Validation of Panoramic Ultrasound Measurement of the Cross-Sectional Area of the Vastus Medialis.

ABSTRACT: Minnehan, KS, Dexter, WW, Holt, CT, Scharnetzki, L, Alex, JP, Chin, KE, and Kokmeyer, DJ. Validation of panoramic ultrasound measurement of the cross-sectional area of the vastus medialis. J Strength Cond Res 37(1): 41-45, 2023-The cross-sectional area (CSA) of the vastus medialis (VM) is an independent predictor of important clinical outcomes in musculoskeletal conditions of the knee, such as pain and long-term function. Previous studies validated ultrasound (US) to measure larger muscles of the thigh, but this approach has limited accuracy in measuring smaller muscles, such as the VM. In this study, we aimed to validate panoramic US measurements of the CSA of the VM and compare the results with those from the gold standard of magnetic resonance imaging (MRI) (significance set p ≤ 0.05). In this retrospective, single-center study, we compared pairs of US and MRIs taken of 25 adults who participated in a 10-week study of non-weight-bearing activity at a National Aeronautics and Space Administration facility. Images were acquired from various locations on the right thigh at multiple time points. Two researchers independently analyzed the US and MRI pairs by outlining the intermuscular border of the VM in the most distal image. We found excellent agreement between the US and MRI measurements of the CSA of the VM analyzed by researcher 1 (interclass correlation coefficient [ICC]: 0.997) and researcher 2 (ICC: 0.980). We also found excellent agreement for interrater reliability for MRI (ICC: 0.988) and US (ICC: 0.982) and intrarater reliability for US for researcher 1 (ICC: 0.999) and researcher 2 (ICC: 0.996). Our findings demonstrate that US is a valid and reliable tool for measuring the CSA of the VM compared with MRI.

Participation in Physical Activity at Time of Presentation to a Specialty Concussion Clinic Is Associated With Shorter Time to Recovery.

INTRODUCTION: Novel research suggests that children engaging in physical activity during recovery from concussion may recover more rapidly. OBJECTIVE: To determine if level of physical activity at presentation to a rehabilitation-based concussion specialty clinic predicted days from injury to recovery. DESIGN: Retrospective cohort. SETTING: A concussion sub-specialty clinic at an academic institution. PATIENTS: Retrospective review of medical records between September 2015 and February 2017 identified 178 children ages 6-17 years (mean age = 13.7 years; standard deviation [SD] = 2.7 years) who presented within 60 days of concussion and were ultimately deemed recovered and cleared to progress to full return to high-risk activities. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Physical activity at initial visit was classified as none-to-light (79%) versus moderate-to-heavy (21%). A doubly robust, inverse probability of exposure weighted linear regression model was used to examine the relationship between physical activity level and days to recovery, while adjusting for 10 demographic and clinical variables. RESULTS: Children participating in moderate-to-heavy activity at initial evaluation in concussion clinic averaged recovery 21 days quicker (95% confidence interval [CI] -27.1, -15.5, P < .001) than children who were engaging in none-to-light activity. This finding did not change when removing children who were deemed recovered at the first visit (who may have initiated physical activity after becoming asymptomatic). CONCLUSIONS: These data add to growing evidence that progressive physical activity during recovery from concussion does not appear to be harmful. Physical activity represents a modifiable variable in recovery, and physicians can potentially expedite symptomatic recovery by recommending noncontact physical activity as tolerated during concussion recovery.

Cartilage Damage Is Related to ACL Stiffness in a Porcine Model of ACL Repair.

Inferior anterior cruciate ligament (ACL) structural properties may inadequately restrain tibiofemoral joint motion following surgery, contributing to the increased risk of post-traumatic osteoarthritis. Using both a direct measure of ACL linear stiffness and an in vivo magnetic resonance imaging (MRI) T2 *-based prediction model, we hypothesized that cartilage damage and ACL stiffness would increase over time, and that an inverse relationship between cartilage damage and ACL stiffness would emerge at a later stage of healing. After either 6, 12, or 24 weeks (w) of healing after ACL repair, ACL linear stiffness was determined from the force-displacement relationship during tensile testing ex vivo and predicted in vivo from the MRI T2 *-based multiple linear regression model in 24 Yucatan minipigs. Tibiofemoral cartilage was graded postmortem. There was no relationship between cartilage damage and ACL stiffness at 6 w (R2 = 0.04; p = 0.65), 12 w (R2 = 0.02; p = 0.77), or when the data from all animals were pooled (R2 = 0.02; p = 0.47). A significant inverse relationship between cartilage damage and ACL stiffness based on both ex vivo measurement (R2 = 0.90; p < 0.001) and in vivo MRI prediction (R2 = 0.78; p = 0.004) of ACL stiffness emerged at 24 w. This result suggests that 90% of the variability in gross cartilage changes is associated with the repaired ACL linear stiffness at 6 months of healing. Clinical Significance: Techniques that provide a higher stiffness to the repaired ACL may be required to mitigate the post-traumatic osteoarthritis commonly seen after ACL injury, and MRI T2 * can be used as a noninvasive estimation of ligament stiffness. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2249-2257, 2019.

