Long-term Assessment of Subchondral Bone Changes and Intralesional Bony Overgrowth After Third-Generation Autologous Chondrocyte Implantation: A Retrospective Study.

BACKGROUND: There is an increasing interest in subchondral bone changes and intralesional bony overgrowth (ILBO) after cartilage repair. Their clinical and predictive relevance is unclear and debated. PURPOSE: To evaluate the long-term development of ILBO and bone marrow edema-like signals (BMELSs) after autologous chondrocyte implantation (ACI) treatment of cartilage defects to find any predictive factors for their appearance. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 130 patients with 160 cartilage defects in the knee joint treated with third-generation ACI were included in this study. Radiological scores as the MOCART (magnetic resonance observation of cartilage repair tissue), the MOCART 2.0 and the 3D-MOCART using magnetic resonance imaging (MRI), and patient-reported outcome measures such as the Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, Noyes Sports Activity Rating Scale (NSARS) score, and Tegner Activity Scale (TAS) score were evaluated between 60 and 120 months (mean, 88 months) postoperatively. The radiological evaluation focused on the occurrence and size of subchondral bone changes, BMELSs, and ILBO during short-, medium-, and long-term follow-up. RESULTS: In long-term evaluation of clinical data, the IKDC score increased preoperatively from 36 to 64, the overall KOOS from 43 to 64, the NSARS score from 30 to 67, and the TAS score from 2 to 3.7. The mean MOCART score was 73; the MOCART 2.0, 69; and the 3D-MOCART, 69 and 70. The authors observed ILBO in 77% and BMELSs in 74% of patients after 60 to 120 months. Previous cartilage surgeries and osteochondral defect buildup showed higher rates of these abnormalities. Early lesions of the subchondral lamina did not predict ILBO in long-term follow-up, but BMELSs predicted later appearance with decreasing size. CONCLUSION: Subchondral changes frequently appeared in long-term MRI evaluation of patients after ACI. BMELSs showed a decreasing diameter over the years, while the size of ILBO increased in the later follow-ups. These findings did not affect the clinical outcome in the study population. However, osteoarthritis is likely to progress. The degenerative effect and influence on longer-term outcomes needs to be clarified in future studies.

Correlation of Arthroscopic Grading and Optical Coherence Tomography as Markers of Early Repair and Predictors of Later Healing Evident on MRI and Histomorphometric Assessment of Cartilage Defects Implanted with Chondrocytes Overexpressing IGF-I.

OBJECTIVE: Injury of articular cartilage is common, and due to the poor intrinsic capabilities of chondrocytes, it can precipitate joint degradation and osteoarthritis (OA). Implantation of autologous chondrocytes into cartilaginous defects has been used to bolster repair. Accurate assessment of the quality of repair tissue remains challenging. This study aimed to investigate the utility of noninvasive imaging modalities, including arthroscopic grading and optical coherence tomography (OCT) for assessment of early cartilage repair (8 weeks), and MRI to determine long-term healing (8 months). DESIGN: Large (15 mm diameter), full-thickness chondral defects were created on both lateral trochlear ridges of the femur in 24 horses. Defects were implanted with autologous chondrocytes transduced with rAAV5-IGF-I, autologous chondrocytes transduced with rAAV5-GFP, naïve autologous chondrocytes, or autologous fibrin. Healing was evaluated at 8 weeks post-implantation using arthroscopy and OCT, and at 8 months post-implantation using MRI, gross pathology, and histopathology. RESULTS: OCT and arthroscopic scoring of short-term repair tissue were significantly correlated. Arthroscopy was also correlated with later gross pathology and histopathology of repair tissue at 8 months post-implantation, while OCT was not correlated. MRI was not correlated with any other assessment variable. CONCLUSIONS: This study indicated that arthroscopic inspection and manual probing to develop an early repair score may be a better predictor of long-term cartilage repair quality following autologous chondrocyte implantation. Furthermore, qualitative MRI may not provide additional discriminatory information when assessing mature repair tissue, at least in this equine model of cartilage repair.

