Chronic Adaptions in Quadriceps Fascicle Mechanics Are Related to Altered Knee Biomechanics After Anterior Cruciate Ligament Reconstruction.

Following anterior cruciate ligament reconstruction (ACLR), patients exhibit abnormal walking mechanics and quadriceps dysfunction. Quadriceps dysfunction has been largely attributed to muscle atrophy and weakness. While important, these factors do not capture intrinsic properties of muscle that govern its ability to generate force and withstand load. While fascicle abnormalities after ACLR have been documented in early stages of recovery (<12 mo), long-term effects of ACLR on fascicle mechanics remain unexplored. We evaluated quadriceps fascicle mechanics during walking 3 years post-ACLR and examined the relationship with knee mechanics. Participants included 24 individuals with ACLR and 24 Controls. Linear mixed models compared the ACLR, Contralateral, and Controls limbs for (1) quadriceps strength, (2) fascicle architecture and mechanics, and (3) knee mechanics. No difference in strength or overall fascicle length excursions was found between limbs. The ACLR limb exhibited longer fascicles at heel strike and peak knee extension moment (P < .001-.004), and smaller fascicle angles at heel strike, peak knee extension moment, and overall suppressed fascicle angle excursions (P < .001-.049) relative to the Contralateral and/or Control limb. This indicates an abnormality in fascicle architecture and mechanics following ACLR and suggests abnormalities in contractile function that cannot be explained by muscle weakness and may contribute to long-term gait irregularities.

Beyond weakness: Exploring intramuscular fat and quadriceps atrophy in ACLR recovery.

Muscle weakness following anterior cruciate ligament reconstruction (ACLR) increases the risk of posttraumatic osteoarthritis (OA). However, focusing solely on muscle weakness overlooks other aspects like muscle composition, which could hinder strength recovery. Intramuscular fat is a non-contractile element linked to joint degeneration in idiopathic OA, but its role post-ACLR has not been thoroughly investigated. To bridge this gap, we aimed to characterize quadriceps volume and intramuscular fat in participants with ACLR (male/female = 15/9, age = 22.8 ± 3.6 years, body mass index [BMI] = 23.2 ± 1.9, time since surgery = 3.3 ± 0.9 years) and in controls (male/female = 14/10, age = 22.0 ± 3.1 years, BMI = 23.3 ± 2.6) while also exploring the associations between intramuscular fat and muscle volume with isometric strength. Linear mixed effects models assessed (I) muscle volume, (II) intramuscular fat, and (III) strength between limbs (ACLR vs. contralateral vs. control). Regression analyses were run to determine if intramuscular fat or volume were associated with quadriceps strength. The ACLR limb was 8%-11% smaller than the contralateral limb (p < 0.05). No between-limb differences in intramuscular fat were observed (p 0.091-0.997). Muscle volume but not intramuscular fat was associated with strength in the ACLR and control limbs (p < 0.001-0.002). We demonstrate that intramuscular fat does not appear to be an additional source of quadriceps dysfunction following ACLR and that muscle size only explains some of the variance in muscle strength.

Development of a Low-cost Epimysial Electromyography Electrode: A Simplified Workflow for Fabrication and Testing.

Electromyography (EMG) is a valuable diagnostic tool for detecting neuromuscular abnormalities. Implantable epimysial electrodes are commonly used to measure EMG signals in preclinical models. Although classical resources exist describing the principles of epimysial electrode fabrication, there is a sparsity of illustrative information translating electrode theory to practice. To remedy this, we provide an updated, easy-to-follow guide on fabricating and testing a low-cost epimysial electrode. Electrodes were made by folding and inserting two platinum-iridium foils into a precut silicone base to form the contact surfaces. Next, coated stainless steel wires were welded to each contact surface to form the electrode leads. Lastly, a silicone mixture was used to seal the electrode. Ex vivo testing was conducted to compare our custom-fabricated electrode to an industry standard electrode in a saline bath, where high levels of signal agreement (sine [intraclass correlation - ICC= 0.993], square [ICC = 0.995], triangle [ICC = 0.958]), and temporal-synchrony (sine [r = 0.987], square [r = 0.990], triangle [r= 0.931]) were found across all waveforms. Low levels of electrode impedance were also quantified via electrochemical impedance spectroscopy. An in vivo performance assessment was also conducted where the vastus lateralis muscle of a rat was surgically instrumented with the custom-fabricated electrode and signaling was acquired during uphill and downhill walking. As expected, peak EMG activity was significantly lower during downhill walking (0.008 ± 0.005 mV) than uphill (0.031 ± 0.180 mV, p = 0.005), supporting the validity of the device. The reliability and biocompatibility of the device were also supported by consistent signaling during level walking at 14 days and 56 days post implantation (0.01 ± 0.007 mV, 0.012 ± 0.007 mV respectively; p > 0.05) and the absence of histological inflammation. Collectively, we provide an updated workflow for the fabrication and testing of low-cost epimysial electrodes.

