Bert R. Mandelbaum

Platelet-Rich Plasma From Basic Science to Clinical Applications

Platelet-rich plasma (PRP) has been utilized in surgery for 2 decades; there has been a recent interest in the use of PRP for the treatment of sports-related injuries. PRP contains growth factors and bioactive proteins that influence the healing of tendon, ligament, muscle, and bone. This article examines the basic science of PRP, and it describes the current clinical applications in sports medicine. This study reviews and evaluates the human studies that have been published in the orthopaedic surgery and sports medicine literature. The use of PRP in amateur and professional sports is reviewed, and the regulation of PRP by antidoping agencies is discussed.

Understanding and Preventing Noncontact Anterior Cruciate Ligament Injuries A Review of the Hunt Valley II Meeting, January 2005

The incidence of noncontact anterior cruciate ligament injuries in young to middle-aged athletes remains high. Despite early diagnosis and appropriate operative and nonoperative treatments, posttraumatic degenerative arthritis may develop. In a meeting in Atlanta, Georgia (January 2005), sponsored by the American Orthopaedic Society for Sports Medicine, a group of physicians, physical therapists, athletic trainers, biomechanists, epidemiologists, and other scientists interested in this area of research met to review current knowledge on risk factors associated with noncontact anterior cruciate ligament injuries, anterior cruciate ligament injury biomechanics, and existing anterior cruciate ligament prevention programs. This article reports on the presentations, discussions, and recommendations of this group.

Clinical Efficacy of the Microfracture Technique for Articular Cartilage Repair in the Knee An Evidence-Based Systematic Analysis

Background Despite the popularity of microfracture as a first-line treatment for articular cartilage defects in the knee, systematic information on its clinical efficacy for articular cartilage repair and long-term improvement of knee function is not available. Hypothesis Systematic analysis of the existing clinical literature of microfracture in the knee can improve the understanding of the advantages and limitations of this cartilage repair technique and can help to optimize its indications and clinical outcomes. Study Design Systematic review. Methods A comprehensive literature search was performed using established search engines (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials) to identify original human studies of articular cartilage repair with microfracture. Modified Coleman Methodology Scores were used to analyze the quality of the existing studies. Clinical efficacy of articular cartilage repair was evaluated by systematic analysis of short- and long-term functional outcome scores, macroscopic and microscopic repair cartilage quality, and findings of postoperative magnetic resonance imaging. Results Twenty-eight studies describing 3122 patients were included in the review. The average follow-up was 41 months, with only 5 studies reporting follow-up of 5 years or more. Six studies were randomized controlled trials and the mean Coleman Methodology Score was 58 (range, 22–97). Microfracture effectively improved knee function in all studies during the first 24 months after microfracture, but the reports on durability of the initial functional improvement were conflicting. Several factors were identified that affected clinical outcome. Defect fill on magnetic resonance imaging was highly variable and correlated with functional outcome. Macroscopic repair cartilage quality positively affected long-term failure rate, while the influence of histologic repair tissue quality remained inconclusive. Conclusion This systematic analysis shows that microfracture provides effective short-term functional improvement of knee function but insufficient data are available on its long-term results. Shortcomings of the technique include limited hyaline repair tissue, variable repair cartilage volume, and possible functional deterioration. The quality of the currently available data on micro-fracture is still limited by the variability of results and study designs. Further well-designed studies are needed to determine the long-term efficacy of microfracture and to define its specific clinical indications compared to other cartilage repair techniques.

A Randomized Controlled Trial to Prevent Noncontact Anterior Cruciate Ligament Injury in Female Collegiate Soccer Players

Background Neuromuscular and proprioceptive training programs can decrease noncontact anterior cruciate ligament injuries; however, they may be difficult to implement within an entire team or the community at large. Hypothesis A simple on-field alternative warm-up program can reduce noncontact ACL injuries. Study Design Randomized controlled trial (clustered); Level of evidence, 1. Methods Participating National Collegiate Athletic Association Division I womens soccer teams were assigned randomly to intervention or control groups. Intervention teams were asked to perform the program 3 times per week during the fall 2002 season. All teams reported athletes’ participation in games and practices and any knee injuries. Injury rates were calculated based on athlete exposures, expressed as rate per 1000 athlete exposures. A z statistic was used for rate ratio comparisons. Results Sixty-one teams with 1435 athletes completed the study (852 control athletes; 583 intervention). The overall anterior cruciate ligament injury rate among intervention athletes was 1.7 times less than in control athletes (0.199 vs 0.340; P = .198; 41 % decrease). Noncontact anterior cruciate ligament injury rate among intervention athletes was 3.3 times less than in control athletes (0.057 vs 0.189; P = .066; 70% decrease). No anterior cruciate ligament injuries occurred among intervention athletes during practice versus 6 among control athletes (P = .014). Game-related noncontact anterior cruciate ligament injury rates in intervention athletes were reduced by more than half (0.233 vs 0.564; P = .218). Intervention athletes with a history of anterior cruciate ligament injury were significantly less likely to suffer another anterior cruciate ligament injury compared with control athletes with a similar history (P = .046 for noncontact injuries). Conclusion This program, which focuses on neuromuscular control, appears to reduce the risk of anterior cruciate ligament injuries in collegiate female soccer players, especially those with a history of anterior cruciate ligament injury.