Assessment of Patellar Vascularity after Patellar Cartilage Restoration via Lateral Parapatellar Approach: Analysis Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

OBJECTIVE: Patellofemoral cartilage restoration procedures, including osteochondral allograft, particulated juvenile cartilage, and matrix-induced autologous chondrocyte implantation, have been shown to be effective treatments for patellofemoral cartilage lesions. However, concerns exist regarding disruption of the patellar vascular supply and secondary stabilizers of the patellofemoral joint during medial parapatellar approaches, especially when combined with a lateral release. A lateral parapatellar approach affords the possibility of avoiding disruption of the medial blood supply to the patella, while also allowing laterally-based soft tissue stabilization procedures. The purpose of this study was to investigate in vivo changes in patellar vascularity following patellofemoral cartilage restoration procedures performed via a lateral parapatellar approach via use of dynamic contrast-enhanced magnetic resonance (MR) imaging. DESIGN: This study is a prospective case series of 5 adult patients undergoing patellofemoral cartilage restoration procedures via a lateral parapatellar approach with pre-operative and post-operative dynamic contrast-enhanced MR imaging to assess changes in patellar vascularity. Secondary outcomes included knee range of motion, need for revision surgery, and complications. RESULTS: There was no significant post-operative difference in patellar vascularity in patients undergoing patellofemoral cartilage restoration procedures via a lateral parapatellar approach, as evaluated by qualitative MR imaging. CONCLUSION: Our results suggest that a lateral parapatellar approach for cartilage restoration procedures may preserve patellar vascularity, while also allowing for lateral release to be performed through the same incision.

Histological and Radiological Assessment of Endogenously Generated Repair Tissue In Vivo Following a Chondral Harvest.

OBJECTIVE: To examine repair tissue formed approximately 15 months after a chondral harvest in the human knee. DESIGN: Sixteen individuals (12 males, 4 females, mean age 36 ± 9 years) underwent a chondral harvest in the trochlea as a pre-requisite for autologous chondrocyte implantation (ACI) treatment. The harvest site was assessed via MRI at 14.3 ± 3.2 months and arthroscopy at 15 ± 3.5 months (using the Oswestry Arthroscopy Score [O-AS] and the International Cartilage Repair Society Arthroscopy Score [ICRS-AS]). Core biopsies (1.8 mm diameter, n = 16) of repair tissue obtained at arthroscopy were assessed histologically (using the ICRS II and OsScore histology scores) and examined via immunohistochemistry for the presence of collagen types I and II. RESULTS: The mean O-AS and ICRS-AS of the repaired harvest sites were 7.2 ± 3.2 and 10.1 ± 3.5, respectively, with 80.3% ± 26% repair fill depth on MRI. The histological quality of the repair tissue formed was variable, with some hyaline cartilage present in 50% of the biopsies; where this occurred, it was associated with a significantly higher ICRS-AS than those with no hyaline cartilage present (median 11 vs. 7.5, P = 0.049). Collagen types I and II were detected in 12/14 and 10/13 biopsies, respectively. CONCLUSIONS: We demonstrate good-quality structural repair tissue formed following cartilage harvest in ACI, suggesting this site can be useful to study endogenous cartilage repair in humans. The trochlea is less commonly affected by osteoarthritis; therefore, location may be critical for spontaneous repair. Understanding the mechanisms and factors influencing this could improve future treatments for cartilage defects.

Cartilage assessment using preoperative planning MRI for femoral component rotational alignment.

BACKGROUND: Surgical planning of posterior referencing total knee arthroplasty (TKA) using computed tomography (CT) might lead to over-rotation of the femoral component because CT could not detect cartilage thickness of the posterior femoral condyle. The purpose of this study was to examine the rotational alignment difference of the femoral component between magnetic resonance imaging (MRI) and CT. METHODS: For elderly varus osteoarthritic patients, 66 varus osteoarthritic knee patients that underwent primary TKA were selected. Twenty-seven young patients who underwent primary anterior cruciate ligament reconstruction were selected as control. After the transepicondylar axis (CEA), the surgical epicondylar axis (SEA) and the posterior femoral condylar line (PCL) were drawn on CT and on MRI at the same angles as CT. Then, the practical PCL was drawn on MRI considering the cartilage thickness (the cartilage PCL). The angle between the SEA and the cartilage PCL (the cartilage posterior condylar angle (PCA)) was measured as preoperative planning. To investigate the accuracy of preoperative MRI measurement, the cartilage thickness on posterior femoral condyles was directly measured during TKA. RESULTS: The cartilage PCA for varus osteoarthritic patients averaged 1.3 ± 1.3°. The cartilage PCA was 1.8 ± 1.0° significantly smaller than the bone PCA (the PCA measured on CT). Meanwhile, the cartilage PCA was 0.2 ± 0.4° significantly larger than the bone PCA in young people. The preoperative angle measurement on MRI strongly correlated with the direct measurement of cartilage thickness during TKA. CONCLUSION: There was 1.8° of divergence between MRI and CT in varus osteoarthritic patients due to cartilage degeneration of the medial femoral condyle. Cartilage assessment using MRI was useful for femoral component rotational alignment.

Editorial Commentary: No Clear Winner When Comparing Cost-Effectiveness of Particulated Juvenile Articular Cartilage With Matrix-Induced Autologous Chondrocyte Implantation: Too Many Assumptions.

