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Background: Young patients are 6 times more likely than adults to have a primary anterior cruciate ligament (ACL) graft failure. Biological factors (ie, tunnel osteolysis) may account for up to a third of these failures. Previous evaluations of patient ACL explants indicated significant bone loss within the entheseal regions. However, it remains unknown if the degree of bone loss within the ACL insertion regions, wherein ACL grafts are fixated, exceeds that of the femoral and tibial condylar bone., Hypothesis: Bone loss in the mineralized matrices of the femoral and tibial ACL entheses is distinct from that clinically reported across the whole knee after injury., Study Design: Controlled laboratory study., Methods: We developed a clinically relevant in vivo mouse ACL injury model to cross-sectionally track the morphological and physiological postinjury changes within the ACL, femoral and tibial entheses, synovial joint space, and load-bearing epiphyseal cortical and trabecular bone components of the knee joint. Right ACLs of 10-week-old C57BL/6J female mice (N = 75) were injured in vivo with the contralateral ACLs serving as controls. Mice were euthanized at 1, 3, 7, 14, or 28 days after injury (n = 12/cohort). Downstream analyses included volumetric cortical and trabecular bone analyses and histopathologic assessments of the knee joint after injury. Gait analyses across all time points were also performed (n = 15 mice)., Results: The majority of the ACL injuries in mice were partial tears. The femoral and tibial cortical bone volumes were 39% and 32% lower, respectively, at 28 days after injury than those of the uninjured contralateral knees ( P < .01). Trabecular bone measures demonstrated little difference between injured and control knees after injury. Across all bone measures, bone loss was similar between the injured knee condyles and ACL entheses. There was also significant inflammatory activity within the knee after injury. By 7 days after injury, synovitis and fibrosis were sigificantly elevated in the injured knee compared with the controls ( P < .01), which corresponded with significantly higher osteoclast activity in bone at this time point compared with the controls. This inflammatory response signficantly persisted throughout the duration of the study ( P < .01). The hindlimb gait after injury deviated from normal, but mice habitually loaded their injured knee throughout the study., Conclusion: Bone loss was acute and persisted for 4 weeks after injury in mice. However, the authors' hypothesis was not confirmed, as bone quality was not significantly lower in the entheses compared with the condylar bone regions after injury. With relatively normal hindlimb loading but a significant physiological response after injury, bone loss in this model may be driven by inflammation., Clinical Relevance: There is persistent bone resorption and fibrotic tissue development after injury that is not resolved. Inflammatory and catabolic activity may have a significant role in the postinjury decline of bone quality in the knee.

Background: Overuse ligament and tendon injuries are prevalent among recreational and competitive adolescent athletes. In vitro studies of the ligament and tendon suggest that mechanical overuse musculoskeletal injuries begin with collagen triple-helix unraveling, leading to collagen laxity and matrix damage. However, there are little in vivo data concerning this mechanism or the physiomechanical response to collagen disruption, particularly regarding the anterior cruciate ligament (ACL)., Purpose: To develop and validate a novel in vivo animal model for investigating the physiomechanical response to ACL collagen matrix damage accumulation and propagation in the ACL midsubstance, fibrocartilaginous entheses, and subchondral bone., Study Design: Controlled laboratory study., Methods: C57BL/6J adolescent inbred mice underwent 3 moderate to strenuous ACL fatigue loading sessions with a 72-hour recovery between sessions. Before each session, randomly selected subsets of mice (n = 12) were euthanized for quantifying collagen matrix damage (percent collagen unraveling) and ACL mechanics (strength and stiffness). This enabled the quasi-longitudinal assessment of collagen matrix damage accrual and whole tissue mechanical property changes across fatigue sessions. Additionally, all cyclic loading data were quantified to evaluate changes in knee mechanics (stiffness and hysteresis) across fatigue sessions., Results: Moderate to strenuous fatigue loading across 3 sessions led to a 24% weaker ( P = .07) and 35% less stiff ( P < .01) ACL compared with nonloaded controls. The unraveled collagen densities within the fatigued ACL and entheseal matrices after the second and third sessions were 38% ( P < .01) and 15% ( P = .02) higher compared with the nonloaded controls., Conclusion: This study confirmed the hypothesis that in vivo ACL collagen matrix damage increases with tissue fatigue sessions, adversely impacting ACL mechanical properties. Moreover, the in vivo ACL findings were consistent with in vitro overloading research in humans., Clinical Relevance: The outcomes from this study support the use of this model for investigating ACL overuse injuries.

