Tibial and femoral articular cartilage exhibit opposite outcomes for T1ρ and T2* relaxation times in response to acute compressive loading in healthy knees.

Abnormal loading is thought to play a key role in the disease progression of cartilage, but our understanding of how cartilage compositional measurements respond to acute compressive loading in-vivo is limited. Ten healthy subjects were scanned at two timepoints (7 ± 3 days apart) with a 3 T magnetic resonance imaging (MRI) scanner. Scanning sessions included T1ρ and T2* acquisitions of each knee in two conditions: unloaded (traditional MRI setup) and loaded in compression at 40 % bodyweight as applied by an MRI-compatible loading device. T1ρ and T2* parameters were quantified for contacting cartilage (tibial and femoral) and non-contacting cartilage (posterior femoral condyle) regions. Significant effects of load were found in contacting regions for both T1ρ and T2*. The effect of load (loaded minus unloaded) in femoral contacting regions ranged from 4.1 to 6.9 ms for T1ρ, and 3.5 to 13.7 ms for T2*, whereas tibial contacting regions ranged from -5.6 to -1.7 ms for T1ρ, and -2.1 to 0.7 ms for T2*. Notably, the responses to load in the femoral and tibial cartilage revealed opposite effects. No significant differences were found in response to load between the two visits. This is the first study that analyzed the effects of acute loading on T1ρ and T2* measurements in human femoral and tibial cartilage separately. The results suggest the effect of acute compressive loading on T1ρ and T2* was: 1) opposite in the femoral and tibial cartilage; 2) larger in contacting regions than in non-contacting regions of the femoral cartilage; and 3) not different visit-to-visit.

Risk Factors for Concomitant Meniscal Injury With Sport-Related Anterior Cruciate Ligament Injury.

Background: Previous studies of concomitant meniscal injury in athletes with anterior cruciate ligament (ACL) injury have examined age, sex, body mass index (BMI), injury mechanism, and time from injury to surgery as potential risk factors. Purpose: To identify additional risk factors for concomitant meniscal injury, including preinjury joint laxity and lower extremity alignment, in athletes with sport-related ACL injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: This study included 180 participants aged 13 to 26 years who underwent ACL reconstruction (ACLR) after a first-time ACL injury sustained during participation in sport. Contralateral lower extremity alignment and joint laxity were used as surrogate measures for the injured knee before trauma. Concomitant meniscal tear patterns were identified at the time of ACLR. Sex-specific analyses were conducted. Results: Concomitant meniscal injury was observed in 60.6% of the subjects. The prevalence of concomitant injury was higher in male than female participants (69.9% vs 54.2%; P = .035) due to a higher prevalence of lateral meniscal injuries (56.2% vs 38.3%; P = .018). Among male patients, there was a significant difference in the prevalence of concomitant lateral meniscal tear according to sport participation (≥9 vs <9 h/week: 67.4% vs 35.7%; P = .032). Among male patients, the likelihood of concomitant injury to both the lateral and medial menisci increased by 28.8% for each 1-mm decrease in navicular drop. Among female patients, the likelihood of concomitant injury to the lateral meniscus increased by 15% per degree increase in genu recurvatum and 14% per degree decrease in standing quadriceps angle, with similar effects on the likelihood of concurrent injury to both the lateral and medial menisci. Conclusion: Measures of lower extremity alignment and genu recurvatum previously identified as risk factors for ACL injury were also associated with concomitant meniscal injury in female patients while other risk factors, including BMI and joint laxity, were not. Increased time spent participating in sport and navicular drop were associated with concomitant meniscal injury in male patients.

Intrinsic Risk Factors for First-Time Noncontact ACL Injury: A Prospective Study of College and High School Athletes.

