David C. Flanigan

Autologous Chondrocyte Implantation: A Systematic Review

BACKGROUND The purpose of the present study was to determine (1) whether the current literature supports the choice of using autologous chondrocyte implantation over other cartilage procedures with regard to clinical outcome, magnetic resonance imaging, arthroscopic assessment, and durability of treatment, (2) whether the current literature supports the use of a specific generation of autologous chondrocyte implantation, and (3) whether there are patient-specific and defect-specific factors that influence outcomes after autologous chondrocyte implantation in comparison with other cartilage repair or restoration procedures. METHODS We conducted a systematic review of multiple databases in which we evaluated Level-I and II studies comparing autologous chondrocyte implantation with another cartilage repair or restoration technique as well as comparative intergenerational studies of autologous chondrocyte implantation. The methodological quality of studies was evaluated with use of Delphi list and modified Coleman methodology scores. Effect size analysis was performed for all outcome measures. RESULTS Thirteen studies (917 subjects) were included. Study methodological quality improved with later publication dates. The mean modified Coleman methodology score was 54 (of 100). Patients underwent autologous chondrocyte implantation (n = 604), microfracture (n = 271), or osteochondral autograft (n = 42). All surgical techniques demonstrated improvement in comparison with the preoperative status. Three of seven studies showed better clinical outcomes after autologous chondrocyte implantation in comparison with microfracture after one to three years of follow-up, whereas one study showed better outcomes two years after microfracture and three other studies showed no difference in these treatments after one to five years. Clinical outcomes after microfracture deteriorated after eighteen to twenty-four months (in three of seven studies). Autologous chondrocyte implantation and osteochondral autograft demonstrated equivalent short-term clinical outcomes, although there was more rapid improvement after osteochondral autograft (two studies). Although outcomes were equivalent between first and second-generation autologous chondrocyte implantation and between open and arthroscopic autologous chondrocyte implantation, complication rates were higher with open, periosteal-cover, first-generation autologous chondrocyte implantation (four studies). Younger patients with a shorter preoperative duration of symptoms and fewer prior surgical procedures had the best outcomes after both autologous chondrocyte implantation and microfracture. A defect size of >4 cm(2) was the only factor predictive of better outcomes when autologous chondrocyte implantation was compared with a non-autologous chondrocyte implantation surgical technique. CONCLUSIONS Cartilage repair or restoration in the knee provides short-term success with microfracture, autologous chondrocyte implantation, or osteochondral autograft. There are patient-specific and defect-specific factors that influence clinical outcomes.

A Systematic Review of Complications and Failures Associated With Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocation

Background: Patellofemoral instability affects activities of daily living and hinders athletic participation. Over the past 2 decades, more attention has been paid to medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent patellar dislocations/subluxations. Numerous techniques have been reported; however, there is no consensus regarding optimal reconstruction. Purpose: This study sought to report on the various techniques for MPFL reconstruction described in the literature and to assess the rate of complications associated with the procedure. Study Design: Meta-analysis. Methods: A systematic review of the literature was performed in early October 2010 using keywords “medial patellofemoral ligament,” “MPFL,” “reconstruction,” “complication(s),” and “failure(s).” Articles meeting the inclusion criteria were reviewed. Graft choice, surgical technique, outcome measures, and complications were recorded and organized in a database. Descriptive statistical analysis was performed on the data collected. Results: Twenty-five articles were identified and reviewed. A total of 164 complications occurred in 629 knees (26.1%). These adverse events ranged from minor to major including patellar fracture, failures, clinical instability on postoperative examination, loss of knee flexion, wound complications, and pain. Twenty-six patients returned to the operating room for additional procedures. Conclusion: Medial patellofemoral ligament reconstruction has a high rate of success for patients with patellofemoral instability; however, the complication rate of 26.1% associated with this procedure is not trivial. This study quantified complications and documented the variety of complications reported in outcomes-based literature.

Prevalence of chondral defects in athletes' knees: a systematic review.

PURPOSE To determine the prevalence of full-thickness focal chondral defects in the athletes knee. METHODS We conducted a systematic review of multiple databases, evaluating studies of the prevalence of articular cartilage defects in athletes. Because of the heterogeneity of data, a meta-analysis could not be performed. RESULTS Eleven studies were identified for inclusion (931 subjects). All studies were level 4 evidence. Defects were diagnosed via magnetic resonance imaging, arthroscopy, or both. Forty percent of athletes were professionals (NBA and NFL). The overall prevalence of full-thickness focal chondral defects in athletes was 36% (range = 2.4%-75% between all studies). Fourteen percent of athletes were asymptomatic at the time of diagnosis. Patellofemoral defects (37%) were more common than femoral condyle (35%) and tibial plateau defects (25%). Medial condyle defects were more common than lateral (68% vs 32%), and patella defects were more common than trochlea (64% vs 36%). Meniscal tear (47%) was the most common concomitant knee pathological finding, followed by anterior cruciate ligament tear (30%) and then medial collateral ligament or lateral collateral ligament tear (14%). CONCLUSIONS Full-thickness focal chondral defects in the knee are more common in athletes than among the general population. More than one-half of asymptomatic athletes have a full-thickness defect. Further study is needed to define more precisely the prevalence of these lesions in this population.