Magnetic resonance measurements of tissue quantity and quality using T2 * relaxometry predict temporal changes in the biomechanical properties of the healing ACL.

The purpose of this study was to develop a magnetic resonance T2 * relaxometry-based multiple linear regression model to predict the structural properties of the healing anterior cruciate ligament (ACL) over a 24-week healing period following ACL repair in Yucatan minipigs. Two hypotheses were tested: (i) that a regression model based on ACL sub-volumes containing short and long T2 * relaxation times would outperform a competing model based on sub-volumes of short T2 * relaxation times only; and (ii) that an optimized regression model would be capable of predicting ACL structural properties between 6 and 24 weeks post-repair. ACLs were imaged in 24 minipigs (8/group) at either 6, 12, or 24 weeks after ACL repair. The structural properties of the ACLs were determined from tensile failure tests. Four multiple linear regression models of increasing complexity were fitted to the data. Akaike Information Criterion values and Bland-Altman tests were used to compare model performance and to test the hypotheses. The structural properties predicted from the multiple linear regression model that was based on the change in ACL sub-volumes of both the short and long T2 * relaxation times over the healing period were in closest agreement to the measured values, suggesting that the amounts of both organized and disorganized collagen, and the change in these quantities over time, are required to predict the structural properties of healing ACLs accurately. CLINICAL SIGNIFICANCE: our time-specific, T2 *-based regression model may allow us to estimate the structural properties of ACL repairs in vivo longitudinally. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1701-1709, 2018.

Transcriptional profiling of synovium in a porcine model of early post-traumatic osteoarthritis.

To determine the transcriptional profile of synovium during the molecular phase of post-traumatic osteoarthritis, anterior cruciate ligament transections (ACL) were performed in 36 Yucatan minipigs. Equal numbers were randomly assigned to no further treatment, ACL reconstruction or repair. Perimeniscal synovium for histopathology and RNA-sequencing was harvested at 1 and 4 weeks post-operatively and from six healthy control animals. Microscopic synovitis scores significantly worsened at 1 (p < 0.001) and 4 weeks (p = 0.003) post-surgery relative to controls, and were driven by intimal hyperplasia and increased stromal cellularity without inflammatory infiltrates. Synovitis scores were similar between no treatment, reconstruction, and repair groups (p ≥ 0.668). Relative to no treatment at 1 week, 88 and 367 genes were differentially expressed in the reconstruction and repair groups, respectively (227 and 277 at 4 weeks). Relative to controls and with the treatment groups pooled, 1,683 transcripts were concordantly differentially expressed throughout the post-surgery time-course. Affected pathways included, proteolysis_connective tissue degradation (including upregulations of protease-encoding MMP1, MMP13, and ADAMTS4), and development_cartilage development (including upregulations of ACAN, SOX9, and RUNX2), among others. Using linear regression, significant associations of post-surgery synovial expression levels of 20 genes with the articular cartilage glycosaminoglycan loss were identified. These genes were predominantly related to embryonic skeletal system development and included RUNX2. In conclusion, this study confirmed an increased synovial expression of genes that may serve as targets to prevent cartilage degradation, including MMP1, MMP13, and ADAMTS4, in knees with microscopic synovitis and cartilage proteoglycan loss. Attractive novel targets include regulators of embryonic developmental processes in synovium. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Transcriptional profiling of articular cartilage in a porcine model of early post-traumatic osteoarthritis.

