Sex Differences in Quadriceps Atrophy After Anterior Cruciate Ligament Tear.

BACKGROUND: Female athletes lag behind their male counterparts in recovery from anterior cruciate ligament (ACL) injury. Quadriceps muscle size and strength are crucial factors for regaining function after ACL injury, but little is known about how these metrics vary due to biological sex. HYPOTHESIS: Female patients have reduced vastus lateralis fiber cross-sectional area (CSA) and lower quadriceps strength after ACL injury than male patients. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 60 participants with recent ACL tear were evaluated for vastus lateralis muscle fiber CSA, isometric quadriceps peak torque, and quadriceps rate of torque development. Linear mixed models were fit to determine differences across sex and limb for each variable of interest. RESULTS: The female group averaged almost 20% atrophy between limbs (P < 0.01), while the male group averaged just under 4% (P = 0.05). Strength deficits between limbs were comparable between female and male groups. CONCLUSION: Immediately after ACL injury, female patients have greater between-limb differences in muscle fiber CSA but between-limb strength deficits comparable with those of male patients. CLINICAL RELEVANCE: These results indicate that the underpinnings of strength loss differ based on biological sex, and thus individual patients could benefit from a sex-specific treatment approach to ACL injury.

Editorial Commentary: Routine Use of Suture Tape Augmentation for Primary Anterior Cruciate Ligament Reconstruction Surgery Is Not Justified.

High rates of graft failure after primary anterior cruciate ligament reconstruction (ACLR) and the need for revision ACLR continue to be a challenge. Multiple studies demonstrate graft failure rates and the need for revision ACLR in 10% to 15% of young patients participating in pivot sporting activities. Currently, a wide range of strategies to mitigate this is problem being investigated, including extra-articular augmentation (with modified lateral extra-articular tenodesis or anterolateral ligament reconstruction) and intra-articular fixation (that aim for primary anterior cruciate ligament healing or augmentation of an ACLR with suture tape). While the early data on suture tape augmentation of primary ACLR seem optimistic, it does not justify its routine use.

The Seated Trunk Control Test: Investigation of Reliability and Known-Groups Validity Using Individuals Post-Anterior Cruciate Ligament Reconstruction.

CONTEXT: Decreased trunk neuromuscular control is a risk factor for both upper- and lower-extremity injuries, yet there are few reliable and valid clinical tests to identify deficits. OBJECTIVE: The purpose of this study was to determine the reliability and known-groups validity of a novel clinical test, the seated trunk control test (STCT). DESIGN: Cross-sectional reliability and known-groups validity study. SETTING: Laboratory. PARTICIPANTS: 89 unique participants: 34 were 3 months postoperative anterior cruciate ligament reconstruction (ACLR) and 55 healthy controls. METHODS: For the STCT, participants sat on a balance board with their eyes closed for three 30-second trials while investigators counted balance errors. Intraclass correlations (ICCs) were used to assess interrater reliability (N = 20) and test-retest reliability (N = 40). To assess known-groups validity, independent t tests were used to compare STCT errors at 3 months post-ACLR with healthy matched controls (N = 34/group). Area under a receiver operating characteristic curve identified an optimal cutoff for distinguishing between groups. RESULTS: The STCT had perfect interrater reliability (ICC2,3 = 1.00) and good test-retest reliability (ICC3,3 = .79; 95% confidence interval = .61-.89). The ACLR group made significantly more errors on the STCT (mean [SD] = 15.5 [5.4]) than controls (mean [SD] = 8.2 [4.1]; P < .001, Cohen d = 1.52). The STCT's ability to distinguish between groups was excellent (area under a ROC curve = 0.86). A cutoff of 12 errors maximized sensitivity (76%) and specificity (85%). CONCLUSIONS: The STCT is reliable between raters and across days. It also has excellent ability to distinguish between individuals with a recent ACLR and healthy matched controls, which provides initial evidence to suggest that the STCT may be clinically useful for identifying deficits in trunk neuromuscular control.

Overexpression of manganese superoxide dismutase mitigates ACL injury-induced muscle atrophy, weakness and oxidative damage.

