Telehealth Potential in Pediatric Orthopaedics and Sports Medicine Care is Comparable to In-Person Care But Disparities Remain.

BACKGROUND: Understanding the challenges and potential of telehealth visits (THVs) in a large population can inform future practice and policy discussion for pediatric orthopaedic and sports medicine (OSM) care. We comprehensively assess telehealth challenges and potential in a large pediatric OSM population based on access, visit completion, patient satisfaction, and technological challenges. METHODS: Demographics, address, insurance, visit information, patient feedback, experience with video visits, and technical challenges of all 2019 to 2020 visits at our hospital were assessed (3,278,006 visits). We evaluated the differences in rate of telehealth utilization, rate of patient adherence, disparities in care access and patient satisfaction, and technological issues. RESULTS: Compared with in-person prepandemic visits, THVs had lower ratios of non-White patients (by 5.8%; P <0.001), Hispanic patients (by 2.8%; P <0.001) and patients with public insurance (by 1.8%; P <0.001), and a higher mean distance between the patient's residence and clinic (by 18.8 miles; P <0.001). There were minimal differences in median household income (average $2297 less in THV; P <0.001) and social vulnerability index (average 0.01 points lower in THV; P <0.001) between groups. THVs had comparable patient satisfaction to in-person visits. Non-White patients, Hispanics, and those with public insurance had lower ratings for both in-person visits and THVs and had more technical difficulties during their THV. CONCLUSIONS: Telehealth is a viable method of care for a range of pediatric OSM conditions, providing a similar quality of care as in-person visits with a greater geographic reach. However, in its current format, reduced disparities were not observed in pediatric OSM THVs. LEVEL OF EVIDENCE: Level III.

Microscopic and transcriptomic changes in porcine synovium one year following disruption of the anterior cruciate ligament.

OBJECTIVE: There is no disease-modifying treatment for posttraumatic osteoarthritis (PTOA). This may be partly due to an incomplete understanding of synovitis, which has been causally linked to PTOA progression. The microscopic and transcriptomic changes in synovium seen in early- to mid-stage PTOA were evaluated to better characterize this knowledge gap. METHODS: Seventy-two Yucatan minipigs underwent transection of the anterior cruciate ligament (ACL). Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair, followed by microscopic synovium evaluation and RNA-sequencing at 1, 4, and 52 weeks. Six additional subjects received no ligament transection and served as 1- and 4-week controls and 12 contralateral knees served as 52-week controls. RESULTS: Synovial lining thickness, stromal cellularity, and overall microscopic synovitis reached their highest levels in the first few weeks following injury. Inflammatory infiltration continued to increase over the course of a year. Leaving the ACL transected, reconstructing the ligament, or repairing the ligament did not modulate synovitis development at 1, 4, or 52 weeks. Differential gene expression analysis of PTOA-affected synovium compared to control synovium revealed increased cell proliferation, angiogenesis, collagen breakdown, and diminished lipid metabolism at 1 and 4 weeks, and increased axonogenesis and focal adhesion with reduced immune activation at 52 weeks. CONCLUSIONS: Synovitis was present one year after ACL injury and was not alleviated by surgical intervention. Gene expression in early synovitis was characterized by cell proliferation, angiogenesis, proteolysis, and reduced lipolysis, which was followed by nerve growth and cellular adhesion with less immune activation at 52 weeks.

Early MRI-based quantitative outcomes are associated with a positive functional performance trajectory from 6 to 24 months post-ACL surgery.