Various treatment options exist for patellar chondral lesions, including nonoperative management, marrow stimulation, cell-based strategies, and osteochondral transplantation, yet there is insufficient evidence to recommend one treatment over another. One frequently discussed downside of cell-based strategies, including particulated juvenile allograft cartilage and matrix-induced autologous chondrocyte implantation, is the associated cost. Markov modeling is a tool used for economic modeling of different treatments and may be a viable option to compare cell-based strategies for patellar chondral defects. Too many assumptions carry great risk of drawing a strong conclusion. Further high-quality studies and comparative outcome studies are needed before any definitive cost-effectiveness conclusion is made.

Mood Disorders Are Associated with Increased Perioperative Opioid Usage and Health Care Costs in Patients Undergoing Knee Cartilage Restoration Procedure.

OBJECTIVE: To identify the prevalence of mood disorder diagnoses in patients undergoing cartilage transplantation procedures and determine the relationship between mood disorders, opioid usage, and postoperative health care costs. DESIGN: Patients with current procedural terminology (CPT) codes for osteochondral autograft transplantation (OAT), osteochondral allograft transplantation (OCA), and autologous chondrocyte implantation (ACI) were identified in the Truven Health Marketscan database (January 2009-September 2014). Patients were grouped based on having a preoperative mood disorder diagnosis (preMDD). Preoperative opioids, postoperative opioids ≥90 days, and health care costs within the year postoperative were compared for those with and without mood disorders. Costs were analyzed, adjusting for preoperative cost, sex, age, and opioid usage, for those with and without mood disorders. RESULTS: A total of 3,682 patients were analyzed (ACI: 690, OAT: 1,294, OCA: 1,698). A quarter of patients had preMDD (ACI: 25.4%, OAT: 20.6%, OCA: 22.7%). Postoperative opioid use was more prevalent in preMDD patients (OAT: 37.1% vs. 24.1%, P < 0.001; OCA: 30.4% vs. 24.8%, P = 0.032; ACI: 33.7% vs. 26.2%, P = 0.070) (odds ratio [OR] ranged from 1.29 to 1.86). First-year postoperative log-transformed costs were significantly greater for preMDD patients (ACI: $7,733 vs. $5,689*, P = 0.012; OAT: $5,221 vs. $3,823*, P < 0.001; OCA: $6,973 vs. $3,992*, P < 0.001; *medians reported). The estimated adjusted first postoperative year cost increase for preMDD OCA patients was 41.7% (P < 0.001) and 28.0% for OAT patients (P = 0.034). There was no statistical difference for ACI patients (P = 0.654). CONCLUSION: Cartilage transplantation patients have a high prevalence of preoperative mood disorders. Opioid use and health care costs were significantly greater for patients with preoperative mood disorder diagnoses. LEVEL OF EVIDENCE: Level III, retrospective therapeutic study.

Particulated Juvenile Articular Cartilage and Matrix-Induced Autologous Chondrocyte Implantation Are Cost-Effective for Patellar Chondral Lesions.

PURPOSE: To compare the cost-effectiveness of nonoperative management, particulated juvenile allograft cartilage (PJAC), and matrix-induced autologous chondrocyte implantation (MACI) in the management of patellar chondral lesions. METHODS: A Markov model was used to evaluate the cost-effectiveness of three strategies for symptomatic patellar chondral lesions: 1) nonoperative management, 2) PJAC, and 3) MACI. Model inputs (transition probabilities, utilities, and costs) were derived from literature review and an institutional cohort of 67 patients treated with PJAC for patellar chondral defects (mean age 26 years, mean lesion size 2.7 cm2). Societal and payer perspectives over a 15-year time horizon were evaluated. The principal outcome measure was the incremental cost-effectiveness ratio (ICER) using a $100,000/quality-adjusted life year (QALY) willingness-to-pay threshold. Sensitivity analyses were performed to assess the robustness of the model and the relative effects of variable estimates on base case conclusions. RESULTS: From a societal perspective, nonoperative management, PJAC, and MACI cost $4,140, $52,683, and $83,073 and were associated with 5.28, 7.22, and 6.92 QALYs gained, respectively. PJAC and MACI were cost-effective relative to nonoperative management (ICERs $25,010/QALY and $48,344/QALY, respectively). PJAC dominated MACI in the base case analysis by being cheaper and more effective, but this was sensitive to the estimated effectiveness of both strategies. PJAC remained cost-effective if PJAC and MACI were considered equally effective. CONCLUSIONS: In the management of symptomatic patellar cartilage defects, PJAC and MACI were both cost-effective compared to nonoperative management. Because of the need for one surgery instead of two, and less costly graft material, PJAC was cheaper than MACI. Consequently, when PJAC and MACI were considered equally effective, PJAC was more cost-effective than MACI. Sensitivity analyses accounting for the lack of robust long-term data for PJAC or MACI demonstrated that the cost-effectiveness of PJAC versus MACI depended heavily on the relative probabilities of yielding similar clinical results. LEVEL OF EVIDENCE: III, economic and decision analysis.