Quadriceps muscle atrophy after non-invasive anterior cruciate ligament injury: evidence linking to autophagy and mitophagy.

Introduction: Anterior cruciate ligament (ACL) injury is frequently accompanied by quadriceps muscle atrophy, a process closely linked to mitochondrial health and mitochondria-specific autophagy. However, the temporal progression of key quadricep atrophy-mediating events following ACL injury remains poorly understood. To advance our understanding, we conducted a longitudinal study to elucidate key parameters in quadriceps autophagy and mitophagy. Methods: Long-Evans rats were euthanized at 7, 14, 28, and 56 days after non-invasive ACL injury that was induced via tibial compression overload; controls were not injured. Vastus lateralis muscle was extracted, and subsequent immunoblotting analysis was conducted using primary antibodies targeting key proteins involved in autophagy and mitophagy cellular processes. Results: Our findings demonstrated dynamic changes in autophagy and mitophagy markers in the quadriceps muscle during the recovery period after ACL injury. The early response to the injury was characterized by the induction of autophagy at 14 days (Beclin1), indicating an initial cellular response to the injury. Subsequently, at 14 days we observed increase in the elongation of autophagosomes (Atg4B), suggesting a potential remodeling process. The autophagosome flux was also augmented between 14- and 28 days (LC3-II/LC3-I ratio and p62). Notably, at 56 days, markers associated with the elimination of damaged mitochondria were elevated (PINK1, Parkin, and VDAC1), indicating a possible ongoing cellular repair and restoration process. Conclusion: These data highlight the complexity of muscle recovery after ACL injury and underscore the overlooked but crucial role of autophagy and mitophagy in promoting the recovery process.

Open-sourced semi-automatic program for ultrasound assessments of femoral trochlea cartilage health.

We developed an open-sourced program that accounts for the current limitations of B-mode ultrasound and extends the clinical utility of ultrasound for assessing femoral trochlear cartilage thickness. Images were collected on 18 patients with a history of knee surgery. By failing to account for ultrasound acoustics and beam refraction, cartilage thickness was underestimated by 26% and overestimated by 0-4%, respectively (p < 0.001). Comprehensive thickness measurements achieved by measuring the Euclidean distance between every point were significantly different than traditional single-location measurements or by using the area/length (p = 0.004-0.006). Sub-regions were significantly different than all whole regions of interest (p = 0.001-0.012).

Eccentric Exercise as a Potent Prescription for Muscle Weakness After Joint Injury.

Lengthening contractions (i.e., eccentric contractions) are capable of uniquely triggering the nervous system and signaling pathways to promote tissue health/growth. This mode of exercise may be particularly potent for patients suffering from muscle weakness after joint injury. Here we provide a novel framework for eccentric exercise as a safe, effective mode of exercise prescription for muscle recovery.

Long-Lasting Impairments in Quadriceps Mitochondrial Health, Muscle Size, and Phenotypic Composition Are Present After Non-invasive Anterior Cruciate Ligament Injury.