PURPOSE: Quantitative magnetic resonance imaging (qMRI) has been used to determine the failure properties of ACL grafts and native ACL repairs and/or restorations. How these properties relate to future clinical, functional, and patient-reported outcomes remain unknown. The study objective was to investigate the relationship between non-contemporaneous qMRI measures and traditional outcome measures following Bridge-Enhanced ACL Restoration (BEAR). It was hypothesized that qMRI parameters at 6 months would be associated with clinical, functional, and/or patient-reported outcomes at 6 months, 24 months, and changes from 6 to 24 months post-surgery. METHODS: Data of BEAR patients (n = 65) from a randomized control trial of BEAR versus ACL reconstruction (BEAR II Trial; NCT02664545) were utilized retrospectively for the present analysis. Images were acquired using the Constructive Interference in Steady State (CISS) sequence at 6 months post-surgery. Single-leg hop test ratios, arthrometric knee laxity values, and International Knee Documentation Committee (IKDC) subjective scores were determined at 6 and 24 months post-surgery. The associations between traditional outcomes and MRI measures of normalized signal intensity, mean cross-sectional area (CSA), volume, and estimated failure load of the healing ACL were evaluated based on bivariate correlations and multivariable regression analyses, which considered the potential effects of age, sex, and body mass index. RESULTS: CSA (r = 0.44, p = 0.01), volume (r = 0.44, p = 0.01), and estimated failure load (r = 0.48, p = 0.01) at 6 months were predictive of the change in single-leg hop ratio from 6 to 24 months in bivariate analysis. CSA (ßstandardized = 0.42, p = 0.01), volume (ßstandardized = 0.42, p = 0.01), and estimated failure load (ßstandardized = 0.48, p = 0.01) remained significant predictors when considering the demographic variables. No significant associations were observed between MRI variables and either knee laxity or IKDC when adjusting for demographic variables. Signal intensity was also not significant at any timepoint. CONCLUSION: The qMRI-based measures of CSA, volume, and estimated failure load were predictive of a positive functional outcome trajectory from 6 to 24 months post-surgery. These variables measured using qMRI at 6 months post-surgery could serve as prospective markers of the functional outcome trajectory from 6 to 24 months post-surgery, aiding in rehabilitation programming and return-to-sport decisions to improve surgical outcomes and reduce the risk of reinjury. LEVEL OF EVIDENCE: Level II.

Biomechanical Outcomes of Bridge-enhanced Anterior Cruciate Ligament Repair Are Influenced by Sex in a Preclinical Model.

BACKGROUND: Despite the well-established role of sex on the anterior cruciate ligament (ACL) injury risk, its effects on ACL surgical outcomes remain controversial. This is particularly critical when developing novel surgical techniques to treat the injury because there are limited data existing on how these procedures will respond in each sex. One such approach is bridge-enhanced ACL repair, in which primary suture repair of the ACL is augmented with a bioactive scaffold saturated with autologous blood. It has shown comparable biomechanical outcomes to ACL reconstruction in preclinical models. QUESTIONS/PURPOSES: We asked (1) whether sex affects the biomechanical outcomes of bridge-enhanced ACL repair; and (2) if suture type (absorbable or nonabsorbable), used to repair the torn ACL, can minimize the potential sex discrepancies in outcomes after 15 weeks of healing in a large animal preclinical model. METHODS: Seventeen (eight males, nine females) Yorkshire pigs (Parson's Farms, Hadley, MA, USA) underwent bilateral ACL transection and received bridge-enhanced ACL repair with an absorbable suture (n=17) on one side and with a nonabsorbable suture (n=17) on the other side. The leg receiving the absorbable suture was randomized within each animal. ACL structural properties and AP knee laxity for each knee were measured after 15 weeks of healing. Mixed linear models were used to compare the biomechanical outcomes between sexes and suture groups. RESULTS: When treated with absorbable suture, females had a lower ACL linear stiffness (females, 11 N/mm [range, 8-42]; males, 31 N/mm [range, 12-56]; difference, 20 N/mm [95% confidence interval {CI}, 4-36]; p=0.032), ACL yield (females, 121 N [range, 56-316]; males, 224 N [range, 55-538]; difference, 103 N [95% CI, 6-200]; p=0.078), and maximum load (females, 128 N [range, 63-332]; males, 241 N [range, 82-538]; difference, 114 N [95% CI, 15-212]; p=0.052) than males after 15 weeks of healing. Female knees treated with absorbable suture had a lower linear stiffness (absorbable, 11 N/mm [range, 8-42]; nonabsorbable, 25 N/mm [range, 8-64]; difference, 14 [95% CI, 2-26] N; p=0.054), ACL yield (absorbable, 121 N [range, 56-316]; nonabsorbable, 230 N [range, 149-573]; difference, 109 N [95% CI, 56-162]; p=0.002), and maximum load (absorbable, 128 N [range, 63-332]; nonabsorbable, 235 N [range, 151-593]; difference, 107 N [95% CI, 51-163]; p=0.002) along with greater AP knee laxity at 30° (absorbable, 9 mm [range, 5-12]; nonabsorbable, 7 mm [range, 2-13]; difference, 2 mm [95% CI, 1-4]; p=0.034) than females treated with nonabsorbable suture. When repaired using nonabsorbable suture, the biomechanical outcomes were similar between female and male knees (p>0.10). CONCLUSIONS: Females had significantly worse biomechanical outcomes than males when the repairs were performed using absorbable sutures. However, the use of nonabsorbable sutures ameliorated these differences between males and females. CLINICAL RELEVANCE: The current findings highlight the critical role of sex on the biomechanical outcomes of bridge-enhanced ACL repair in a relevant large animal model. Better understanding of the mechanisms responsible for these observations using preclinical models and concomitant clinical studies in human patients may allow for additional development of sex-specific surgical and rehabilitative strategies with potentially improved outcomes in women.

