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Background: Anterior cruciate ligament (ACL) tear (ACLT) leads to protracted quadriceps muscle atrophy. Protein turnover largely dictates muscle size and is highly responsive to injury and loading. Regulation of quadriceps molecular protein synthetic machinery after ACLT has largely been unexplored, limiting development of targeted therapies. Purpose: To define the effect of ACLT on (1) the activation of protein synthetic and catabolic signaling within quadriceps biopsy specimens from human participants and (2) the time course of alterations to protein synthesis and its molecular regulation in a mouse ACL injury model. Study Design: Descriptive laboratory study. Methods: Muscle biopsy specimens were obtained from the ACL-injured and noninjured vastus lateralis of young adult humans after an overnight fast (N = 21; mean ± SD, 19 ± 5 years). Mice had their limbs assigned to ACLT or control, and whole quadriceps were collected 6 hours or 1, 3, or 7 days after injury with puromycin injected before tissue collection for assessment of relative protein synthesis. Muscle fiber size and expression and phosphorylation of protein anabolic and catabolic signaling proteins were assessed at the protein and transcript levels (RNA sequencing). Results: Human quadriceps showed reduced phosphorylation of ribosomal protein S6 (–41%) in the ACL-injured limb (P =.008), in addition to elevated phosphorylation of eukaryotic initiation factor 2α (+98%; P =.006), indicative of depressed protein anabolic signaling in the injured limb. No differences in E3 ubiquitin ligase expression were noted. Protein synthesis was lower at 1 day (P =.01 vs control limb) and 3 days (P =.002 vs control limb) after ACLT in mice. Pathway analyses revealed shared molecular alterations between human and mouse quadriceps after ACLT. Conclusion: (1) Global protein synthesis and anabolic signaling deficits occur in the quadriceps in response to ACL injury, without notable changes in measured markers of muscle protein catabolism. (2) Importantly, these deficits occur before the onset of significant atrophy, underscoring the need for early intervention. Clinical Relevance: These findings suggest that blunted protein anabolism as opposed to increased catabolism likely mediates quadriceps atrophy after ACL injury. Thus, future interventions should aim to restore muscle protein anabolism rapidly after ACLT. [ABSTRACT FROM AUTHOR]

Context: There is a lack of consensus regarding test batteries for return to sport (RTS) after anterior cruciate ligament reconstruction (ACLR). Objective: To report the RTS test batteries for individuals after ACLR and to examine alignment with the American Academy of Orthopaedic Surgeons (AAOS) Appropriate Use Criteria (AUC). Finally, to examine how published RTS batteries prior to the AAOS AUC (2010-2015) compared with those after publication of the AUC (2016-2020). Data Source: A systematic search of PubMed (2010-2020). Study Selection: Studies were included if they were published from 2010 to 2020, patients underwent primary ACLR and were tested between 6 months and 2 years postoperatively and included a minimum of 2 assessments. Studies were excluded if patients were tested outside the designated time; had undergone a revision, contralateral, or multiligament injury; included healthy participants; were level 5 evidence or the study was a systematic review. A total of 1012 articles were reviewed and 63 met the criteria. Study Design: Systematic review. Level of Evidence: Level 4. Data Extraction: Information regarding the RTS batteries and patient demographics were extracted from the included articles. Results: A total of 63 studies met the inclusion and exclusion criteria (22 from 2010-2015 and 41 from 2016-2020). The most common RTS batteries included the hop test, quadriceps strength test, and patient-reported outcome measures. No study met all 7 AUC; the most common criteria met were functional skills (98.4%), followed by confidence (22.2%), then range of motion and knee stability (20.6%). Conclusion: The test batteries in the current literature show high variability and a lack of essential components necessary for RTS. No study met the AUC guidelines, suggesting a disconnect between recommended guidelines and clinical practice. Test battery research has expanded over the past decade; however, standardized, clinically applicable batteries that encompass all criteria are needed. [ABSTRACT FROM AUTHOR]