INTRODUCTION: Despite rigorous rehabilitation aimed at restoring muscle health, anterior cruciate ligament (ACL) injury is often hallmarked by significant long-term quadriceps muscle weakness. Derangements in mitochondrial function are a common feature of various atrophying conditions, yet it is unclear to what extent mitochondria are involved in the detrimental sequela of quadriceps dysfunction after ACL injury. Using a preclinical, non-invasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on mitochondrial function, muscle atrophy, and muscle phenotypic transitions. METHODS: A total of 40 male and female, Long Evans rats (16-week-old) were exposed to non-invasive ACL injury, while 8 additional rats served as controls. Rats were euthanized at 3, 7, 14, 28, and 56 days after ACL injury, and vastus lateralis muscles were extracted to measure the mitochondrial respiratory control ratio (RCR; state 3 respiration/state 4 respiration), mitochondrial reactive oxygen species (ROS) production, fiber cross sectional area (CSA), and fiber phenotyping. Alterations in mitochondrial function and ROS production were detected using two-way (sex:group) analyses of variance. To determine if mitochondrial characteristics were related to fiber atrophy, individual linear mixed effect models were run by sex. RESULTS: Mitochondria-derived ROS increased from days 7 to 56 after ACL injury (30-100%, P < 0.05), concomitant with a twofold reduction in RCR (P < 0.05). Post-injury, male rats displayed decreases in fiber CSA (days 7, 14, 56; P < 0.05), loss of IIa fibers (day 7; P < 0.05), and an increase in IIb fibers (day 7; P < 0.05), while females displayed no changes in CSA or phenotyping (P > 0.05). Males displayed a positive relationship between state 3 respiration and CSA at days 14 and 56 (P < 0.05), while females only displayed a similar trend at day 14 (P = 0.05). CONCLUSION: Long-lasting impairments in quadriceps mitochondrial health are present after ACL injury and play a key role in the dysregulation of quadriceps muscle size and composition. Our preclinical data indicate that using mitoprotective therapies may be a potential therapeutic strategy to mitigate alterations in muscle size and characteristic after ACL injury.

Relationship between altered knee kinematics and subchondral bone remodeling in a clinically translational model of ACL injury.

Abnormal joint kinematics are commonly reported in the acute and chronic stages of recovery after anterior cruciate ligament (ACL) injury and have long been mechanistically implicated as a primary driver in the development of posttraumatic osteoarthritis (PTOA). Though strongly theorized, it is unclear to what extent biomechanical adaptations after ACL injury culminate in the development of PTOA, as data that directly connects these factors does not exist. Using a preclinical, noninvasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on joint kinematics and the pathogenetic mechanisms involved in the development of PTOA. A total of 32, 16-week-old Long-Evans rats were exposed to a noninvasive ACL injury. Marker-less deep learning software (DeepLabCut) was used to track animal movement for sagittal-plane kinematic analyses and micro computed tomography was used to evaluate subchondral bone architecture at days 7, 14, 28, and 56 following injury. There was a significant decrease in peak knee flexion during walking (p < .05), which had a moderate-to-strong negative correlation (r = -.59 to -.71; p < .001) with subchondral bone plate porosity in all load bearing regions of the femur and tibia. Additional comprehensive analyses of knee flexion profiles revealed dramatic alterations throughout the step cycle. This occurred alongside considerable loss of epiphyseal trabecular bone and substantial changes in anatomical orientation. Knee flexion angle and subchondral bone microarchitecture are severely impacted after ACL injury. Reductions in peak knee flexion angle after ACL injury are directly associated with subchondral bone plate remodeling.

Temporal disruption of neuromuscular communication and muscle atrophy following noninvasive ACL injury in rats.

