Annemarie K. Tilton

Autologous Chondrocyte Implantation Improves Knee-Specific Functional Outcomes and Health-Related Quality of Life in Adolescent Patients

Background: Existing studies of autologous chondrocyte implantation (ACI) in adolescent patients have primarily reported outcomes that have not been validated for cartilage repair and have failed to include measures of general health or health-related quality of life. Purpose: This study assesses validated knee-specific functional outcomes and health-related quality of life after ACI in adolescent patients. Study Design: Case series; Level of evidence, 4. Methods: Patients younger than 18 years who underwent ACI between 1999 and 2011 with a minimum 2-year clinical follow-up were identified from a prospectively collected database. A total of 37 patients were included in the analysis. Patient demographic data and pre- and postoperative functional outcomes scores were collected and chondral lesion characteristics were assessed. Primary outcome measures were the International Knee Documentation Committee (IKDC) subjective score and the Knee Injury and Osteoarthritis Outcome Score–Quality of Life (KOOS-QOL) subscore; secondary outcome measures were Short Form–12 (SF-12) and other KOOS subscores. In subgroup analyses, we assessed whether primary outcome results differed based on lesion location, concurrent meniscal allograft transplantation (MAT), and subsequent surgery after ACI. Results: Study patients had a mean 4.6 ± 2.4 years of follow-up, a mean age of 16.7 ± 1.5 years, and a mean lesion size of 4.0 ± 2.2 cm2. The IKDC subjective score improved from 34.9 preoperatively to 64.6 postoperatively (mean improvement, 29.7 points [95% CI, 20.7 to 38.7 points]; P < .001) and the KOOS-QOL subscore improved from 24.3 to 55.3 (mean improvement, 31.0 points [95% CI, 21.3 to 40.7 points]; P < .001) at final follow-up. All other KOOS subscales and the SF-12 physical component score also showed significant improvements (P < .008 in all cases), whereas the SF-12 mental component score showed no improvement (P = .464). There was a 37.8% rate of subsequent surgery after ACI (most commonly, chondral debridement [54%], meniscectomy [11%], microfracture [9%], and loose body removal [9%]). Subgroup analysis showed no effect of lesion location, concurrent MAT, or subsequent surgery on improvement in IKDC subjective scores and KOOS-QOL subscores (P > .05 in all cases). Conclusion: ACI is an effective treatment for adolescent patients with symptomatic, large chondral lesions, resulting in significant improvements in knee-specific functional outcome scores and health-related quality of life scores. Although patients must be cautioned on the relatively high reoperation rate (37.8%) and limitations in knee function even after ACI, all patients in this study exhibited improvements over preoperative knee function at the most recent follow-up regardless of ACI location, concurrent MAT, or subsequent surgery.

DeNovo NT Particulated Juvenile Cartilage Implant

Biological repair of focal chondral defects represents a significant clinical challenge as cartilage lacks intrinsic healing ability. Although it can be difficult to measure the objective success of cartilage repair techniques, the primary objective is symptom relief leading to less pain and improved function for the patient. Likely, the most important key to success is proper clinical indications. Second to this, the type of cartilage treatment utilized should be based on lesion location, size, depth, and other patient factors. One such treatment is DeNovo Natural Tissue. This method relies on the ability of juvenile chondrocytes to migrate from cartilage explants after being secured in a cartilage defect. Although approximately 8700 cases have been performed since 2007, long-term clinical outcomes are not yet available. However, basic science and early clinical data are promising.

Hyaluronic Acid versus Platelet-Rich Plasma Double-blind Randomized Controlled Trial Comparing Clinical Outcomes and Intra-Articular Biology for Treatment of Knee Arthritis