Failures, re-operations, and complications after autologous chondrocyte implantation – a systematic review

OBJECTIVE To determine and compare failure, re-operation, and complication rates of all generations and techniques of autologous chondrocyte implantation (ACI). METHODS A systematic review of multiple medical databases was performed according to PRISMA guidelines. Levels I-IV evidence were included. Generations of ACI and complications after ACI were explicitly defined. All subject and defect demographic data were analyzed. Modified Coleman Methodology Scores (MCMSs) were calculated for all studies. RESULTS 82 studies were identified for inclusion (5276 subjects were analyzed; 6080 defects). Ninety percent of the studies in this review were rated poor according to the MCMS. There were 305 failures overall (5.8% subjects; mean time to failure 22 months). Failure rate was highest with periosteal ACI (PACI). Failure rates after PACI, collagen-membrane cover ACI (CACI), second generation, and all-arthroscopic, second-generation ACI were 7.7%, 1.5%, 3.3%, and 0.83%, respectively. The failure rate of arthrotomy-based ACI was 6.1% vs 0.83% for all-arthroscopic ACI. Overall rate of re-operation was 33%. Re-operation rate after PACI, CACI, and second-generation ACI was 36%, 40%, and 18%, respectively. However, upon exclusion of planned second-look arthroscopy, re-operation rate was highest after PACI. Unplanned re-operation rates after PACI, CACI, second-generation, and all-arthroscopic second-generation ACI were 27%, 5%, 5%, and 1.4%, respectively. Low numbers of patients undergoing third-generation ACI precluded comparative analysis of this group. CONCLUSIONS Failure rate after all ACI generations is low (1.5-7.7%). Failure rate is highest with PACI, and lower with CACI and second-generation techniques. One out of three ACI patients underwent a re-operation. Unplanned re-operations are seen most often following PACI. Hypertrophy and delamination is most commonly seen after PACI. Arthrofibrosis is most commonly seen after arthrotomy-based ACI. Use of a collagen-membrane cover, second-generation techniques, and all-arthroscopic, second-generation approaches have reduced the failure, complication, and re-operation rate after ACI.

The Influence of Hamstring Autograft Size on Patient- Reported Outcomes and Risk of Revision After Anterior Cruciate Ligament Reconstruction: A Multicenter Orthopaedic Outcomes Network (MOON) Cohort Study

PURPOSE The purpose of this study was to evaluate the effect of graft size on patient-reported outcomes and revision risk after anterior cruciate ligament (ACL) reconstruction. METHODS A retrospective chart review of prospectively collected cohort data was performed, and 263 of 320 consecutive patients (82.2%) undergoing primary ACL reconstruction with hamstring autograft were evaluated. We recorded graft size; femoral tunnel drilling technique; patient age, sex, and body mass index at the time of ACL reconstruction; Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee score preoperatively and at 2 years postoperatively; and whether each patient underwent revision ACL reconstruction during the 2-year follow-up period. Revision was used as a marker for graft failure. The relation between graft size and patient-reported outcomes was determined by multiple linear regression. The relation between graft size and risk of revision was determined by dichotomizing graft size at 8 mm and stratifying by age. RESULTS After we controlled for age, sex, operative side, surgeon, body mass index, graft choice, and femoral tunnel drilling technique, a 1-mm increase in graft size was noted to correlate with a 3.3-point increase in the KOOS pain subscale (P = .003), a 2.0-point increase in the KOOS activities of daily living subscale (P = .034), a 5.2-point increase in the KOOS sport/recreation function subscale (P = .004), and a 3.4-point increase in the subjective International Knee Documentation Committee score (P = .026). Revision was required in 0 of 64 patients (0.0%) with grafts greater than 8 mm in diameter and 14 of 199 patients (7.0%) with grafts 8 mm in diameter or smaller (P = .037). Among patients aged 18 years or younger, revision was required in 0 of 14 patients (0.0%) with grafts greater than 8 mm in diameter and 13 of 71 patients (18.3%) with grafts 8 mm in diameter or smaller. CONCLUSIONS Smaller hamstring autograft size is a predictor of poorer KOOS sport/recreation function 2 years after primary ACL reconstruction. A larger sample size is required to confirm the relation between graft size and risk of revision ACL reconstruction. LEVEL OF EVIDENCE Level III, retrospective comparative study.