BACKGROUND: A comprehensive understanding of the intrinsic risk factors for anterior cruciate ligament (ACL) disruption is important for identifying individuals at increased risk for suffering this trauma and developing interventions to mitigate risk. HYPOTHESIS: A variety of risk factors predispose athletes to first-time, noncontact ACL injury and some of these differ between male and female athletes. STUDY DESIGN: Prospective cohort study with nested case-control sampling. LEVEL OF EVIDENCE: Level 2. METHODS: Sport teams at 28 high schools and 8 colleges were monitored prospectively over 4 years, and 109 of 130 athletes who suffered their first noncontact ACL injury participated in the study. At the time of injury, matched control subjects were randomly selected from among the case's teammates and a total of 227 athletes participated. Demographic characteristics, joint laxity, lower extremity alignment, strength, and personality characteristics were measured. The association of each risk factor with injury risk was assessed by conditional logistic regression. RESULTS: The risk factors that were associated with ACL injury in both male and female athletes included having a parent with prior ACL injury and increases of the following variables: body weight, anterior displacement of the tibia relative to the femur, genu recurvatum, and generalized joint laxity. Risk factors that are unique to female athletes included increased body mass index, increased trunk flexion strength, and prior non-ACL knee injury. The risk factors specific to male athletes were decreased standing quadriceps angle, decreased hip adduction strength, and chronic disease. CONCLUSION: A diverse set of risk factors predispose both male and female athletes to ACL injury, whereas others appear to be sex-specific. CLINICAL RELEVANCE: Different approaches for assessing risk and preventing ACL injury are needed for male and female athletes. In addition, personalized prevention strategies may be needed to target the specific characteristics that place an individual at increased risk of suffering this trauma.

The Duration of Thigh Tourniquet Use Associated With Anterior Cruciate Ligament Reconstruction Does Not Produce Cellular-Level Contractile Dysfunction of the Quadriceps Muscle at 3 Weeks After Surgery.

BACKGROUND: Anterior cruciate ligament (ACL) trauma and ACL reconstruction (ACLR) are associated with the loss of strength and function of the muscles that span the knee joint. The underlying mechanism associated with this is not completely understood. PURPOSE: To determine whether the duration of tourniquet use during ACLR has an effect on knee extensor muscle contractile function and size at the cellular (ie, fiber) level 3 weeks after surgery and at the whole-muscle level at 6 months after surgery. STUDY DESIGN: Descriptive laboratory study and case series; Level of evidence, 4. METHODS: Study participants sustained an acute, first-time ACL injury. All participants underwent ACLR with the use of a tourniquet placed in a standardized location on the thigh; the tourniquet was inflated (pressure range, 250-275 mm Hg), and the time of tourniquet use during surgery was documented. Participants were evaluated 1 week before surgery (to measure patient function, strength, and subjective outcome with the Knee injury and Osteoarthritis Outcome Score [KOOS] and International Knee Documentation Committee [IKDC] score), at 3 weeks after ACLR surgery (to obtain muscle biopsy specimens of the vastus lateralis and assess muscle fiber cross-sectional area, contractile function, and mitochondrial content and morphometry), and at 6 months after ACLR (to evaluate patient function, strength, and subjective outcomes via KOOS and IKDC scores). Data were acquired on both the injured/surgical limb and the contralateral, normal side to facilitate the use of a within-subjects study design. Results are based on additional analysis of data acquired from previous research that had common entry criteria, treatments, and follow-up protocols. RESULTS: At 3 weeks after ACLR, the duration of tourniquet use at the time of surgery did not explain the variation in single-muscle fiber contractile function or cross-sectional area (myosin heavy chain [MHC] I and II fibers) or subsarcolemmal and intermyofibrillar mitochondrial content or morphometry. At 6 months after ACLR, the duration of tourniquet use was not associated with the peak isometric and isokinetic torque measurements, patient function, or patient-reported outcomes. CONCLUSION: The duration of tourniquet use at the time of ACLR surgery did not explain variation in muscle fiber size, contractile function, or mitochondrial content at 3 weeks after surgery or strength of the quadriceps musculature or patient-reported function or quality of life at 6-month follow-up.

Effects of total knee arthroplasty on skeletal muscle structure and function at the cellular, organellar, and molecular levels.

