rehabilitation programs for individuals with increased knee laxity.

Context Temporal prediction of the lower extremity (LE) injury risk will benefit clinicians by allowing them to better leverage limited resources and target those athletes most at risk. Objective To characterize the instantaneous risk of LE injury by demographic factors of sex, sport, body mass index (BMI), and injury history. Design Descriptive epidemiologic study. Setting National Collegiate Athletic Association Division I athletic program. Patients or Other Participants A total of 278 National Collegiate Athletic Association Division I varsity student-athletes (119 males, 159 females; age = 19.07 ± 1.21 years, height = 175.48 ± 11.06 cm, mass = 72.24 ± 12.87 kg). Main Outcome Measure(s) Injuries to the LE were tracked for 237 ± 235 consecutive days. Sex-stratified univariate Cox regression models were used to investigate the association between time to first LE injury and sport, BMI, and LE injury history. The instantaneous LE injury risk was defined as the injury risk at any given point in time after the baseline measurement. Relative risk ratios and Kaplan-Meier curves were generated. Variables identified in the univariate analysis were included in a multivariate Cox regression model. Results Female athletes displayed similar instantaneous LE injury risk to male athletes (hazard ratio [HR] = 1.29; 95% CI= 0.91, 1.83; P = .16). Overweight athletes (BMI >25 kg/m2) had similar instantaneous LE injury risk compared with athletes with a BMI of <25 kg/m2 (HR = 1.23; 95% CI = 0.84, 1.82; P = .29). Athletes with previous LE injuries were not more likely to sustain subsequent LE injury than athletes with no previous injury (HR = 1.09; 95% CI = 0.76, 1.54; P = .64). Basketball (HR = 3.12; 95% CI = 1.51, 6.44; P = .002) and soccer (HR = 2.78; 95% CI = 1.46, 5.31; P = .002) athletes had a higher risk of LE injury than cross-country athletes. In the multivariate model, instantaneous LE injury risk was greater in female than in male athletes (HR = 1.55; 95% CI = 1.00, 2.39; P = .05), and it was greater in male athletes with a BMI of >25 kg/m2 than that in all other athletes (HR = 0.44; 95% CI = 0.19, 1.00; P = .05), but these findings were not significantly different. Conclusions In a collegiate athlete population, previous LE injury was not a contributor to the risk of future LE injury, whereas being female or being male with a BMI of >25 kg/m2 resulted in an increased risk of LE injury. Clinicians can use these data to extrapolate the LE injury risk occurrence to specific populations.

OBJECTIVE:To critically assess the literature focused on sex-specific trajectories in physical characteristics associated with anterior cruciate ligament (ACL) injury risk by age and maturational stage.DATA SOURCES:PubMed, CINAHL, Scopus, and SPORTDiscus databases were searched through December 2021.STUDY SELECTION:Longitudinal and cross-sectional studies of healthy 8- to 18-year-olds, stratified by sex and age or maturation on ≥1 measure of body composition, lower extremity strength, ACL size, joint laxity, knee-joint geometry, lower extremity alignment, balance, or lower extremity biomechanics were included.DATA EXTRACTION:Extracted data included study design, participant characteristics, maturational metrics, and outcome measures. We used random-effects meta-analyses to examine sex differences in trajectory over time. For each variable, standardized differences in means between sexes were calculated.DATA SYNTHESIS:The search yielded 216 primary and 22 secondary articles. Less fat-free mass, leg strength, and power and greater general joint laxity were evident in girls by 8 to 10 years of age and Tanner stage I. Sex differences in body composition, strength, power, general joint laxity, and balance were more evident by 11 to 13 years of age and when transitioning from the prepubertal to pubertal stages. Sex differences in ACL size (smaller in girls), anterior knee laxity and tibiofemoral angle (greater in girls), and higher-risk biomechanics (in girls) were observed at later ages and when transitioning from the pubertal to postpubertal stages. Inconsistent study designs and data reporting limited the number of included studies.CONCLUSIONS:Critical gaps remain in our knowledge and highlight the need to improve our understanding of the relative timing and tempo of ACL risk factor development.