To identify the molecular pathophysiology present in early post-traumatic osteoarthritis (PTOA), the transcriptional profile of articular cartilage and its response to surgical PTOA induction were determined. Thirty six Yucatan minipigs underwent anterior cruciate ligament (ACL) transection and were randomly assigned in equal numbers to no further treatment, reconstruction or ligament repair. Cartilage was harvested at 1 and 4 weeks post-operatively and histology and RNA-sequencing were performed and compared to controls. Microscopic cartilage scores significantly worsened at 1 (p = 0.028) and 4 weeks (p = 0.001) post-surgery relative to controls, but did not differ between untreated, reconstruction or repair groups. Gene expression after ACL reconstruction and ACL transection were similar, with only 0.03% (including SERPINB7 and CR2) and 0.2% of transcripts (including INHBA) differentially expressed at 1 and 4 weeks respectively. COL2A1, COMP, SPARC, CHAD, and EF1ALPHA were the most highly expressed non ribosomal, non mitochondrial genes in the controls and remained abundant after surgery. A total of 1,275 genes were differentially expressed between 1 and 4 weeks post-surgery. With the treatment groups pooled, 682 genes were differentially expressed at both time-points, with the most significant changes observed in MMP1, COCH, POSTN, CYTL1, and PTGFR. This study confirmed the development of a microscopic PTOA stage after ACL surgery in the porcine model. Upregulation of multiple proteases (including MMP1 and ADAMTS4) were found; however, the level of expression remained orders of magnitude below that of extracellular matrix protein-coding genes (including COL2A1 and ACAN). In summary, genes with established roles in PTOA as well as novel targets for specific intervention were identified. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:318-329, 2018.

Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage After Destabilization of the Medial Meniscus in the Yucatan Minipig.

BACKGROUND: Lubricin, or proteoglycan 4 (PRG4), is a glycoprotein responsible for joint boundary lubrication. PRG4 has been shown previously to be down-regulated after traumatic joint injury such as a meniscal tear. Preliminary evidence suggests that intra-articular injection of PRG4 after injury will reduce cartilage damage in rat models of surgically induced posttraumatic osteoarthritis. OBJECTIVE: To determine the efficacy of intra-articular injection of full-length recombinant human lubricin (rhPRG4) for reducing cartilage damage after medial meniscal destabilization (DMM) in a preclinical large animal model. STUDY DESIGN: Controlled laboratory study. METHODS: Unilateral DMM was performed in 29 Yucatan minipigs. One week after DMM, animals received 3 weekly intra-articular injections (3 mL per injection): (1) rhPRG4 (1.3 mg/mL; n = 10); (2) rhPRG4+hyaluronan (1.3 mg/mL rhPRG4 and 3 mg/mL hyaluronan [~950 kDA]; n = 10); and (3) phosphate-buffered saline (PBS; n = 9). Hindlimbs were harvested 26 weeks after surgery. Cartilage integrity was evaluated by use of macroscopic (India ink) and microscopic (safranin O-fast green and hematoxylin and eosin) scoring systems. Secondary outcomes evaluated via enzyme-linked immunosorbent assay (ELISA) included PRG4 levels in synovial fluid, carboxy-terminal telepeptide of type II collagen (CTX-II) concentrations in urine and serum, and interleukin 1ß (IL-1ß) levels in synovial fluid and serum. RESULTS: The rhPRG4 group had significantly less macroscopic cartilage damage in the medial tibial plateau compared with the PBS group ( P = .002). No difference was found between the rhPRG4+hyaluronan and PBS groups ( P = .23). However, no differences in microscopic damage scores were observed between the 3 groups ( P = .70). PRG4 production was elevated in the rhPRG4 group synovial fluid compared with the PBS group ( P = .033). The rhPRG4 group presented significantly lower urinary CTX-II levels, but not serum levels, when compared with the PBS ( P = .013) and rhPRG4+hyaluronan ( P = .011) groups. In serum and synovial fluid, both rhPRG4 ( P = .006; P = .017) and rhPRG4+hyaluronan groups ( P = .009; P = .03) presented decreased IL-1ß levels. CONCLUSION: All groups exhibited significant cartilage degeneration after DMM surgery. However, animals treated with rhPRG4 had the least amount of cartilage damage and less inflammation, providing evidence that intra-articular injections of rhPRG4 may slow the progression of posttraumatic osteoarthritis. CLINICAL RELEVANCE: Patients with meniscal trauma are at high risk for posttraumatic osteoarthritis. This study demonstrates that an intra-articular injection regimen of rhPRG4 may attenuate cartilage damage after meniscal injury.

Extracellular matrix-blood composite injection reduces post-traumatic osteoarthritis after anterior cruciate ligament injury in the rat.