Background: The lateral femoral condyle index (LFCI)-a recently developed measure of the sphericity of the lateral femoral condyle-was reported to be a risk factor for anterior cruciate ligament (ACL) injury. However, issues have been raised regarding how the index was measured and regarding the patient group and the knee in which it was measured., Purpose: To investigate the association between the LFCI and the risk of sustaining a primary, noncontact ACL injury, and to examine whether this association was moderated by the posterior-inferior-directed slope of the lateral tibial plateau., Study Design: Cross-sectional study; Level of evidence, 3., Methods: A secondary analysis was conducted of deidentified magnetic resonance images of the uninjured knees of 86 athletes with ACL injury and the corresponding knees of 86 control athletes, matched for sports team, sex, and age. From those images, we measured the LFCI and the posterior-inferior-directed slope of the middle region articular cartilage surface of the tibial plateau's lateral compartment. Conditional logistic regressions were performed to determine whether the LFCI was significantly associated with ACL injury risk and whether the lateral tibial compartment middle cartilage slope moderated this association. Data were analyzed for female and male participants separately as well as for both groups combined., Results: The LFCI was not found to be significantly associated with experiencing a primary, noncontact ACL injury for all analyses. The lateral tibial slope measure was not found to moderate the association between the LFCI and ACL injury. A conditional logistic regression analysis using the LFCI data of the injured knees, instead of the uninjured knees, of the participants with ACL injury revealed that the LFCI was significantly associated with ACL injury., Conclusion: In this population of athletically active female and male participants, the LFCI was not found to be a risk factor for noncontact ACL injury, regardless of the geometric features of the lateral tibial slope.

Background: Recently developed multivariate sex-specific statistical models can predict anterior cruciate ligament (ACL) injury risk using various knee anatomic factors. However, screening tools able to identify individuals at an increased injury risk are unlikely to be developed based on these models, given that sophisticated and time-consuming methods were used to measure those factors on research-grade resolution magnetic resonance images (MRIs)., Purpose: To determine whether simpler methods, amenable to using clinical-grade resolution MRIs, can identify the same knee anatomic factors previously found to contribute to ACL injury risk using sophisticated methods and research-grade resolution images., Study Design: Cohort study (diagnosis); Level of evidence, 2., Methods: High-resolution 3-dimensional MRIs previously acquired from 87 patients with primary, noncontact, grade III ACL injury and 87 uninjured matched control participants for a series of published studies were downgraded to clinical-grade resolution images. The 4 knee anatomic factors found to contribute to ACL injury risk in women and in men in these published studies-femoral intercondylar notch width at the anterior outlet of the ACL (NW&#95;O), posterior-inferior directed slope of the middle region articular cartilage surface of the tibial plateau's lateral compartment (L at T ib MCS), ACL volume, and tibial plateau's lateral compartment posterior meniscus to subchondral bone wedge angle (L at T ib MBA)-were measured using clinical-grade resolution MRI-based methods. Stepwise multivariate conditional logistic regressions were used to identify the combinations of factors most highly associated with an ACL injury risk in women and men separately., Results: The multivariate model that best predicted ACL injury risk in the female participants included the L at T ib MCS and the NW&#95;O. For the male participants, this model included the ACL volume and the L at T ib MBA. These results corroborate the previously published results that reported models with the same knee anatomic factors to best predict injury risk in this group of young women and men., Conclusion: Simpler methods using MRIs downgraded to a clinical-grade resolution can identify the same knee anatomic factors previously found to significantly contribute to ACL injury risk using sophisticated methods and research-grade resolution MRIs.