Background: The ability to accurately recall specific reproductive health events is an integral aspect of medical decision making and evaluating a female's overall health and wellness across their lifespan. The Health and Reproductive Survey (HeRS) was developed to recall reproductive events and environmental influences on reproductive characteristics throughout the lifespan of a female. This study aimed to determine how reliably women recall certain events during menarche and early reproductive years. It was hypothesized that age at menarche, hormonal contraceptive use, and physical activity would be recalled reliably among all age ranges, while the recall reliability for cycle regularity and length would be more inconsistent with advancing age. Materials and Methods: A total of 144 participants (age: 32.73 ± 11.92), completed the HeRS on two occasions spaced 4 months apart to investigate recall reliability. Cohen's kappa coefficient was used to assess the consistency of categorical responses and 95% limits of agreement were used for continuous data. Results: Although physical activity changes had greater variability than anticipated (0.79), the recall reliability among the youngest (1) and oldest (0.89) age groups was high, and females were able to consistently recall the age of menarche (0.83), physical activity level (0.9), cessation of period during early reproductive years (0.91), and birth control use following menarche (0.85) and during the early reproductive years (0.9). Conclusions: The HeRS is a useful tool for reliably recalling reproductive history and physical activity participation across multiple age ranges and can be utilized to gather crucial information throughout the reproductive lifespan.

The timing of puberty and menarche (early versus late) have been shown to influence BMI in females, yet less is known about body composition (FMI and FFMI, respectively) related to these events. PURPOSE: To assess the influence of early versus late puberty and menarche on FMI and FFMI in females. METHODS: As part of a larger longitudinal study, BMI (lab-based height and weight), body composition and pubertal variables (pubertal development scale; PDS) were collected from females (N = 98). At age 10, mothers reported pubertal development (PDS; Range 1-4;1-2 = late puberty (N = 50), 3-4 = early puberty (N = 48)). At age 15 girls self-reported age at menarche (median split for early versus late menarche). BMI and body composition were measured in early emerging adulthood (21.1 ± 0.68 years) and FMI and FFMI for pubertal or menarche groups were compared across BMI groups (<.5 SD, ±.5 SD or > .5 SD of puberty or menarche group means for low [LBMI], mean [MBMI] or high [HBMI] BMI groups, respectively) using two-way MANOVAs with interaction terms. Post hoc univariate tests with Tukey post-hoc adjustments were run to probe significant interaction terms. RESULTS: Age 10 BMI was higher in girls with early puberty than those with late puberty (23.3 vs 18.2 kg/m2; p < .001), but age 10 BMI was similar when girls were stratified by early versus late menarche (21.0 vs 20.2 kg/m2, respectively). There was a significant interaction between pubertal development and BMI on FMI and FFMI (Λ = .599, p = 0.002), with early pubertal timing associated with higher FMI than late pubertal timing in the MBMI (p = .012) and HBMI (p < .001) groups but not in LBMI (p = .96). There was no interaction effect in the univariate test for pubertal timing and BMI on FFMI or for menarche timing and BMI on FMI and FFMI (Λ = .938, p = 0.276). CONCLUSIONS: In emerging adulthood, body composition in females was associated with early pubertal timing but not with early menarche, suggesting that differences in FMI and FFMI during this time are influenced largely by the age of onset of puberty and less by age of menarche. While timing of puberty may be a critical contributor to fat mass, further research is needed to delineate the role of early childhood body composition on pubertal versus menarche timing and the ability of physical activity to alter adolescent body composition trajectories.

Background: Restricted ankle dorsiflexion range of motion (DFROM) has been linked to lower extremity biomechanics that place an athlete at higher risk for injury. Whether reduced DFROM during dynamic movements is due to restrictions in joint motion or underutilization of available ankle DFROM motion is unclear. Hypothesis: We hypothesized that both lesser total ankle DFROM and underutilization of available motion would lead to high-risk biomechanics (ie, greater knee abduction, reduced knee flexion). Study Design: Cross-sectional study. Level of Evidence: Level 3. Methods: Nineteen active female athletes (age, 20.0 ± 1.3 years; height, 1.61 ± 0.06 m; mass, 67.0 ± 10.7 kg) participated. Maximal ankle DFROM (clinical measure of ankle DFROM [DF-CLIN]) was measured in a weightbearing position with the knee flexed. Lower extremity biomechanics were measured during a drop vertical jump with 3-dimensional motion and force plate analysis. The percent of available DFROM used during landing (DF-%USED) was calculated as the peak DFROM observed during landing divided by DF-CLIN. Univariate linear regressions were performed to identify whether DF-CLIN or DF-%USED predicted knee and hip biomechanics commonly associated with injury risk. Results: For every 1.0° less of DF-CLIN, there was a 1.0° decrease in hip flexion excursion ( r2 = 0.21, P = 0.05), 1.2° decrease in peak knee flexion angles ( r2 = 0.37, P = 0.01), 0.9° decrease in knee flexion excursion ( r2 = 0.40, P = 0.004), 0.002 N·m·N−1·cm−1 decrease in hip extensor work ( r2 = 0.28, P = 0.02), and 0.001 N·m·N−1·cm−1 decrease in knee extensor work ( r2 = 0.21, P = 0.05). For every 10% less of DF-%USED, there was a 3.2° increase in peak knee abduction angles ( r2 = 0.26, P = 0.03) and 0.01 N·m·N−1·cm−1 lesser knee extensor work ( r2 = 0.25, P = 0.03). Conclusion: Lower levels of both ankle DFROM and DF-%USED are associated with biomechanics that are considered to be associated with a higher risk of sustaining injury. Clinical Relevance: While total ankle DFROM can predict some aberrant movement patterns, underutilization of available ankle DFROM can also lead to higher risk movement strategies. In addition to joint specific mobility training, clinicians should incorporate biomechanical interventions and technique feedback to promote the utilization of available motion.