Validation of porcine knee as a sex-specific model to study human anterior cruciate ligament disorders.

BACKGROUND: Animal models have long been considered an important modality for studying ACL injuries. However, to our knowledge, the value of these preclinical models to study sex-related phenomena associated with ACL injury and recovery has not been evaluated. QUESTIONS/PURPOSES: We asked whether (1) prominent anatomic and (2) biomechanical factors differ between female and male porcine knees, particularly those known to increase the risk of ACL injury. METHODS: Eighteen intact minipig knees (nine males, nine females) underwent MRI to determine the femoral bicondylar width, intercondylar notch size (width, area and index), medial and lateral tibial slope, ACL size (length, cross-sectional area, and volume), and medial compartment tibiofemoral cartilage thickness. AP knee laxity at 30°, 60°, and 90° flexion and ACL tensile structural properties were measured using custom-designed loading fixtures in a universal tensile testing apparatus. Comparisons between males and females were performed for all anatomic and biomechanical measures. The findings then were compared with published data from human knees. RESULTS: Female pigs had smaller bicondylar widths (2.9 mm, ratio=0.93, effect size=-1.5) and intercondylar notches (width: 2.0 mm, ratio=0.79, effect size=-2.8; area: 30.8 mm2, ratio=0.76, effect size=-2.1; index: 0.4, ratio=0.84, effect size=-2.0), steeper lateral tibial slope (4.3°, ratio=1.13, effect size=1.1), smaller ACL (length: 2.7 mm, ratio=0.91, effect size=-1.1; area: 6.8 mm2, ratio=0.74, effect size=-1.5; volume: 266.2 mm3, ratio=0.68, effect size=-1.5), thinner medial femoral cartilage (0.4 mm, ratio=0.8, effect size=-1.1), lower ACL yield load (275 N, ratio=0.81, effect size=-1.1), and greater AP knee laxity at 30° (0.7 mm, ratio=1.32, effect size=1.1) and 90° (0.5 mm, ratio=1.24, effect size=1.1) flexion compared with their male counterparts. These differences were significant for all parameters (p≤0.04). Observed sex-related differences were similar to those reported for the human knee. CONCLUSIONS: Significant differences exist between knees of male and female pigs with respect to prominent anatomic and biomechanical factors. Our findings strongly agreed with published data regarding human knees. CLINICAL RELEVANCE: The findings highlight the use of the porcine large animal model to study the role of sex on ACL injuries and surgical outcome. This validated preclinical model may facilitate the development of novel, sex-specific interventions to prevent and treat ACL injuries for male and female patients.

Bio-enhanced repair of the anterior cruciate ligament.

Suture repair of the anterior cruciate ligament (ACL) has been widely abandoned in favor of ACL reconstruction, largely because of the high rates of failure and unreliability of the outcomes after suture repair. However, there have been recent basic science studies that suggest that combining a suture repair with a biological adjunct may improve the results of suture repair of the ACL, with several studies in large animal models showing equivalent strength of an ACL treated with bio-enhanced repaired to that of an ACL graft at 3, 6, and 12 months after surgery. In addition, the groups treated with bio-enhanced repair had significantly less osteoarthritis when compared with the animals undergoing ACL reconstruction. These findings have led to a renewed interest in bio-enhanced primary repair as a way to make repair of the ACL a viable option for a select group of patients in the future.

Increased platelet concentration does not improve functional graft healing in bio-enhanced ACL reconstruction.