Objectives: Osteoarthritis (OA) is a debilitating disease that, in some form, affects up to 47 million Americans each year and is estimated to affect 67 million by 2030. Hyaluronic acid (HA) is currently utilized as an intra-articular injection for treatment of patients with knee OA. A movement in biochemical research has emerged that focuses on analysis of catabolic and anabolic growth factors of the joint. It is proposed that platelet-rich plasma (PRP) is a biologic alternative to HA that may alter the intra-articular biologic milieu to mitigate the symptoms of OA. The purpose of this double-blind prospective randomized clinical trial is to compare the effects of PRP to HA for the treatment of OA in the knee using validated clinical outcome measures and biologic correlates associated with OA. Methods: Patients with a minimum of 3 months of symptomatic unilateral knee OA and Kellgren-Lawrence Grade 1-3 OA were randomized into two cohorts. One cohort received three weekly ultrasound-guided injections of HA and the other received three weekly injections of PRP. Patients in both cohorts were seen again at 6-, 12-, and 24-weeks following their index treatment. At each visit, including the treatment and index visits, patients completed a survey that included Lysholm, IKDC, WOMAC, and VAS pain, and underwent a clinical examination. Patients also underwent an ultrasound-guided aspiration of the knee for synovial fluid analysis during each of the treatment visits and at 3-month and 6-month follow up. Synovial fluid was grouped and analyzed via ELISA assay. Results: 111 patients (mean age 56.2 +/- 10.2 years; 53 male, 58 female) met inclusion criteria and were randomized into either the HA or PRP cohort. Eleven (9.9 %) patients were lost to follow-up or unwilling to complete the study. In all of the scales measured, outcomes improved significantly from the index visit at 6 months post treatment (p<.01). PRP had a higher IKDC (p<.02) at 6-month follow up when compared to HA. Patients in the PRP group also reported lower VAS pain scores at 6-month follow up as well (p<.01). The remainder of the outcome measures (Lysholm, WOMAC) demonstrated trends toward greater improvement in the PRP group but did not demonstrate statistical significance. Synovial fluid aspirated was analyzed using ELISA assay for catabolic factors TNF-α, IL-1B/IL-F2, IL-1ra/IL-1F3, IL-6, and CXCL8/IL-8. The PRP cohort had significantly higher IL-6 concentration than the HA cohort at 6-month follow up (p=.02). The PRP and HA groups were not found to have significant differences in concentrations of the other catabolic factors analyzed. Conclusion: The findings of this study support a significant improvement of pain and function at 6 months with the use of intra-articular PRP as well as HA for the treatment of OA. Findings further suggest that PRP may be a superior treatment for the active patient with OA.

Clinical Outcomes After Microfracture of the Knee: Midterm Follow-up:

Background: Microfracture is a single-stage arthroscopic procedure used to treat small- and medium-sized cartilage defects, the clinical results of which have been mixed to date. Purpose: To retrospectively evaluate prospectively collected patient-reported outcomes (PROs) after microfracture as well as to determine patient-related and defect-related factors associated with clinical outcomes and which factors predict the need for additional surgery. Study Design: Case-control study; Level of evidence, 3. Methods: All patients between the ages of 10 and 70 years who underwent microfracture by the senior author for a focal chondral defect of the knee between January 1, 2005, and March 1, 2010, were eligible for study enrollment. Patients were excluded if they underwent concomitant procedures that violated the subchondral bone. Functional outcomes were determined using preoperative and final follow-up PROs, including the Lysholm, International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short Form–12 (SF-12), and overall satisfaction scores. Patient-related factors (sex, age, body mass index [BMI]) and defect-related factors (lesion size, location, concomitant procedures, prior procedures) were analyzed for correlations with outcome scores. All patient-related and defect-related factors were also analyzed as predictors for subsequent surgery. Results: Overall, 101 patients (102 knees; 55 male, 46 female; mean age, 35.87 ± 12.52 years; mean BMI, 26.3 ± 5.5 kg/m2; mean defect size, 2.635 ± 1.805 cm2) were included. Lesion location included 44.90% at the medial femoral condyle, 21.43% at the trochlea, 11.22% at the lateral femoral condyle, 10.20% at multiple sites, 8.16% at the patella, and 4.08% at the tibial plateau. Microfracture was performed alone in 72 of 102 (71%) knees. At a mean follow-up of 5.66 ± 2.54 years (range, 2-11 years), clinically meaningful and statistically significant improvements were seen in all PROs (P < .05) except the SF-12 mental component score. Patients who had an isolated tibial plateau defect or multiple defects demonstrated reduced improvements in the symptom rate (P = .0237). Patients with a BMI >30 kg/m2 had lower postoperative scores on the KOOS activities of daily living subscale (P = .0261) and poorer WOMAC function and WOMAC pain scores (P = .029 and .0307, respectively). Patient BMI, age, sex, defect location, concomitant procedures, and operative side were not significant predictors for additional surgery. Larger defect size (>3.6 cm2) and prior knee surgery were independent risk factors for additional knee surgery after microfracture. Conclusion: After microfracture, all PROs demonstrated clinically and statistically significant improvements at 5.7 years. Functionally, male patients benefited more from microfracture than female patients. Microfracture of tibial lesions and multisite microfracture provided less benefit than microfracture of isolated femoral defects. Larger lesion size (>3.6 cm2) and prior knee surgery predicted the need for additional knee surgery after microfracture.