Oxidative stress has been implicated in the etiology of skeletal muscle weakness following joint injury. We investigated longitudinal patient muscle samples following knee injury (anterior cruciate ligament tear). Following injury, transcriptomic analysis revealed downregulation of mitochondrial metabolism-related gene networks, which were supported by reduced mitochondrial respiratory flux rates. Additionally, enrichment of reactive oxygen species (ROS)-related pathways were upregulated in muscle following knee injury, and further investigation unveiled marked oxidative damage in a progressive manner following injury and surgical reconstruction. We then investigated whether antioxidant protection is effective in preventing muscle atrophy and weakness after knee injury in mice that overexpress Mn-superoxide dismutase (MnSOD+/-). MnSOD+/- mice showed attenuated oxidative damage, atrophy, and muscle weakness compared to wild type littermate controls following ACL transection surgery. Taken together, our results indicate that ROS-related damage is a causative mechanism of muscle dysfunction after knee injury, and that mitochondrial antioxidant protection may hold promise as a therapeutic target to prevent weakness and development of disability.

GDF8 inhibition enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following joint injury.

Musculoskeletal disorders contribute substantially to worldwide disability. Anterior cruciate ligament (ACL) tears result in unresolved muscle weakness and posttraumatic osteoarthritis (PTOA). Growth differentiation factor 8 (GDF8) has been implicated in the pathogenesis of musculoskeletal degeneration following ACL injury. We investigated GDF8 levels in ACL-injured human skeletal muscle and serum and tested a humanized monoclonal GDF8 antibody against a placebo in a mouse model of PTOA (surgically induced ACL tear). In patients, muscle GDF8 was predictive of atrophy, weakness, and periarticular bone loss 6 months following surgical ACL reconstruction. In mice, GDF8 antibody administration substantially mitigated muscle atrophy, weakness, and fibrosis. GDF8 antibody treatment rescued the skeletal muscle and articular cartilage transcriptomic response to ACL injury and attenuated PTOA severity and deficits in periarticular bone microarchitecture. Furthermore, GDF8 genetic deletion neutralized musculoskeletal deficits in response to ACL injury. Our findings support an opportunity for rapid targeting of GDF8 to enhance functional musculoskeletal recovery and mitigate the severity of PTOA after injury.

Vitamin D status associates with skeletal muscle loss after anterior cruciate ligament reconstruction.

BACKGROUNDAlthough 25-hydroxyvitamin D [25(OH)D] concentrations of 30 ng/mL or higher are known to reduce injury risk and boost strength, the influence on anterior cruciate ligament reconstruction (ACLR) outcomes remains unexamined. This study aimed to define the vitamin D signaling response to ACLR, assess the relationship between vitamin D status and muscle fiber cross-sectional area (CSA) and bone density outcomes, and discover vitamin D receptor (VDR) targets after ACLR.METHODSTwenty-one young, healthy, physically active participants with recent ACL tears were enrolled (17.8 ± 3.2 years, BMI 26.0 ± 3.5 kg/m2). Data were collected through blood samples, vastus lateralis biopsies, dual energy x-ray bone density measurements, and isokinetic dynamometer measures at baseline, 1 week, 4 months, and 6 months after ACLR. The biopsies facilitated CSA, Western blotting, RNA-seq, and VDR ChIP-seq analyses.RESULTSACLR surgery led to decreased circulating bioactive vitamin D and increased VDR and activating enzyme expression in skeletal muscle 1 week after ACLR. Participants with less than 30 ng/mL 25(OH)D levels (n = 13) displayed more significant quadriceps fiber CSA loss 1 week and 4 months after ACLR than those with 30 ng/mL or higher (n = 8; P < 0.01 for post hoc comparisons; P = 0.041 for time × vitamin D status interaction). RNA-seq and ChIP-seq data integration revealed genes associated with energy metabolism and skeletal muscle recovery, potentially mediating the impact of vitamin D status on ACLR recovery. No difference in bone mineral density losses between groups was observed.CONCLUSIONCorrecting vitamin D status prior to ACLR may aid in preserving skeletal muscle during recovery.FUNDINGNIH grants R01AR072061, R01AR071398-04S1, and K99AR081367.

Prevalence and Predictors of Postoperative Depression and Anxiety After Anterior Cruciate Ligament Reconstruction.