Abstract Purpose Greater femoral internal rotation (via anteversion or passive hip ROM) is associated with knee biomechanics thought to contribute to anterior cruciate ligament (ACL) injury, but it is unknown if femoral internal rotation contributes to actual ACL injury occurrence. The objective of this systematic review and meta-analysis was to quantify the extent to which femoral anteversion and hip range of motion (ROM) influence knee biomechanics consistent with ACL injury and actual ACL injury occurrence. Methods Using PRISMA guidelines, PubMed, CINAHL, SportDiscus, and Scopus databases were searched. Inclusion criteria were available passive hip ROM or femoral anteversion measure, ACL injury OR biomechanical analysis of functional task. Two reviewers independently reviewed titles, abstracts, and full texts when warranted. Included studies were submitted to Downs & Black Quality Assessment Tool. Meta-analyses were conducted for comparisons including at least two studies. Results Twenty-three studies were included (11 injury outcome, 12 biomechanical outcome). Decreased internal rotation ROM was significantly associated with history of ACL injury (MD -5.02°; 95% CI [-8.77°—-1.27°]; p = 0.01; n = 10). There was no significant effect between passive external rotation and ACL injury (MD -2.62°; 95% CI [-5.66°—- 0.41°]; p = 0.09; n = 9) Participants displaying greater frontal plane knee projection angle had greater passive external rotation (MD 4.77°; 95% CI [1.17° – 8.37°]; p = 0.01; n = 3). There was no significant effect between femoral anteversion and ACL injury (MD -0.46°; 95% CI [-2.23°—1.31°]; p = 0.61; n = 2). No within-sex differences were observed between injured and uninjured males and females (p range = 0.09 – 0.63). Conclusion Though individuals with injured ACLs have statistically less passive internal and external rotation, the observed heterogeneity precludes generalizability. There is no evidence that femoral anteversion influences biomechanics or ACL injury. Well-designed studies using reliable methods are needed to investigate biomechanical patterns associated with more extreme ROM values within each sex, and their prospective associations with ACL injury. Level of evidence: IV.

A growing body of evidence suggests that the direction of attentional focus to external cues during training may amplify the effects of traditional neuromuscular training designed to improve performance. The degree to which these effects might be due to changes in brain white-matter pathways remains largely unknown. PURPOSE: To relate changes in white matter architecture to changes in single leg hop performance (SLHP) after an eight-week training intervention and test for differences between externally and internally focused groups. METHODS: Twenty-nine healthy, recreationally active participants (17 females; Age = 21.9 ± 3.2 years) were randomly assigned to one of three training groups: external (n = 10), internal (n = 9) or no focus of attention (n = 10). All participants performed lower extremity body-weight strength and stabilization exercises three times per week for 8 weeks. SLHP was assessed before and after training. Structural (MPRAGE) and diffusion-weighted MRI (64 directions; bval = 1300 s/mm2) were performed before and after training. Individual diffusion MRI data were reconstructed in standard space to calculate spin distribution functions that define a ‘local’ connectome. Group connectometry was performed to test for changes that were i) associated with changes in SLHP and ii) different between the attentional focus groups. Bootstrap resampling (4000 permutations) estimated the false discovery rate (FDR). RESULTS: SLHP improved on average across all groups [t(28) = 5.1, p < .0001]. Increased SLHP was associated with increased connectivity in the left corticostriatal tract and longitudinal fasciculus (FDR = .030) and decreased connectivity in the right corticostriatal tract and thalamic radiation (FDR = .020). Compared to internally focused training, externally focused training was associated with a large increase in SLHP (Cohen’s d = .85), increased connectivity in bilateral corticostriatal tracts and longitudinal fasciculus (FDR = .001), and decreased connectivity in the right thalamic radiation (FDR = .005). CONCLUSION: The benefits of neuromuscular training may be related to neuroplasticity in white matter tracts within brain motor and association pathways. Improvements observed after externally focused training may be associated with more diffuse effects in similar circuits.