Many patients with anterior cruciate ligament (ACL) injuries have persistent quadriceps muscle atrophy, even after considerable time in rehabilitation. Understanding the factors that regulate muscle mass, and the time course of atrophic events, is important for identifying therapeutic interventions. With a noninvasive animal model of ACL injury, a longitudinal study was performed to elucidate key parameters underlying quadriceps muscle atrophy. Male Long-Evans rats were euthanized at 6, 12, 24, or 48 h or 1, 2, or 4 wk after ACL injury that was induced via tibial compression overload; controls were not injured. Vastus lateralis muscle size was determined by wet weight and fiber cross-sectional area (CSA). Evidence of disrupted neuromuscular communication was assessed via the expression of neural cell adhesion molecule (NCAM) and genes associated with denervation and neuromuscular junction instability. Abundance of muscle RING-finger protein-1 (MuRF-1), muscle atrophy F-box (MAFbx), and 45 s pre-rRNA along with 20S proteasome activity were determined to investigate mechanisms related to muscle atrophy. Finally, muscle damage-related parameters were assessed by measuring IgG permeability, centronucleation, CD68 mRNA, and satellite cell abundance. When compared with controls, we observed a greater percentage of NCAM-positive fibers at 6 h postinjury, followed by higher MAFbx abundance 48 h postinjury, and higher 20S proteasome activity at 1 wk postinjury. A loss of muscle wet weight, smaller fiber CSA, and the elevated expression of run-related transcription factor 1 (Runx1) were also observed at the 1 wk postinjury timepoint relative to controls. There also were no differences observed in any damage markers. These results indicate that alterations in neuromuscular communication precede the upregulation of atrophic factors that regulate quadriceps muscle mass early after noninvasive ACL injury.NEW & NOTEWORTHY A novel preclinical model of ACL injury was used to establish that acute disruptions in neuromuscular communication precede atrophic events. These data help to establish the time course of muscle atrophy after ACL injury, suggesting that clinical care may benefit from the application of acute neurogenic interventions and early gait reloading strategies.

Mechanisms of Arthrogenic Muscle Inhibition.

CONTEXT: Arthrogenic muscle inhibition (AMI) continues to be a limiting factor in joint rehabilitation as the inability to volitionally activate muscle significantly dampens recovery. New evidence acquired at higher brain centers and in clinical populations continues to reshape our perspective of what AMI is and how to treat it. This review aims to stimulate discussion about the far-reaching effects of AMI by exploring the interconnected pathways by which it evolves. OBJECTIVES: To discuss how reflexive inhibition can lead to adaptations in brain activity, to illustrate how changes in descending motor pathways limit our ability to contract muscle following injury, and to summarize the emerging literature on the wide-reaching effects of AMI on other interconnected systems. DATA SOURCES: The databases PubMed, SPORTDiscus, and Web of Science were searched for articles pertaining to AMI. Reference lists from appropriate articles were cross-referenced. CONCLUSION: AMI is a sequential and cumulative neurological process that leads to complex clinical impairments. Originating with altered afferent information arising from an injured joint, patients experience changes in afferent information, reflexive muscle inhibition, deficiencies in somatosensation, neuroplastic compensations in higher brain centers, and ultimately decreased motor output to the muscle surrounding the joint. Other aspects of clinical function, like muscle structure and psychological responses to injury, are also impaired and influenced by AMI. Removing, or reducing, AMI should continue to be a focus of rehabilitation programs to assist in the optimization of health after joint injury.

Suppressed quadriceps fascicle behavior is present in the surgical limbs of those with a history of ACL reconstruction.

The balance of published data have largely focused on adaptations in muscle and fiber size after anterior cruciate ligament reconstruction (ACLR), failing to account for the dynamic changes in the behavior of the muscles' contractile elements that strongly contribute to force production. To better understand the sources of quadriceps dysfunction, the purpose of our research was to determine if alterations in fascicle behavior are present after ACLR. Unilateral ACLR individuals (9 m/9f; 21 ± 3 yrs; 1.74 ± 0.12 m;71.58 ± 13.31 kg; months from surgery:38 ± 36) and healthy controls (3 m/6f; 23 ± 2 yrs; 1.67 ± 0.10 m; 63.51 ± 10.11 kg) participated. In-vivo vastus lateralis fascicle behavior was recorded using ultrasonography during three maximal isokinetic knee extensions (60°·s-1). Fascicle length, angle, and shortening velocity were calculated and analyzed from rest to peak torque. Peak knee extension torque was averaged between isokinetic trials (Nm·kg-1). Group by limb interactions were assessed using separate two-way analyses of variance and were further evaluated by comparing 95% confidence intervals where appropriate. Significant interactions were present for fascicle angle at peak torque (P = 0.01), fascicle length excursion (P = 0.05), fascicle angle excursion (P < 0.01), fascicle shortening velocity (P = 0.05) and strength (P = 0.03). Upon post-hoc evaluation, the surgical limb displayed altered in-vivo fascicle behavior compared to all limbs (P < 0.05) and reduced strength compared to the contralateral and right control limbs (P < 0.05). No other significant interactions were present (P > 0.05). Our data show that those with a history of ACLR have fascicles that are slower, lengthen less and operate with lower angles relative to the axis of force production. Altered fascicle behavior after ACLR may be an important underlying factor to explaining the protracted quadriceps dysfunction.

