Degraded RNA from Human Anterior Cruciate Ligaments Yields Valid Gene Expression Profiles.

Correlating gene expression patterns with biomechanical properties of connective tissues provides insights into the molecular processes underlying the tissue growth and repair. Cadaveric specimens such as human knees are widely considered suitable for biomechanical studies, but their usefulness for gene expression experiments is potentially limited by the unavoidable, nuclease-mediated degradation of RNA. Here, we tested whether valid gene expression profiles can be obtained using degraded RNA from human anterior cruciate ligaments (ACLs). Human ACL RNA (N = 6) degraded in vitro by limited ribonuclease digestion resemble highly degraded RNA isolated from cadaveric tissue. PCR threshold cycle (Ct) values for 90 transcripts (84 extracellular matrix, 6 housekeeping) in degraded RNAs variably ranged higher than values obtained from their corresponding non-degraded RNAs, reflecting both the expected loss of target templates in the degraded preparations as well as differences in the extent of degradation. Relative Ct values obtained for mRNAs in degraded preparations strongly correlated with the corresponding levels in non-degraded RNA, both for each ACL as well as for the pooled results from all six ACLs. Nuclease-mediated degradation produced similar, strongly correlated losses of housekeeping and non-housekeeping gene mRNAs. RNA degraded in situ yielded comparable results, confirming that in vitro digestion effectively modeled degradation by endogenous ribonucleases in frozen and thawed ACL. We conclude that, contrary to conventional wisdom, PCR-based expression analyses can yield valid mRNA profiles even from RNA preparations that are more than 90% degraded, such as those obtained from connective tissues subjected to biomechanical studies. Furthermore, legitimate quantitative comparisons between variably degraded tissues can be made by normalizing data to appropriate housekeeping transcripts.

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.

Compliance and Fidelity With an Injury Prevention Exercise Program in High School Athletics.

BACKGROUND: Use of injury prevention programs (IPPs) by high school athletes has increased but their success in reducing injury depends on program compliance and fidelity of exercise performance. HYPOTHESIS: Compliance with the 11+ IPP and exercise performance fidelity by high school athletic teams depend on sex, sport, and level of play. STUDY DESIGN: Secondary analyses of data from a randomized controlled trial (RCT). LEVEL OF EVIDENCE: Level 2. METHODS: The 11+ IPP was implemented by 100 male and female high school athletic teams (American football, soccer, basketball, and lacrosse). Team compliance and fidelity with the program were evaluated by direct observation of warm-up routines and a weekly online survey completed by coaches. Differences in compliance and fidelity due to sport, sex, and level of play were assessed by analysis of variance. RESULTS: Coaches reported that their teams performed the full IPP an average of 1.45 times per week, and 28% of observed warm-ups included all exercises in the IPP. Compliance differed by sport but not by level of play or the athletes' sex. At the end of the season, cueing was observed 19% of the time and differed by sport. Good technique was observed 66% of the time and varied by level of play. CONCLUSION: Team compliance with the IPP varied by sport and was below the recommended number of sessions per week needed to reduce injury. Removal of implementation barriers and improved support from coaches are needed at all levels of play for IPPs to be effective. CLINICAL RELEVANCE: Clinical and sports practitioners intending to implement an IPP at the high school level should anticipate and address barriers that affect program compliance and fidelity of exercise performance. Frequent follow-up and instruction may be necessary for successful adoption of the IPP.

Association of Geometric Characteristics of Knee Anatomy (Alpha Angle and Intercondylar Notch Type) With Noncontact ACL Injury.