Flexion Posteroanterior Radiographs Affect Both Enrollment for and Outcomes After Injection Therapy for Knee Osteoarthritis

Background: Knee injection therapy is less effective for severe osteoarthritis (OA), specifically Kellgren-Lawrence (KL) grade 4. Patient selection for knee injection trials has historically been based on extension anteroposterior (AP) radiographic evaluation; however, emerging evidence suggests that KL grading using a flexion posteroanterior (PA) radiograph more accurately and reproducibly predicts disease severity. The impact of radiographic view on patient selection and outcome after knee injection therapy remains unknown. Hypothesis: A 45° flexion PA radiograph will reveal more advanced knee OA in certain patients. These patients will report worse pre- and postinjection outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: Four raters independently graded extension AP and flexion PA radiographs from 91 patients previously enrolled in a knee injection trial. Patients determined to have KL grade 4 OA by any rater on extension AP radiographs were excluded. Among included patients, those upgraded to KL grade 4 on flexion PA radiographs by at least 2 raters constituted group 2, while all remaining patients constituted group 1. Demographic data and patient-reported outcome scores before injection and at 6 weeks, 3 months, 6 months, and 12 months postinjection were compared between groups. Results: Overall, 64 patients met the inclusion criteria, of which 19 patients (30%) constituted group 2. Compared with group 1, patients in group 2 were older (58.7 vs 52.3 years, P = .02), had worse visual analog scale pain scores before (6.6 vs 5.3, P = .03) and 6 months after injection (5.3 vs 3.5, P = .01), had less improvement in both Lysholm (8.5 vs 20.5, P = .02) and Short Form–12 physical component (–2.2 vs 1.7, P = .03) scores from preinjection to 6 months postinjection, and had less improvement in both Lysholm (1.6 vs 13.1, P = .03) and Knee injury and Osteoarthritis Outcome Score sport subscale (–2.1 vs 16, P = .01) scores from preinjection to 12 months postinjection. Conclusion: One in 3 patients considered to have mild to moderate knee OA on extension AP radiography is upgraded to severe knee OA (KL grade 4) on flexion PA radiography. These patients report worse preinjection outcomes, worse pain scores at short-term follow-up, and decreased improvement in knee function scores between 6 months and 1 year postinjection.

Criteria for Return to Play After Anterior Cruciate Ligament Reconstruction

Anterior cruciate ligament reconstruction (ACLR) is a common orthopaedic procedure often sustained during sports-related trauma. Many patients desire to return to play (RTP) following surgery, and modern advances in rehabilitation and surgical techniques aim to facilitate this. Preoperative rehabilitation and postoperative accelerated rehabilitations programs have both demonstrated positive outcomes in facilitating RTP following ACLR. Many preoperative, intraoperative, and postoperative factors influence time to RTP and rate of re-injury, including patient demongraphics, graft choice, and postoperative rehabilitation program. To maximize safe RTP, these factors need to be considered. Work is underway to develop objective guidelines for the time to RTP, and current research suggests that a combination of kinematic, neuromuscular, and psychological factors need to be considered.

Can Competitive Athletes Sustain High-Level Play Following Osteochondral Allograft Transplantation of the Knee?