PURPOSE: Preoperative mood disorders influence postoperative outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR), but the prevalence and risk factors associated with postoperative depression/anxiety development remain unknown. The purposes of this study were to quantify the prevalence of postoperative diagnoses of depression or anxiety following ACLR in patients under the age of 25 and assess the interplay between patient sex and ACL reoperation on the prevalence of a depression or anxiety diagnosis following ACLR. METHODS: ACLR patients under the age of 25 years old were identified in the Truven Healthcare Marketscan database. Patients with incomplete coverage +/- one year of the index surgical procedure were excluded. Patients were categorized by the presence of preoperative, postoperative, or no depression/anxiety using the International Classification of Diseases, Ninth Revision (ICD-9) codes. We compared patient demographics and reoperation rates following the index ACLR between the depression and anxiety categories. Additionally, logistic regression was fit to assess the interaction between sex and either ipsilateral or contralateral ACL surgery on postoperative depression/anxiety diagnosis. RESULTS: Of the 42,174 patients, 10.7% had a new depression/anxiety diagnosis after ACLR. Postoperative depression/anxiety was nearly twice as prevalent for females (F: 14.4%, M: 7.6%) despite having similar rates of secondary ACLR (F: 15.5%, M: 13.0%). Those with postoperative depression/anxiety had a considerably greater prevalence of reoperation (18.8%) than those without depression/anxiety (13.7%) and those with pre-existing preoperative depression/anxiety (12.9%). Sex and reoperation were independently associated with postoperative depression/anxiety diagnosis. CONCLUSION: Female sex and secondary ACL surgery are independently associated with an increased prevalence of postoperative depression/anxiety. Nearly one in seven young females are diagnosed with depression/anxiety after ACLR. Similarly, a greater proportion of patients who suffer a secondary ACL surgery are subsequently diagnosed with depression/anxiety. The orthopedic community must be cognizant of the increased risk of postoperative depression/anxiety for females and those who suffer a secondary ACL surgery, and screening for depression/anxiety in these at-risk populations with referrals to mental health professionals may be warranted.

Comparison of Physical Therapy Utilization and Motion-Related Re-operations Between Isolated Anterior Cruciate Ligament and Multi-Ligament Knee Injuries.

The increased prevalence of postoperative arthrofibrosis after multi-ligament knee injuries (MLKI) compared to isolated anterior cruciate ligament (ACL) injuries has been proposed to be due, in part, to patient factors limiting physical therapy utilization. The purpose of this study was to compare demographic factors, pre- and postoperative physical therapy utilization, and the need for motion-restoring surgery between MLKI and ACL-injured patients. Using the PearlDiver Mariner 151 database, two cohorts matched by age and sex were identified using current procedural terminology (CPT) codes and included those age 16 or greater that underwent isolated ACL (n=3801) vs. MLKI reconstruction (n=3801). The number of pre- and postoperative physical therapy visits was recorded, as was the need for motion-restoring surgery (arthroscopic lysis of adhesions or manipulation under anesthesia). Demographic factors, physical therapy utilization, and the prevalence of motion-restoring surgery were compared between the MLKI and ACL groups using t-tests or chi-square tests, as appropriate. A significantly greater proportion of those with MLKI underwent subsequent motion-restoring surgery (MLKI=412/3081 (13.4%) vs. ACL=84/3081 (2.7%), p<0.001; odds ratio = 5.5 (95% CI: 4.3, 7.0), p<0.0001). Following surgery, less than half of those with MLKI that underwent subsequent motion-restoring surgery attended physical therapy, which was significantly lower than those who did not require motion-restoring surgery (p<0.0001). The prevalence of motion-restoring surgery was significantly greater after MLKI when compared to an isolated ACL injury. While the etiology of arthrofibrosis after MLKI is likely complex, the current results suggest that demographic factors and physical therapy utilization are not solely responsible for the increased risk of arthrofibrosis after MLKI.

Leveraging Insurance Claims Data to Identify Risk Factors for Posttraumatic Osteoarthritis After Multiligament Knee Reconstruction.

