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OBJECTIVE: To study the effect of anterior cruciate ligament (ACL) injury on lubricin concentrations in synovial fluid (SF) and its correlation with time postinjury, inflammatory cytokines, lubricin-degrading enzymes, and SF proteoglycan content. METHODS: SF samples were obtained from both knees of 30 patients with unilateral ACL insufficiency, 32-364 days postinjury. Lubricin, inflammatory cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor alpha [TNFalpha], and IL-6), and catabolic enzymes (procathepsin B and neutrophil elastase) were measured in SF from injured and contralateral (uninjured) joints, by enzyme-linked immunosorbent assay. Sulfated glycosaminoglycan (sGAG) levels in the SF were measured by Alcian blue binding assay. RESULTS: SF lubricin concentrations were significantly (P < 0.001) reduced at an early stage following ACL injury when compared with those in the contralateral joint. Within 12 months, the lubricin concentration in the injured knee (slope = 0.006, SE = 0.00010, P < 0.001) approached that in the contralateral knee, which did not change with time (slope = -0.0002, SE = 0.00050, P = 0.71). TNFalpha levels showed a significant negative relationship with log(2) lubricin levels. IL-1beta, TNFalpha, IL-6, procathepsin B, and neutrophil elastase concentrations in SF from injured knees were greater in samples from recently injured knees compared with those that were chronically injured. There were no detectable cytokines or enzymes in the SF of contralateral joints. Concentrations of sGAG were significantly (P = 0.0002) higher in the SF from injured knees compared with the contralateral joints. CONCLUSION: The decrease in SF lubricin concentrations following ACL injury may place the joint at an increased risk of wear-induced damage as a consequence of lack of boundary lubrication, potentially leading to secondary osteoarthritis. The decrease in SF lubricin was associated with an increase in levels of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) reconstruction can effectively return athletes to the playing field, but they are still at risk of developing posttraumatic osteoarthritis (PTOA). No studies have used multivariable analysis to evaluate the predictors of radiographic PTOA in the lateral compartment of the knee at short-term follow-up after ACL reconstruction., Purpose: To determine the predictors of radiographic joint space narrowing in the lateral compartment 2 to 3 years after ACL reconstruction in a young, active cohort., Study Design: Cohort study; Level of evidence, 2., Methods: A nested cohort of 358 patients from the Multicenter Orthopaedic Outcomes Network (MOON) prospective cohort who were aged ≤33 years, were injured playing a sport, and had never undergone surgery on the contralateral knee were followed up 2 years after ACL reconstruction with questionnaires and with weightbearing knee radiographs using the metatarsophalangeal (MTP) joint technique. The joint space width in the lateral compartment was measured using a semiautomatic computerized method, and multivariable predictive modeling was used to evaluate the relationship between meniscus treatment, cartilage injury, graft type, and joint space while adjusting for age, sex, body mass index, and Marx activity score., Results: The mean lateral joint space width was 0.11 mm narrower on the ACL-reconstructed knee compared with the contralateral healthy knee (7.69 mm vs 7.80 mm, respectively; P < .01). Statistically significant predictors of a narrower joint space width on the ACL-reconstructed knee included lateral meniscectomy ( P < .001) and a Marx activity score less than 16 points ( P < .001)., Conclusion: This study identifies lateral meniscectomy and a lower baseline Marx activity score to be predictors of radiographic joint space narrowing in the lateral compartment 2 to 3 years after ACL reconstruction in young, active patients without a prior knee injury.