Factors Associated With Noncontact Injury in Collegiate Soccer: A 12-Team Prospective Study of NCAA Division I Men's and Women's Soccer.

BACKGROUND: Multiteam, multi-institution prospective studies of both women's and men's sports are essential for collectively investigating injury and primary to the generalization and individualization of injury prevention strategies. HYPOTHESIS: Characteristics of workload, sleep, and contextual factors will be associated with injury risk in collegiate soccer athletes. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Injuries, workload, and sleep characteristics were recorded daily throughout a complete season for 256 athletes from 12 separate National Collegiate Athletic Association Division I men's and women's soccer teams. Workload and contextual factors were assessed via multilevel Poisson regression to capture differences in injury incidence rate ratio (IRR). Paired t test and multilevel logistic regressions were used to assess the relationship between sleep behavior and injury. RESULTS: Collegiate soccer athletes had lower rates of noncontact injury in the in-season (IRR, 0.42) and postseason (IRR, 0.48) compared with preseason, lower rates of injury in training (IRR, 0.64) compared with matches, and higher injury rates with only 1 day of rest in the previous week (IRR, 1.58) compared with >1 day. Injury rates peaked when training occurred 4 days before a match (IRR, 2.24) compared with a match. Injury rate increased exponentially with increases in the number of noncontact injuries incurred throughout the season (IRR, 2.23). Lower chronic loading, higher training monotony, and acute spikes and lulls in workload were associated with higher noncontact injury rates. Alterations in previous week sleep quality were associated with injury, while chronic sleep behavior and acute alterations (<7 days) in sleep behavior were not (P > .05). CONCLUSION: Athlete and schedule-specific contextual factors, combined with characteristics of workload and weekly sleep behavior, are significantly associated with injury in collegiate soccer. Multiteam prospective cohort studies involving objective and subjective monitoring allow for the identification of multiple injury risk factors in sports, which can be used to guide injury prevention strategies. Maintaining higher chronic workloads, lowering training monotony, minimizing acute spikes or lulls in workloads, managing workloads during preseason and for athletes with previous injury, integrating more rest and recovery during congested periods, and optimizing sleep quality are all practical considerations for reducing injury risk in collegiate soccer.

The Utility of Functional Data Analyses to Reveal Between-Limbs Asymmetries in Those With a History of Anterior Cruciate Ligament Reconstruction.

CONTEXT: Researchers have traditionally used motion capture to quantify discrete data points (peak values) during hop testing. However, these analyses restrict the evaluation to a single time point (ie, certain percentage of stance) and provide only a narrow view of movement. Applying more comprehensive analyses may help investigators identify important characteristics that are masked by discrete analyses often used to screen patients for activity. OBJECTIVE: To examine the utility of functional data analyses to reveal asymmetries that are undetectable using discrete (ie, single time point) evaluations in participants with a history of anterior cruciate ligament reconstruction (ACLR) who achieved clinical hop symmetry. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Fifteen participants with unilateral ACLR (age = 21 ± 3 years, time from surgery = 4 ± 3 years) and 15 control participants without ACLR (age = 23 ± 2 years). INTERVENTION(S): Lower extremity biomechanics during the triple-hop-for-distance task for the ACLR and contralateral limbs of patients and a representative limb of control participants were measured. MAIN OUTCOME MEASURE(S): Peak sagittal-plane joint power, joint work, and power profiles were determined. RESULTS: Using discrete analyses, we identified lower peak knee power and work in the ACLR limb compared with the contralateral and control limbs (P < .05) but were unable to demonstrate differences at the ankle or hip. Using functional data analyses, we observed asymmetries at the ankle, knee, and hip between the ACLR and contralateral or control limbs throughout stance (P < .05), and it was revealed that these asymmetries stemmed from knee power deficits that were prominent during early loading. CONCLUSIONS: Despite achieving hop-distance symmetry, the ACLR knees absorbed less power. Although this information was revealed using discrete analyses, underlying asymmetries at the ankle and hip were masked. Using functional data analyses, we found interlimb asymmetries at the ankle, knee, and hip. Importantly, we found that functional data analyses more fully elucidated the extent and source of asymmetries, which can be used by clinicians and researchers alike to aid in clinical decision making.