PURPOSE: The use of an extracellular matrix scaffold (ECM) combined with platelets to enhance healing of an anterior cruciate ligament (ACL) graft ("bio-enhanced ACL reconstruction") has shown promise in animal models. However, the effects of platelet concentration on graft healing remain unknown. The objectives of this study were to determine whether increasing the platelet concentration in the ECM scaffold would (1) improve the graft biomechanical properties and (2) decrease cartilage damage after surgery. METHODS: Fifty-five adolescent minipigs were randomized to five treatment groups: untreated ACL transection (n = 10), conventional ACL reconstruction (n = 15) and bio-enhanced ACL reconstruction using 1× (n = 10), 3× (n = 10) or 5× (n = 10) platelet-rich plasma. The graft biomechanical properties, anteroposterior (AP) knee laxity, graft histology and macroscopic cartilage integrity were measured at 15 weeks. RESULTS: The mean linear stiffness of the bio-enhanced ACL reconstruction procedure using the 1× preparation was significantly greater than traditional reconstruction, while the 3× and 5× preparations were not. The failure loads of all the ACL-reconstructed groups were equivalent but significantly greater than untreated ACL transection. There were no significant differences in the Ligament Maturity Index or AP laxity between reconstructed knees. Macroscopic cartilage damage was relatively minor, though significantly less when the ECM-platelet composite was used. CONCLUSIONS: Only the 1× platelet concentration improved healing over traditional ACL reconstruction. Increasing the platelet concentration from 1× to 5× in the ECM scaffold did not further improve the graft mechanical properties. The use of an ECM-platelet composite decreased the amount of cartilage damage seen after ACL surgery.

A normative study of the synovial fluid proteome from healthy porcine knee joints.

Synovial fluid in an articulating joint contains proteins derived from the blood plasma and proteins that are produced by cells within the joint tissues, such as synovium, cartilage, ligament, and meniscus. The proteome composition of healthy synovial fluid and the cellular origins of many synovial fluid components are not fully understood. Here, we present a normative proteomics study using porcine synovial fluid. Using our optimized method, we identified 267 proteins with high confidence in healthy synovial fluid. We also evaluated mRNA expression data from tissues that can contribute to the synovial fluid proteome, including synovium, cartilage, blood, and liver, to better estimate the relative contributions from these sources to specific synovial fluid components. We identified 113 proteins in healthy synovial fluid that appear to be primarily derived from plasma transudates, 37 proteins primarily derived from synovium, and 11 proteins primarily derived from cartilage. Finally, we compared the identified synovial fluid proteome to the proteome of human plasma, and we found that the two body fluids share many similarities, underlining the detected plasma derived nature of many synovial fluid components. Knowing the synovial fluid proteome of a healthy joint will help to identify mechanisms that cause joint disease and pathways involved in disease progression.

Expression of modulators of extracellular matrix structure after anterior cruciate ligament injury.

The ability of the anterior cruciate ligament (ACL) to heal after injury declines within the first 2 weeks after ACL rupture. To begin to explore the mechanism behind this finding, we quantified the expression of genes for collagen I and III, decorin, tenascin-C, and alpha smooth muscle actin, as well as matrix metalloproteinase (MMP)-1 and -13 gene expression within multiple tissues of the knee joint after ACL injury in a large animal model over a 2-week postinjury period. Gene expression of collagen I and III, decorin, and MMP-1 was highest in the synovium, whereas the highest MMP-13 gene expression levels were found in the ACL. The gene expression for collagen and decorin increased over the 2 weeks to levels approaching that in the ligament and synovium; however, no significant increase in either of the MMPs was found in the provisional scaffold. This suggests that although the ACL and synovium up-regulate both anabolic and catabolic factors, the provisional scaffold is primarily anabolic in function. The relative lack of provisional scaffold formation within the joint environment may thus be one of the key reasons for ACL degradation after injury.

How Research Improves Clinical Care: The Case for Orthopaedic Surgeon Research Leadership and Collaboration: AOA Critical Issues Symposium.

ABSTRACT: Improving the performance and impact of orthopaedic research is a critical leadership challenge. Musculoskeletal (MSK) conditions are a leading cause of disability worldwide, for which research investment and performance lags far behind the burden of disease. In the United States, MSK disorders account for the highest health care costs, have increased in incidence at the fastest rate, and exceed the combined costs of cardiovascular diseases and neoplasms. Despite the cost to society, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), with primary responsibility for MSK research, receives <1.4% of the funds allocated to the National Institutes of Health (NIH). Although orthopaedic surgeons are leading providers of MSK clinical care, the dearth of orthopaedic clinician-scientists also greatly reduces representation of MSK scientific and clinical expertise among academic and scientific leaders. The goals of this symposium were to highlight the critical need for greater prioritization and investment in orthopaedic research and to engage orthopaedic leaders in addressing these needs. Compelling stories of research success from 3 orthopaedic chairs were featured to highlight how orthopaedic surgeon leadership in bench-to-bedside research substantially advances MSK clinical care. Seminar participants also emphasized the need to improve evidence-based clinical practice for which multicenter prospective cohort and registry studies represent opportunities for broader involvement. Prioritization of orthopaedic clinician-scientist development and formation of multidisciplinary partnerships with basic and translational scientists were emphasized as critical needs to advance MSK health. It is critical for orthopaedic chairs to "be invested in" and to "invest in" the success of orthopaedic research. This investment includes developing a professional climate that values research achievement and collaboration as well as implementing strategies to support and sustain research success. Finally, orthopaedic leaders need to advocate for federal research funding to be proportional to the economic burden of disease for which MSK conditions carry the highest current and projected costs. With health-care costs accounting for nearly one-fifth of the U.S. economy, increasing the investment in orthopaedic research to reduce the prevalence, disability, and morbidity from MSK disease needs to be a top orthopaedic and national leadership priority.