BACKGROUND: The femoral intercondylar notch type and the alpha angle (the angle between the femoral notch roof and the long axis of the femur) are easily measured in clinical settings; however, their associations with anterior cruciate ligament (ACL) injury remain unclear. HYPOTHESIS/PURPOSE: The purpose was to determine if the alpha angle and the femoral notch type are associated with noncontact ACL injury univariately and in combination with previously identified knee geometric risk factors. We hypothesized that the alpha angle and the femoral notch type are associated with noncontact ACL injury and that the association differs between men and women. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: The alpha angle and the femoral notch type were measured via 3T magnetic resonance imaging (MRI) acquired from 61 women and 25 men with a first-time noncontact ACL injury. Each injured patient was matched with a control participant based on age, sex, and participation on the same sports team. A conditional logistic regression was used to assess univariate associations with ACL injury as well as multivariate associations using MRI-based risk factors of knee geometry identified in previous analyses: femoral intercondylar notch width at the anterior outlet, femoral intercondylar notch anteromedial ridge thickness, volume of the ACL, tibial plateau lateral compartment subchondral bone slope, lateral compartment middle articular cartilage slope, lateral compartment meniscus-cartilage height, lateral compartment meniscus-bone angle, and medial tibial spine volume. RESULTS: For female athletes, the alpha angle (odds ratio, [OR], 1.82 per 1-degree increase; P = .001), the tibial lateral compartment articular cartilage slope (OR, 1.25 per 1-degree increase in the posterior-inferior directed slope; P = .022), and the femoral notch anteromedial ridge thickness (OR, 3.36 per 1-mm increase; P = .027) were independently associated with ACL disruption. For men, no other variables entered the models after the alpha angle was inputted as the first step (OR, 2.19 per 1-degree increase; P = .010). CONCLUSION: For women, ACL injury was most strongly associated with increased alpha angle, increased tibial plateau slope, and increased femoral notch ridge thickness. For men, increased alpha angle was the most significant factor associated with ACL injury. The mechanism of injury might be associated with a combination of impingement of the ACL against the bone and increased ligament loading.

A Poster Summarizing the American Academy of Orthopaedic Surgeons Knee Osteoarthritis Clinical Practice Guideline Is a Powerful Tool for Patient Education: A Randomized Controlled Trial.

BACKGROUND: In 2013, the American Academy of Orthopaedic Surgeons (AAOS) published an evidence-based clinical practice guideline (CPG) on conservative treatment options for patients with knee osteoarthritis (OA). The purpose of this study is to evaluate the effectiveness of a poster outlining the AAOS knee OA CPG on patient comprehension and satisfaction in the clinic. METHODS: This is a prospective 2-armed randomized controlled trial. Patients were eligible if they were of age 40-85 years, had degenerative knee OA, and did not consent for surgery. Patients were randomized to nonposter (standard care) and poster rooms. Knee OA treatment options were described to the patient verbally and posters were used as a teaching tool when present. The main outcomes were comprehension and satisfaction scores on a survey. RESULTS: Of the 105 patients enrolled, 51 (48.6%) were randomized to usual care (control) and 54 (51.4%) to the intervention (poster). Poster patients outperformed control patients with an average of 55.3% ± 16.7% (mean ± SD) compared to 39.5% ± 13.3% correct answers (P < .001). And 66.7% of poster patients and 29.4% of control patients achieved an adequately informed status of >50% correct answers (P < .001; 50.5% overall). With a maximum possible score of 10, visit satisfaction scores were 9.4 ± 1.0 in poster patients and 9.2 ± 1.7 in control patients (P = .50). CONCLUSION: Patients educated using an AAOS knee CPG poster showed significant improvements in knowledge and were more likely to achieve an adequately informed status. No difference existed in visit satisfaction. A poster offers a low-cost, effective educational tool. LEVEL OF EVIDENCE: Level 1.

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).

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.

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.

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.

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.

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.

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.

Moderate-intensity resistance exercise alters skeletal muscle molecular and cellular structure and function in inactive older adults with knee osteoarthritis.