Total knee arthroplasty (TKA) is an important treatment option for knee osteoarthritis (OA) that improves self-reported pain and physical function, but objectively measured physical function typically remains reduced for years after surgery due, in part, to precipitous reductions in lower extremity neuromuscular function early after surgery. The present study examined intrinsic skeletal muscle adaptations during the first 5 weeks post-TKA to identify skeletal muscle attributes that may contribute to functional disability. Patients with advanced stage knee OA were evaluated prior to TKA and 5 weeks after surgery. Biopsies of the vastus lateralis were performed to assess muscle fiber size, contractility, and mitochondrial content, along with assessments of whole muscle size and function. TKA was accompanied by marked reductions in whole muscle size and strength. At the fiber (i.e., cellular) level, TKA caused profound muscle atrophy that was approximately twofold higher than that observed at the whole muscle level. TKA markedly reduced muscle fiber force production, contractile velocity, and power production, with force deficits persisting in myosin heavy chain (MHC) II fibers after expression relative to fiber size. Molecular level assessments suggest reduced strongly bound myosin-actin cross bridges and myofilament lattice stiffness as a mechanism underlying reduced force per unit fiber size. Finally, marked reductions in mitochondrial content were apparent and more prominent in the subsarcolemmal compartment. Our study represents the most comprehensive evaluation of skeletal muscle cellular adaptations to TKA and uncovers novel effects of TKA on muscle fiber size and intrinsic contractility early after surgery that may contribute to functional disability.NEW & NOTEWORTHY We report the first evaluation of the effects of total knee arthroplasty (TKA) on skeletal muscle at the cellular and subcellular levels. We found marked effects of TKA to cause skeletal muscle fiber atrophy and contractile dysfunction in older adults, as well as molecular mechanisms underlying impaired contractility. Our results reveal profound effects of TKA on muscle fiber size and intrinsic contractility early after surgery that may contribute to functional disability.

Articular cartilage thickness changes differ between males and females 4 years following anterior cruciate ligament reconstruction.

Anterior cruciate ligament injury and reconstruction (ACLR) affects articular cartilage thickness profiles about the tibial, femoral, and patellar surfaces; however, it's unclear whether the magnitudes of change in cartilage thickness, as well as the locations and areas over which these changes occur, differ between males and females. This is important to consider as differences exist between the sexes with regard to knee biomechanics, patellofemoral pain, and anatomic alignment, which influence risk of an index and repeated injury. Subjects underwent ACLR with a bone-patella tendon-bone autograft. At 4-year follow-up, they had asymptomatic knees; however, significant ACL injured-to-contralateral normal knee differences in articular cartilage thickness values were observed. Both thickening and thinning of cartilage occurred about the tibiofemoral and patellofemoral joints, relative to matched control subjects with normal knees. Further, the location of the areas and magnitudes of thickening and thinning were different between females and males. Thickening (swelling) of articular cartilage is an early finding associated with the onset of posttraumatic osteoarthritis (PTOA). Therefore, the increases in cartilage thickness that were observed in this cohort may represent early signs of the onset of PTOA that occur prior to the patient developing symptoms and radiographic evidence of this disease. The different locations of areas that underwent a change in cartilage thicknesses between males and females suggest that each sex responds differently to knee ligament trauma, reconstruction, rehabilitation, and return to activity, and indicates that sex-specific analysis should be utilized in studies of PTOA.

Skeletal muscle cellular contractile dysfunction after anterior cruciate ligament reconstruction contributes to quadriceps weakness at 6-month follow-up.

Muscle dysfunction following anterior cruciate ligament reconstruction (ACLR) may evolve from alterations in muscle contractility at the myofilament protein level. Using a prospective, within-subject case-control design, we evaluated cellular-level contractility, cross-sectional area (CSA), and myosin heavy chain (MHC) isoform expression on single muscle fibers 3 weeks post ACLR, and evaluated their relationship to whole muscle strength and patient-oriented outcomes 6 months post operation. Biopsies of the vastus lateralis were performed 3 weeks post ACLR in 11 subjects (5 females, mean age ± SD = 24.7 ± 6.5 years, height = 172.7 ± 8.2 cm, mass = 75.7 ± 12.5 kg) following first-time ACL rupture and whole muscle strength and self-reported pain, function, and quality of life assessed 6 months post ACLR. At 3 weeks post ACLR, force production was reduced (p < 0.01) in MHC I (-36%) and IIA (-48%) fibers compared with the non-injured leg. When force production was expressed relative to CSA to account for fiber atrophy, reductions remained in MHC IIA fibers (-40%; p < 0.001), but MHC I fibers showed only a trend toward being lower (-13%; p = 0.09). Finally, skeletal muscle fiber functional deficits at 3 weeks post ACLR were associated with whole muscle weakness and less favorable patient-reported outcomes at 6-month follow-up. Thus, ACLR promotes early cellular contractile dysfunction that may contribute to decreased whole muscle strength and patient function, and increased patient-reported symptoms, at 6-month follow-up.