Pediatric and Adolescent Distal Radius Fractures: Current Concepts and Treatment Recommendations.

Distal radius fractures are the most common skeletal injuries requiring intervention in children. These injuries are classified by fracture pattern, location, displacement, and angulation. While each unique fracture pattern warrants slightly modified treatment plans and follow-up, the goals of treatment remain constant. Successful outcomes depend on restoration of motion and function, and attaining acceptable sagittal and coronal alignment is a necessary first step. For displaced fractures, closed reduction is often necessary to restore alignment; well-molded cast application is important to maintain fracture alignment. Fractures with bayonet apposition, if well aligned, may not need formal reduction in some patients. Special attention should be paid to the physis-not only for physeal-involving fractures but also for all distal radius fractures-given that the proximity to the physis and amount of remaining skeletal growth help guide treatment decisions. Casting technique is essential in optimizing the best chance in maintaining fracture reduction. Surgical intervention may be indicated for a subset of fractures when acceptable alignment is not achieved or is lost at subsequent follow-up. Even among experts in the field, there is little consensus as to the optimal treatment of displaced metaphyseal fractures, illustrating the need for prospective, randomized studies to establish best practices.

Bridge-Enhanced Anterior Cruciate Ligament Restoration: 6-Year Results From the First-in-Human Cohort Study.

Background: Bridge-enhanced anterior cruciate ligament restoration (BEAR) combines suture repair of the anterior cruciate ligament (ACL) with an extracellular matrix implant plus autologous blood to facilitate native ACL healing. Purpose/Hypothesis: The purpose of this study was to compare the 6-year follow-up outcomes of patients who underwent the BEAR procedure with those of a nonrandomized concurrent control group receiving autograft ACL reconstruction (ACLR) in the first-in-human safety study of the BEAR implant (BEAR I trial). Based on the 2-year results, it was hypothesized that isometric hamstring strength after the BEAR procedure would be greater than that after ACLR and that there would be no other differences in outcomes at 6 years. Study Design: Cohort study, Level of evidence, 2. Methods: Ten patients underwent BEAR and 10 received ACLR with a 4-stranded hamstring autograft. Outcomes assessed included the record of subsequent surgeries, the International Knee Documentation Committee (IKDC) Subjective Knee Score, IKDC physical examination grade, the Knee injury and Osteoarthritis Outcome Score, instrumented knee laxity, functional outcomes (ie, muscle strength assessments and hop testing), and qualitative magnetic resonance imaging assessment. Comparisons between treatments were based on computations of the mean differences and the associated 95% CIs. Results: One patient in the BEAR group and 3 patients in the ACLR group were lost to follow-up. In the period between 2 and 6 years, 1 patient in each group underwent revision surgery. There were no differences between groups at the 6-year follow-up in any of the outcome measures except for isometric hamstring strength, which was approximately equal to that of the contralateral knee in the BEAR group and <44% of that in the contralateral knee in the ACLR group (P < .01). Conclusion: This preliminary study suggests that the outcomes of BEAR and ACLR with a hamstring tendon graft may be similar at the 6-year follow-up and warrants investigation of the BEAR procedure in a larger cohort of patients.

Prevalence and Predictors of Concomitant Meniscal Surgery During Pediatric and Adolescent ACL Reconstruction: Analysis of 4729 Patients Over 20 Years at a Tertiary-Care Regional Children's Hospital.