PURPOSE: Greater body mass index (BMI) is associated with greater risk of lower extremity injury, particularly, anterior cruciate ligament injury in women. To elucidate the sex-specific impact of greater BMI on lower extremity injury risk in women, we examined the lean versus fat mass composition of the lower extremities in males and females stratified by their BMI. METHODS: Physically active females (F; N=159; 21.7±2.9yr, 165.5±7.4cm, 62.4±7.7kg, 22.8±2.4kg/m2) and males (M; N=123; 22.3±3.0yr, 176.6±6.7cm, 76.0±9.3kg, 24.4±2.6kg/m2) were stratified according to their deviation from the sex-specific mean BMI as low (LO, <0.5SD), mean (MN, ±0.5SD), or high (HI >0.5SD), and compared on DXA-derived leg lean mass index (LLMI = lean mass/m2) and leg fat mass index (LFMI = fat mass/m2) using RMANOVA [2 (sex) x 3 (BMI group) x 2 (mass index)]. Bonferroni adjustments were made for post hoc analyses. RESULTS: Leg mass index (average LLMI and LFMI) was greater in M vs F (4.12±.35 > 4.01±.36, P=.02) and HI vs MN vs LO BMI groups (4.5±.39 > 4.1±.35 > 3.6±.36, P<.01), with no sex difference by BMI group (P=.570). Sex influenced the contribution of LLMI vs LFMI by BMI groups (P<.001). In M, both LLMI (6.4±0.5 < 6.9±0.7 < 7.4±0.8) and LFMI (0.9±0.4 < 1.2±0.4 < 1.8±0.7) increased linearly (and in a similar amount) from LO to MN to HI (all P<.013). For F, LFMI increased linearly (LO 1.9±0.4 < MN 2.5±0.6 < HI 3.5±0.7; P<.001), while LLMI increased from LO to MN (5.1±0.5 vs 5.6±0.8; P=.02), then plateaued from MN to HI (5.5±0.9; P=1.00) (total LFMI increase 1.6 kg/m2, LLMI increase 0.5 kg/m2). This resulted in substantially smaller proportions of LLMI relative to total leg mass index in HI (58%) compared to LO and MN females (66-69%) and males (range 77 to 83%). CONCLUSION: Females with above average BMIs have proportionally less relative leg muscle mass to control their body weight during sport activity. The extent to which this may impact other biological and biomechanical risk factors deserves further study. Supported by NIH Grant R01 AR053172, NATA Foundation, and NFL Charities

The ACL Research Retreat IX was held March 17–19, 2022, at High Point University in High Point, North Carolina. This meeting brought together clinicians and researchers to present and discuss recent research advances across the entire anterior cruciate ligament (ACL) injury continuum to include primary, secondary, and tertiary risk identification, outcomes, and prevention strategies. An illustration of this continuum was provided in the 2019 "Anterior Cruciate Ligament Research Retreat VIII Summary Statement."1 The unique focus of the current meeting was the pediatric athlete (aged 8 to 18 years). We have seen rising numbers of ACL injury diagnoses and ACL reconstructions (ACLRs) in this age group over the past 3 decades,2–5 and these increases were substantially greater than in older age groups. Epidemiologic studies consistently indicated that few ACL injuries occurred before the age of 10 and then they increased rapidly and steadily from age 11 to 17 years,2,6–8 when girls developed a 3-fold to 4-fold greater risk than similarly trained boys.9,10 Moreover, young girls were more likely to incur a second ACL injury soon after returning to sport participation.11–14 Thus, evidence-based screening and strategies to mitigate the risk of both primary and secondary injuries and improve long-term outcomes are critically needed in this age group. Because many risk factors associated with ACL injury develop or change during physical maturation, we sought to understand the maturational biopsychosocial factors that contribute to primary and secondary ACL injuries and affect both short-term and long-term joint health.To provide a framework for the meeting and our discussions, we introduced a theoretical risk factor model (Figure) to connect the initial risk of ACL injury to long-term knee-joint–related disability, such as posttraumatic osteoarthritis (PTOA). As the model suggests, at several key time points, targeted screenings and interventions may mitigate the risk of primary ACL injury and secondary ACL injury and the subsequent risk of PTOA. To that end, ACL Research Retreat IX featured 3 keynote presentations and 42 platform presentations that provided new insights to inform ACL injury risk and prevention across this continuum.The first keynote from Matthew Fisher, PhD, of North Carolina State University and the University of North Carolina at Chapel Hill, addressed basic science research seeking to characterize ACL structure and functional biomechanics during growth and development. Highlights from this keynote included the following:In the next keynote, Laura Schmitt, PT, MPT, PhD, of The Ohio State University, discussed optimizing knee rehabilitation outcomes and return-to-play criteria after ACLR in adolescents. She focused on the need for improved methods of determining the functional capacity of the injured limb post-ACLR:In the final keynote, Theodore Ganley, MD, of Children's Hospital of Philadelphia, addressed optimizing surgical techniques and outcomes for the immature knee. Highlights from this keynote included the following:The retreat also featured 42 platform presentations that provided new insights across the ACL injury continuum and are available in this special ACL issue (doi:10.4085/1062-6050-1005.22). Platform presentations were organized around themes of ACL injury risk assessment, ACL injury risk