Christina R. Allen

The effects of platelet-derived growth factor-BB on healing of the rabbit medial collateral ligament : An in vivo study

We report a biologic approach to improve medial collateral ligament healing using growth factors normally expressed in healing tissue. Our previous in vitro work demonstrated that platelet-derived growth factor-BB and transforming growth factor- 1 promoted fibroblast proliferation and matrix synthesis, respectively. Therefore, these growth factors were used in vivo to determine whether they could improve medial collateral ligament healing, whether this effect was dose-dependent, and if combinations of growth factors could improve healing more than individual growth factors. Thirty-seven rabbits had various doses of growth factors applied to the ruptured right medial collateral ligaments using a fibrin sealant delivery vehicle. The five groups consisted of 1) two groups receiving two doses of platelet-derived growth factor-BB, 2) two groups receiving two doses of this growth factor plus transforming growth factor- 1, and 3) one group receiving fibrin sealant only. After sacrifice at 6 weeks, biomechanical and histologic evaluations of the healing ligament were performed. Femur-medial collateral ligament-tibia complexes of the knees given the higher dose of platelet-derived growth factor-BB had ultimate load, energy absorbed to failure, and ultimate elongation values that were 1.6, 2.4, and 1.6 times greater than the same complexes of the control group. Adding transforming growth factor- 1 did not lead to any further increases in the structural properties of the complex compared with treatment with platelet-derived growth factor-BB. These encouraging results suggest that use of platelet-derived growth factor-BB may improve the quality of the healing medial collateral ligament, and that it may also have a similar potential for promoting healing of other ligaments.

Descriptive epidemiology of the Multicenter ACL Revision Study (MARS) cohort.

Background Revision anterior cruciate ligament (ACL) reconstruction has worse outcomes than primary reconstructions. Predictors for these worse outcomes are not known. The Multicenter ACL Revision Study (MARS) Group was developed to perform a multisurgeon, multicenter prospective longitudinal study to obtain sufficient subjects to allow multivariable analysis to determine predictors of clinical outcome. Purpose To describe the formation of MARS and provide descriptive analysis of patient demographics and clinical features for the initial 460 enrolled patients to date in this prospective cohort. Study Design Cross-sectional study; Level of evidence, 2. Methods After training and institutional review board approval, surgeons began enrolling patients undergoing revision ACL reconstruction, recording patient demographics, previous ACL reconstruction methods, intra-articular injuries, and current revision techniques. Enrolled subjects completed a questionnaire consisting of validated patient-based outcome measures. Results As of April 1, 2009, 87 surgeons have enrolled a total of 460 patients (57% men; median age, 26 years). For 89%, the reconstruction was the first revision. Mode of failure as deemed by the revising surgeon was traumatic (32%), technical (24%), biologic (7%), combination (37%), infection (<1%), and no response (<1%). Previous graft present at the time of injury was 70% autograft, 27% allograft, 2% combination, and 1% unknown. Sixty-two percent were more than 2 years removed from their last reconstruction. Graft choice for revision ACL reconstruction was 45% autograft, 54% allograft, and more than 1% both allograft and autograft. Meniscus and/or chondral damage was found in 90% of patients. Conclusion The MARS Group has been able to quickly accumulate the largest revision ACL reconstruction cohort reported to date. Traumatic reinjury is deemed by surgeons to be the most common single mode of failure, but a combination of factors represents the most common mode of failure. Allograft graft choice is more common in the revision setting than autograft. Concomitant knee injury is extremely common in this population.

Revision anterior cruciate ligament reconstruction

Revision ACL surgery is indicated in patients who present with pathologic anterior laxity on clinical examination that reproduces their symptoms of instability during activities of daily living or athletic activities. The goals of the revision ACL surgery are to stabilize the knee, prevent further injury to the articular cartilage and menisci, and maximize the patients function. Successful revision ACL surgery requires a thorough preoperative evaluation, including a detailed history, physical examination, and radiographic evaluation. Preoperative planning begins with a determination of the mechanisms of failure for the initial ACL reconstruction. Often a primary, as well as secondary cause, for failure can be identified. The determination of the cause of failure is the first step in a carefully-constructed treatment plan, which includes consideration of skin incisions to be used, method of graft removal, hardware removal, the need for a staged procedure or concomitant surgery, graft material selection, tunnel placement, graft fixation, and postoperative rehabilitation protocol. Despite the most meticulous planning, unanticipated findings may be encountered in the operating room, and the preoperative plan should have enough flexibility to accommodate these developments. Finally, it is crucial to counsel the patient preoperatively to limit his or her expectations regarding their surgical outcome. Given the complexity of revision ACL reconstruction, patient expectations must be adjusted to realistically match the potential for success. With proper planning, attention to detail, and appropriate patient expectations, revision ACL surgery can result in a beneficial and satisfying patient outcome.