BACKGROUND: The incidence of subsequent posttraumatic osteoarthritis (OA) diagnosis after surgery and the associated risk factors have been well reported after single-ligament anterior cruciate ligament (ACL) reconstruction; however, to date, the incidence of posttraumatic OA for those who have experienced multiligament knee injury (MLKI) has been reported only in relatively small, single-center studies. PURPOSE: To compare the incidence of OA diagnoses between patients with ACL injury versus patients with MLKI and to identify risk factors for OA diagnosis after MLKI. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study used the PearlDiver Mariner database, which contains insurance claims information on >151 million orthopaedic patients. We identified 2 cohorts for this study by using Current Procedural Terminology codes. The cohorts included patients between the ages of 16 and 60 who underwent either isolated ACL reconstruction (n = 114,282) or MLKI reconstruction (n = 3325) between July 1, 2010, and August 30, 2016. MLKI reconstruction was operationally defined as ACL reconstruction plus concurrent surgical treatment of ≥1 additional ligaments. Demographic factors, concomitant meniscal and cartilage procedures, and subsequent reoperation to restore motion were recorded, as was the incidence of knee OA diagnosis within 5 years of the index surgical procedure. OA incidence and demographic and surgical factors were compared (1) between ACL and MLKI groups and (2) between patients with MLKI either with or without OA diagnosis. RESULTS: A significantly greater proportion of patients with MLKI were diagnosed with knee OA within 5 years of surgery (MLKI = 299/3325 [9.0%] vs ACL = 6955/114,282 [6.1%]; P < .0001) (odds ratio [OR], 1.52; 95% CI, 1.35-1.72; P < .001). Factors associated with increased odds of OA diagnosis after MLKI included age ≥30 years (OR, 5.90), reoperation to restore motion (OR, 2.54), obesity (OR, 1.96), mood disorder diagnoses (OR, 1.85), partial meniscectomy (OR, 1.85), and tobacco use (OR, 1.72). Concomitant meniscal repair was protective against OA diagnosis (OR, 0.06). CONCLUSION: OA incidence was greater after MLKI reconstruction than after isolated ACL reconstruction. Potentially modifiable risk factors for OA after MLKI were identified and include obesity, tobacco use, depression, and the need for motion-restoring surgery.

Relationship Between Quadriceps Strength and Knee Joint Power During Jumping After ACLR.

Background: Knee joint power is significantly impaired during the propulsive phase of jumping after anterior cruciate ligament reconstruction (ACLR); however, it is currently unknown how quadriceps strength influences knee joint power. Purpose: To (1) evaluate the relationship between quadriceps strength, joint power, and the percentage contribution of the hip, knee, and ankle joints to total limb power during the propulsive phase of jumping and (2) establish a quadriceps strength cutoff value for maximizing the likelihood of having knee joint power characteristics similar to healthy participants. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 75 participants were included in this study-40 patients who underwent ACLR 6 months before (18 females; mean age, 19.3 ± 5.7 years) and 35 healthy controls (HC) (20 females; mean age, 21.5 ± 4.5 years). Participants performed a drop vertical jump and underwent isometric quadriceps strength testing. The peak joint power was calculated as the product of the internal joint moment and joint angular velocity. Pearson product-moment correlations were used to assess the relationship between quadriceps strength and knee joint power. Paired samples t tests were used to quantify differences between limbs. Receiver operating characteristic (ROC) curve analysis was used to determine a quadriceps strength cutoff. Results: The involved limbs of the ACLR cohort (INV) had significantly lower peak knee joint power and percentage contribution from the knee joint during jumping compared with the uninvolved limbs (NON) and limbs of the controls (INV, 2.5 ± 1.2 W/kg; NON, 4.4 ± 1.5 W/kg; HC, 4.3 ± 1.7 W/kg [P < .0001]). Quadriceps strength was associated with knee joint power in involved limbs and limbs of controls (INV, r = 0.50; HC, r = 0.60). A quadriceps strength cutoff value of 2.07 N·m/kg had an area under the ROC curve of 0.842, indicating good predictive accuracy. Conclusion: Athletes at 6 months after ACLR demonstrated knee-avoidant jumping mechanics and had significant reductions in knee joint power on the involved limb. A quadriceps strength cutoff value of 2.07 N·m/kg can help predict which athletes will display knee joint power characteristics similar to those of healthy controls.

Synovial Fluid Inflammatory Profiles did not Differ between Isolated Anterior Cruciate Ligament and Multi-ligament Knee Injuries.