Utility of Neuromuscular Electrical Stimulation to Preserve Quadriceps Muscle Fiber Size and Contractility After Anterior Cruciate Ligament Injuries and Reconstruction: A Randomized, Sham-Controlled, Blinded Trial.

BACKGROUND: Anterior cruciate ligament (ACL) injuries and reconstruction (ACLR) promote quadriceps muscle atrophy and weakness that can persist for years, suggesting the need for more effective rehabilitation programs. Whether neuromuscular electrical stimulation (NMES) can be used to prevent maladaptations in skeletal muscle size and function is unclear. PURPOSE: To examine whether early NMES use, started soon after an injury and maintained through 3 weeks after surgery, can preserve quadriceps muscle size and contractile function at the cellular (ie, fiber) level in the injured versus noninjured leg of patients undergoing ACLR. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients (n = 25; 12 men/13 women) with an acute, first-time ACL rupture were randomized to NMES (5 d/wk) or sham (simulated microcurrent electrical nerve stimulation; 5 d/wk) treatment to the quadriceps muscles of their injured leg. Bilateral biopsies of the vastus lateralis were performed 3 weeks after surgery to measure skeletal muscle fiber size and contractility. Quadriceps muscle size and strength were assessed 6 months after surgery. RESULTS: A total of 21 patients (9 men/12 women) completed the trial. ACLR reduced single muscle fiber size and contractility across all fiber types (P < .01 to P < .001) in the injured compared with noninjured leg 3 weeks after surgery. NMES reduced muscle fiber atrophy (P < .01) through effects on fast-twitch myosin heavy chain (MHC) II fibers (P < .01 to P < .001). NMES preserved contractility in slow-twitch MHC I fibers (P < .01 to P < .001), increasing maximal contractile velocity (P < .01) and preserving power output (P < .01), but not in MHC II fibers. Differences in whole muscle strength between groups were not discerned 6 months after surgery. CONCLUSION: Early NMES use reduced skeletal muscle fiber atrophy in MHC II fibers and preserved contractility in MHC I fibers. These results provide seminal, cellular-level data demonstrating the utility of the early use of NMES to beneficially modify skeletal muscle maladaptations to ACLR. CLINICAL RELEVANCE: Our results provide the first comprehensive, cellular-level evidence to show that the early use of NMES mitigates early skeletal muscle maladaptations to ACLR. REGISTRATION: NCT02945553 (ClinicalTrials.gov identifier).

Effect of neuromuscular electrical stimulation on skeletal muscle size and function in patients with breast cancer receiving chemotherapy.

Exercise has numerous benefits for patients with cancer, but implementation is challenging because of practical and logistical hurdles. This study examined whether neuromuscular electrical stimulation (NMES) can serve as a surrogate for classic exercise by eliciting an exercise training response in skeletal muscle of women diagnosed with breast cancer undergoing chemotherapy. Patients (n = 22) with histologically confirmed stage I, II, or III breast cancer scheduled to receive neoadjuvant or adjuvant chemotherapy were randomized to 8 wk of bilateral neuromuscular electrical stimulation (NMES; 5 days/wk) to their quadriceps muscles or control. Biopsy of the vastus lateralis was performed at baseline and after 8 wk of intervention to assess muscle fiber size, contractility, and mitochondrial content. Seventeen patients (8 control/9 NMES) completed the trial and were included in analyses. NMES promoted muscle fiber hypertrophy (P < 0.001), particularly in fast-twitch, myosin heavy chain (MHC) IIA fibers (P < 0.05) and tended to induce fiber type shifts in MHC II fibers. The effects of NMES on single-muscle fiber contractility were modest, and it was unable to prevent declines in the function in MHC IIA fibers. NMES did not alter intermyofibrillar mitochondrial content/structure but was associated with reductions in subsarcolemmal mitochondria. Our results demonstrate that NMES induces muscle fiber hypertrophy and fiber type shifts in MHC II fibers but had minimal effects on fiber contractility and promoted reductions in subsarcolemmal mitochondria. Further studies are warranted to evaluate the utility of NMES as an exercise surrogate in cancer patients and other conditions.NEW & NOTEWORTHY This is the first study to evaluate whether neuromuscular electrical stimulation (NMES) can be used as an exercise surrogate to improve skeletal muscle fiber size or function in cancer patients receiving treatment. We show that NMES promoted muscle fiber hypertrophy and fiber type shifts but had minimal effects on single-fiber contractility and reduced subsarcolemmal mitochondria.