Objectives: The purpose of this study is to investigate the ability of competitive athletes to remain at a high level of competition following osteochondral allograft transplantation (OCA) of the knee. Methods: A retrospective review was performed to identify all competitive athletes (high school, collegiate, professional) who underwent an isolated femoral condyle OCA between 2004 and 2012. Patient reported outcome (PRO) questionnaires (Lysholm, International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMasters Universities Arthritis Index (WOMAC), Short Form-12 (SF-12), Tegner, and Marx) and custom return-to-sport surveys were administered. All subsequent reoperations were documented. Results: A total of 13 (7 male, 6 female) athletes were identified with an average follow-up of 5.9 ± 2.5 years. Four athletes competed at an intercollegiate level, while 9 played high-level high-school sports. Seven athletes returned to competitive sport (54%) at an average of 7.9 ± 3.5 months, five of whom were returned to pre-injury levels of play. Of the eight athletes who either did not return to sport or failed to sustain their high level of play, the most common reasons cited were a change in life circumstances, such as graduation, or a fear of re-injury (Figure 1). At final follow-up, regardless of return-to-play, all athletes had significant improvements in all PRO scores except for KOOS-Sport, WOMAC-Stiffness, and SF-12 Mental subscales. Tegner Activity scores dropped significantly from pre-injury to final follow-up (8.2 ± 2.4, 4.5 ± 2.1, p < 0.01). There were three reoperations and zero instances of graft failure. Conclusion: OCAs provide acceptable rates of return-to-play and excellent long-term outcomes for high-level athletes with large osteochondral defects. Social factors are three times more likely than persistent pain to prevent return to sport.

Prospective Clinical Outcomes Following Microfracture Surgery For Isolated and Multi-Site Defects: Mid-Term Follow-Up

Objectives: The purpose of the current study was: 1) to evaluate the outcomes of patients who underwent microfracture and 2) to determine the patient-related and defect-related factors associated with outcomes including factors predicting additional surgery. Methods: Patients who underwent microfracture for focal chondral defect(s) of the knee were eligible. Patients were excluded if concomitant procedures violated the subchondral bone. Outcomes were determined using preoperative and final follow-up patient reported outcomes (PROs) including; IKDC, KOOS, WOMAC, SF-12 and Overall Satisfaction. Patient-related factors and defect-related factors were analyzed for correlations with outcome. All patient-related and defect-related factors were also analyzed as predictors for subsequent surgery. Results: Overall 101 patients (55M/46F) mean age: 35.9±12.5 years, BMI 26.3±5.5 kg/m2, mean defect size: 2.64±1.81 cm2 underwent microfracture and met enrollment criteria. Lesion location included: 44.90% medial femoral condyle, 21.43% trochlea, 11.22% lateral femoral condyle, 10.20% multiple site, 8.16% patella, and 4.08% tibial plateau. In 72 of 101 (71%) knees, microfracture was performed in insolation. At mean follow-up of 5.7±2.5 years, statistically significant and clinically meaningful improvements (MCID and MCD) were seen in all PROs (p<0.05), aside from SF-12 mental scores which improved although not significantly (p=0.07) (Figure 1). Increased age, higher BMI, isolated tibial microfracture, multi-site microfracture and increased defect size all correlated with lower final follow-up PROs (p<0.05). Males demonstrated greater magnitude of improvement in KOOS symptoms and sports subscales (p=0.006 and p=0.037). In the multivariate analysis, larger defect size (>3.6 cm2) and prior knee surgery were independent risk factors for additional knee surgery. Conclusion: Following microfracture all patients demonstrated significant and clinically meaningful improvements in outcomes at a mean of 5.7 years. Increasing age and BMI are the patient-related factors that may predict a poor outcome. Defect-related predictors of poor outcome include microfracture of tibial lesions and multi-site microfracture as compared to isolated femoral defect microfracture. Larger lesion size (>3.6 cm2) and a history of prior knee surgery may predict the need for additional knee surgery following microfracture.

Outcomes of Autologous Chondrocyte Implantation in the Knee following Failed Microfracture