Background: Many patients live with long-term deficits in knee function after an anterior cruciate ligament reconstruction (ACLR). However, research is inconclusive as to which physical performance measure is most strongly related to long-term patient-reported outcomes after ACLR.Hypothesis: Quadriceps strength would be most strongly associated with patient-reported long-term outcomes after ACLR.Study Design: Cross-sectional study.Level Of Evidence: Level 3.Methods: A total of 40 patients (29 female) consented and participated an average of 10.9 years post-ACLR (range, 5-20 years). Patients completed the Lower Extremity Functional Scale (LEFS), the International Knee Documentation Committee (IKDC) Scale, Knee injury and Osteoarthritis Outcome Score Quality of Life (KOOS QoL) and Sport (KOOS Sport) subscales, and the Tampa Scale of Kinesiophobia (TSK-17). Each patient subsequently performed maximal isometric quadriceps contraction, a 60-second single-leg step-down test, and the single-leg single hop and triple hop for distance tests. Multivariate linear and logistic regression models determined how performance testing was associated with each patient-reported outcome when controlling for time since surgery, age, and TSK-17.Results: When controlling for time since surgery, age at the time of consent, and TSK-17 score, maximal isometric quadriceps strength normalized to body weight was the sole physical performance measure associated with IKDC (P < 0.001), KOOS Sport (P = 0.006), KOOS QoL (P = 0.001), and LEFS scores (P < 0.001). Single-leg step-down, single hop, and triple hop did not enter any of the linear regression models (P > 0.20). Additionally, TSK-17 was associated with all patient-reported outcomes (P ≤ 0.01) while time since surgery was not associated with any outcomes (P > 0.05).Conclusion: Isometric quadriceps strength and kinesiophobia are significantly associated with long-term patient-reported outcomes after ACLR.Clinical Relevance: These results suggest that training to improve quadriceps strength and addressing kinesiophobia in the late stages of recovery from ACLR may improve long-term self-reported function. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) tears result in significant quadriceps muscle atrophy that is resistant to recovery despite extensive rehabilitation. Recent work suggests an elevated fibrotic burden in the quadriceps muscle after the injury, which may limit recovery. Elucidating the mechanisms and cell types involved in the progression of fibrosis is critical for developing new treatment strategies. Purpose: To identify factors contributing to the elevated fibrotic burden found after the injury. Study Design: Descriptive laboratory study. Methods: After an ACL injury, muscle biopsy specimens were obtained from the injured and noninjured vastus lateralis of young adults (n = 14, mean ± SD: 23 ± 4 years). The expression of myostatin, transforming growth factor β, and other regulatory factors was measured, and immunohistochemical analyses were performed to assess turnover of extracellular matrix components. Results: Injured limb skeletal muscle demonstrated elevated myostatin gene (P <.005) and protein (P <.0005) expression, which correlated (R 2 = 0.38, P <.05) with fibroblast cell abundance. Immunohistochemical analysis showed that human fibroblasts express the activin type IIB receptor and that isolated primary human muscle-derived fibroblasts increased proliferation after myostatin treatment in vitro (P <.05). Collagen 1 and fibronectin, primary components of the muscle extracellular matrix, were significantly higher in the injured limb (P <.05). The abundance of procollagen 1–expressing cells as well as a novel index of collagen remodeling was also elevated in the injured limb (P <.05). Conclusion: These findings support a role for myostatin in promoting fibrogenic alterations within skeletal muscle after an ACL injury. Clinical Relevance: The current work shows that the cause of muscle quality decline after ACL injury likely involves elevated myostatin expression, and future studies should explore therapeutic inhibition of myostatin to facilitate improvements in muscle recovery and return to sport. [ABSTRACT FROM AUTHOR]

Background: Rate of torque development (RTD) measures the ability of a muscle to produce torque quickly. Decreased quadriceps RTD may impair performance of sporting tasks after surgery. Currently, little is known about variations in quadriceps RTD between anterior cruciate ligament (ACL)–reconstructed and noninjured limbs. Purpose: To determine the differences in RTD of the quadriceps, the rate and timing of knee extensor moment (KEM) development, and knee flexion excursion during running after ACL reconstruction with patellar tendon autograft. Study Design: Cross-sectional study; Level of evidence, 3. Methods: This study involved 21 patients (11 female) 6 months after ACL reconstruction with patellar tendon autograft (median [IQR]: age, 18 [16-20] years; mass, 68.18 [61.34-75] kg; height, 1.74 [1.66-1.78] m). Patients performed four 5-second maximal voluntary isometric strength trials of both limbs on an isokinetic dynamometer. RTD was calculated as the mean slope of the torque-time curve between 20% and 80% of total time to peak torque. Then, patients underwent 3-dimensional motion analysis while running on an instrumented treadmill at a self-selected running speed (mean ± SD, 2.68 ± 0.28 m/s). The rate of knee extensor moment (RKEM) was calculated as the mean slope of the moment curve between 10% and 30% of stance phase. Between-limb comparisons were determined with a paired t test for peak KEM, RKEM, knee flexion excursion during 10% to 30% of stance, and time to generate KEM. Results: In the reconstructed limb, deficits in the peak rate of quadriceps torque development compared with the noninjured limb existed both isometrically (RTD, 257.56 vs 569.11 Nm/s; P < .001) and dynamically (RKEM, 16.47 vs 22.38 Nm/kg·m·s; P < .001). The reconstructed limb also generated a KEM later in the stance phase compared with the noninjured limb (11.37% vs 9.61% stance; P < .001) and underwent less knee flexion excursion (15.5° vs 19.8°; P < .001). Conclusion: After ACL reconstruction with patellar tendon autograft, patients have lower RTD and RKEM in the reconstructed limb. Deviations in RTD and the timing of the KEM can change the way the knee is loaded and can potentially increase injury risk and future development of posttraumatic osteoarthritis. Rehabilitation should consider exercises designed to improve RTD and prepare the limb for the demands of sport performance. [ABSTRACT FROM AUTHOR]