Good healing potential of patellar chondral defects after all-arthroscopic autologous chondrocyte implantation with spheroids: a second-look arthroscopic assessment.

PURPOSE: To report second-look arthroscopic assessment after all-arthroscopic autologous chondrocyte implantation (ACI) for articular cartilage defects at the patella. METHODS: A second-look arthroscopy after all-arthroscopic ACI using chondrospheres® (ACT3D) was performed in 30 patients with 30 full-thickness retropatellar cartilage defects. The mean time from ACI to second-look arthroscopy was 14.9 ± 16.3 (6-71) months. The quality of cartilage regeneration was evaluated by the International Cartilage-Repair Score (ICRS)-Cartilage Repair Assessment (CRA). RESULTS: Eleven lesions (36.7%) were classified as CRA grade I (normal) and 19 lesions (63.3%) as grade II (nearly normal). Concerning the degree of defect repair, 25 lesions (83.3%) were repaired up to the height of the surrounding articular retropatellar cartilage. Five lesions (16.7%) showed 75% repair of defect depth. The border zone was completely integrated into the surrounding articular cartilage shoulder in 28 lesions (93.3%) and demarcated within 1 mm in 2 lesions (6.7%). Macroscopically and by probing, 12 lesions (40%) had intact smooth surface, 17 lesions (56.7%) had fibrillated surface and 1 lesion (3.3%) had small, scattered fissures. A negative correlation was found between the overall repair assessment score and the defect size (r2 = - 0.430, p = 0.046) and between integration into border zone and defect size (r2 = - 0.340, p = 0.045). A positive correlation was found between macroscopic appearance and age (r2 = + 0.384, p = 0.036). CONCLUSIONS: All-arthroscopic ACI using chondrospheres® (ACT3D) for full-thickness retropatellar articular cartilage defects proved to be reproducible and reliable. The advantage of the procedure is that it is minimal invasive. Arthroscopic second-look demonstrated a high grade of normal or nearly normal cartilage regeneration. Although statistically significant differences were not observed, larger defect size and younger age may compromise the result of overall repair. LEVEL OF EVIDENCE: III.

Morphological Assessment of MACI Grafts in Patients with Revision Surgery and Total Joint Arthroplasty.

OBJECTIVE: To compare the histological and immunohistochemical characteristics of matrix-assisted chondrocyte implantation (MACI) grafts between patients with revision surgery and patients with total joint arthroplasty. METHODS: Biopsies of MACI grafts from patients with revision and total joint arthroplasty. The graft tissue characteristics and subchondral bone were examined by qualitative histology, ICRS (International Cartilage Repair Society) II scoring and semiquantitative immunohistochemistry using antibodies specific to type I and type II collagen. RESULTS: A total of 31 biopsies were available, 10 undergoing total knee arthroplasty (TKA) and 21 patients undergoing revision surgery. Patients in the clinically failed group were significantly older (46.3 years) than patients in the revision group (36.6 years) (P = 0.007). Histologically, the predominant tissue in both groups was of fibrocartilaginous nature, although a higher percentage of specimens in the revision group contained a hyaline-like repair tissue. The percentages of type I collagen (52.9% and 61.0%) and type II collagen (66.3% and 42.2%) were not significantly different between clinically failed and revised MACI, respectively. The talar dome contained the best and patella the worst repair tissue. Subchondral bone pathology was present in all clinically failed patients and consisted of bone marrow lesions, including edema, necrosis and fibrosis, intralesional osteophyte formation, subchondral bone plate elevation, intralesional osteophyte formation, subchondral bone cyst formation, or combinations thereof. CONCLUSIONS: MACI grafts in patients with revision and total joint arthroplasty were predominantly fibrocartilage in repair type, did not differ in composition and were histologically dissimilar to healthy cartilage. Clinically failed cases showed evidence of osteochondral unit failure, rather than merely cartilage repair tissue failure. The role of the subchondral bone in relation to pain and failure and the pathogenesis warrants further investigation.

Arthroscopic Treatment of Patellar and Trochlear Cartilage Lesions with Matrix Encapsulated Chondrocyte Implantation versus Microfracture: Quantitative Assessment with MRI T2-Mapping and MOCART at 4-Year Follow-up.