Objective and design: The purpose of this study was to compare synovial concentrations of pro- and anti-inflammatory cytokines between multiple-ligament knee injured (MLKI) and anterior cruciate ligament (ACL)-injured patients. Subjects: 14 patients with MLKI and 10 patients with isolated ACL injury. Methods: Synovial fluid was aspirated from the operative knee at the time of surgery and the concentrations of pro- and anti-inflammatory markers in the synovial fluid were determined. Structures injured, the time between injury and surgery, and demographic factors were collected. Linear regressions were used to determine the association between injury pattern and synovial inflammatory markers when controlling for age, BMI, and time between injury and surgery. Results: When adjusting for group differences in age, BMI and the time between injury and surgery, no group differences were detected (interferon gamma (p = 0.11), interleukin-1beta (IL-1b, p = 0.35), IL-2 (p = 0.28), IL-4 (p = 0.64), IL-6 (p = 0.37), IL-8 (p = 0.54), IL-10 (p = 0.25), IL-12p70 (p = 0.81), IL-13 (p = 0.31), and tumor necrosis factor-alpha (p = 0.90)). Conclusion: Synovial fluid inflammatory markers did not differ between MLKI and isolated ACL injuries. MLKIs have a greater prevalence of postoperative arthrofibrosis when compared to isolated ACL injuries; however, this may be due in part to factors other than the inflammatory status of the joint.

Depressed Protein Synthesis and Anabolic Signaling Potentiate ACL Tear-Resultant Quadriceps Atrophy.

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.

Injury rates in the National Football League during the 2020 COVID-19 season.

OBJECTIVES: The National Football League (NFL) altered the 2020 season due to the COVID-19 pandemic, which resulted in canceled preseason games and a dynamic regular season schedule to accommodate for canceled games. The purpose of this study was to evaluate if the disrupted training and preseason schedule lead to increased injury rates as seen in other professional sports. We hypothesized that the overall injury rate would be higher in the 2020 season compared to the 2018-2019 seasons and that this increase will affect all body regions equally. METHODS: Publicly released NFL weekly injury reports were queried to identify players listed as out or placed on the injured reserve for at least one game in the 2018-2020 seasons. Injuries were categorized into upper extremity, lower extremity, spine/core, head, illness, not injury related and undisclosed injuries. Incidents per 1000 athlete exposures were calculated for the prior two seasons (2018-2019) and for the 2020 season separately. Percentage of injuries occurring in each position was calculated separately for the pre-COVID-19 (2018 and 2019) and post-COVID-19 (2020) cohorts. Incidence rate ratios (IRR) and confidence intervals were used to compare injury rates in 2018-2019 versus 2020. The z-test for proportions was used to determine significant differences between injury incidences. RESULTS: The overall incidence rate per 1000 athlete exposures in 2020 was not significantly different compared to pre-COVID-19 seasons (21.6 versus 23.1, IRR 0.94, 95% CI: 0.9-1.0 p > 0.999). The proportion of injuries by position did not change before and after COVID-19 either (p > 0.999). Out listings due to illness were significantly increased during the 2020 season (0.8 versus 0.3, IRR 2.8, 95% CI: 1.4-5.2, p = 0.004). CONCLUSION: The incidence of NFL injuries did not significantly change in 2020. The distribution of injuries did not change with respect to position.

Psychosocial factors 3-months after anterior cruciate ligament reconstruction predict 6-month subjective and objective knee outcomes.