Alterations in Quadriceps Neurologic Complexity After Anterior Cruciate Ligament Reconstruction.

CONTEXT: Traditionally, quadriceps activation failure after anterior cruciate ligament reconstruction (ACLR) is estimated using discrete isometric torque values, providing only a snapshot of neuromuscular function. Sample entropy (SampEn) is a mathematical technique that can measure neurologic complexity during the entirety of contraction, elucidating qualities of neuromuscular control not previously captured. OBJECTIVE: To apply SampEn analyses to quadriceps electromyographic activity in order to more comprehensively characterize neuromuscular deficits after ACLR. DESIGN: Cross-sectional. SETTING: Laboratory. PARTICIPANTS: ACLR: n = 18; controls: n = 24. INTERVENTIONS: All participants underwent synchronized unilateral quadriceps isometric strength, activation, and electromyography testing during a superimposed electrical stimulus. MAIN OUTCOME MEASURES: Group differences in strength, activation, and SampEn were evaluated with t tests. Associations between SampEn and quadriceps function were evaluated with Pearson product-moment correlations and hierarchical linear regressions. RESULTS: Vastus medialis SampEn was significantly reduced after ACLR compared with controls (P = .032). Vastus medialis and vastus lateralis SampEn predicted significant variance in activation after ACLR (r2 = .444; P = .003). CONCLUSIONS: Loss of neurologic complexity correlates with worse activation after ACLR, particularly in the vastus medialis. Electromyographic SampEn is capable of detecting underlying patterns of variability that are associated with the loss of complexity between key neurophysiologic events after ACLR.

Muscle Atrophy After ACL Injury: Implications for Clinical Practice.

CONTEXT: Distinct from the muscle atrophy that develops from inactivity or disuse, atrophy that occurs after traumatic joint injury continues despite the patient being actively engaged in exercise. Recognizing the multitude of factors and cascade of events that are present and negatively influence the regulation of muscle mass after traumatic joint injury will likely enable clinicians to design more effective treatment strategies. To provide sports medicine practitioners with the best strategies to optimize muscle mass, the purpose of this clinical review is to discuss the predominant mechanisms that control muscle atrophy for disuse and posttraumatic scenarios, and to highlight how they differ. EVIDENCE ACQUISITION: Articles that reported on disuse atrophy and muscle atrophy after traumatic joint injury were collected from peer-reviewed sources available on PubMed (2000 through December 2019). Search terms included the following: disuse muscle atrophy OR disuse muscle mass OR anterior cruciate ligament OR ACL AND mechanism OR muscle loss OR atrophy OR neurological disruption OR rehabilitation OR exercise. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 5. RESULTS: We highlight that (1) muscle atrophy after traumatic joint injury is due to a broad range of atrophy-inducing factors that are resistant to standard resistance exercises and need to be effectively targeted with treatments and (2) neurological disruptions after traumatic joint injury uncouple the nervous system from muscle tissue, contributing to a more complex manifestation of muscle loss as well as degraded tissue quality. CONCLUSION: Atrophy occurring after traumatic joint injury is distinctly different from the muscle atrophy that develops from disuse and is likely due to the broad range of atrophy-inducing factors that are present after injury. Clinicians must challenge the standard prescriptive approach to combating muscle atrophy from simply prescribing physical activity to targeting the neurophysiological origins of muscle atrophy after traumatic joint injury.

Michigan Initiative for Anterior Cruciate Ligament Rehabilitation (MiACLR): A Protocol for a Randomized Clinical Trial.