Effect of Graft Choice on the Outcome of Revision Anterior Cruciate Ligament Reconstruction in the Multicenter ACL Revision Study (MARS) Cohort

Background: Most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome; however, graft choice for revision may be limited due to previously used grafts. Hypotheses: Autograft use would result in increased sports function, increased activity level, and decreased osteoarthritis symptoms (as measured by validated patient-reported outcome instruments). Autograft use would result in decreased graft failure and reoperation rate 2 years after revision ACL reconstruction. Study Design: Cohort study; Level of evidence, 2. Methods: Patients undergoing revision ACL reconstruction were identified and prospectively enrolled by 83 surgeons at 52 sites. Data collected included baseline demographics, surgical technique, pathologic abnormalities, and the results of a series of validated, patient-reported outcome instruments (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], and Marx activity rating score). Patients were followed up at 2 years and asked to complete the identical set of outcome instruments. Incidences of additional surgery and reoperation due to graft failure were also recorded. Multivariate regression models were used to determine the predictors (risk factors) of IKDC, KOOS, WOMAC, Marx scores, graft rerupture, and reoperation rate at 2 years after revision surgery. Results: A total of 1205 patients (697 [58%] males) were enrolled. The median age was 26 years. In 88% of patients, this was their first revision, and 341 patients (28%) were undergoing revision by the surgeon who had performed the previous reconstruction. The median time since last ACL reconstruction was 3.4 years. Revision using an autograft was performed in 583 patients (48%), allograft was used in 590 (49%), and both types were used in 32 (3%). Questionnaire follow-up was obtained for 989 subjects (82%), while telephone follow-up was obtained for 1112 (92%). The IKDC, KOOS, and WOMAC scores (with the exception of the WOMAC stiffness subscale) all significantly improved at 2-year follow-up (P < .001). In contrast, the 2-year Marx activity score demonstrated a significant decrease from the initial score at enrollment (P < .001). Graft choice proved to be a significant predictor of 2-year IKDC scores (P = .017). Specifically, the use of an autograft for revision reconstruction predicted improved score on the IKDC (P = .045; odds ratio [OR] = 1.31; 95% CI, 1.01-1.70). The use of an autograft predicted an improved score on the KOOS sports and recreation subscale (P = .037; OR = 1.33; 95% CI, 1.02-1.73). Use of an autograft also predicted improved scores on the KOOS quality of life subscale (P = .031; OR = 1.33; 95% CI, 1.03-1.73). For the KOOS symptoms and KOOS activities of daily living subscales, graft choice did not predict outcome score. Graft choice was a significant predictor of 2-year Marx activity level scores (P = .012). Graft rerupture was reported in 37 of 1112 patients (3.3%) by their 2-year follow-up: 24 allografts, 12 autografts, and 1 allograft and autograft. Use of an autograft for revision resulted in patients being 2.78 times less likely to sustain a subsequent graft rupture compared with allograft (P = .047; 95% CI, 1.01-7.69). Conclusion: Improved sports function and patient-reported outcome measures are obtained when an autograft is used. Additionally, use of an autograft shows a decreased risk in graft rerupture at 2-year follow-up. No differences were noted in rerupture or patient-reported outcomes between soft tissue and bone–patellar tendon–bone grafts. Surgeon education regarding the findings of this study has the potential to improve the results of revision ACL reconstruction.

Posterior cruciate ligament injuries

There is a relative lack of research and literature investigating injuries to the posterior cruciate ligament (PCL), despite the fact that it is an important knee stabilizer. The PCL is injured less frequently than other knee ligaments, and the mechanism is usually a direct blow to the anterior aspect of a flexed knee. Clinical examination of a PCL-deficient knee may reveal a positive posterior drawer, quadriceps active test, or Godfrey test. Chronic PCL insufficiency may result in patellofemoral and medial compartment degenerative arthritis. Controversy exists over the treatment of PCL injuries, with the exception of surgical treatment of avulsion fractures. Many believe that isolated PCL injuries of any grade may be treated nonoperatively with an excellent outcome. However, PCL reconstruction is recommended for patients with grade III PCL injuries who remain symptomatic despite adequate physical therapy or if the PCL deficiency is part of a multiple-ligament knee injury.