A Cyber-Physical System for Near Real-Time Monitoring of At-Home Orthopedic Rehabilitation and Mobile-Based Provider-Patient Communications to Improve Adherence: Development and Formative Evaluation.

BACKGROUND: Knee extensor muscle performance is reduced after lower extremity trauma and orthopedic surgical interventions. At-home use of neuromuscular electrical stimulation (NMES) may improve functional recovery, but adherence to at-home interventions is low. Greater benefits from NMES may be realized with closer monitoring of adherence to at-home prescriptions and more frequent patient-provider interactions. OBJECTIVE: This study aimed to develop a cyber-physical system to monitor at-home adherence to NMES prescription and facilitate patient-provider communications to improve adherence in near real time. METHODS: The RehabTracker cyber-physical system was developed to accomplish this goal and comprises four components: (1) hardware modifications to a commercially available NMES therapy device to monitor device use and provide Bluetooth functionality; (2) an iPhone Operating System-based mobile health (mHealth) app that enables patient-provider communications in near real time; (3) a clinician portal to allow oversight of patient adherence with device use; and (4) a back-end server to store data, enable adherence analysis, and send automated push notifications to the patient. These four elements were designed to be fully compliant with the Health Insurance Portability and Accountability Act. The system underwent formative testing in a cohort of patients following anterior cruciate ligament rupture (n=7) to begin to assess face validity. RESULTS: Compared with the NMES device software-tracked device use, the RehabTracker system recorded 83% (40/48) of the rehabilitation sessions, with 100% (32/32) of all sessions logged by the system in 4 out of 7 patients. In patients for whom tracking of automated push notifications was enabled, 100% (29/29) of the push notifications sent by the back-end server were received by the patient. Process, hardware, and software issues contributing to these inaccuracies are detailed. CONCLUSIONS: RehabTracker represents a promising mHealth app for tracking and improving adherence with at-home NMES rehabilitation programs and warrants further refinement and testing.

Combined Injury to the ACL and Lateral Meniscus Alters the Geometry of Articular Cartilage and Meniscus Soon After Initial Trauma.

Combined injury to the anterior cruciate ligament (ACL) and meniscus is associated with earlier onset and increased rates of post-traumatic osteoarthritis compared with isolated ACL injury. However, little is known about the initial changes in joint structure associated with these different types of trauma. We hypothesized that trauma to the ACL and lateral meniscus has an immediate effect on morphometry of the articular cartilage and meniscus about the entire tibial plateau that is more pronounced than an ACL tear without meniscus injury. Subjects underwent magnetic resonance imaging scanning soon after injury and prior to surgery. Those that suffered injury to the ACL and lateral meniscus underwent changes in the lateral compartment (increases in the posterior-inferior directed slopes of the articular cartilage surface, and the wedge angle of the posterior horn of the meniscus) and medial compartment (the cartilage-to-bone height decreased in the region located under the posterior horn of the meniscus, and the thickness of cartilage increased and decreased in the mid and posterior regions of the plateau, respectively). Subjects that suffered an isolated ACL tear did not undergo the same magnitude of change to these articular structures. A majority of the changes in morphometry occurred in the lateral compartment of the knee; however, change in the medial compartment of the knee with a normal appearing meniscus also occurred. Statement of clinical significance: Knee injuries that involve combined trauma to the ACL and meniscus directly affect both compartments of the knee, even if the meniscus and articular cartilage appears normal upon arthroscopic examination. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:759-767, 2020.