Objectives: Marrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects of the knee. For young patients who have failed microfracture, cartilage restoration techniques such as autologous chondrocyte implantation (ACI), OATS, and osteochondral allograft and are frequently employed. Nevertheless, there a few reports in the literature evaluating the results of ACI following failed microfracture and those available suggest inferior outcomes compared to primary ACI. This study was performed to evaluate the clinical outcomes of autologous chondrocyte implantation (ACI) following failed microfracture in the knee and compare these outcomes to those of primary ACI. Methods: Patients were identified who underwent autologous chondrocyte implantation for symptomatic chondral lesions of the knee refractory to previous microfracture. Postoperative data were collected using several subjective scoring systems (Noyes, Tegner, Lysholm, IKDC, KOOS, SF12). An age-matched cohort of 103 patients who underwent primary ACI of the knee was used as a control group. Statistics were performed in a paired manner using a Student’s t-test for ordinal data and chi-square test for categorical data. Results: Ninety-two patients met the inclusion criteria. The average patient age was 30.1 years (range, 14-49 years) at the time of ACI. The average duration from microfracture to ACI was 21.2 months (range, 1-88 months). ACI was performed in the tibiofemoral compartment in 42 patients, the patellofemoral compartments in 38 patients, and in both in 12 patients. The primary lesion treated with ACI involved the MFC in 38 patients, the trochlea in 25 patients, the patella in 19 patients, and the LFC in 10 patients. The lesions averaged 467mm3 in the trochlea, 445mm3 in the LFC, 265mm3 in the patella, and 295mm3 in the patella. Nineteen patients underwent concurrent ACI to multiple lesions. Thirty-one patients underwent concomitant patellar anteromedialization, 9 patients underwent meniscal allograft, and 6 underwent realignment ostetomies (5 HTO, 1 DFO). Follow-up was available on 84 of 92 patients (91%) at an average length of follow-up of 47 months (range, 24-102 months). The control group of patients was well matched with regard to age, gender, BMI, workers compensation status, and preoperative subjective scores. Failure, defined by need for further cartilage restoration or knee arthroplasty, occurred in 8 patients (3 osteochondral allograft, 3 TKA, 1 revision ACI, 1 Denovo NT). Seventeen additional patients underwent reoperation for intra-articular debridement. There was no difference between the failure rate (8.7% v. 2.9%, p=0.21) or reoperation rate (27.2% v. 27.2%, p=0.98) in the study and control groups. For the study group, significant improvements were witnessed postoperatively for all measured questionairre parameters. No significant differences were witnessed between the study and control groups (p>0.05) with regard to any of the postoperative subjective parameters (Figure). Conclusion: In patients with discrete articular cartilage lesions of the knee and history of failed microfracture, ACI may render favorable clinical outcomes comparable to primary ACI. While other series have demonstrated inferior results following previous microfracture, our series suggests that in appropriately selected patients ACI may be used successfully as a second line treatment following failed microfracture.

Does Prior Shoulder Surgery Negatively Impact Shoulder Arthroplasty Outcomes

Objectives: Several studies have shown a negative correlation between prior knee arthroscopy and ultimate knee arthroplasty outcomes compared to patients without prior arthroscopy. The purpose of this study was to determine the effects of prior shoulder surgery on patients undergoing total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (rTSA) compared to patients without prior shoulder surgery. Methods: A retrospective review of prospectively collected data was performed on 107 patients undergoing TSA or rTSA. All medical records were analyzed for demographic variables, type of prior shoulder surgery, and type of arthroplasty. All patients underwent a clinical follow-up evaluation, and were evaluated with the American Shoulder and Elbow Society (ASES), Simple Shoulder Test (SST), and Visual Analog Scale (VAS) outcomes scores. Complications, failures, and reoperations were also recorded an analyzed. Results: A total of 107 patients (47 males, 60 females) were included with an average follow-up of 24 months (minimum 12 months). Seventy-one patients (underwent arthroplasty without prior surgery (30 rTSA, 41 TSA) while 50 patients underwent arthroplasty with a history of at least one prior shoulder surgery (27 rTSA, 9 TSA). Prior surgeries included a mix of both open and arthroscopic procedures, including open and arthroscopic rotator cuff repair, open and arthroscopic stabilization (with and without bone augmentation), arthroscopic capsular release, and arthroscopic debridement. Following arthroplasty, both groups experienced significant improvements in ASES, SST, and VAS scores compared to preoperative scores (P<0.05 for all). There was a statistically significant difference in postoperative ASES scores in the no-surgery group compared to the prior-surgery group (84.49 versus 71.67, P=0.0003) as well as in the SST scores (8.97 versus 5.47, P<0.0001); there were no differences in the VAS score (0.83 vs 1.40, P=0.104). Conclusion: Shoulder arthroplasty after undergoing prior shoulder surgery results in overall clinically improved outcomes, however these results are inferior compared to patients without a history of prior shoulder surgery. Further research examining this correlation is needed.