Background: The rate of concomitant meniscal procedures performed in conjunction with anterior cruciate ligament (ACL) reconstruction is increasing. Few studies have examined these procedures in high-risk pediatric cohorts. Hypotheses: That (1) the rates of meniscal repair compared with meniscectomy would increase throughout the study period and (2) patient-related factors would be able to predict the type of meniscal operation, which would differ according to age. Study Design: Cohort study (prevalence); Level of evidence, 2. Methods: Natural language processing was used to extract clinical variables from notes of patients who underwent ACL reconstruction between 2000 and 2020 at a single institution. Patients were stratified to pediatric (5-13 years) and adolescent (14-19 years) cohorts. Linear regression was used to evaluate changes in the prevalence of concomitant meniscal surgery during the study period. Logistic regression was used to determine predictors of the need for and type of meniscal procedure. Results: Of 4729 patients (mean age, 16 ± 2 years; 54.7% female) identified, 2458 patients (52%) underwent concomitant meniscal procedures (55% repair rate). The prevalence of lateral meniscal (LM) procedures increased in both pediatric and adolescent cohorts, whereas the prevalence of medial meniscal (MM) repair increased in the adolescent cohort (P = .02). In the adolescent cohort, older age was predictive of concomitant medial meniscectomy (P = .031). In the pediatric cohort, female sex was predictive of concomitant MM surgery and of undergoing lateral meniscectomy versus repair (P≤ .029). Female sex was associated with decreased odds of concomitant LM surgery in both cohorts (P≤ .018). Revision ACLR was predictive of concomitant MM surgery and of meniscectomy (medial and lateral) in the adolescent cohort (P < .001). Higher body mass index was associated with increased odds of undergoing medial meniscectomy versus repair in the pediatric cohort (P = .03). Conclusion: More than half of the young patients who underwent ACLR had meniscal pathology warranting surgical intervention. The prevalence of MM repair compared with meniscectomy in adolescents increased throughout the study period. Patients who underwent revision ACLR were more likely to undergo concomitant meniscal surgeries, which were more often meniscectomy. Female sex had mixed effects in both the pediatric and adolescent cohorts.

Prevalence and Predictors of Concomitant Meniscal and Ligamentous Injuries Associated With ACL Surgery: An Analysis of 20 Years of ACL Reconstruction at a Tertiary Care Children's Hospital.

BACKGROUND: There is an increasing rate of procedures being performed for concomitant injuries during anterior cruciate ligament (ACL) surgery. Few studies have examined risk factors for these associated injuries in young patients. HYPOTHESIS: There are patient-related factors predictive of concomitant knee pathology that differ between age-based cohorts. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Natural language processing was used to extract clinical variables from available notes of patients undergoing ACL surgery between 2000 and 2020 at a single institution (5174 ACL surgeries; mean age, 17 ± 4 years; 53.1% female; accuracy, >98%). Patients were stratified to pediatric (5-13 years), adolescent (14-19 years), and young adult (20-35 years) cohorts. Logistic regression was used to determine predictors of concomitant injury to the menisci, medial collateral ligament (MCL), posterolateral corner (PLC), and posterior cruciate ligament (PCL). RESULTS: Between 2000 and 2020, 54% of pediatric, 71% of adolescent, and 70% of adult patients had ≥1 concomitant soft tissue injury. In children and adolescents, increased age was consistently predictive of sustaining a concomitant injury (P < .02). Female children had increased odds of concomitant medial meniscal injury, while female adults had decreased odds (P≤ .046). Adolescent and adult female patients had decreased odds of concomitant lateral meniscal injury (P≤ .027). Female children had increased odds of injury to the MCL (P = .015), whereas female children and adolescents had decreased odds of PCL injury (P≤ .044). Adolescents undergoing revision ACL surgery had increased odds of meniscal injury (P≤ .001) and decreased odds of concomitant MCL injury (P = .028). Increased body mass index (BMI) was associated with increased odds of concomitant medial meniscal injury in all cohorts (P≤ .041), lateral meniscal injury in adults (P = .045), and PLC injury in children (P = .016). Contact injuries were associated with increased odds of MCL injury in adolescents (P = .017) and PLC injury in adolescents and adults (P < .014). CONCLUSION: These findings support the hypothesis, as there were multiple factors that significantly affected the risk of concomitant injuries that differed between cohorts. Increased age, BMI, and contact injury history were generally associated with increased odds of sustaining a concomitant injury, whereas female sex and revision ACL surgery had mixed effects. Further studies are essential to investigate the sex-based differences in risk for concomitant injuries and to develop tailored treatment plans that minimize the risk of secondary ACL injury.

Comprehensive evaluation of magnetic resonance imaging sequences for signal intensity based assessment of anterior cruciate ligament healing following surgical treatment.