Objective: To identify risk factors for radiographic signs of post-traumatic osteoarthritis (OA) 2-3 years after anterior cruciate ligament (ACL) reconstruction through multivariable analysis of minimum joint space width (mJSW) differences in a specially designed nested cohort., Methods: A nested cohort within the Multicenter Orthopaedic Outcomes Network (MOON) cohort included 262 patients (148 females, average age 20) injured in sport who underwent ACL reconstruction in a previously uninjured knee, were 35 or younger, and did not have ACL revision or contralateral knee surgery. mJSW on semi-flexed radiographs was measured in the medial compartment using a validated computerized method. A multivariable generalized linear model was constructed to assess mJSW difference between the ACL reconstructed and contralateral control knees while adjusting for potential confounding factors., Results: Unexpectedly, we found the mean mJSW was 0.35 mm wider in ACL reconstructed than in control knees (5.06 mm (95% CI 4.96-5.15 mm) vs 4.71 mm (95% CI 4.62-4.80 mm), P < 0.001). However, ACL reconstructed knees with meniscectomy had narrower mJSW compared to contralateral normal knees by 0.64 mm (95% C.I. 0.38-0.90 mm) (P < 0.001). Age (P < 0.001) and meniscus repair (P = 0.001) were also significantly associated with mJSW difference., Conclusion: Semi-flexed radiographs can detect differences in mJSW between ACL reconstructed and contralateral normal knees 2-3 years following ACL reconstruction, and the unexpected wider mJSW in ACL reconstructed knees may represent the earliest manifestation of post-traumatic osteoarthritis and warrants further study., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Clinical, functional, and patient-oriented outcomes are commonly used to evaluate the efficacy of treatments after anterior cruciate ligament (ACL) injury; however, these evaluation techniques do not directly measure the biomechanical changes that occur with healing., Purpose: To determine if the magnetic resonance (MR) image-derived parameters of graft volume and signal intensity (SI), which have been used to predict the biomechanical (ie, structural) properties of the graft in animal models, correlate with commonly used clinical (anteroposterior [AP] knee laxity), functional (1-legged hop), and patient-oriented outcome measures (Knee Injury and Osteoarthritis Outcome Score [KOOS]) in patients 3 and 5 years after ACL reconstruction., Study Design: Cohort study (diagnosis); Level of evidence, 3., Methods: Based on a subset of participants enrolled in an ongoing ACL reconstruction clinical trial, AP knee laxity, 1-legged hop test, and KOOS were assessed at 3- and 5-year follow-up. Three-dimensional, T1-weighted MR images were collected at each visit. Both the volume and median SI of the healing graft were determined and used as predictors in a multiple regression linear model to predict the traditional outcome measures., Results: Graft volume combined with median SI in a multiple linear regression model predicted 1-legged hop test at both the 3- and 5-year follow-up visits (R(2) = 0.40, P = .008 and R(2) = 0.62, P = .003, respectively). Similar results were found at the 5-year follow-up for the KOOS quality of life (R(2) = 0.49, P = .012), sport/function (R(2) = 0.37, P = .048), pain (R(2) = 0.46, P = .017), and symptoms (R(2) = 0.45, P = .021) subscores, although these variables were not significant at 3 years. The multiple linear regression model for AP knee laxity at 5-year follow-up approached significance (R(2) = 0.36, P = .088)., Conclusion: The MR parameters (volume and median SI) used to predict ex vivo biomechanical properties of the graft in an animal model have the ability to predict clinical or in vivo outcome measures in patients at 3- and 5-year follow-up., Clinical Relevance: Results from this study may enhance clinical evaluation of graft health by relating the MR parameters of volume and median SI to traditional outcome measures and could potentially aid researchers in determining the appropriate timing for athletes to return to sport., (© 2014 The Author(s).)

Background: The initial graft tension applied at the time of anterior cruciate ligament (ACL) reconstruction alters joint contact and may influence cartilage health. The objective was to compare outcomes between 2 commonly used "laxity-based" initial graft tension protocols., Hypotheses: (1) The high-tension group would have less knee laxity, improved clinical and patient-oriented outcomes, and less cartilage damage than would the low-tension group after 36 months of healing. (2) The outcomes of the high-tension group would be equivalent to those of a matched control group., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: Ninety patients with isolated unilateral ACL injuries were randomized to undergo ACL reconstruction using 1 of 2 initial graft tension protocols: (1) autografts tensioned to restore normal anterior-posterior (AP) laxity at the time of surgery (ie, low tension; n = 46) and (2) autografts tensioned to overconstrain AP laxity by 2 mm (ie, high tension; n = 44). Sixty matched healthy patients formed the control group. Outcomes were assessed preoperatively, intraoperatively, and at 6, 12, and 36 months after surgery., Results: No significant differences were found between the 2 initial graft tension protocols for any of the outcome measures at 36 months. However, there were differences when comparing the 2 treatment groups to the control group. On average, AP laxity was 2 mm greater in the ACL-reconstructed groups than in the control group (P < .007). International Knee Documentation Committee (IKDC) knee evaluation scores, peak isokinetic knee extension torques, and 4 of 5 Knee Osteoarthritis Outcome Scores (KOOS) were significantly worse than the control group (P < .001, P < .027, and P < .05, respectively). Short Form-36 Health Survey (SF-36) scores and reinjury rates were similar between groups at 36 months. Although there were significant changes in radiography and magnetic resonance imaging present in the ACL-reconstructed knees of both treatment groups, the magnitude was relatively small and likely clinically insignificant at 36 months., Conclusion: Both laxity-based initial graft tension protocols produced similar outcomes without fully restoring joint function or patient-oriented outcomes (KOOS) when compared with the control group. There was minimal evidence of cartilage damage 36 months after surgery.