High-intensity resistance exercise (REX) training increases physical capacity, in part, by improving muscle cell size and function. Moderate-intensity REX, which is more feasible for many older adults with disease and/or disability, also increases physical function, but the mechanisms underlying such improvements are not understood. Therefore, we measured skeletal muscle structure and function from the molecular to the tissue level in response to 14 wk of moderate-intensity REX in physically inactive older adults with knee osteoarthritis (n = 17; 70 ± 1 yr). Although REX training increased quadriceps muscle cross-sectional area (CSA), average single-fiber CSA was unchanged because of reciprocal changes in myosin heavy chain (MHC) I and IIA fibers. Intermyofibrillar mitochondrial content increased with training because of increases in mitochondrial size in men, but not women, with no changes in subsarcolemmal mitochondria in either sex. REX increased whole muscle contractile performance similarly in men and women. In contrast, adaptations in single-muscle fiber force production per CSA (i.e., tension) and contractile velocity varied between men and women in a fiber type-dependent manner, with adaptations being explained at the molecular level by differential changes in myosin-actin cross-bridge kinetics and mechanics and single-fiber MHC protein expression. Our results are notable compared with studies of high-intensity REX because they show that the effects of moderate-intensity REX in older adults on muscle fiber size/structure and myofilament function are absent or modest. Moreover, our data highlight unique sex-specific adaptations due to differential cellular and subcellular structural and functional changes.NEW & NOTEWORTHY Moderate-intensity resistance training causes sex-specific adaptations in skeletal muscle structure and function at the cellular and molecular levels in inactive older adult men and women with knee osteoarthritis. However, these responses were minimal compared with high-intensity resistance training. Thus adjuncts to moderate-intensity training need to be developed to correct underlying cellular and molecular structural and functional deficits that are at the root of impaired physical function in this mobility-limited population.

Relationship between geometry of the extensor mechanism of the knee and risk of anterior cruciate ligament injury.

The complex inter-segmental forces that are developed across an extended knee by body weight and contraction of the quadriceps muscle group transmits an anteriorly directed force on the tibia that strain the anterior cruciate ligament (ACL). We hypothesized that a relationship exists between geometry of the knees extensor mechanism and the risk of sustaining a non-contact ACL injury. Geometry of the extensor mechanism was characterized using MRI scans of the knees of 88 subjects that suffered their first non-contact ACL injury and 88 matched control subjects with normal knees that were on the same team. The orientation of the patellar tendon axis was measured relative to the femoral flexion-extension axis to determine the extensor moment arm (EMA), and relative to tibial long axis to measure coronal patellar tendon angle (CPTA) and sagittal patellar tendon angle (SPTA). Associations between these parameters and ACL injury risk were tested with and without adjustment for flexion and internal rotation position of the tibia relative to the femur during MRI data acquisition. After adjustment for internal rotation position of the tibia relative to the femur there were no associations between EMA, CPTA, and SPTA and risk of suffering an ACL injury. However, increased internal rotation position of the tibia relative to the femur was significantly associated with increased risk of ACL injury in female athletes both in univariate analysis (Odds Ratio = 1.16 per degree of internal rotation of the tibia, p = 0.002), as well as after adjustment for EMA, CPTA, and SPTA.: © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:965-973, 2017.

Geometric Risk Factors Associated With Noncontact Anterior Cruciate Ligament Graft Rupture.

BACKGROUND: Anterior cruciate ligament (ACL) graft rupture occurs at a high rate, especially in young athletes. The geometries of the tibial plateau and femoral intercondylar notch are risk factors for first-time ACL injury; however, little is known about the relationship between these geometries and risk of ACL graft rupture. HYPOTHESIS: The geometric risk factors for noncontact graft rupture are similar to those previously identified for first-time noncontact ACL injury, and sex-specific differences exist. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Eleven subjects who suffered a noncontact ACL graft rupture and 44 subjects who underwent ACL reconstruction but did not experience graft rupture were included in the study. Using magnetic resonance imaging, the geometries of the tibial plateau subchondral bone, articular cartilage, meniscus, tibial spines, and femoral notch were measured. Risk factors associated with ACL graft rupture were identified using Cox regression. RESULTS: The following were associated with increased risk of ACL graft injury in males: increased posterior-inferior-directed slope of the articular cartilage in the lateral tibial plateau measured at 2 locations (hazard ratio [HR] = 1.50, P = .029; HR = 1.39, P = .006), increased volume (HR = 1.45, P = .01) and anteroposterior length (HR = 1.34, P = .0023) of the medial tibial spine, and increased length (HR = 1.18, P = .0005) and mediolateral width (HR = 2.19, P = .0004) of the lateral tibial spine. In females, the following were associated with increased risk of injury: decreased volume (HR = 0.45, P = .02) and height (HR = 0.46, P = .02) of the medial tibial spine, decreased slope of the lateral tibial subchondral bone (HR = 0.72, P = .01), decreased height of the posterior horn of the medial meniscus (HR = 0.09, P = .001), and decreased intercondylar notch width at the anterior attachment of the ACL (HR = 0.72, P = .02). CONCLUSION: The geometric risk factors for ACL graft rupture are different for males and females. For females, a decreased femoral intercondylar notch width and a decreased height of the posterior medial meniscus were risk factors for ACL graft rupture that have also been found to be risk factors for first-time injury. There were no risk factors in common between ACL graft injury and first-time ACL injury for males.