Normalized signal intensity (SI) obtained from magnetic resonance imaging (MRI) has been used to track anterior cruciate ligament (ACL) postoperative remodeling. We aimed to assess the effect of MRI sequence (PD: proton density-weighted; T2: T2-weighted; CISS: constructive interference in steady state) on postoperative changes in healing ACLs/grafts. We hypothesized that CISS is better at detecting longitudinal SI and texture changes of the healing ACL/graft compared to the common clinical sequences (PD and T2). MR images of patients who underwent ACL surgery were evaluated and separated into groups based on surgical procedure (Bridge-Enhanced ACL Repair (BEAR; n = 50) versus ACL reconstruction (ACLR; n = 24)). CISS images showed decreasing SI across all timepoints in both the BEAR and ACLR groups (p < 0.01), PD and T2 images showed decreasing SI in the 6-to-12- and 12-to-24-month postoperative timeframes in the BEAR group (p < 0.02), and PD images additionally showed decreasing SI between 6- and 24-months postoperation in the ACLR group (p = 0.02). CISS images showed texture changes in both the BEAR and ACLR groups, showing increases in energy and decreases in entropy in the 6-to-12- and 6-to-24-month postoperative timeframes in the BEAR group (p < $\lt $ 0.04), and increases in energy, decreases in entropy, and increases in homogeneity between 6 and 24 months postoperation in the ACLR group (p < 0.04). PD images showed increases in energy and decreases in entropy between 6- and 24-months postoperation in the ACLR group (p < 0.008). Finally, CISS was estimated to require a smaller sample size than PD and T2 to detect SI differences related to postoperative remodeling.

Effects of suture choice on biomechanics and physeal status after bioenhanced anterior cruciate ligament repair in skeletally immature patients: a large-animal study.

PURPOSE: The objective of this study was to assess the effect of absorbable or nonabsorbable sutures in bioenhanced anterior cruciate ligament (ACL) repair in a skeletally immature pig model on suture tunnel and growth plate healing and biomechanical outcomes. METHODS: Sixteen female skeletally immature Yorkshire pigs were randomly allocated to receive unilateral, bioenhanced ACL repair with an absorbable (Vicryl) or nonabsorbable (Ethibond) suture augmented by an extracellular matrix-based scaffold (MIACH). After 15 weeks of healing, micro-computed tomography was used to measure residual tunnel diameters and growth plate status, and biomechanical outcomes were assessed. RESULTS: At 15 weeks postoperatively, there was a significant difference in tunnel diameter with significantly larger diameters in the nonabsorbable suture group (4.4 ± 0.3 mm; mean ± SD) than in the absorbable group (1.8 ± 0.5 mm; P < .001). The growth plate showed a significantly greater affected area in the nonabsorbable group (15.2 ± 3.4 mm(2)) than in the absorbable group (2.7 ± 0.8 mm(2), P < .001). There was no significant difference in the linear stiffness of the repairs (29.0 ± 14.8 N/mm for absorbable v 43.3 ± 28.3 N/mm for nonabsorbable sutures, P = .531), but load to failure was higher in the nonabsorbable suture group (211 ± 121.5 N) than in the absorbable suture group (173 ± 101.4 N, P = .002). There was no difference between the 2 groups in anteroposterior laxity at 30° (P = .5117), 60° (P = .3150), and 90° (P = .4297) of knee flexion. CONCLUSIONS: The use of absorbable sutures for ACL repair resulted in decreased physeal plate damage after 15 weeks of healing; however, use of nonabsorbable sutures resulted in 20% stronger repairs. CLINICAL RELEVANCE: Choice of suture type for ACL repair or repair of tibial avulsion fractures may depend on patient skeletal age and size, with absorbable sutures preferred in very young, small patients at higher risk with physeal damage and nonabsorbable sutures preferred in larger, prepubescent patients who may place higher loads on the repair.

Responding to ACL Injury and its Treatments: Comparative Gene Expression between Articular Cartilage and Synovium.

The relationship between cartilage and synovium is a rapidly growing area of osteoarthritis research. However, to the best of our knowledge, the relationships in gene expression between these two tissues have not been explored in mid-stage disease development. The current study compared the transcriptomes of these two tissues in a large animal model one year following posttraumatic osteoarthritis induction and multiple surgical treatment modalities. Thirty-six Yucatan minipigs underwent transection of the anterior cruciate ligament. Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair augmented with an extracellular matrix (ECM) scaffold, followed by RNA sequencing of the articular cartilage and synovium at 52 weeks after harvest. Twelve intact contralateral knees served as controls. Across all treatment modalities, the primary difference in the transcriptomes was that the articular cartilage had greater upregulation of genes related to immune activation compared to the synovium-once baseline differences between cartilage and synovium were adjusted for. Oppositely, synovium featured greater upregulation of genes related to Wnt signaling compared to articular cartilage. After adjusting for expression differences between cartilage and synovium seen following ligament reconstruction, ligament repair with an ECM scaffold upregulated pathways related to ion homeostasis, tissue remodeling, and collagen catabolism in cartilage relative to synovium. These findings implicate inflammatory pathways within cartilage in the mid-stage development of posttraumatic osteoarthritis, independent of surgical treatment. Moreover, use of an ECM scaffold may exert a chondroprotective effect over gold-standard reconstruction through preferentially activating ion homeostatic and tissue remodeling pathways within cartilage.