Background: Evidence, mainly from animal models, suggests that exercise during periods of pubertal growth can produce a hypertrophied anterior cruciate ligament (ACL) and improve its mechanical properties. In humans, the only evidence of ACL hypertrophy comes from a small cross-sectional study of elite weight lifters and control participants; that study had methodological weaknesses and, thus, more evidence is needed., Purpose: To investigate bilateral differences in the ACL cross-sectional area (CSA) for evidence of unilateral hypertrophy in athletes who have habitually loaded 1 leg more than the other., Study Design: Cross-sectional study; Level of evidence, 3., Methods: We recruited 52 figure skaters and springboard divers (46 female and 6 male; mean age, 20.2 ± 2.7 years) because the former always land/jump on the same leg while the latter always drive the same leg into the board during their hurdle approach. Sport training for all participants began before puberty and continued throughout as well as after. Using oblique axial- and oblique sagittal-plane magnetic resonance imaging, we measured the ACL CSA and the anteroposterior diameter of the patellar tendon, respectively. In addition, isometric and isokinetic knee extensor and flexor peak torques were acquired using a dynamometer. Bilateral differences in the ACL CSA, patellar tendon diameter, and knee muscle strength were evaluated via 2-sided paired-samples t tests. Correlations between the bilateral difference in the ACL CSA and age of training onset as well as between the bilateral difference in the ACL CSA and years of training were also examined., Results: A significantly larger ACL CSA (mean difference, 4.9% ± 14.0%; P = .041), as well as patellar tendon diameter (mean difference, 4.7% ± 9.4%; P = .002), was found in the landing/drive leg than in the contralateral leg. The bilateral difference in the ACL CSA, however, was not associated with the age of training onset or years of training. Last, the isometric knee flexor peak torque was significantly greater in the landing/drive leg than the contralateral leg (mean difference, 14.5% ± 33.8%; P = .019)., Conclusion: Athletes who habitually loaded 1 leg more than the other before, during, and after puberty exhibited significant unilateral ACL hypertrophy. This study suggests that the ACL may be able to be "trained" in athletes. If done correctly, it could help lower the risk for ACL injuries.

Background: Anterior cruciate ligament (ACL) tears are common in contact athletics and have a significant effect on the athletic performance and well-being of affected players. The prevalence, timing, and characteristics of ACL tears in National Football League (NFL) athletes are lacking., Purpose: To define the epidemiology of ACL tears among NFL athletes., Study Design: Descriptive epidemiology study., Methods: This retrospective study includes all ACL injuries entered into the NFL injury database through the centralized leaguewide electronic health record system for the 2015-2019 seasons., Results: A total of 314 ACL injuries occurred during the 5-year study period, with a mean of 62 per year. The overall 1-season injury risk of an NFL player sustaining an ACL injury was 1.9% (95% CI, 1.7%-2.1%). Most ACL injuries occurred during games (n = 199), with a higher rate observed in the preseason games as compared with the regular season games (6.1 vs 2.7 per 10,000 player-plays; P < .01). NFL players with ≤3 of experience had a higher preseason injury rate (9.57 ACL tears per 1000 player-seasons) than those with ≥4 years of experience (5.12 ACL tears per 1000 player-seasons; P < .01). NFL athletes playing on special teams had the highest rate of ACL injuries (7.6 per 10,000 player-plays) in comparison with all other player positions., Conclusion: ACL injury incidence was fairly consistent across all years studied and occurred more frequently in players with ≤3 years of NFL experience. Tears were more common during games, special teams play, and the preseason.