reduction, neurocognitive factors for primary risk, neurocognitive considerations in primary and secondary risk reduction, risk considerations for individuals post-ACLR, and considerations for ACLR surgical implications and PTOA. Substantial time was provided throughout the conference for group discussion to summarize recent advances and emerging trends and identify strategic initiatives for future research. The summary of these presentations and conversations is organized by primary ACL injury, secondary ACL injury, and tertiary injury (osteoarthritis [OA]). This summary is not designed to be a sweeping consensus but rather an executive summary of the key findings and discussion highlights with the goal of encouraging and steering future research directions.Our discussion of primary ACL injury covered the identification of risk factors, injury risk screening, and intervention strategies.The conference began with the presentation of a systematic review that examined the sex-specific trajectories of changing physical risk factors by chronological age and maturity status. Evidence was provided for a sequential, sex-specific development of physical risk factors that began with early sex differentiation in the trajectory of body composition, followed by leg strength and power, knee-joint anatomy and laxity, and lower extremity biomechanics.21 These data clearly showed that body mass index (weight by stature), which has been consistently identified as an independent risk factor for ACL injury,22–24 was a poor representation of body composition during maturation. Although body mass index increased similarly in boys and girls during the pubertal transition, the proportions of the fat mass index and fat-free mass index (FFMI) differed markedly, with boys already having a greater FFMI by age 10, and, by about the age of 13, the fat mass index increased more in girls and the FFMI more in boys. Additionally, sex-specific trajectories in ACL size (emerging at 14 years) closely followed sex-specific trajectories in thigh-muscle-mass development (emerging at 13 years), which led to discussions of ACL size and the extent to which these trajectories could be altered (ie, restraint capacity increased) during the developmental process. Research has indicated that ACL size is more strongly associated with muscle size than with other body dimensions25,26 and was also associated with prolonged training,27,28 particularly when training began at younger ages.27 Despite widespread evidence of bone and tendon adaptations to increases in load, how ligamentous tissue responds to increases in training load or if the training load alone is sufficient to increase this capacity is not widely understood. The ability to positively affect ACL structure through training also has implications for developmental changes in knee-joint laxity,21,29 an additional risk factor for ACL injury.23,24Along with physical risk development, multiple authors and much conversation addressed the role of the central nervous system (CNS) in the ACL injury risk. Sensory processing, neurocognition, motor planning and execution, and psychological preparedness for activity were all examined. Work presented at the meeting provided evidence that sensory information during ACL loading may differ in lax individuals (Park-Braswell et al), suggesting that a lax ligament may have neurofunctional and neurostructural implications for knee sensorimotor control. Whereas previous investigators30 associated a history of concussion with a risk of ACL injury, Zuleger et al supplied preliminary data for a potential central mechanism for the elevated ACL injury risk in those with a concussion history. Adolescent female athletes with a history of concussion showed reduced neural activity and concurrent connectivity alterations that indicated possible proprioceptive processing deficits. The authors of several studies offered at the meeting identified prospective neurologic factors that may have contributed to the neuromuscular control that propagates injury. Reduced knee motor coordination of a lower extremity task performed during functional magnetic resonance imaging by adolescent female athletes was associated with less activity in regions of the brain linked to visuospatial integration and working memory (Kim et al). Preliminary prospective work indicated that female adolescents who went on to tear their ACLs had greater brain activity associated with proprioceptive processing demands to coordinate bilateral knee motor control than uninjured participants (Diekfuss et al). These findings supported other CNS research into deficits in neurocognitive testing (associated with CNS function) that predicted ACL injury,31 which led to a discussion about when we should begin to use such measures in a pediatric population. As do other physiological systems during physical maturation, the CNS undergoes structural changes.32 Further, we understand that white matter structure and function do not mature until early adulthood.33 Age-related differences in brain activity in a pediatric population were noted during a leg-press activity (Warren et al). Specifically, increasing age (12–17 years) was associated with less brain activity in areas involving spatial cognition, self-location, and attention.Collectively, these investigations provided additional evidence that central factors may be important in the rapid increase in ACL injuries during the maturational process and pointed to the