METHODS: Seventeen patients aged 18 to 55 years with symptomatic full-thickness cartilage lesions on either patella or trochlea were treated with matrix autologous chondrocyte implantation (MACI) or microfracture (MF). Both procedures combined with unloading/realigning techniques. Clinical assessment and T2-mapping were evaluated at 48-months. RESULTS: Clinically results from pre-op to 48-months improved significantly in MACI and MF for Lysholm (p = 0.001, p = 0.001), IKDC-S (p = 0.001, p = 0.002), KOOS-P (p = 0.000, p = 0.002), KOOS-DLA (p = 0.002, p = 0.003), KOOS-Sports/Rec (p = 0.000, p = 0.004), KOOS-QoL (p = 0.000, p = 0.003), KOOS-symptoms (p = 0.001, p = 0.020), and Kujala (p = 0.000, p = 0.01), respectively. Tegner was significant between baseline and 48 months only for MACI (p < 0.008) compared with MF (p = 0.25). No significant difference was observed between groups for any score at 3, 12, 24, and 48-months (p > 0.05). T2-mapping values improved significantly over time in MACI compared with MF at 24 months (39.35 vs. 50.44, p = 0.007) and 48 months (36.54 vs. 48.37, p = 0.005). When comparing control values to MACI at 12-m (p = 0.714), 24-m (p = 0.175), and 48-m (p = 0.097), no significant difference was found. MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score comparison gave no statistical difference between groups. CONCLUSIONS: Clinically both techniques improved significantly over time. However, quantitative assessment showed that only newly formed tissue with MACI technique improves significantly since 12-months and maintains stable values compared with native cartilage until 48-month follow-up. MF results were never comparable to those native values. Level of evidence II.

First Clinical Application of Polyurethane Meniscal Scaffolds with Mesenchymal Stem Cells and Assessment of Cartilage Quality with T2 Mapping at 12 Months.

BACKGROUND: Complex meniscal lesions often require meniscectomy with favorable results in the short term but a high risk of early osteoarthritis subsequently. Partial meniscectomy treated with meniscal substitutes may delay articular cartilage degeneration. PURPOSE: To evaluate the status of articular cartilage by T2 mapping after meniscal substitution with polyurethane scaffolds enriched with mesenchymal stem cells (MSC) and comparison with acellular scaffolds at 12 months. METHODS: Seventeen patients (18-50 years) with past meniscectomies were enrolled in 2 groups: (1) acellular polyurethane scaffold (APS) or (2) polyurethane scaffold enriched with MSC (MPS). Patients in the MPS group received filgrastim to stimulate MSC production, and CD90+ cells were obtained and cultured in the polyurethane scaffold. The scaffolds were implanted arthroscopically into partial meniscus defects. Concomitant injuries (articular cartilage lesions or cartilage lesions) were treated during the same procedure. Changes in the quality of articular cartilage were evaluated with T2 mapping in femur and tibia at 12 months. RESULTS: In tibial T2 mapping, values for the MPS group increased slightly at 9 months but returned to initial values at 12 months (P > 0.05). In the APS group, a clear decrease from 3 months to 12 months was observed (P > 0.05). This difference tended to be significantly lower in the APS group compared with the MPS group at the final time point (P = 0.18). In the femur, a slight increase in the MPS group (47.8 ± 3.4) compared with the APS group (45.3 ± 4.9) was observed (P > 0.05). CONCLUSION: Meniscal substitution with polyurethane scaffold maintains normal T2 mapping values in adjacent cartilage at 12 months. The addition of MSC did not show any advantage in the protection of articular cartilage over acellular scaffolds (P > 0.05).

An Increase in Medial Joint Space Width After Medial Open-Wedge High Tibial Osteotomy Is Associated With an Increase in the Postoperative Weight-Bearing Line Ratio Rather Than With Cartilage Regeneration: Comparative Analysis of Patients Who Underwent Second-Look Arthroscopic Assessment.