OBJECTIVE: Restoring quadriceps muscle strength following anterior cruciate ligament reconstruction (ACLR) may prevent the posttraumatic osteoarthritis that affects over 50% of knees with ACLR. However, a fundamental gap exists in our understanding of how to maximize muscle strength through rehabilitation. Neurological deficits and muscle atrophy are 2 of the leading mechanisms of muscle weakness after ACLR. High-intensity neuromuscular electrical stimulation (NMES) and eccentric exercise (ECC) have been shown to independently target these mechanisms. If delivered in succession, NMES and then ECC may be able to significantly improve strength recovery. The objectives of this study were to evaluate the ability of NMES combined with ECC to restore quadriceps strength and biomechanical symmetry and maintain cartilage health at 9 and 18 months after ACLR. METHODS: This study is a randomized, double-blind, placebo-controlled, single-center clinical trial conducted at the University of Michigan. A total of 112 participants between the ages of 14 and 45 years and with an anterior cruciate ligament rupture will be included. Participants will be randomly assigned 1:1 to NMES combined with ECC or NMES placebo combined with ECC placebo. NMES or NMES placebo will be delivered 2 times per week for 8 weeks beginning 10 to 14 days postoperatively and will be directly followed by 8 weeks of ECC or ECC placebo delivered 2 times per week. The co-primary endpoints are change from baseline to 9 months and change from baseline to 18 months after ACLR in isokinetic quadriceps strength symmetry. Secondary outcome measures include isometric quadriceps strength, quadriceps activation, quadriceps muscle morphology (cross-sectional area), knee biomechanics (sagittal plane knee angles and moments), indexes of patient-reported function, and cartilage health (T1ρ and T2 relaxation time mapping on magnetic resonance imaging). IMPACT: The findings from this study might identify an intervention capable of targeting the lingering quadriceps weakness after ACLR and in turn prevent deterioration in cartilage health after ACLR, thereby potentially improving function in this patient population.

What Are Our Patients Really Telling Us? Psychological Constructs Associated With Patient-Reported Outcomes After Anterior Cruciate Ligament Reconstruction.

CONTEXT: Depressed patient-reported outcomes (PROs) are directly related to suboptimal recovery after anterior cruciate ligament reconstruction (ACLR). Various PROs commonly used after ACLR can provide a gross estimation of function but do not fully elucidate the causes of self-perceived disability. OBJECTIVE: To more fully characterize the factors driving responses on PROs. DESIGN: Cross-sectional study. A mixed-methods approach was used, in which qualitative interviews were conducted alongside administration of PROs to uncover the themes behind a participant's PRO responses. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-one individuals with unilateral ACLR (age = 20.90 ± 2.86 years, height = 172.0 ± 11.03 cm; mass = 71.52 ± 13.59 kg, postsurgery = 3.66 ± 3.03 years). MAIN OUTCOME MEASURE(S): Patient-reported outcome measures were administered and qualitative interviews were conducted. The PROs consisted of the International Knee Documentation Committee form, Knee Injury and Osteoarthritis Outcomes Score (KOOS), ACL-Return to Sport after Injury (ACL-RSI) scale, and Tampa Scale of Kinesiophobia (TSK). A hierarchical cluster analysis was used to identify subgroups based on PRO responses. Qualitative interviews provided supplemental insight into perceived disability. Independent t tests examined cluster differences for themes. Spearman ρ correlations indicated associations between PRO responses and themes. RESULTS: Two clusters (perceived high or low disability) emerged. Individuals with low perceived disability scored better on all PROs (P < .05) except for the KOOS-Activities of Daily Living. Internal and external facilitators or barrier subthemes emerged from the interviews. A significant difference was present between clusters and themes. Lower TSK andgreater ACL-RSI and KOOS-Quality of Life scores were associated with more perceived facilitators. CONCLUSIONS: Participants with greater internal motivation and confidence and a support network had improved PROs. Those with avoidance tendencies, fear, lack of clear expectations, and less social support scored worse on PROs. The TSK, ACL-RSI, and KOOS-Quality of Life scales were best able to capture the constructs associated with perceived wellness, which reinforces their utility in recovery.

Quadriceps Inhibition After Naturally Occurring Patellar Tendon Damage and Pain.