Background: Thigh muscle weakness after anterior cruciate ligament reconstruction (ACLR) can persist after returning to activity. While resistance training can improve muscle function, "nonfunctional" training methods are not optimal for inducing transfer of benefits to activities such as walking. Here, we tested the feasibility of a novel functional resistance training (FRT) approach to restore strength and function in an individual with ACLR., Hypothesis: FRT would improve knee strength and function after ACLR., Study Design: Case report., Level of Evidence: Level 5., Methods: A 15-year-old male patient volunteered for an 8-week intervention where he performed 30 minutes of treadmill walking, 3 times per week, while wearing a custom-designed knee brace that provided resistance to the thigh muscles of his ACLR leg. Thigh strength, gait mechanics, and corticospinal and spinal excitability were assessed before and immediately after the 8-week intervention. Voluntary muscle activation was evaluated immediately after the intervention., Results: Knee extensor and flexor strength increased in the ACLR leg from pre- to posttraining (130 to 225 N·m [+74%] and 44 to 88 N·m [+99%], respectively) and increases in between-limb extensor and flexor strength symmetry (45% to 92% [+74%] and 47% to 72% [+65%], respectively) were also noted. After the intervention, voluntary muscle activation in the ACLR leg was 72%, compared with the non-ACLR leg at 75%. Knee angle and moment during late stance phase decreased (ie, improved) in the ACLR leg and appeared more similar to the non-ACLR leg after FRT training (18° to 14° [-23.4] and 0.07 to -0.02 N·m·kg -1 ·m -1 [-122.8%], respectively). Corticospinal and spinal excitability in the ACLR leg decreased (3511 to 2511 [-28.5%] and 0.42 to 0.24 [-43.7%], respectively) from pre- to posttraining., Conclusion: A full 8 weeks of FRT that targeted both quadriceps and hamstring muscles lead to improvements in strength and gait, suggesting that FRT may constitute a promising and practical alternative to traditional methods of resistance training., Clinical Relevance: FRT may serve as a viable approach to improve knee strength and function after ACL reconstruction.

Background: Lower extremity injuries are the most common injuries in professional sports and carry a high burden to players and teams in the National Football League (NFL). Injury prevention strategies can be refined by a foundational understanding of the occurrence and effect of these injuries on NFL players., Purpose: To determine the incidence of specific lower extremity injuries sustained by NFL players across 4 NFL seasons., Study Design: Descriptive epidemiology study., Methods: This retrospective, observational study included all time-loss lower extremity injuries that occurred during football-related activities during the 2015 through 2018 seasons. Injury data were collected prospectively through a leaguewide electronic health record (EHR) system and linked with NFL game statistics and player participation to calculate injury incidence per season and per 10,000 player-plays for lower extremity injuries overall and for specific injuries. Days lost due to injury were estimated through 2018 for injuries occurring in the 2015 to 2017 seasons., Results: An average of 2006 time-loss lower extremity injuries were reported each season over this 4-year study, representing a 1-season risk of 41% for an NFL player. Incidence was stable from 2015 to 2018, with an estimated total missed time burden each NFL season of approximately 56,700 player-days lost. Most (58.7%) of these injuries occurred during games, with an overall higher rate of injuries observed in preseason compared with regular season (11.5 vs 9.4 injuries per 10,000 player-plays in games). The knee was the most commonly injured lower extremity region (29.3% of lower body injuries), followed by the ankle (22.4%), thigh (17.2%), and foot (9.1%). Hamstring strains were the most common lower extremity injury, followed by lateral ankle sprains, adductor strains, high ankle sprains, and medial collateral ligament tears., Conclusion: Lower extremity injuries affect a high number of NFL players, and the incidence did not decrease over the 4 seasons studied. Prevention and rehabilitation protocols for these injuries should continue to be prioritized.