Open-Source Remote Gait Analysis: A Post-Surgery Patient Monitoring Application.

Critical to digital medicine is the promise of improved patient monitoring to allow assessment and personalized intervention to occur in real-time. Wearable sensor-enabled observation of physiological data in free-living conditions is integral to this vision. However, few open-source algorithms have been developed for analyzing and interpreting these data which slows development and the realization of digital medicine. There is clear need for open-source tools that analyze free-living wearable sensor data and particularly for gait analysis, which provides important biomarkers in multiple clinical populations. We present an open-source analytical platform for automated free-living gait analysis and use it to investigate a novel, multi-domain (accelerometer and electromyography) asymmetry measure for quantifying rehabilitation progress in patients recovering from surgical reconstruction of the anterior cruciate ligament (ACL). Asymmetry indices extracted from 41,893 strides were more strongly correlated (r = -0.87, p < 0.01) with recovery time than standard step counts (r = 0.25, p = 0.52) and significantly differed between patients 2- and 17-weeks post-op (p < 0.01, effect size: 2.20-2.96), and controls (p < 0.01, effect size: 1.74-4.20). Results point toward future use of this open-source platform for capturing rehabilitation progress and, more broadly, for free-living gait analysis.

Fiber typing human skeletal muscle with fluorescent immunohistochemistry.

Skeletal muscle myosin heavy chain (MyHC) fiber type composition is a critical determinant of overall muscle function and health. Various approaches interrogate fiber type at the single cell, but the two most commonly utilized are single-muscle fiber sodium dodecyl sulfate-polyacrylamide gel electrophoresis (smfSDS-PAGE) and fluorescent immunohistochemistry (IHC). Although smfSDS-PAGE is generally considered the "gold standard," IHC is more commonly used because of its time-effectiveness and relative ease. Unfortunately, there is lingering inconsistency on how best to accurately and quickly determine fiber type via IHC and an overall misunderstanding regarding pure fiber type proportions, specifically the abundance of fibers exclusively expressing highly glycolytic MyHC IIX in humans. We therefore 1) present information and data showing the low abundance of pure MyHC IIX muscle fibers in healthy human skeletal muscle and 2) leverage this information to provide straightforward protocols that are informed by human biology and employ inexpensive, easily attainable antibodies for the accurate determination of fiber type.

Risk Factors Associated With a Noncontact Anterior Cruciate Ligament Injury to the Contralateral Knee After Unilateral Anterior Cruciate Ligament Injury in High School and College Female Athletes: A Prospective Study.

BACKGROUND: The incidence of contralateral anterior cruciate ligament (CACL) injuries after recovery from a first-time anterior cruciate ligament (ACL) disruption is high in women; however, little is known about the risk factors associated with this trauma. HYPOTHESIS: Patient characteristics, strength, anatomic alignment, and neuromuscular characteristics of the contralateral uninjured leg at the time of the first ACL trauma are associated with risk of subsequent CACL injury, and these risk factors are distinct from those for a first-time ACL injury. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Sixty-one women who suffered a first-time noncontact ACL injury while participating in high school or college sports and underwent measurement of potential risk factors on their contralateral limb soon after the initial ACL injury and before reconstruction were followed until either a CACL injury or an ACL graft injury occurred, or until the last date of contact. RESULTS: Follow-up information was available for 55 (90.0%) of the 61 athletes and 11 (20.0%) suffered a CACL injury. Younger age, decreased participation in sport before the first ACL disruption, decreased anterior stiffness of the contralateral knee, and increased hip anteversion were associated with increases in the risk of suffering a CACL injury. CONCLUSION: A portion of CACL injury risk factors were modifiable (time spent participating in sport and increasing anterior knee stiffness with bracing), while others were nonmodifiable (younger age and increased hip anteversion). The relationship between younger age at the time of an initial ACL injury and increased risk of subsequent CACL trauma may be explained by younger athletes having more years available to be exposed to at-risk activities compared with older athletes. A decrease of anterior stiffness of the knee is linked to decreased material properties and width of the ACL, and this may explain why some women are predisposed to bilateral ACL trauma while others only suffer the index injury. The risk factors for CACL injury are unique to women who suffer bilateral ACL trauma compared with those who suffer unilateral ACL trauma. This information is important for the identification of athletes who may benefit from risk reduction interventions.