need for future research in this area (also see related papers in this special issue). However, although standardized neurocognitive assessment is typically much easier to perform, we need to better understand brain function during physical activity and how this may predict ACL injury. Such factors are especially apparent as behavior (neurocognitive performance) can normalize at the expense of sensorimotor neural activity compensations.34 Attendees also expressed a desire for normative, task-based functional magnetic resonance imaging measures to reduce the requirement for a control group when identifying those with a sensorimotor neural activation strategy that poses a high injury risk. However, thus far, the neuroimaging data have been preliminary and specific to group-related or task-related contrasts. Normative data to determine a threshold of excessive or inadequate activation of specific brain regions for classifying individuals with a sensorimotor activation strategy reflecting a high injury risk is a future research objective.Other primary risk factors centered on the concept of physical activity patterns and literacy during the physical maturational process. We must understand the timing of, types of, and changes in physical activity patterns during growth and development to establish how these factors may affect the development of high-risk biomechanical patterns associated with ACL injury. How and when physical activity may be associated with strength development and contribute to a reduction in the risk of ACL injury was also addressed.Debate focused on what should be measured as part of the screening process and when screening should occur, as prioritizing cost-effective field and clinically accessible measures to evaluate risk potential is critically important. This is especially true when working with a pediatric population, in whom the patient and parent or guardian burden becomes even more significant. The consensus was that ACL injuries were rarely seen in patients younger than age 11; the risk increased incrementally thereafter until full maturity. Vital questions were when and how we should begin to assess risk in the pediatric population if we are to be most effective in preventing primary injury. The feasibility of using maturation versus age as a marker of when to begin risk assessment was considered. Given the wide age ranges at which boys and girls initiate and progress through the pubertal transition and the fact that this transition occurs 1 to 2 years later in boys, attendees agreed that maturation was a better metric than age for assessing the timing of risk development. Which maturational measure (eg, Tanner stage, age and peak height velocity, skeletal age) should be used and when assessment should begin are still unknown. However, for large-scale risk assessment, simple and noninvasive tools that relate well to physiological growth spurts (eg, height and weight measures, self-reported pubertal assessment, shoe size) were required. Another topic was how often risk should be assessed and when a child "ages out" of the need for assessment. That is, what is the appropriate interval for a follow-up risk assessment? Based on the timing and tempo of Tanner stage progression, an ideal timeframe of every 6 months was suggested, with ≤1 year elapsing between assessments.Changes in strength and movement biomechanics among young female athletes in response to a variety of neuromuscular training programs were presented (Ford et al, Nguyen et al). Plyometric-based neuromuscular training resulting in brain activation during a lower extremity task indicated a neural efficiency adaptation for motor coordination (Chaput et al). Beyond established neuromuscular training programs, investigations involved the manipulation of feedback through a variety of mechanisms: biofeedback focused on a specific body region (Ford et al), autonomy support (Hogg et al, Nijmeijer et al), enhanced expectancies (Hogg et al), and visual feedback (Slutsky-Ganesh et al). One group's research demonstrated that emphasizing feedback on the underlying mechanism of aberrant biomechanics (hip focused) may provide greater transfer to other sporting tasks than a more localized knee-centric approach (Ford et al). Support continues to build for understanding the role of cognitive manipulation in prevention programming and how manipulating neuromuscular training programs may result in positive neuroplastic adaptations, which may benefit longer-term motor learning, redetection, and transference.Recognizing and appreciating the difficulty of performing large-scale prospective prevention studies, we focused on the factors that may help researchers conduct these experiments successfully. A large randomized controlled trial (Ford et al, Nguyen et al) with excellent adherence and compliance rates >90% spoke to the value of achieving rapport and a therapeutic alliance with all stakeholders, including the athletes, parents, and members of the coaching staff and club or school administrators. Others suggested that involving stakeholders to identify needs and their willingness to engage can help with rapport building and allow for a more tailored approach to intervention designs.As during previous retreats, the concept that reducing the incidence of ACL injury may benefit from a more public health perspective was reiterated. To promote the best-practice decisions by the patient and health care provider, we must put