Predicting anterior cruciate ligament failure load with T2* relaxometry and machine learning as a prospective imaging biomarker for revision surgery.

Non-invasive methods to document healing anterior cruciate ligament (ACL) structural properties could potentially identify patients at risk for revision surgery. The objective was to evaluate machine learning models to predict ACL failure load from magnetic resonance images (MRI) and to determine if those predictions were related to revision surgery incidence. It was hypothesized that the optimal model would demonstrate a lower mean absolute error (MAE) than the benchmark linear regression model, and that patients with a lower estimated failure load would have higher revision incidence 2 years post-surgery. Support vector machine, random forest, AdaBoost, XGBoost, and linear regression models were trained using MRI T2* relaxometry and ACL tensile testing data from minipigs (n = 65). The lowest MAE model was used to estimate ACL failure load for surgical patients at 9 months post-surgery (n = 46) and dichotomized into low and high score groups via Youden's J statistic to compare revision incidence. Significance was set at alpha = 0.05. The random forest model decreased the failure load MAE by 55% (Wilcoxon signed-rank test: p = 0.01) versus the benchmark. The low score group had a higher revision incidence (21% vs. 5%; Chi-square test: p = 0.09). ACL structural property estimates via MRI may provide a biomarker for clinical decision making.

Transcriptomic changes in porcine articular cartilage one year following disruption of the anterior cruciate ligament.

To determine the transcriptomic changes seen in early- to mid-stage posttraumatic osteoarthritis (PTOA) development, 72 Yucatan minipigs underwent transection of the anterior cruciate ligament. Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair, followed by articular cartilage harvesting and RNA-sequencing at three different postoperative timepoints (1, 4, and 52 weeks). Six additional subjects received no ligament transection and provided cartilage tissue to serve as controls. Differential gene expression analysis between post-transection cartilage and healthy cartilage revealed an initial increase in transcriptomic differences at 1 and 4 weeks followed by a stark reduction in transcriptomic differences at 52 weeks. This analysis also showed how different treatments genetically modulate the course of PTOA following ligament disruption. Specific genes (e.g., MMP1, POSTN, IGF1, PTGFR, HK1) were identified as being upregulated in the cartilage of injured subjects across all timepoints regardless of treatment. At the 52-week timepoint, 4 genes (e.g., A4GALT, EFS, NPTXR, ABCA3) that-as far as we know-have yet to be associated with PTOA were identified as being concordantly differentially expressed across all treatment groups when compared to controls. Functional pathway analysis of injured subject cartilage compared to control cartilage revealed overarching patterns of cellular proliferation at 1 week, angiogenesis, ECM interaction, focal adhesion, and cellular migration at 4 weeks, and calcium signaling, immune system activation, GABA signaling, and HIF-1 signaling at 52 weeks.

Three-dimensional magnetic resonance imaging analysis shows sex-specific patterns in changes in anterior cruciate ligament cross-sectional area along its length.

Smaller anterior cruciate ligament (ACL) size in females has been hypothesized to be a key contributor to a higher incidence of ACL tears in that population, as a lower cross-sectional area (CSA) directly corresponds to a larger stress on the ligament for a given load. Prior studies have used a mid-length CSA measurement to quantify ACL size. In this study, we used magnetic resonance imaging to quantify the CSA along the entire length of the intact ACL. We hypothesized that changes in the ACL CSA along its length would have different patterns in males and females. We also hypothesized that changes in ACL CSA along its length would be associated with body size or knee size with different associations in females and males. MR images of contralateral ACL-intact knees of 108 patients (62 females, 13-35 years) undergoing ACL surgery were used to measure the CSA along the ACL length, using a custom program. For both females and males, the largest CSA was located at 37%-39% of ACL length from the tibial insertion. Compared to females, males had a significantly larger CSA only within the distal 41% of the ACL (p < 0.001). ACL CSA was associated with patient height and weight in males (r > 0.3; p < 0.05), whereas it was associated with intercondylar notch width in females (r > 0.3; p < 0.05). These findings highlight the importance of standardizing the location of measurement of ACL CSA.