Articular Cartilage Lesions of the Knee

From *Santa Monica Orthopaedic and Sports Medicine Group, Santa Monica, California; ‡University of Missouri at Kansas City and University of Kansas, Shawnee Mission, Kansas; §Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; iDivision of Sports Medicine, Children’s Hospital, Boston, Massachusetts; Baylor Sports Medicine Group, Houston, Texas; Orthopaedische Universitaetsklinik, Freiburg, Germany; Brigham Orthopedic Association, Boston, Massachusetts; and Gothenburg Medical Center, Vastra Frolunda, Sweden

Autologous chondrocyte implantation of the knee: multicenter experience and minimum 3-year follow-up.

ObjectiveTo determine clinical outcome and graft survivorship in patients undergoing autologous chondrocyte implantation (ACI) for the repair of chondral defects of the knee. DesignProspective cohort study. Setting19 centers in the United States. Patients50 patients (37 males, 13 females). Mean age was 36 years (range: 19–53). Defects were grade III or IV with a mean size of 4.2 cm 2 . All patients had a minimum of 36 months postoperative follow-up. Main Outcome MeasurementsClinician and patient evaluation based on the modified Cincinnati Knee Rating System. Graft failure was defined as replacement or removal of the graft due to mechanical symptoms or pain. ResultsClinician and patient evaluation indicated median improvements of 4 and 5 points, respectively, at 36 months following ACI (p < 0.001). Previous treatment with marrow stimulation techniques and size of defect did not impact the results with ACI. The most common adverse events reported were adhesions and arthrofibrosis and hypertrophic changes. Three patients had graft failure and required reimplantation or treatment with alternative cartilage repair techniques. Kaplan-Meier estimated freedom from graft failure was 94% at 36 months postoperatively (95% CI = 88–100%). ConclusionsThese results of this study indicate excellent graft survivorship using ACI as well as substantial improvement in functional outcome.

Injection of Platelet-rich Plasma in Patients with Primary and Secondary Knee Osteoarthritis: A Pilot Study

Sampson S, Reed M, Silvers H, Meng M, Mandelbaum B: Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: A pilot study. Objective:To evaluate the clinical effects of intraarticular platelet-rich plasma (PRP) injections in a small group of patients with primary and secondary osteoarthritis. Most of the current treatments for osteoarthritis are palliative and attack the symptoms rather than influencing the biochemical environment of the joint. Autologous platelet-rich plasma has emerged as a treatment option for tendinopathies and chronic wounds. In addition to release of growth factors, platelet-rich plasma also promotes concentrated anti-inflammatory signals including interleukin-1ra, which has been a focus of emerging treatments for osteoarthritis. Design:In this single-center, uncontrolled, prospective preliminary study, 14 patients with primary and secondary knee osteoarthritis who met the study criteria received three platelet-rich plasma injections in the affected knee at ∼4-wk intervals. Outcome measures included the Brittberg-Peterson Visual Pain (Visual Analog Scale [VAS]), Activities, and Expectations score and the Knee Injury and Osteoarthritis Outcome Scores at preinjection visit at 2-, 5-, 11-, 18-, and 52-wk follow-up visits. Musculoskeletal ultrasound was used to measure cartilage thickness. Results:There were no adverse events reported. The study demonstrated significant and almost linear improvements in Knee Injury and Osteoarthritis Outcome Scores, including pain and symptom relief. Brittberg-Peterson VAS showed many improvements including reduced pain after knee movement and at rest. Cartilage assessment was limited because of the small sample size. The majority of the patients expressed a favorable outcome at 12 mos after treatment. Conclusions:The positive trends and safety profile demonstrated could potentially be used to inspire a larger, blinded, and randomized clinical trial to determine whether platelet-rich plasma is safe and effective for the treatment of knee osteoarthritis.

Clinical outcome of autologous chondrocyte implantation at 5 years in US subjects.