The effects of age on rabbit MCL fibroblast matrix synthesis in response to TGF-β1 or EGF

In this study, we examined the effects of age on collagen and total protein synthesis by ligament fibroblasts in response to growth factors. Three different doses of transforming growth factor-beta 1 (TGF-beta 1) or epidermal growth factor (EGF) were individually added to in vitro fibroblast cultures from the medial collateral ligament (MCL) of skeletally immature (age 3 months), mature (age 12 months) and senescent (age 48-51 months) rabbits. Analysis of the effects of age revealed that fibroblasts from senescent rabbits produced significantly less collagen in response to TGF-beta 1 or EGF stimulation when compared to fibroblasts from immature rabbits. Furthermore, increased age was found to result in significant reductions in the baseline levels of collagen synthesis but not total protein synthesis. Additionally, collagen and total protein synthesis by MCL fibroblasts were significantly affected by the TFG-beta 1 dose, but not by the EGF dose. When fibroblasts were normalized to their own controls, the increase in collagen and total protein synthesis due to TGF-beta 1 and EGF for the senescent group were found to be greater than those for the skeletally immature rabbits at all doses. This demonstrates that MCL fibroblasts from senescent rabbits are responsive to growth factors.

Differences in mechanisms of failure, intraoperative findings, and surgical characteristics between single- and multiple-revision ACL reconstructions: a MARS cohort study.

Background: The factors that lead to patients failing multiple anterior cruciate ligament (ACL) reconstructions are not well understood. Hypothesis: Multiple-revision ACL reconstruction will have different characteristics than first-time revision in terms of previous and current graft selection, mode of failure, chondral/meniscal injuries, and surgical charactieristics. Study Design: Case-control study; Level of evidence, 3. Methods: A prospective multicenter ACL revision database was utilized for the time period from March 2006 to June 2011. Patients were divided into those who underwent a single-revision ACL reconstruction and those who underwent multiple-revision ACL reconstructions. The primary outcome variable was Marx activity level. Primary data analyses between the groups included a comparison of graft type, perceived mechanism of failure, associated injury (meniscus, ligament, and cartilage), reconstruction type, and tunnel position. Data were compared by analysis of variance with a post hoc Tukey test. Results: A total of 1200 patients (58% men; median age, 26 years) were enrolled, with 1049 (87%) patients having a primary revision and 151 (13%) patients having a second or subsequent revision. Marx activity levels were significantly higher (9.77) in the primary-revision group than in those patients with multiple revisions (6.74). The most common cause of reruptures was a traumatic, noncontact ACL graft injury in 55% of primary-revision patients; 25% of patients had a nontraumatic, gradual-onset recurrent injury, and 11% had a traumatic, contact injury. In the multiple-revision group, a nontraumatic, gradual-onset injury was the most common cause of recurrence (47%), followed by traumatic noncontact (35%) and nontraumatic sudden onset (11%) (P < .01 between groups). Chondral injuries in the medial compartment were significantly more common in the multiple-revision group than in the single-revision group, as were chondral injuries in the patellofemoral compartment. Conclusion: Patients with multiple-revision ACL reconstructions had lower activity levels, were more likely to have chondral injuries in the medial and patellofemoral compartments, and had a high rate of a nontraumatic, recurrent injury of their graft.

Neuromuscular and Biomechanical Adaptations of Patients with Isolated Deficiency of the Posterior Cruciate Ligament

Background Functional adaptations of patients with posterior cruciate ligament deficiency (grade II) are largely unknown despite increased recognition of this injury. Hypothesis Posterior cruciate ligament-deficient subjects (grade II, 6- to 10-mm bilateral difference in posterior translation) will present with neuromuscular and biomechanical adaptations to overcome significant mechanical instability during gait and drop-landing tasks. Study Design Controlled laboratory study. Methods Bilateral comparisons were made among 10 posterior cruciate ligament-deficient subjects using radiographic, instrumented laxity, and range of motion examinations. Biomechanical and neuromuscular characteristics of the involved limb of the posterior cruciate ligament-deficient subjects were compared to their uninvolved limb and to 10 matched control subjects performing gait and drop-landing tasks. Results Radiographic (15.3 ± 2.9 to 5.6 ± 3.7 mm; P =. 008) and instrumented laxity (6.3 ± 2.0 to 1.4 ± 0.5 mm; P <. 001) examinations demonstrated significantly greater posterior displacement of the involved knee within the posterior cruciate ligament-deficient group. The posterior cruciate ligament-deficient group had a significantly decreased maximum knee valgus moment and greater vertical ground reaction force at midstance during gait compared to the control group. During vertical landings, the posterior cruciate ligament-deficient group demonstrated a significantly decreased vertical ground reaction force loading rate. All other analyses reported no significant differences within or between groups. Conclusion Posterior cruciate ligament-deficient subjects demonstrate minimal biomechanical and neuromuscular differences despite significant clinical laxity. Clinical Relevance The findings of this study indicate that individuals with grade II posterior cruciate ligament injuries are able to perform gait and drop-landing activities similar to a control group without surgical intervention.