Background: A major goal of rehabilitation after anterior cruciate ligament reconstruction (ACLR) is restoring quadriceps muscle strength. Unfortunately, current rehabilitation paradigms fall short of this goal, such that substantial quadriceps muscle strength deficits can limit return to play and increase the risk of recurrent injuries. Blood flow restriction training (BFRT) involves the obstruction of venous return to working muscles during exercise and may lead to better recovery of quadriceps muscle strength after ACLR., Purpose: To examine the efficacy of BFRT with high-intensity exercise on the recovery of quadriceps muscle function in patients undergoing ACLR., Study Design: Randomized controlled trial; Level of evidence, 2., Methods: A total of 34 patients (19 female, 15 male; mean age, 16.5 ± 2.7 years; mean height, 169.0 ± 19.7 cm; mean weight, 73.2 ± 17.7 kg) scheduled to undergo ACLR were randomly assigned to 1 of 4 groups: concentric (n = 8), eccentric (n = 8), concentric with BFRT (n = 9), and eccentric with BFRT (n = 9). The exercise component of the intervention consisted of patients performing a single-leg isokinetic leg press, at an intensity of 70% of the patients' 1-repetition maximum during either the concentric or eccentric action, for 4 sets of 10 repetitions 2 times per week for 8 weeks beginning at 10 weeks postoperatively. Patients randomized to the BFRT groups performed the leg-press exercise with a cuff applied to the thigh, set to a limb occlusion pressure of 80%. Isometric and isokinetic (60 deg/s) quadriceps peak torque, quadriceps muscle activation, and rectus femoris muscle volume were assessed before ACLR, after BFRT, and at the time that patients returned to activity and were converted to the change in values from baseline for analysis. Also, 1-way analyses of covariance were used to compare the change in values for each dependent variable between groups after BFRT and at return to activity ( P ≤ .05)., Results: No significant differences were found between groups for any outcome measures at either time point ( P > .05)., Conclusion: An 8-week BFRT plus high-intensity exercise intervention did not significantly improve quadriceps muscle strength, activation, or volume. On the basis of our findings, the use of BFRT in conjunction with high-intensity resistance exercise in patients undergoing ACLR to improve quadriceps muscle function may not be warranted., Registration: NCT03141801 ( ClinicalTrials.gov identifier).

Background: "Research-ready" evidence platforms that link sports data with anonymized electronic health records (EHRs) or other data are important tools for evaluating injury occurrence in response to changes in games, training, rules, and other factors. While there is agreement that high-quality data are essential, there is little evidence to guide data curation., Hypothesis: We hypothesized that an EHR used in the course of clinical care and curated for research readiness can provide a robust evidence platform. Our purpose was to describe the data curation used for active injury surveillance by the National Football League (NFL)., Study Design: Dynamic cohort study., Level of Evidence: Level 2., Methods: Players provide informed consent for research activities through the collective bargaining process. A league-wide EHR is used to record injuries that come to the attention of the teams' athletic trainers and physicians, NFL medical spotters, or unaffiliated neurotrauma consultants. Information about football activities and injuries are linkable by player, setting, and event to other sports-related data, including game statistics and game-day stadium quality measures, using a unique player identification designed to protect player privacy. Ongoing data curation is used to review data completeness and accuracy and is adjusted over time in response to findings., Results: The core data curation activities include monthly injury summaries to team staff, queries to resolve incomplete reporting, and periodic external checks. Experiences derived from producing more than 100 reports per year on diverse topics are used to update coding training and related guidance documents in response to missing data or inconsistent coding that is observed. Roughly 20% more injuries were recorded for the same "reportable" injuries after switching from targeted reporting to an EHR., Conclusion: Research-ready databases need systematic curation for quality and completeness, along with related action plans. More injuries were reported through EHR than through targeted reporting., Clinical Relevance: Evidence-driven decision-making thrives on reliable data fine-tuned through systematic use, review, and ongoing adjustments to the curation process.

Background: Persistent quadriceps weakness and activation failure are common in individuals with anterior cruciate ligament (ACL) reconstruction. A growing body of evidence indicates that this chronic quadriceps dysfunction could be partly mediated due to reduced corticospinal excitability. However, current rehabilitation approaches do not directly target corticospinal deficits, which may be critical for restoring optimal clinical outcomes after the surgery. This case study tested the feasibility of operant conditioning of torque responses evoked by transcranial magnetic stimulation (TMS) to improve quadriceps function after ACL reconstruction., Hypothesis: Operant conditioning of motor evoked torque responses would improve quadriceps strength, voluntary activation, and corticospinal excitability., Study Design: Case study and research report., Level of Evidence: Level 5., Methods: A 24-year-old male with an ACL reconstruction (6 months postsurgery) trained for 20 sessions (2-3 times per week for 8 weeks) to increase his TMS-induced motor evoked torque response (MEP torque) of the quadriceps muscles using operant conditioning principles. Knee extensor strength, voluntary quadriceps muscle activation, and quadriceps corticospinal excitability were evaluated at 3 time points: preintervention (pre), 4 weeks (mid), and immediately after the intervention (post)., Results: The participant was able to successfully condition (ie, increase) the quadriceps MEP torque after 1 training session, and the conditioned MEP torque gradually increased over the course of 20 training sessions to reach about 500% of the initial value at the end of training. The participant's control MEP torque values and corticospinal excitability, which were measured outside of the conditioning paradigm, also increased with training. These changes were paralleled by improvements in knee extensor strength and voluntary quadriceps muscle activation., Conclusion: This study shows that operant conditioning of MEP torque is a feasible approach to improving quadriceps corticospinal excitability and quadriceps function after ACL reconstruction and encourages further testing in a larger cohort of ACL-reconstructed individuals., Clinical Relevance: Operant conditioning may serve as a potential therapeutic adjuvant for ACL rehabilitation.