The objective of this study was to determine if an injection of a novel extracellular matrix scaffold and blood composite (EMBC) after anterior cruciate ligament (ACL) injury would have a mitigating effect on post-traumatic osteoarthritis (PTOA) development in rat knees. Lewis rats underwent unilateral ACL transection and were divided into three groups as follows: (1) no further treatment (ACLT; n = 10); (2) an intra-articular injection of EMBC on day 0 (INJ0; n = 11); and (3) an intra-articular injection of EMBC on day 14 (INJ14; n = 11). Ten additional animals received capsulotomy only (n = 10, SHAM group). The OARSI histology scoring of the tibial cartilage and micro-CT of the tibial epiphysis were performed after 35 days. The ratio of intact/treated hind limb forces during gait was determined using a variable resistor walkway. The OARSI cartilage degradation sum score and total degeneration width were significantly greater in the ACLT group when compared to the INJ0 (p = 0.031, and p = 0.005) and INJ14 (p = 0.022 and p = 0.04) group. Weight bearing on the operated limb only decreased significantly in the ACLT group (p = 0.048). In the rat ACL transection model, early or delayed injection of EMBC ameliorated the significant decrease in weight bearing and cartilage degradation seen in knees subjected to ACL transection without injection. The results indicate that the injection of EMBC may slow the process of PTOA following ACL injury and may provide a promising treatment for PTOA. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:995-1003, 2016.

Effect of Matching or Overconstraining Knee Laxity During Anterior Cruciate Ligament Reconstruction on Knee Osteoarthritis and Clinical Outcomes: A Randomized Controlled Trial With 84-Month Follow-up.

BACKGROUND: The "initial graft tension" applied at the time of graft fixation during anterior cruciate ligament (ACL) reconstruction surgery modulates joint contact mechanics, which in turn may promote posttraumatic osteoarthritis (OA). PURPOSE/HYPOTHESES: The study objectives were to compare clinical, functional, patient-reported, and OA imaging outcomes between 2 different initial laxity-based graft tension cohorts and a matched uninjured control group as well as to evaluate the effects of laxity-based graft tension on OA development at 84-month follow-up. The 2 laxity-based tension protocols were (1) to restore normal anteroposterior (AP) laxity at the time of surgery relative to the contralateral uninjured knee (low-tension group) or (2) to overconstrain AP laxity by 2 mm relative to the contralateral uninjured knee (high-tension group). The hypotheses were that (1) the high-tension group would have improved outcomes and decreased OA compared with the low-tension group after 84 months, and (2) the outcomes for the high-tension group would be equivalent to those for an age-, sex-, race-, and activity-matched group of control participants with uninjured knees. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients had their ACLs reconstructed with either a bone-patellar tendon-bone or 4-stranded hamstring autograft, and outcomes were compared with a matched control group. Outcomes were evaluated preoperatively and at 60 and 84 months postoperatively and included clinical (KT-1000 arthrometer AP laxity measurement and International Knee Documentation Committee [IKDC] examination score), functional (1-legged hop for distance and knee extensor torque), patient-reported (Knee injury and Osteoarthritis Outcome Score [KOOS], Short Form-36 [SF-36], and patient satisfaction survey), and OA imaging (measurement of joint space width [JSW], Osteoarthritis Research Society International [OARSI] radiographic score, and Whole-Organ Magnetic Resonance Imaging Score [WORMS]) components. Repeated-measures analyses of variance were used to evaluate differences in outcomes between the treatment groups and the control group. RESULTS: There were significant differences between the 2 tension groups in 1 of 5 KOOS subscales (sports and recreation; P = .04) and 2 of 8 SF-36 subscales (vitality, mental health; P < .04) at 84 and 60 months, respectively. Both tension groups scored significantly worse than the control group in the IKDC examination (P < .001), 1-legged hop (P ≤ .017), KOOS quality of life and symptoms subscales (P < .03), and OARSI radiographic score (P ≤ .02) at 84 months. The low-tension group performed significantly worse than the control group on the KOOS pain subscale (P = .03), SF-36 general health and social functioning (P < .04), OARSI radiographic score (P < .001), and WORMS (P = .001), while the high-tension group had statistically different results than the control group in AP knee laxity (P < .001), radiographic JSW (P = .003), and OARSI radiographic score (P = .02) as well as significantly more subsequent knee injuries (P = .02) at 84 months. CONCLUSION: The results do not support the hypotheses that the high-tension group would have improved outcomes when compared with the low-tension group after 84 months of healing or that the outcomes for the high-tension group would be equivalent to those for the matched control group. While there were minor differences in patient-reported outcomes between the 2 laxity-based tension groups, all other outcomes were similar. REGISTRATION: NCT00434837.