PURPOSE: To investigate relevant factors influencing increases in medial joint space width (JSW) after medial open-wedge high tibial osteotomy (MOWHTO). METHODS: Between January 2010 and December 2018, the electronic medical records of consecutive patients who underwent MOWHTO and subsequent second-look arthroscopic assessment at least 12 months after MOWHTO were retrospectively evaluated. The patients were classified into 2 groups according to changes in the medial JSW of the knee at the time of the second-look operation compared with that at baseline before the initial surgical procedure. Various radiographic parameters, arthroscopic findings, and clinical scores were compared between the groups, and regression analysis was performed to identify factors related to increases in medial JSW. RESULTS: A total of 114 patients were analyzed. In a bivariate analysis, patients who experienced an increase in medial JSW showed a significantly higher postoperative weight-bearing line ratio (WBLR) (P = .008) and a greater proportion of severe preoperative cartilage lesions in the medial compartment of the knee compared with patients with a maintained or reduced medial JSW (P = .035). In terms of clinical scores, patients with an increased medial JSW showed relatively favorable clinical outcomes at the time of the second-look operation. Regression analysis indicated only postoperative WBLR as a relevant factor associated with an increase in medial JSW after MOWHTO (odds ratio, 1.057; P = .01). Additional analysis with patients reclassified according to the postoperative WBLR showed that as the postoperative WBLR increased, the medial JSW increased, without a significant change in the lateral JSW. CONCLUSIONS: An increase in the medial JSW of the knee joint after MOWHTO appears to be associated with an increase in the postoperative WBLR, not with cartilage regeneration. Obtaining adequate correction so that the postoperative WBLR is within 60% to 70% would be desirable in terms of postoperative changes in the medial JSW, as well as clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Comparison of Autologous Chondrocyte Implantation and Osteochondral Allograft Transplantation of the Knee in a Large Insurance Database: Reoperation Rate, Complications, and Cost Analysis.

OBJECTIVE: To compare (1) the reoperation rates, (2) risk factors for reoperation, (3) 30-day complication rates, and (4) cost differences between autologous chondrocyte implantation (ACI) and osteochondral allograft transplantation (OCA) of the knee in a large insurance database. DESIGN: Subjects who underwent knee ACI (Current Procedural Terminology [CPT] code 27412) or OCA (CPT code 27415) with minimum 2-year follow-up were queried from a national insurance database. Reoperation was defined by ipsilateral knee procedure after index surgery. Multivariate logistic regression models were built to determine the effect of independent variables (age, sex, tobacco use, obesity, diabetes, and concomitant osteotomy) on reoperation rates. The 30-day complication rates were assessed using ICD-9-CM codes. The cost of the procedures per patient was calculated. Statistical comparisons were made. All P values were reported with significance set at P < 0.05. RESULTS: A total of 909 subjects (315 ACI and 594 OCA) were included (mean follow-up 39.2 months). There was a significantly higher reoperation rate after index ACI compared with OCA (67.6% vs. 40.4%, P < 0.0001). Concomitant osteotomy at the time of index procedure significantly reduced the risk for reoperation in both groups (odds ratio [OR] 0.2, P < 0.0001 and OR 0.2, P = 0.009). The complication rates were similar between ACI (1.6%) and OCA (1.2%) groups (P = 0.24). Day of surgery payments were significantly higher after ACI compared with OCA (P = 0.013). CONCLUSIONS: Autologous chondrocyte implantation had significantly higher reoperation rates and cost with similar complication rates compared with OCA. Concomitant osteotomy significantly reduced the risk for reoperation in both groups.

Compensation claims after knee cartilage surgery is rare. A registry-based study from Scandinavia from 2010 to 2015.

BACKGROUND: Focal cartilage defects (FCDs) in the knee joint has a high prevalence. A broad range of treatment options exists for symptomatic patients. Knowledge of patient compensation claims following surgical treatment of FCDs is missing. The purpose of this study is to evaluate compensation claims filed to the Scandinavian registries for patient compensation following treatment of FCDs in the knee joint from 2010 to 2015 and identify possible areas of improvement. METHODS: A cross-sectional study design was used to obtain all complaints following surgical treatment of FCDs from the Scandinavian registries from 2010 to 2015. Data such as age, gender, type of treatment, type of complaint, reason of verdict and amount of compensation were collected and systematically analyzed. RESULTS: 103 patients filed a compensation claim. 43 had received debridement (41.7%), 54 microfracture (MF) (52.4%), 3 mosaicplasty (2.9%) and 3 autologous chondrocyte implantation (ACI) (2.9%). Of the 103 claims, 36 were granted (35%). 21 following debridement (58.3%), 13 after MF (36.1%), 1 following mosaicplasty (2.8%) and 1 after ACI (2.8%). The most common reason for complaint was infection (22.1%), of which 89% were granted. The average compensation was €24.457 (range €209 - €458.943). CONCLUSION: Compensation claims following surgical treatment of knee cartilage injuries in Scandinavia are rare. Establishing nationwide cartilage registries can add further knowledge on this troublesome disease.

Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments Correlate Better With Legacy Measures in Knee Cartilage Patients at Postoperative Than at Preoperative Assessment.