Osteoarthritis classification scales: Interobserver reliability and arthroscopic correlation

BACKGROUND Osteoarthritis of the knee is commonly diagnosed and monitored with radiography. However, the reliability of radiographic classification systems for osteoarthritis and the correlation of these classifications with the actual degree of confirmed degeneration of the articular cartilage of the tibiofemoral joint have not been adequately studied. METHODS As the Multicenter ACL (anterior cruciate ligament) Revision Study (MARS) Group, we conducted a multicenter, prospective longitudinal cohort study of patients undergoing revision surgery after anterior cruciate ligament reconstruction. We followed 632 patients who underwent radiographic evaluation of the knee (an anteroposterior weight-bearing radiograph, a posteroanterior weight-bearing radiograph made with the knee in 45° of flexion [Rosenberg radiograph], or both) and arthroscopic evaluation of the articular surfaces. Three blinded examiners independently graded radiographic findings according to six commonly used systems-the Kellgren-Lawrence, International Knee Documentation Committee, Fairbank, Brandt et al., Ahlbäck, and Jäger-Wirth classifications. Interobserver reliability was assessed with use of the intraclass correlation coefficient. The association between radiographic classification and arthroscopic findings of tibiofemoral chondral disease was assessed with use of the Spearman correlation coefficient. RESULTS Overall, 45° posteroanterior flexion weight-bearing radiographs had higher interobserver reliability (intraclass correlation coefficient = 0.63; 95% confidence interval, 0.61 to 0.65) compared with anteroposterior radiographs (intraclass correlation coefficient = 0.55; 95% confidence interval, 0.53 to 0.56). Similarly, the 45° posteroanterior flexion weight-bearing radiographs had higher correlation with arthroscopic findings of chondral disease (Spearman rho = 0.36; 95% confidence interval, 0.32 to 0.39) compared with anteroposterior radiographs (Spearman rho = 0.29; 95% confidence interval, 0.26 to 0.32). With respect to standards for the magnitude of the reliability coefficient and correlation coefficient (Spearman rho), the International Knee Documentation Committee classification demonstrated the best combination of good interobserver reliability and medium correlation with arthroscopic findings. CONCLUSIONS The overall estimates with the six radiographic classification systems demonstrated moderate (anteroposterior radiographs) to good (45° posteroanterior flexion weight-bearing radiographs) interobserver reliability and medium correlation with arthroscopic findings. The International Knee Documentation Committee classification assessed with use of 45° posteroanterior flexion weight-bearing radiographs had the most favorable combination of reliability and correlation. LEVEL OF EVIDENCE Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Meniscal and Articular Cartilage Predictors of Clinical Outcome After Revision Anterior Cruciate Ligament Reconstruction

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have worse outcomes compared with primary ACL reconstructions. Purpose/Hypothesis: The purpose of this study was to determine if the prevalence, location, and/or degree of meniscal and chondral damage noted at the time of revision ACL reconstruction predicts activity level, sports function, and osteoarthritis symptoms at 2-year follow-up. The hypothesis was that meniscal loss and high-grade chondral damage noted at the time of revision ACL reconstruction will result in lower activity levels, decreased sports participation, more pain, more stiffness, and more functional limitation at 2 years after revision surgery. Study Design: Cohort study; Level of evidence, 2. Methods: Between 2006 and 2011, a total of 1205 patients who underwent revision ACL reconstruction by 83 surgeons at 52 hospitals were accumulated for study of the relationship of meniscal and articular cartilage damage to outcome. Baseline demographic and intraoperative data, including the International Knee Documentation Committee (IKDC) subjective knee evaluation, Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx activity score, were collected initially and at 2-year follow-up to test the hypothesis. Regression analysis was used to control for age, sex, body mass index, smoking status, activity level, baseline outcome scores, revision number, time since last ACL reconstruction, incidence of having a previous ACL reconstruction on the contralateral knee, previous and current meniscal and articular cartilage injury, graft choice, and surgeon years of experience to assess the meniscal and articular cartilage risk factors for clinical outcomes 2 years after revision ACL reconstruction. Results: At 2-year follow-up, 82% (989/1205) of the patients returned their questionnaires. It was found that previous meniscal injury and current articular cartilage damage were associated with the poorest outcomes, with prior lateral meniscectomy and current grade 3 to 4 trochlear articular cartilage changes having the worst outcome scores. Activity levels at 2 years were not affected by meniscal or articular cartilage pathologic changes. Conclusion: Prior lateral meniscectomy and current grade 3 to 4 changes of the trochlea were associated with worse outcomes in terms of decreased sports participation, more pain, more stiffness, and more functional limitation at 2 years after revision surgery, but they had no effect on activity levels. Registration: NCT00625885