Resistance training-induced gains in knee extensor strength are related to increased neural cell adhesion molecule expression in older adults with knee osteoarthritis.

OBJECTIVE: Resistance training (RT) can improve whole muscle strength without increasing muscle fiber size or contractility. Neural adaptations, which lead to greater neural activation of muscle, may mediate some of these improvements, particularly in older adults, where motor neuron denervation is common. The purpose of this study was to explore the relationship of neural adaptations, as reflected by neural cell adhesion molecule (NCAM) expression, to improvements in (1) whole muscle strength and (2) muscle fiber size following RT in older adults with knee osteoarthritis. We performed whole muscle strength measurements and immunohistochemical analysis of fiber size, type, and NCAM expression before and after a 14-week RT program. RESULTS: RT increased whole-muscle strength as measured by 1-repetition maximum (1-RM) leg press (P = 0.01), leg extension (P = 0.03), and knee extensor peak torque (P = 0.050), but did not alter NCAM expression. Greater NCAM expression in myosin heavy chain (MHC) II fibers was associated with greater whole muscle strength gains (knee extensor peak torque r = 0.93; P < 0.01) and greater MHC II fiber size (r = 0.79; P < 0.01). Our results suggest that training-induced NCAM expression, and neural adaptations more generally, may be important for RT-induced morphological and functional improvements in older adults. Trial registration NCT01190046.

Implementation of the FIFA 11+ Injury Prevention Program by High School Athletic Teams Did Not Reduce Lower Extremity Injuries: A Cluster Randomized Controlled Trial.

BACKGROUND: Lower extremity injuries are common in high school sports and are costly, and some have poor outcomes. The FIFA 11+ injury prevention program has been shown to decrease injuries in elite athletes by up to 72%. HYPOTHESIS: High schools in which coaches implement the FIFA 11+ injury prevention program in their athletic programs will have a decreased incidence of lower extremity injuries compared with schools using their usual prepractice warm-up. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Fourteen high schools that employed an athletic trainer were randomly assigned to either the FIFA 11+ group or control group (usual warm-up routine). Exposure to sports and injuries were recorded and used to determine the incidence rates of lower extremity injuries per athlete-exposure (AE). The FIFA 11+ program was implemented by coaches and complicance with the program recorded. RESULTS: There were 196 lower extremity injuries among 1825 athletes in the FIFA 11+ group and 172 injuries among 1786 athletes in the control group (1.59 and 1.47 injuries per 1000 AEs, respectively; P = .771). The distribution of the types of injury in the 2 groups did not differ, but the body locations where the injuries occurred differed somewhat (P = .051). The FIFA 11+ group had larger proportions of thigh and foot injuries, while the control group had higher proportions of knee and ankle injuries. Group differences in injury rates varied with sport (P = .041 for interaction), but there were no significant differences in injury rates between the FIFA 11+ and control groups by sport, level of play, and sex. In the FIFA 11+ group, 62% of the coaches reported that their teams completed the full FIFA 11+ program at least once a week, and 32% reported that they completed it at least twice a week. CONCLUSION: This study did not demonstrate a reduction in lower extremity injuries in schools randomized to use the FIFA 11+ program compared with schools using their usual prepractice warm-up program. Coach-reported compliance with performing the FIFA 11+ program at least twice a week was low.

Skeletal muscle atrophy and dysfunction in breast cancer patients: role for chemotherapy-derived oxidant stress.

How breast cancer and its treatments affect skeletal muscle is not well defined. To address this question, we assessed skeletal muscle structure and protein expression in 13 women who were diagnosed with breast cancer and receiving adjuvant chemotherapy following tumor resection and 12 nondiseased controls. Breast cancer patients showed reduced single-muscle fiber cross-sectional area and fractional content of subsarcolemmal and intermyofibrillar mitochondria. Drugs commonly used in breast cancer patients (doxorubicin and paclitaxel) caused reductions in myosin expression, mitochondrial loss, and increased reactive oxygen species (ROS) production in C2C12 murine myotube cell cultures, supporting a role for chemotherapeutics in the atrophic and mitochondrial phenotypes. Additionally, concurrent treatment of myotubes with the mitochondrial-targeted antioxidant MitoQ prevented chemotherapy-induced myosin depletion, mitochondrial loss, and ROS production. In patients, reduced mitochondrial content and size and increased expression and oxidation of peroxiredoxin 3, a mitochondrial peroxidase, were associated with reduced muscle fiber cross-sectional area. Our results suggest that chemotherapeutics may adversely affect skeletal muscle in patients and that these effects may be driven through effects of these drugs on mitochondrial content and/or ROS production.