PURPOSE: To define the psychometric properties of the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), Pain Interference (PI), and Depression computer adaptive tests (CATs) in patients undergoing knee cartilage surgical procedures. METHODS: The PROMIS PF, PI, and Depression CATs were administered preoperatively and at 6 months alongside legacy knee patient-reported outcome measures (PROMs) in patients undergoing knee cartilage surgical procedures. Statistical analysis consisted of the time to completion, psychometric analysis for correlative strengths, absolute and relative floor and ceiling effects, and Cohen effect size. RESULTS: Our study included 250 patients (57.2% male patients), averaging 1.87, 1.53, and 1.91 minutes for completion of the PF, PI, and Depression CATs, respectively. Preoperatively, the PROMIS PF and PI CATs showed wide ranges of correlation coefficients with respect to function (r = 0.14-0.72 and r = 0.29-0.77, respectively) and health-related quality-of-life PROMs (r = 0.64-0.70). At 6 months, the PROMIS PF CAT (r = 0.82-0.93) and PI CAT (r = 0.77-0.93) both exhibited excellent correlations with respect to legacy function and health-related quality-of-life PROMs except for the Marx Activity Rating Scale (r = 0.36-0.44). None of the PROMIS instruments exhibited any significant floor or ceiling effects. CONCLUSIONS: The PROMIS PF, PI, and Depression CATs performed better with respect to legacy PROMs in the postoperative period than the preoperative period. In addition, the PROMIS PF and PI measures performed best with respect to the International Knee Documentation Committee questionnaire, and no floor or ceiling effects were identified for the PROMIS instruments. The PROMIS instruments may be more suited to track outcomes postoperatively than to establish preoperative baselines in cartilage surgery patients. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Articular cartilage repair using autologous collagen-induced chondrogenesis (ACIC): a pragmatic and cost-effective enhancement of a traditional technique.

PURPOSE: The autologous collagen-induced chondrogenesis technique is described, and the results of a 6-year follow-up clinical study using this technique are presented. METHODS: 30 patients with International Cartilage Repair Society (ICRS) Grade III/IVa symptomatic chondral defects of the knee treated with enhanced microdrilling using atelocollagen were prospectively examined in this clinical series. The median age of the patients was 39.0 years (range 19-61 years). Patients were followed up to 72 months. Clinical evaluation was performed using functional knee scores and radiologically. Both quantitative and qualitative assessments were performed. RESULTS: Statistically significant and clinically relevant improvement was observed in 2 years and was sustained for the 6 years of the study observation. At 6 years, the mean Lysholm score was 79.7 (SD 6.8) compared to 52.6 (SD 10.7) pre-operatively (p < 0.05). The symptomatic Knee Injury and Osteoarthritis Outcome Score (KOOS) improved from 68.3 (SD 11.4) to 90.2 (SD 4.3) (p < 0.05). The subjective International Knee Documentation Committee (IKDC) also showed improvement from 39.1 (SD 4.1) to 81.6 (SD 7.8) (p < 0.05). The calculated T2* relaxation times were 26.0 (SD 4.2) seconds and 30.3 (SD 6.2) seconds for the repair tissue and native cartilage, respectively. The average magnetic resonance observation of cartilage repair tissue (MOCART) score was 78.5 (SD 9.6) for all lesions. CONCLUSION: The enhanced microdrilling using atelocollagen is an enhancement of the traditional microfracture method using an off-the-shelf product. When used to treat moderate to severe chondral lesions, this enhancement produces hyaline-like cartilage with a corresponding improvement in symptoms. LEVEL OF EVIDENCE: IV.

Assessment of Cartilage Repair Quality With the International Cartilage Repair Society Score and the Oswestry Arthroscopy Score.

The International Cartilage Repair Society (ICRS) score and the Oswestry Arthroscopic Score (OAS) have been validated to evaluate repair tissue quality. However, the performance of these scores has not been studied in typical patients undergoing cartilage repair and who have lesions of varying sizes. In this study, we compared the performance of the ICRS and the OAS scores and analyzed the effect of lesion characteristics on the performance of these two scores. Cartilage repair quality was assessed in a total of 104 arthroscopic observations of cartilage repair sites of the knee in 62 patients after autologous chondrocyte implantation. Two observers scored the repair areas independently with the ICRS and the OAS scores. The performance of both scores was evaluated according to internal consistency and inter-rater reliability and correlation between the scores. The frequency and proportion of disagreements were analyzed according to the repair site area and the given score. The correlation between the scores was good (r = 0.91, 95% confidence interval [CI]: 0.87-0.94). Both scores showed moderate internal consistency and inter-rater reliability. Cronbach's α was 0.88 (95% CI: 0.80-0.92) for the ICRS score and 0.79 (95% CI: 0.70-0.86) for the OAS score. The intraclass correlation coefficient was 0.89 (95% CI: 0.84-0.92) for the ICRS and 0.81 (95% CI: 0.74-0.87) for the OAS scores. The frequency and proportion of disagreements were higher in larger repair sites. In arthroscopic use, both ICRS and OAS scores perform similarly, however, their reliability deteriorates as the lesion size increases. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:555-562, 2020.