Treatment of Chondral Defects in the Athlete's Knee

PURPOSE To determine which surgical technique(s) has improved outcomes and enables athletes to return to their preinjury level of sports and which patient and defect factors significantly affect outcomes after cartilage repair or restoration. METHODS We conducted a search of multiple medical databases, evaluating studies of articular cartilage repair in athletes. RESULTS We identified 11 studies for inclusion (658 subjects). Only 1 randomized clinical trial was identified. All other studies were prospective cohorts, case-control studies, or case series reporting results after either microfracture or autologous chondrocyte implantation (ACI) or osteoarticular transplantation (OATS). Eight different clinical outcomes measures were used. Better clinical outcomes were observed after ACI and OATS versus microfracture. Results after microfracture tended to deteriorate with time. The overall rate of return to preinjury level of sports was 66%. The timing of return to the preinjury level of sports was fastest after OATS and slowest after ACI. Defect size of less than 2 cm(2), preoperative duration of symptoms of less than 18 months, no prior surgical treatment, younger patient age, and higher preinjury and postsurgical level of sports all correlated with improved outcomes after cartilage repair, especially ACI. Results after microfracture were worse with larger defects. The rate of return to sports was generally lower after microfracture versus ACI or OATS, and if a patient was able to return to sports, performance was diminished as well. CONCLUSIONS Management of chondral defects in the athlete is complex and multifactorial. There is little high-level evidence to support one procedure over another, although good short-term and midterm outcomes with a fair rate of return to preinjury level of sports can be achieved with cartilage repair and restoration in the athlete. LEVEL OF EVIDENCE Level IV, systematic review.

How to write a systematic review

Background: The role of evidence-based medicine in sports medicine and orthopaedic surgery is rapidly growing. Systematic reviews and meta-analyses are also proliferating in the medical literature. Purpose: To provide the outline necessary for a practitioner to properly understand and/or conduct a systematic review for publication in a sports medicine journal. Study Design: Review. Methods: The steps of a successful systematic review include the following: identification of an unanswered answerable question; explicit definitions of the investigation’s participant(s), intervention(s), comparison(s), and outcome(s); utilization of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines and PROSPERO registration; thorough systematic data extraction; and appropriate grading of the evidence and strength of the recommendations. Results: An outline to understand and conduct a systematic review is provided, and the difference between meta-analyses and systematic reviews is described. The steps necessary to perform a systematic review are fully explained, including the study purpose, search methodology, data extraction, reporting of results, identification of bias, and reporting of the study’s main findings. Conclusion: Systematic reviews or meta-analyses critically appraise and formally synthesize the best existing evidence to provide a statement of conclusion that answers specific clinical questions. Readers and reviewers, however, must recognize that the quality and strength of recommendations in a review are only as strong as the quality of studies that it analyzes. Thus, great care must be used in the interpretation of bias and extrapolation of the review’s findings to translation to clinical practice. Without advanced education on the topic, the reader may follow the steps discussed herein to perform a systematic review.

Anterior cruciate ligament reconstruction and concomitant articular cartilage injury: incidence and treatment.

PURPOSE Articular cartilage injuries commonly occur in conjunction with anterior cruciate ligament (ACL) injury. The exact incidence of this combined injury pattern, as well as the optimal treatment for it, has not been well studied in the literature. The purpose of this study was to systematically review the literature regarding the incidence of concomitant articular cartilage and ACL injury and the results of combined surgical treatment of these injuries. METHODS We performed a systematic review of studies investigating the incidence of articular cartilage injury in conjunction with ACL injury and the results of combined surgical treatment for these injuries. RESULTS On the basis of 5 studies in the literature, the incidence of severe articular cartilage injury in acute ACL tears is between 16% and 46%. On the basis of 3 studies on combined osteochondral autografts and ACL reconstruction and 2 studies on combined autologous chondrocyte implantation and ACL reconstruction, patients can have reasonable short-term outcomes after combined surgery. CONCLUSIONS Articular cartilage injury is often encountered at the time of ACL reconstruction, and combined surgery can result in reasonable outcomes. Additional studies are needed to better define both the incidence of combined injury and the outcome, particularly in the long term, after these procedures.

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.

Anterior cruciate ligament-injured subjects have smaller anterior cruciate ligaments than matched controls: a magnetic resonance imaging study.

Background Very few studies examining the predisposing anatomical factors leading to anterior cruciate ligament (ACL) injuries have examined the ACL itself, and none of these directly examined the difference in ACL properties between injured and matched control subjects. Hypothesis The ACL total volume in people who have experienced a noncontact ACL injury is smaller than that of matched controls. Study Design Case control study; Level of evidence, 3. Methods Contours of the ACL were manually identified in sagittal magnetic resonance images, and volumes were calculated for 27 contralateral, healthy knees of individuals after noncontact ACL injury and for 27 control subjects matched for gender, height, age, and weight. Validation of this method was performed on 5 porcine knees. Stepwise multiple regression was used to determine the difference in ACL volume between injured and control subjects while considering gender, height, weight, and age as potential covariates. Results Contralateral ACL volume for injured subjects was significantly smaller than for noninjured subjects (P = .0208) by 231 mm3 after adjusting for weight, which was also a significant contributor to ACL volume (P < .0001). At the average body mass of 72.7 kg, subjects with a noncontact ACL injury had an average contralateral ACL volume of 1921 mm3, while the corresponding control group had an average volume of 2151 mm3. Gender, height, and age were not significant when weight was included in the regression model. Conclusion This study shows that there are anthropometric differences between the knees of subjects with a noncontact ACL injury and those without an ACL injury, suggesting that ACL volume may play a direct role in noncontact ACL injury.