Background: Nearly three-quarters of anterior cruciate ligament (ACL) injuries occur as "noncontact" failures from routine athletic maneuvers. Recent in vitro studies revealed that repetitive strenuous submaximal knee loading known to especially strain the ACL can lead to its fatigue failure, often at the ACL femoral enthesis., Hypothesis: ACL failure can be caused by accumulated tissue fatigue damage: specifically, chemical and structural evidence of this fatigue process will be found at the femoral enthesis of ACLs from tested cadaveric knees, as well as in ACL explants removed from patients undergoing ACL reconstruction., Study Design: Controlled laboratory study., Methods: One knee from each of 7 pairs of adult cadaveric knees were repetitively loaded under 4 times-body weight simulated pivot landings known to strain the ACL submaximally while the contralateral, unloaded knee was used as a comparison. The chemical and structural changes associated with this repetitive loading were characterized at the ACL femoral enthesis at multiple hierarchical collagen levels by employing atomic force microscopy (AFM), AFM-infrared spectroscopy, molecular targeting with a fluorescently labeled collagen hybridizing peptide, and second harmonic imaging microscopy. Explants from ACL femoral entheses from the injured knee of 5 patients with noncontact ACL failure were also characterized via similar methods., Results: AFM-infrared spectroscopy and collagen hybridizing peptide binding indicate that the characteristic molecular damage was an unraveling of the collagen molecular triple helix. AFM detected disruption of collagen fibrils in the forms of reduced topographical surface thickness and the induction of ~30- to 100-nm voids in the collagen fibril matrix for mechanically tested samples. Second harmonic imaging microscopy detected the induction of ~10- to 100-µm regions where the noncentrosymmetric structure of collagen had been disrupted. These mechanically induced changes, ranging from molecular to microscale disruption of normal collagen structure, represent a previously unreported aspect of tissue fatigue damage in noncontact ACL failure. Confirmatory evidence came from the explants of 5 patients undergoing ACL reconstruction, which exhibited the same pattern of molecular, nanoscale, and microscale structural damage detected in the mechanically tested cadaveric samples., Conclusion: The authors found evidence of accumulated damage to collagen fibrils and fibers at the ACL femoral enthesis at the time of surgery for noncontact ACL failure. This tissue damage was similar to that found in donor knees subjected in vitro to repetitive 4 times-body weight impulsive 3-dimensional loading known to cause a fatigue failure of the ACL., Clinical Relevance: These findings suggest that some ACL injuries may be due to an exacerbation of preexisting hierarchical tissue damage from activities known to place larger-than-normal loads on the ACL. Too rapid an increase in these activities could cause ACL tissue damage to accumulate across length scales, thereby affecting ACL structural integrity before it has time to repair. Prevention necessitates an understanding of how ACL loading magnitude and frequency are anabolic, neutral, or catabolic to the ligament.

Fibular hemimelia is a rare congenital malformation that is commonly associated with other lower limb abnormalities. This is a unique case of a bicruciate ligament, anterior cru ciate ligament/posterior cruciate ligament (ACL/PCL) deficiency in a 6-year-old female with fibular hemimelia in which we describe an ACL reconstruction using autograft-allograft hybrid technique. This case focuses on the technical aspects of an ACL reconstruction using a physeal-sparing technique with a hybrid ACL graft in a pediatric patient with fibular hemimelia. When evaluating patients with fibular hemimelia, it is important to consider implications of treatment in a stepwise manner as this condition commonly presents with other abnormalities that will most likely require multiple procedures, including limb lengthening., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.