Multivariate Analysis of the Risk Factors for First-Time Noncontact ACL Injury in High School and College Athletes: A Prospective Cohort Study With a Nested, Matched Case-Control Analysis.

BACKGROUND: Multivariate analysis that identifies the combination of risk factors associated with anterior cruciate ligament (ACL) trauma is important because it provides insight into whether a variable has a direct causal effect on risk or an indirect effect that is mediated by other variables. It can also reveal risk factors that might not be evident in univariate analyses; if a variable's effect is moderated by other variables, its association with risk may be apparent only after adjustment for the other variables. Most important, multivariate analyses can identify combinations of risk factors that are more predictive of risk than individual risk factors. HYPOTHESIS: A diverse combination of risk factors predispose athletes to first-time noncontact ACL injury, and these relationships are different for male and female athletes. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Athletes competing in organized sports at the high school and college levels participated in this study. Data from injured subjects (109 suffering an ACL injury) and matched controls (227 subjects) from the same athletic team were analyzed with multivariate conditional logistic regression to examine the effects of combinations of variables (demographic characteristics, joint laxity, lower extremity alignment, strength, and personality traits) on the risk of suffering their first ACL injury and to construct risk models. RESULTS: For male athletes, increases in anterior-posterior displacement of the tibia relative to the femur (knee laxity), posterior knee stiffness, navicular drop, and a decrease in standing quadriceps angle were jointly predictive of suffering an ACL injury. For female athletes the combined effects of having a parent who had suffered an ACL injury and increases in anterior-posterior knee laxity and body mass index were predictive of ACL injury. CONCLUSION: Multivariate models provided more information about ACL injury risk than individual risk factors. Both male and female risk models included increased anterior-posterior knee laxity as a predictor of ACL injury but were otherwise dissimilar.

Evaluation of an Algorithm to Predict Menstrual-Cycle Phase at the Time of Injury.

CONTEXT: Women are 2 to 8 times more likely to sustain an anterior cruciate ligament (ACL) injury than men, and previous studies indicated an increased risk for injury during the preovulatory phase of the menstrual cycle (MC). However, investigations of risk rely on retrospective classification of MC phase, and no tools for this have been validated. OBJECTIVE: To evaluate the accuracy of an algorithm for retrospectively classifying MC phase at the time of a mock injury based on MC history and salivary progesterone (P4) concentration. DESIGN: Descriptive laboratory study. SETTING: Research laboratory. PARTICIPANTS: Thirty-one healthy female collegiate athletes (age range, 18-24 years) provided serum or saliva (or both) samples at 8 visits over 1 complete MC. MAIN OUTCOME MEASURE(S): Self-reported MC information was obtained on a randomized date (1-45 days) after mock injury, which is the typical timeframe in which researchers have access to ACL-injured study participants. The MC phase was classified using the algorithm as applied in a stand-alone computational fashion and also by 4 clinical experts using the algorithm and additional subjective hormonal history information to help inform their decision. To assess algorithm accuracy, phase classifications were compared with the actual MC phase at the time of mock injury (ascertained using urinary luteinizing hormone tests and serial serum P4 samples). Clinical expert and computed classifications were compared using κ statistics. RESULTS: Fourteen participants (45%) experienced anovulatory cycles. The algorithm correctly classified MC phase for 23 participants (74%): 22 (76%) of 29 who were preovulatory/anovulatory and 1 (50%) of 2 who were postovulatory. Agreement between expert and algorithm classifications ranged from 80.6% (κ = 0.50) to 93% (κ = 0.83). Classifications based on same-day saliva sample and optimal P4 threshold were the same as those based on MC history alone (87.1% correct). Algorithm accuracy varied during the MC but at no time were both sensitivity and specificity levels acceptable. CONCLUSIONS: These findings raise concerns about the accuracy of previous retrospective MC-phase classification systems, particularly in a population with a high occurrence of anovulatory cycles.