information in stakeholders' hands. The authors of a systematic review of knowledge, attitudes, and beliefs among sport stakeholders (Hawkinson et al) reported that implementation science frameworks have the potential to identify the barriers to implementation and could be beneficial in developing programming (based on the best science) that may meet the needs of stakeholders most effectively. It is imperative that the research community disseminate information in a manner appropriate to the target audience. Although coaches and athletes may be receptive to prevention strategies, our responsibility is to make the information accessible.Regarding secondary injury, even though many of the risk factors of the primary injury persist after the initial ACL injury, the risk factors that may be unique to secondary ACL injury should continue to be refined. Given the likely interaction of multiple factors, we need to develop a model that better describes primary versus secondary injury and what cluster of variables is most critical in determining injury risk.As with primary injury, evaluating lower extremity strength and biomechanics was a principal focus in assessing the patient's readiness to safely return to sporting activity post-ACLR. Based on a retrospective case-control design, female athletes with a lower hip-knee extensor strength ratio post-ACLR were at greater risk of ACL reinjury (Straub and Powers). Although the participants were not all youngsters, long-lasting impairments in quadriceps mitochondrial health (Davi et al) and differential patterns of muscle asymmetry (Hartshorne and Padua, Hart et al) were evident after ACL injury. Comparisons of adolescent and adult gait patterns showed that adolescents walked at slower gait speeds and displayed more-crouched gait kinematics characterized by less knee-flexion excursion (Lisee et al) but demonstrated no apparent difference in gait variability (Armitano-Lago et al). How such gait patterns may localize tibiofemoral compartment loading was considered.The psychological readiness to return to activity was another focus of attention—specifically, the constructs of confidence and kinesiophobia. As fear is a necessary human emotion that aids in survival, attendees emphasized taking a biopsychosocial, holistic approach when studying these constructs. Challenges to the validity of assessing these in the clinic or laboratory environment and then applying the results to the activity setting were acknowledged. Ecological momentary assessment may allow clinicians and researchers to better relate the psychosocial state to the actual activity of the patient.The concept of an individualized medicine approach to understanding the risks surrounding return to activity after a primary ACL injury was deliberated. The development of a promising machine-learning model of pediatric ACL reinjury risk was presented (Greenberg et al). Such a model has the potential to individually assess risk and provide customized methods of better directing secondary injury prevention. Similarly, a dashboard or business informatics platform approach was suggested (Kuenze et al) that would offer the clinician age-specific and sex-specific reference variables, thereby allowing more individualized decision making.Improving and refining return-to-sport testing was a frequent topic. Although wearable activity monitoring was not directly explored at the meeting, how such physiological devices may help us to better understand cumulative physical activity and its role in injury causation was the subject of much conversation. Related was the need to comprehend the role of fatigue in return-to-play testing. Questions exist about the robustness of return-to-play testing when the athlete is in a more fatigued state, which may affect the ability to avoid further joint injury.The role of ACL injury, surgery, and rehabilitation in the onset and progression of PTOA was explored in multiple ways. As with the primary and secondary injury risks, the role of psychosocial measures was examined. In a younger female population (aged 13–25 years), poor psychological readiness and elevated injury-related fear after ACLR was associated with greater odds of experiencing early knee OA symptoms (Baez et al). In an adolescent ACLR population (13–17 years), at 6 to 12 months post-ACLR, 47% of patients met the criteria for early knee OA symptoms. Although this percentage was greater in adults, it merits attention from health care providers (Harkey et al) who have the potential to implement a more targeted program to minimize OA symptoms beyond the traditional return-to-play rehabilitation timeframe. The necessity of separating structural joint changes (disease) from patient-reported symptoms (illness) was cited. This perspective may help to better focus research into providing better care of the patient post-ACLR.Another subject was how the onset and progression of OA may be modified by an intervention program. Despite substantial challenges in determining the effectiveness of such programs due to the very long-term longitudinal designs needed, such work will be helpful in identifying the types of interventions that should be tested. Interventions could include strength training, novel gait retraining, lifestyle modification, activity modification, and anxiety modification, for example. Also important is specifying appropriate criteria for inclusion in clinical trials to evaluate who will develop OA rapidly