Arthroscopic matrix-associated, injectable autologous chondrocyte transplantation of the hip: significant improvement in patient-related outcome and good transplant quality in MRI assessment.

PURPOSE: Acetabular chondral lesions are common in patients with FAI. For large full-thickness cartilage defects, arthroscopic matrix-associated autologous chondrocyte transplantation (MACT) using an injectable in situ crosslinking product is an option. Aim of the study was to evaluate clinical and MRI results 12 months after MACT of acetabular cartilage defects in FAI patients. METHODS: We report data on 21 patients with a focal cartilage defect of the hip [2.97 ± 1.44 cm2 (mean ± SD)] caused by FAI treated with an arthroscopically conducted MACT combined with FAI surgery. The results were assessed with patient-reported outcome measures (iHOT33, EQ-5D) pre- as well as post-operatively and by MRI using MOCART scoring system 6 and 12 months post-operatively. RESULTS: The iHOT33 score improved from 52.9 ± 21.14 (mean ± SD) pre-operative to 81.08 ± 22.04 (mean ± SD; p = 0.0012) 12 months post-operatively. The lower the pre-operative iHOT33 score and the larger the defect size, the greater the observed improvement compared to pre-operative scores at 12 months. Patients showed a significant improvement in EQ-5D-5L index value (p = 0.0015) and EQ-5D VAS (p = 0.0006). MRI analysis after 12 months revealed a complete integration of the transplant in 16 of 20 patients. CONCLUSIONS: Injectable MACT is a promising minimally invasive treatment option for full-thickness cartilage defects of the hip caused by FAI. A significant improvement in symptoms and function associated with an increase in quality of life was detected in patients treated with injectable MACT combined with FAI surgery. This is of considerable clinical relevance, since, in addition to the elimination of the mechanical cause, MACT allows the successful therapy of consequential cartilage damage. LEVEL OF EVIDENCE: Level 4, case series.

Autologous Chondrocyte Implantation with Chondrosphere for Treating Articular Cartilage Defects in the Knee: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Chondrosphere (Spherox) is a form of autologous chondrocyte implantation (ACI). It is licensed for repair of symptomatic articular cartilage defects of the femoral condyle and the patella of the knee with defect sizes up to 10 cm2 in adults. In a single technology appraisal (STA) [TA508] undertaken by the National Institute of Health and Care Excellence (NICE), Warwick Evidence was the Evidence Review Group (ERG) invited to independently review the evidence submitted by the manufacturer, Co.Don. The clinical effectiveness data came from their COWISI randomised controlled trial (RCT), which compared Chondrosphere with microfracture (MF). The timing of this appraisal was unfortunate given that MF was no longer the most relevant comparator because NICE had contemporaneously published guidance approving ACI in place of MF. Moreover, the COWISI RCT enrolled mostly patients with small defect sizes. Evidence of clinical effectiveness for Chondrosphere used in people with larger defect size came from another RCT, which compared three doses of Chondrosphere and that by design could not provide evidence comparing Chondrosphere to any other forms of ACI. To estimate the relative clinical performance of Chondrosphere versus other ACI, Co.Don conducted an indirect treatment comparison by network meta-analyses (NMA). The NMA was flawed in that the distribution of population characteristics that are effect modifiers greatly differed across the treatment comparisons of the network. The ERG questioned both the appropriateness of the NMA and the validity of the resulting estimates. Co.Don estimated the cost-effectiveness of Chondrosphere using a lifetime Markov model with all patients receiving the first repair during the first cycle of the model then moving into one of three health states: success, no further repair (NFR), or a second repair, if necessary. Subsequent to the first cycle, those who were a success either remained a success or moved to second repair. All those in NFR remained in NFR. The cost-effectiveness of Chondrosphere compared to other ACI forms relied on the clinical effectiveness estimates of success and failure rates obtained from the company's indirect comparisons, the validity of which the ERG questioned. The company revised cost-effectiveness estimates for Chondrosphere versus MF and for Chondrosphere versus matrix-applied characterised autologous cultured chondrocyte implant (MACI) were £4360 and around £18,000 per quality-adjusted life year gained, respectively. NICE recommended ACI using Chondrosphere for treating symptomatic articular cartilage defects of the femoral condyle and patella of the knee in adults only if certain requirements were met.