The objective of the study was to determine if psychological readiness for sport and knee self-efficacy assessed early (3 months) after anterior cruciate ligament reconstruction (ACLR) are predictive of self-reported functional outcomes, quadriceps strength, and knee mechanics while running at the time of return to sport training (6 months). Thirty athletes with unilateral ACLR completed the ACL Return to Sport after Injury (ACL-RSI) and Knee Self-Efficacy Scale (K-SES) 3 months after ACLR and completed self-reported functional outcomes, isometric quadriceps strength testing, and three-dimensional running gait analysis 6 months after ACLR. The 3-month ACL-RSI significantly correlated with the 6-month International Knee Documentation Committee (IKDC; r = 0.565, p = 0.001), Knee Injury and Osteoarthritis Outcome Score (KOOS) sport/recreational activities (KOOSSport ; r = 0.548, p = 0.002) and quality of life (KOOSQoL ; r = 0.431, p = 0.017), and quadriceps strength (r = 0.528, p = 0.003). The 3-month K-SES significantly correlated with the 6-month IKDC (r = 0.528, p = 0.003), KOOSSport (r = 0.430, p = 0.018), KOOSQoL (r = 0.411, p = 0.024), quadriceps strength (r = 0.465, p = 0.010), and knee flexion excursion (r = 0.472, p = 0.008). With multivariate modeling, both the ACL-RSI and K-SES were predictive of the IKDC (R2 = 0.411; p = 0.001). Only the ACL-RSI was predictive of the KOOSSport (R2 = 0.300; p = 0.002), KOOSQoL (R2 = 0.186; p = 0.017), and quadriceps strength (R2 = 0.279; p = 0.003), whereas only the K-SES was predictive of knee flexion excursion (R2 = 0.173; p = 0.022). Athletes with greater psychological readiness for sport and knee self-efficacy at 3 months demonstrated higher scores on self-reported functional outcomes, greater quadriceps strength, and greater knee flexion excursion at 6 months after ACLR. This study indicates that psychosocial measures may be important to include into early post-surgical evaluations to help guide and facilitate interventions to restore subjective and objective knee function.

Test Batteries After Primary Anterior Cruciate Ligament Reconstruction: A Systematic Review.

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.

Secondary Injuries After Pediatric Anterior Cruciate Ligament Reconstruction: A Systematic Review With Quantitative Analysis.

BACKGROUND: In the skeletally mature anterior cruciate ligament (ACL) reconstruction population, patients aged <25 years are at significantly increased risk of graft failure and injury to the contralateral ACL. Skeletal immaturity often affects graft selection and reconstruction technique. PURPOSE: To examine the incidence of ipsilateral graft failure and contralateral ACL injury in the skeletally immature patient population. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Using the PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines, we reviewed all literature that involved ACL reconstruction performed on skeletally immature patients between May 1976 and May 2019. Patient demographics, surgical technique, and the prevalence of ipsilateral graft failure or subsequent contralateral ACL injury were recorded. Ipsilateral, contralateral, and secondary ACL injuries were then compared between sexes via chi-square tests. RESULTS: A total of 24 articles (1254 children; 1258 knees) met inclusion criteria for analysis. Ipsilateral graft failures occurred in 105 of 1258 patients (8.3%), and there were no statistically significant sex differences in the prevalence of graft failures (female, 9.7%; male patients, 7.1%; P = .14). The prevalence of contralateral ACL injury was significantly greater in female (29/129; 22.5%) than male (18/206; 8.7%; P = .0004) patients in the 9 studies that reported contralateral injury. Skeletally immature female patients were at significantly increased risk of contralateral ACL injury (odds ratio = 3.0; P = .0006) when compared with their male counterparts. CONCLUSION: In the literature to date, 1 in 3 female skeletally immature patients experienced an ipsilateral graft failure or contralateral ACL injury. Regardless of sex, the 24% prevalence of secondary injury after pediatric ACL reconstruction is almost identical to previously published secondary injury rates in skeletally mature patients <25 years old. As such, skeletal maturity alone does not seem to be a determinant of secondary injury; however, there is a clear need to improve postoperative rehabilitation, activity progression, and return-to-play testing to allow a safe return to sports that protects the long-term health of the reconstructed and contralateral limbs, especially for female patients.

Anterior cruciate ligament reconstruction reinitiates an inflammatory and chondrodegenerative process in the knee joint.