enough to assess the benefit of such changes.The incidence of ACL injuries in young athletes has increased over the last 3 decades, with girls showing the greatest increases.2 As athletes reach their mid-teens and progress into later maturational stages, sport-related ACL injuries continue to rise. Therefore, the early to mid-teens would appear to be an optimal window for injury-prevention interventions compared with targeting the late teens and early adult years.35 A primary take-home message from the discussions of primary risk was the importance of continued efforts to recognize the earliest onset of risk development at the individual level, so that we can determine the optimal window and targets for interventions. It is also becoming increasingly evident that we must move beyond physical risk assessment and address cognitive factors as well. Still, despite our best preventive efforts, some individuals will go on to experience ACL injuries. Attendees at this meeting identified a number of key directions for future research in the areas of primary and secondary risk-factor identification and optimizing interventions for reducing secondary injury while ensuring the best outcomes for long-term joint health. Specific to the prevention of secondary ACL injury, we need more evidence-based return-to-play criteria and a greater emphasis on psychological readiness. Psychosocial factors relative to the onset and progression of OA were considered, as were interventions for slowing or mitigating this disease. In summary, it is important to focus on the whole person and individual-level factors as ACL injury research continues to evolve.Retreat participants were as follows: Tine Alkjaer, Cortney Armitano-Lago, Beth Bacon, Shelby Baez, Kim Barber Foss, Anne Benjaminse, Michael Biller, Elizabeth Bjornsen, Matthew Bobman, Rob Bowen, Amelia Bruce, Meredith Chaput, Joseph Cimino, Stephanie Cone, Jed Diekfuss, Nakiah Dornbusch, Byrnadeen Farraye, Justin Fegley, Matthew Fisher, Kevin Ford, Alexis Slutsky-Ganesh, Theodore Ganley, Francesca Genoese, Josh Geruso, Don Goss, Reg Grant, Elliot Greenberg, Dustin Grooms, Henry Haltiwanger, Matt Harkey, Joe Hart, Matthew Hartshorne, Lauren Hawkinson, Taylor Heckert, Johanna Hoch, Ian Hoelker, Jennifer Hogg, Haleigh Hopper, Danielle Howe, Christopher Johnston, Cassidy Kershner, HoWon Kim, Jamie Kronenberg, Chris Kuenze, Liz Lefever, Pete Leno, Adam Lepley, Lindsey Lepley, Caroline Lisee, Jake McGregor, Amanda Munsch, Gregory Myer, Shannon Neville, Yum Nguyen, Eline Nijmeijer, Kayla Nugent, Darin Padua, Katie Pantano, Kyoungyoun Park-Braswell, Mark Paterno, Anne Pauw, Camryn Petit, Erich Petushek, Brett Pexa, Kate Pfile, Brian Pietrosimone, Christopher Powers, Bennett Prosser, Nicholas Reilly, Marcelo Rodriguez Cruz, Elizabeth Saunders, Andrew Schille, Laura Schmitt, Randy Schmitz, Amber Schnittjer, Sandy Shultz, Janet Simon, Jake Slaton, Steve Swanson, Dan Tarara, Jeffrey Taylor, Jacob Thompson, Michael Twardowski, Michelle Walaszek, Shayla Warren, Justin Waxman, Mitchell Wheatley, McKenzie White, Katherine Yakel, Emma Zuk, Taylor Zuleger, Christy Zwolski

BACKGROUND: Menstrual cycle (MC) characteristics (i.e., presence, regularity) change across a female’s lifespan. MC disturbances are particularly common post-menarche and can have implications later in life. The Health and Reproductive Survey (HeRS) is a retrospective tool designed to collect reproductive history and physical activity status among females to comprehensively understand MC variations across the lifespan. PURPOSE: To determine the ability of women to reliably recall their MC characteristics and physical activity status at menarche. METHODS: This survey was assessed in a test-retest design across a 4-month span to determine recall reliability of survey responses and focused on questions pertaining to menstrual cycle regularity and physical activity status. For the recall reliability of survey questions, a Cohen’s Kappa agreement was performed using the following cut points: 0 = chance; 0.1-0.2 = slight; 0.21-0.4 = fair; 0.41-0.6 = moderate; 0.61-0.8 = substantial; 0.81-0.99 = near perfect; 1 = perfect. To determine absolute error between values reported at baseline and 4-months, 95% Limits of agreement (LOA) were reported. RESULTS: Of the 144 females (age: 32.73 +/- 11.9) who completed the HeRS at both time points, females reliably recalled their status and the number of hours completed per week when asked to categorically describe physical activity. 43% reported irregular cycles (>12 cycles or < 10 cycles per year) and 18% reported physician diagnosis of disordered MCs. Recall reliability of the ‘average number of MC per year’ was within 1.5 years in 95% of the cases (LOA = -0.04+/-1.5 yrs), while recall of ‘whether a cycle stopped for 2+ months’ had moderate-substantial agreement (0.61). The ability to recall the ‘longest length of time a cycle stopped’ was more variable (95% LOA = 1.5 +/- 13.1 mo). There was moderate agreement (0.58) of one’s ‘ability to recall being diagnosed with a MC disturbance’ (e.g. amenorrhea), while the ability to recall use (0.9) and form (0.8) of birth control revealed substantial-near perfect agreements. CONCLUSIONS: The findings of this study revealed more diagnoses of MC disorders than previously reported, and largely support the fidelity of utilizing the HeRS to retrospectively assess menstrual characteristics and physical activity status at the onset of menses.