Validation of the Knee Injury and Osteoarthritis Outcome Score (KOOS) for the treatment of focal cartilage lesions

SummaryObjectiveTo validate the Knee Injury and Osteoarthritis Outcome Score (KOOS) for the treatment of focal cartilage lesions.MethodsA total of 40 patients (mean age 35±12 years,) treated for a focal cartilage lesion in the knee were included in this study. Test–retest data were collected with an intermediate period of 2 days. Patients were asked to complete the Dutch KOOS and complementary questionnaires [short form-36 (SF-36), Lysholm, EuroQol-5D (EQ-5D)] to evaluate the clinimetric properties of the KOOS in terms of internal consistency (Cronbach's alpha), reliability [intra-class-correlation (ICC) and Bland and Altman plots], construct validity (Spearman's rank correlation), floor and ceiling effects and responsiveness.ResultsThe Cronbach's alpha of the KOOS subdomains and total score ranged from 0.74 to 0.96. The overall ICC of the KOOS was 0.97 while the subscales ranged from 0.87 to 0.95. The Bland and Altman plots showed a small individual variance between the two assessments in time. Spearman's rank correlations between the subscales of the KOOS and representative subscales of the SF-36, Lysholm and EQ-5D were high to moderate ranging from 0.43 to 0.70. We observed no floor effect while the largest observed ceiling effect was 10.3%. The responsiveness was moderate to large with the effect size ranging from 0.70 to 1.32 and the standardized response mean 0.61 to 0.87.ConclusionThis study illustrates the validity and reliability of the KOOS in measuring the clinical condition of patients after treatment of focal cartilage lesions. This study provides a basis for the use of the KOOS for future clinical research in cartilage repair

Articular Cartilage Evaluation After TruFit Plug Implantation Analyzed by Delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC)

Background: Quantitative MRI of articular cartilage has rapidly developed in recent years and provides the clinician with a noninvasive tool to determine the biological consequence of an intervention. Purpose: To evaluate the quality of intra-articular cartilage, using the dGEMRIC scanning technique, 1 year after TruFit implantation. The hypothesis was that implantation of a TruFit plug does not lead to damage at the opposing articular cartilage. Study Design: Case series; Level of evidence, 4. Methods: A total of 13 patients (age, 32 ± 8 years) were evaluated with dGEMRIC at 12 ± 4 months after treatment of an osteochondral lesion by implantation of 1 or multiple TruFit plugs. The dGEMRIC scanning protocol was applied 90 minutes after intravenous Magnevist (0.2 mmol/kg body weight) injection. Different regions of interest (ROIs) were defined: the femur cartilage, cartilage directly surrounding the implanted TruFit plug, the TruFit plug, and the articulating and nonarticulating tibia cartilage. The average dGEMRIC index (T1gd; magnetic resonance imaging relaxation time per ROI) was calculated by a pixel-by-pixel curve fitting using the Levenberg-Marquardt method. Differences between the mean T1gd of the individual ROI for all patients were tested using analysis of variance with post hoc Bonferroni correction. A P value <.05 was considered statistically significant. Results: The average T1gd of the TruFit ROI (385 ± 74 ms) was comparable with those in the femur (409 ± 49 ms) and surrounding (392 ± 64 ms) ROIs (P ≥ .339). The average T1gds for the articulating (578 ± 133 ms) and nonarticulating (516 ± 118 ms) ROIs were higher compared with the femur (409 ± 49 ms), surrounding (392 ± 64 ms), and TruFit (385 ± 74 ms) ROIs (P < .002), while no difference was observed between the tibia ROIs (P = .160). Conclusion: Implantation of the TruFit plug in osteochondral lesions does not damage the opposing or surrounding surface, and newly formed tissue inside the plug has cartilage-like dGEMRIC characteristics 12 months after implantation. The implantation of synthetic TruFit plugs is safe for the opposing cartilage, an item that is frequently discussed when using such materials to treat focal cartilage defects

One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats

SummaryObjectiveThe combination of chondrocytes and mononuclear fraction (MNF) cells might solve the expansion induced dedifferentiation problem of reimplanted cells in autologous chondrocytes implantation as sufficient cells would be available for direct, one-stage, implantation. Earlier in vitro work already showed a positive stimulation of cartilage specific matrix production when chondrocytes and MNF cells were combined. Therefore, this study aimed to evaluate cartilage regeneration using a one-stage procedure combining MNF cells and primary chondrocytes for the treatment of focal cartilage lesions in goats compared to microfracture treatment.DesignFreshly created focal cartilage defects were treated with either a combination of chondrocytes and MNF cells embedded in fibrin glue or microfracture treatment. After 6 months follow-up local regeneration as well as the general joint cartilage health were evaluated using validated scores and biochemical assays.ResultsMacroscopic (P = 0.015) scores for the cartilage surface at the treated defect were, after 6 months, significantly higher for the chondrocyteMNF treatment compared to microfracture-treated defects, but microscopic scores were not (P = 0.067). The articulating cartilage showed more (P = 0.005) degeneration following microfracture treatment compared to chondrocyteMNF treatment. Biochemical glycosaminoglycans (GAG) evaluation did not reveal differences between the treatments. Both treatments had resulted in a slight to moderate cartilage degeneration at other locations in the joint.ConclusionIn conclusion, treatment of focal articular cartilage lesions in goats using a combination of MNF cells from bone marrow and unexpanded chondrocytes leads to better macroscopic regeneration compared to microfracture, however needs further fine-tuning to decrease the negative influence on other joint compartments

Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model

Introduction: This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.Methods: IL-6 concentrations were determined by ELISA in synovial fluid and in conditioned media of chondrocytes regenerating cartilage. Chondrocytes were obtained from donors with symptomatic cartilage defects, healthy and osteoarthritic donors. The effect of IL-6 on cartilage regeneration and on metabolism of the resident cartilage in the knee was studied by both inhibition of endogen

Towards one-stage cell-based treatment and non-invasive evaluation of cartilage defects

The central aim of this thesis is to improve the clinical outcome of patients with a focal articular cartilage lesion treated with autologous chondrocyte implantation (ACI), by improvement of the surgical technique, the development of specific treatment algorithms and the evaluation and validation of suited outcome tools. Two surgeries in ACI are inevitable because the number of harvested cells is insufficient to directly fill the defect. As a consequence culture-expanded cells are reimplanted during a second surgery which creates a fibrocartilaginous tissue. This thesis shows that combining chondrocytes and MSCs positively influences cartilage-specific matrix production. This stimulation os most likely be initiated by trophic factors excreted by the MSC. Such a cell combination provides sufficient cells to fill the defect within one surgery. This one-stage cell-based treatment showed to be superior to microfracture treatment in goats. This thesis also shows that a new MRI technique (dGEMRIC) can validly be applied to evaluate the quality of cartilage regeneration where conventional MRI only provides information on defect fill. The last section of this thesis presents an evidence-based treatment algorithm which should preferably be used to select the proper treatment for your patient. Moreover, we also present patient characteristics that influence treatment outcome. These could be used to create realistic patient expectations prior to surgery. The clinical outcome of patients with a focal articular cartilage lesion can only be influenced by improvement of treatment selection, surgical therapy and outcome evaluation and by acknowledging that these factors are part of a larger process at which the patient and his characteristics play the leading role