Background: Quantifying changes in meniscal volume in vivo before and after partial meniscectomy (PM) could help elucidate the mechanisms involved in osteoarthritis development after meniscal injury and its surgical treatment. Purpose/, Hypothesis: To determine whether quantitative magnetic resonance imaging (qMRI) can detect the immediate reduction in meniscal volume created by PM, while ruling out changes in unresected structures. We hypothesized that qMRI would be reliable for determining meniscal volume within the repeated images of unresected menisci. Additionally, we expected no significant difference in volume between the uninjured menisci of the injured knees and the same menisci of the uninjured knees., Study Design: Cohort study (Diagnosis); Level of evidence, 2., Methods: Ten subjects with meniscal tears were evaluated with 3-T MRI before and after arthroscopic PM. Manual segmentation was used to create models of the menisci and to determine the preoperative and postoperative meniscal volumes for each subject. The responsiveness and reliability of qMRI for determining meniscal volume in vivo were evaluated using these measurements. We expected a decrease in volume of the resected menisci, but not in the uninjured menisci, after surgery., Results: The mean preoperative volume of the injured menisci was significantly greater than the mean postoperative volume (2896 +/- 277 vs 2480 +/- 277 mm(3); P = .000). There was no significant difference between the mean preoperative and postoperative volumes of the uninjured menisci (2687 +/- 256 vs 2694 +/- 256 mm(3); P = 1.000)., Conclusion: Manual segmentation demonstrated a significant reduction in the volume of the surgically resected menisci after PM, but no significant change in the volume of unresected meniscal tissue, indicating that the manual segmentation method is responsive., Clinical Relevance: This approach offers a novel, reliable method to study the relationship between the volume of meniscal tissue removed during PM and subsequent patient outcomes during long-term clinical studies.

Objective: Early detection of glycosaminoglycan (GAG) loss may provide insight into mechanisms of cartilage damage in the anterior cruciate ligament (ACL)-injured patient. We hypothesized that tibial and femoral Delayed Gadolinium-Enhanced MR Imaging of Cartilage (dGEMRIC) indices would be lower in the medial compartment of the ACL-injured knee than in the contralateral, uninjured knee, and that scan order (i.e., whether the injured or the uninjured knee was imaged first) would not affect the indices., Methods: 15 subjects with unilateral ACL injuries received a double dose of gadolinium [Gd(DTPA)(2-)] intravenously. After 90 min, both knees were sequentially imaged. The injured knee was scanned first in the odd-numbered subjects and second in the even-numbered subjects. The dGEMRIC indices of the median slice of the medial compartment were determined using the MRIMapper software. Index comparisons were made between knee status (ACL-injured vs uninjured), scan order (ACL-injured first vs uninjured first), and cartilage location (tibia vs femur) using a mixed model., Results: There was a significant difference in the mean dGEMRIC indices of the medial compartment between injured and uninjured knees (P<0.007). On average, there was a 13% decrease in the dGEMRIC index of the injured knee compared to the uninjured knee. There were no significant effects due to test order (P=0.800) or cartilage location (P=0.439)., Conclusions: The results demonstrate lower GAG concentrations in the medial compartment of the femoral and tibial articular cartilage of the ACL-injured knee when compared to the contralateral uninjured knee. The dGEMRIC indices were not sensitive to scan order; thus, sequential imaging of both knees is possible in this patient population., (Copyright 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

This study aimed to evaluate sources of variability when the metatarsal-phalangeal (MTP) semiflexed radiographic technique is used to measure the tibiofemoral joint space width in the medial and lateral compartments of the knee. Three independent digital MTP radiographs were obtained from both knees of 9 participants. The joint space widths of both compartments of each knee were measured 3 times by 2 independent examiners. Intraclass correlation coefficients were high between repeated radiographs, between examiners, and within examiners (range, 0.91-0.98). These 3 error components accounted for 9% and 14% of the total variance for the medial and lateral compartments, respectively. The estimated SDs across radiographs for the medial and lateral compartments were 0.093 mm and 0.155 mm. The digital radiographic technique based on the MTP view is a simple and reliable technique for measuring the joint space width that can be readily used to track longitudinal changes in cartilage thickness after knee joint surgery.

Background: Many receptors located within the intra-articular knee structures contribute to the neuromuscular responses of the knee. The purpose was to compare the automatic postural response induced by a perturbation at the foot before and after an intra-articular injection of a local anesthetic (bupivicaine), after a saline (sham) injection, and after no intra-articular injection (control) in the knee., Methods: Muscle onset latencies and automatic response magnitudes for the vastus medialis, vastus lateralis, biceps femoris, medial hamstrings, tibialis anterior, and gastrocnemius were measured using electromyography (EMG) when anteriorly directed perturbations were applied to the feet of 30 subjects. All subjects then received a lidocaine skin injection followed by: an intra-articular bupivicaine injection (treatment group); an intra-articular saline injection (sham group); or no injection (control group), depending on their randomized group assignment. The perturbation tests were then repeated., Findings: Muscle onset latencies and automatic response magnitudes did not change as a result of the intra-articular injections. Latencies were significantly greater for the vastus medialis and vastus lateralis when compared to the medial hamstrings, biceps femoris and tibialis anterior (P<0.001). Automatic response magnitudes for the tibialis anterior were significantly greater than those of the hamstrings, which were greater than those of the quadriceps (P<0.001)., Interpretation: There were no differences in muscle response when anteriorly directed perturbations were applied to the foot with or without an injection of local anesthetic in the knee. Intra-articular receptors were either unaffected by the anesthetic or the extra-articular receptors or receptors of the other joints were able to compensate for their loss.