Anterior cruciate ligament (ACL) injury leads to a sustained increase in synovial fluid concentrations of inflammatory cytokines and biomarkers of cartilage breakdown. While this has been documented post-injury, it remains unclear whether ACL reconstruction surgery contributes to the inflammatory process and/or cartilage breakdown. This study is a secondary analysis of 14 patients (nine males/five females, mean age = 9, mean BMI = 28) enrolled in an IRB-approved randomized clinical trial. Arthrocentesis was performed at initial presentation (mean = 6 days post-injury), immediately prior to surgery (mean = 23 days post-injury), 1-week post-surgery, and 1-month post-surgery. Enzyme-linked immunosorbant assay kits were used to determine concentrations of carboxy-terminal telopeptides of type II collagen (CTXII), interleukin-6 (IL-6), and IL-1ß in the synovial fluid. The log-transformed IL-1ß was not normally distributed; therefore, changes between time points were evaluated using a non-parametric Kruskal-Wallis one-way ANOVA. IL-1ß concentrations significantly increased from the day of surgery to the first postoperative time point (P ≤ .001) and significantly decreased at the 4-week postoperative visit (P = .03). IL-1ß concentrations at the 4-week postoperative visit remained significantly greater than both preoperative time points (P > .05). IL-6 concentrations at 1-week post-surgery were significantly higher than at initial presentation (P = .013), the day of surgery (P < .001), and 4 weeks after surgery (P = .002). CTX-II concentrations did not differ between the first three-time points (P > .99) but significantly increased at 4 weeks post-surgery (P < .01). ACL reconstruction appears to reinitiate an inflammatory response followed by an increase in markers for cartilage degradation. ACL reconstruction appears to initiate a second "inflammatory hit" resulting in increased chondral breakdown suggesting that post-operative chondroprotection may be needed.

Treatment After Anterior Cruciate Ligament Injury: Panther Symposium ACL Treatment Consensus Group.

Treatment strategies for anterior cruciate ligament (ACL) injuries continue to evolve. Evidence supporting best-practice guidelines for the management of ACL injury is to a large extent based on studies with low-level evidence. An international consensus group of experts was convened to collaboratively advance toward consensus opinions regarding the best available evidence on operative versus nonoperative treatment for ACL injury. The purpose of this study was to report the consensus statements on operative versus nonoperative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. There were 66 international experts on the management of ACL injuries, representing 18 countries, who were convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the scientific organizing committee and session chairs for the 3 working groups. Panel participants reviewed preliminary statements before the meeting and provided initial agreement and comments on the statement via online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Ultimately, 80% agreement was defined a priori as consensus. A total of 11 of 13 statements on operative versus nonoperative treatment of ACL injury reached consensus during the symposium. Overall, 9 statements achieved unanimous support, 2 reached strong consensus, 1 did not achieve consensus, and 1 was removed because of redundancy in the information provided. In highly active patients engaged in jumping, cutting, and pivoting sports, early anatomic ACL reconstruction is recommended because of the high risk of secondary meniscal and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight-plane activities, nonoperative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomic ACL reconstruction is indicated. The consensus statements derived from international leaders in the field will assist clinicians in deciding between operative and nonoperative treatment with patients after an ACL injury.

Dysregulated Inflammatory Response Related to Cartilage Degradation after ACL Injury.

PURPOSE: Elevated synovial fluid (SF) concentrations of proinflammatory cytokines, degradative enzymes, and cartilage breakdown markers at the time of anterior cruciate ligament (ACL) reconstruction are associated with worse postoperative patient-reported outcomes and cartilage quality. However, it remains unclear if this is due to a more robust or dysregulated inflammatory response or is a function of a more severe injury. The objective of this study was to evaluate the association of the molecular composition of the SF, patient demographics, and injury characteristics to cartilage degradation after acute ACL injury. METHODS: We performed a cluster analysis of SF concentrations of proinflammatory and anti-inflammatory cytokines, and biomarkers of cartilage degradation, bony remodeling, and hemarthrosis. We evaluated the association of biomarker clusters with patient demographics, days between injury, Visual Analogue Scale pain, SF aspirate volumes, and bone bruise volumes measured on magnetic resonance imaging. RESULTS: Two clusters were identified from the 35 patients included in this analysis, dysregulated inflammation and low inflammation. The dysregulated inflammation cluster consisted of 10 patients and demonstrated significantly greater concentrations of biomarkers of cartilage degradation (P < 0.05) as well as a lower ratio of anti-inflammatory to proinflammatory cytokines (P = 0.053) when compared with the low inflammation cluster. Patient demographics, bone bruise volumes, SF aspirate volumes, pain, and concomitant injuries did not differ between clusters. CONCLUSIONS: A subset of patients exhibited dysregulation of the inflammatory response after acute ACL injury which may increase the risk of posttraumatic osteoarthritis. This response does not appear to be a function of injury severity.