Peterson’s pioneering experience with the first clinical application of autologous chondrocyte implantation showed improvement in clinical outcomes, durable as much as 11 years, for a difficult patient population. An assessment of the general applicability of this technology in the United States requires long-term, multicenter followup. The purpose of this multicenter cohort study was to assess the clinical outcomes of patients treated with autologous chondrocyte implantation for lesions of the distal femur. Modified 10-point scales of the Cincinnati knee rating system were used to measure outcomes assessments at baseline and at 5 years. Eighty-seven percent (87 of 100) of patients completed 5-year followup assessments. Patients were an average 37 years of age, had a mean total defect size of 4.9 cm2, and had low baseline overall condition scores. At least one prior cartilage repair procedure had failed in 70% of the patients. At followup, 87 patients reported a mean improvement of 2.6 points in the overall condition score, including 62 with improved conditions, six with no change in condition, and 19 with worsened conditions. Of the 62 patients who improved, the mean overall condition score improved 4.1 points at followup. Patients treated with autologous chondrocyte implantation for large cartilage defects in the distal femur reported improvement in outcome scores at 5 years followup. Level of Evidence: Therapeutic study, Level II-1 (prospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Articular Cartilage Repair in Soccer Players With Autologous Chondrocyte Transplantation Functional Outcome and Return to Competition

Background The ability of autologous chondrocyte transplantation to produce and maintain an effective articular cartilage repair under high mechanical demands has not been investigated. Hypothesis Autologous chondrocyte transplantation provides a reliable and durable repair of full-thickness knee articular cartilage lesions in high-demand athletes. Study Design Case series; Level of evidence, 4. Methods A total of 45 soccer players were evaluated 41 ± 4 months after autologous chondrocyte transplantation for their ability to return to soccer, the timing of their return, skill level, and functional outcome rating by the Tegner activity rating scale score and Brittberg score. The factors influencing the return to sport were analyzed. Results Of these players, 72% reported good to excellent results, with significant overall improvement of Tegner activity rating scale scores; 33% returned to soccer, including 83% of competitive-level players and 16% of recreational players. Of the returning players, 80% returned to the same skill level and 87% maintained their ability to play soccer at 52 ± 8 months postoperatively. Players who successfully returned to soccer were significantly younger and had a shorter preoperative duration of symptoms than did patients who did not return to the sport. Concomitant adjuvant procedures did not adversely affect the ability to return to soccer. Conclusion Repair of knee articular cartilage lesions by autologous chondrocyte transplantation in high-performance athletes is particularly successful in younger, competitive athletes with limited preoperative intervals.

Outcomes After a Single-Stage Procedure for Cell-Based Cartilage Repair A Prospective Clinical Safety Trial With 2-year Follow-up

Background: There are currently several approaches being pursued to treat focal defects of articular cartilage, each having specific advantages or challenges. A single-stage procedure that uses autologous cartilage fragments, Cartilage Autograft Implantation System (CAIS), is being evaluated in patients and may offer a clinically effective option. Purpose: To establish the safety of CAIS and to test whether CAIS improves quality of life by using standardized outcomes assessment tools. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Patients (n = 29) were randomized (1:2) with the intent to treat with either a control (microfracture [MFX]) or an experimental (CAIS) procedure. Patients were followed at predetermined time points for 2 years using several standardized outcomes assessment tools (SF-36, International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS]). Magnetic resonance imaging was performed at baseline, 3 weeks, and 6, 12, and 24 months. Results: Lesion size and International Cartilage Repair Society (ICRS) grade were similar in both groups. General outcome measures (eg, physical component score of the SF-36) indicated an overall improvement in both groups, and no differences in the number of adverse effects were noted in comparisons between the CAIS and MFX groups. The IKDC score of the CAIS group was significantly higher (73.9 ± 14.72 at 12 months and 82.95 ± 14.88 at 24 months) compared with the MFX group (57.78 ± 18.31 at 12 months and 59.5 ± 13.44 at 24 months). Select subdomains (4/5) in the KOOS instrument were significantly different at 12 and 18 months, and all subdomains (Symptoms and Stiffness, Pain, Activities of Daily Living, Sports and Recreation, Knee-related Quality of Life) were significantly increased at 24 months in CAIS with scores of 88.47 ± 11.68, 90.64 ± 7.87, 97.29 ± 3.8, 78.16 ± 22.06, and 69 ± 23.15 compared with 75 ± 9.31, 78.94 ± 13.73, 89.46 ± 8.13, 51.67 ± 26.01, and 37.15 ± 21.67 in the MFX group. These significant improvements were maintained at 24 months in both IKDC and KOOS. Qualitative analysis of the imaging data did not note differences between the 2 groups in fill of the graft bed, tissue integration, or presence of subchondral cysts. Patients treated with MFX had a significantly higher incidence of intralesional osteophyte formation (54% and 70% of total number of lesions treated) at 6 and 12 months when compared with CAIS (8% and 25% of total number of lesions treated). Conclusion: The first clinical experience in using CAIS for treating patients with focal chondral defects indicates that it is a safe, feasible, and effective method that may improve long-term clinical outcomes.