CONTEXT: After knee-joint injury, pain, effusion, and mechanoreceptor damage alter afferent signaling, which can result in quadriceps inhibition and subsequent weakness. The individual contributions of each factor to inhibition remain unclear due to confounding knee-joint injuries and indirect experimental models. OBJECTIVE: To characterize the influence of naturally occurring knee damage and pain on quadriceps neuromuscular function in individuals with patellar tendinopathy. DESIGN: Cross-sectional study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty participants who self-reported patellar tendinopathy (PT) and 10 healthy control individuals underwent ultrasonic tendon assessment. Injured participants were dichotomized by an orthopaedic surgeon into groups with (1) pain and structural tendon abnormality and (2) regional pain alone. MAIN OUTCOME MEASURE(S): Quadriceps inhibition was assessed with the Hoffman reflex and the central activation ratio via the superimposed-burst technique. Normally distributed measures were analyzed using a 1-way analysis of variance and post hoc independent t tests. Kruskal-Wallis tests with post hoc Mann-Whitney U tests were used to analyze nonnormally distributed data. An a priori α level of P ≤ .05 was set. RESULTS: Control participants presented with more spinal-reflex excitability (0.37 ± 0.23) than the PT (0.10 ± 0.06; P = .03) and regional-pain (0.18 ± 0.05; P = .02) groups. Knee-extension strength was greater in the control (3.37 ± 0.59 Nm/kg) than in the PT (2.41 ± 0.67 Nm/kg; P = .01) group but not the regional-pain group (3.05 ± 0.66 Nm/kg; P = .24). Control individuals presented with more quadriceps activation (97.93% ± 3.12) than the PT (84.44% ± 16.98; P < .01) and regional-pain (91.17% ± 10.56; P = .01) groups. No differences were present for any measures between the PT and regional-pain groups (P values > .05). CONCLUSIONS: Deficits in spinal-reflex excitability, quadriceps activation, and strength were present in both the PT and regional-pain groups. A combination of pain and structural damage appeared to have the greatest negative effect on quadriceps function, as only the PT group presented with neuromuscular outcomes that failed to meet clinical thresholds.

Morphology and Anabolic Response of Skeletal Muscles Subjected to Eccentrically or Concentrically Biased Exercise.

CONTEXT: Long-term eccentric exercise is known to promote muscle growth better than concentric exercise, but its acute effect on muscle is not well understood because of misinterpreted modeling and in situ and in vitro stretch protocols. Knowing if the initial bout of eccentric exercise promotes muscle growth and limits damage is critical to understanding the effect of this mode of exercise. OBJECTIVE: To directly evaluate the immediate effects of eccentric and concentric exercises on untrained muscle when fiber strains were physiological and exercise doses were comparable. DESIGN: Controlled laboratory study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 40 skeletally mature male Long-Evans rats (age = 16 weeks, mass = 452.1 ± 35.2 g) were randomly assigned to an eccentric exercise (downhill walking, n = 16), concentric exercise (uphill walking, n = 16), or control (no exercise, n = 8) group. INTERVENTION(S): Rats were exposed to a single 15-minute bout of eccentric or concentric exercise on a motorized treadmill and then were euthanized at 6 or 24 hours postexercise. We harvested the vastus lateralis muscle bilaterally. MAIN OUTCOME MEASURE(S): The percentage increase or decrease in protein abundance in exercised animals relative to that in unexercised control animals was evaluated as elevated phosphorylated p70S6k relative to total p70S6k. Fiber damage was quantified using immunoglobulin G permeability staining. One-way analysis of variance and post hoc Tukey tests were performed. RESULTS: Rats exposed to eccentric exercise and euthanized at 24 hours had higher percentage response protein synthesis rates than rats exposed to eccentric exercise and euthanized at 6 hours (P = .02) or to concentric exercise and euthanized at 6 (P = .03) or 24 (P = .03) hours. We assessed 9446 fibers for damage and found only 1 fiber was infiltrated (in the concentric exercise group euthanized at 6 hours). Furthermore, no between-groups differences in immunoglobulin G fluorescent intensity were detected (P = .94). CONCLUSIONS: Incorporating eccentric exercise is a simple, universally available therapeutic intervention for promoting muscle recovery. A single 15-minute dose of eccentric exercise to a novice muscle can better exert an anabolic effect than a comparable dose of concentric exercise, with very limited evidence of fiber damage.