Characterization of Prepractice Injury Prevention Exercises of High School Athletic Teams.

BACKGROUND: Static and dynamic exercises are performed before activity to decrease injury risk and increase performance. Although evidence supports using dynamic over static stretching and performing Fédération Internationale de Football Association (FIFA) 11+ as a dynamic prepractice routine, we do not know the frequency at which these exercises are utilized in high school populations. HYPOTHESIS: We hypothesize that there is a wide variety of preparticipation exercises performed by high school athletes, and that few high school teams perform FIFA 11+ as an injury prevention program in its entirety. STUDY DESIGN: Observational study. LEVEL OF EVIDENCE: Level 4. METHODS: High school prepractice routines were observed for 185 teams (football, soccer, basketball, and lacrosse) over 1 season. The percentages of team warm-up routines that included components of FIFA 11+ were calculated, and the chi-square test was used to compare sex, sport, and level of competition. RESULTS: Of a total 644 warm-up observations, 450 (69.9%) included only non-FIFA 11+ exercises, 56 (8.7%) included at least 1 FIFA 11+ exercise, and 38 (5.9%) included only jogging; 69 (10.6%) consisted only of sport-specific activities. The type of warm-up differed significantly between males and females ( P = 0.002), sports ( P < 0.001), and level of competition ( P < 0.001). Static stretching and athletes stretching on their own were observed in 14% and 15% of all observations. No team performed the FIFA 11+ injury prevention routine in its entirety. CONCLUSION: The type of warm-up differed by sex, sport, and level of competition. Static stretching was performed more frequently than anticipated, and an entire FIFA 11+ warm-up was never performed. CLINICAL RELEVANCE: We need to identify the exercises that decrease injury and increase performance and better inform the athletic population about the risks and benefits of static and dynamic warm-up programs.

Geometric Characteristics of the Knee Are Associated With a Noncontact ACL Injury to the Contralateral Knee After Unilateral ACL Injury in Young Female Athletes.

BACKGROUND: Contralateral anterior cruciate ligament (CACL) injury after recovery from a first-time ACL rupture occurs at a high rate in young females; however, little is known about the risk factors associated with bilateral ACL trauma. HYPOTHESIS: The geometric characteristics of the contralateral knee at the time of the initial ACL injury are associated with risk of suffering a CACL injury in these female athletes. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Sixty-two female athletes who suffered their first noncontact ACL injury while participating in sports at the high school or college level were identified, and geometry of the femoral notch, ACL, tibial spines, tibial subchondral bone, articular cartilage surfaces, and menisci of the contralateral, uninjured, knee was characterized in 3 dimensions. We were unable to contact 7 subjects and followed the remaining 55 until either a CACL injury or an ACL graft injury occurred or, if they were not injured, until the date of last contact (mean, 34 months after their first ACL injury). Cox regression was used to identify risk factors for CACL injury. RESULTS: Ten (18.2%) females suffered a CACL injury. Decreases of 1 SD in femoral intercondylar notch width (measured at its outlet and anterior attachment of the ACL) were associated with increases in the risk of suffering a CACL injury (hazard ratio = 1.88 and 2.05, respectively). Likewise, 1 SD decreases in medial-lateral width of the lateral tibial spine, height of the medial tibial spine, and thickness of the articular cartilage located at the posterior region of the medial tibial compartment were associated with 3.59-, 1.75-, and 2.15-fold increases in the risk of CACL injury, respectively. CONCLUSION: After ACL injury, subsequent injury to the CACL is influenced by geometry of the structures that surround the ACL (the femoral notch and tibial spines). This information can be used to identify individuals at increased risk for CACL trauma, who might benefit from targeted risk-reduction interventions.