RESUMO
Background: Multiligament reconstruction (MLR) has become the standard surgical approach for treating multiligament knee injuries (MLKIs). Purpose: To identify prognostic factors for patient-reported outcome measures, return to work (RTW), return to sports, and radiographic osteoarthritis (OA) (Kellgren-Lawrence grade ≥2) after MLR for MLKI. Study Design: Case-control study; Level of evidence 3. Methods: Included were 52 consecutive patients (age, 35.5 ± 11 years; 75% men), with MLKI sustained between 2013 and 2019 and treated with MLR. At a mean follow-up of 3.8 ± 1.6 years, patient-reported outcome measure scores-including the International Knee Documentation Committee (IKDC), the Knee injury and Osteoarthritis Outcome Score (KOOS), the Anterior Cruciate Ligament-Return to Sport after Injury (ACL-RSI), and the 12-Item Short-Form Health Survey-RTW, return to sports, and weightbearing radiographs were obtained. A total of 20 determinants were hypothesized and tested by univariate logistic regression for binary variables or linear regression for continuous variables. Only factors identified as significant (P < .10) were entered into a multivariate logistic regression model. Results: The prevalence of injury severity according to the Schenck knee dislocation (KD) classification was as follows: KD I (44%), KD III (36%), KD IV (10%), and KD V (10%). Increased KD grades resulted in decreased IKDC (P = .002) and all 5 KOOS subscales (P≤ .007 for all) scores. Medial meniscectomy (23%) was associated with a worse ACL-RSI score (P = .007) and RTW failure (odds ratio [OR], 36.8; P = .035). Peroneal nerve palsy (6%) was associated with a worse ACL-RSI score (P≤ .001). Radiographic OA was observed in 38%, with distribution predominantly patellofemoral (80%) and medial tibiofemoral (45%). Traumatic cartilage damage (Outerbridge grade >2 [37%]) was associated with secondary patellofemoral (OR, 10; P = .012) and medial tibiofemoral (OR, 10; P = .019) OA. Anterior cruciate ligament reconstruction failure (7%) was a risk factor for medial tibiofemoral OA (OR, 25.8; P = .006). Conclusion: Increased Schenck KD grade, permanent peroneal nerve palsy, and irreparable medial meniscus lesions were prognostic factors for worse functional outcomes 3.8 years after MLKI was treated with MLR. Traumatic cartilage damage and anterior cruciate ligament failure were associated with the development of early OA.
RESUMO
Cultured autologous human articular chondrocyte (HAC) implantation has been extensively investigated for safe and effective promotion of structural and functional restoration of knee cartilage lesions. HAC-based cytotherapeutic products for clinical use must be manufactured under an appropriate quality assurance system and follow good manufacturing practices (GMP). A prospective clinical trial is ongoing in the Lausanne University Hospital, where the HAC manufacturing processes have been implemented internally. Following laboratory development and in-house GMP transposition of HAC cell therapy manufacturing, a total of 47 patients have been treated to date. The main aim of the present study was to retrospectively analyze the available manufacturing records of the produced HAC-based cytotherapeutic products, outlining the inter-individual variability existing among the 47 patients regarding standardized transplant product preparation. These data were used to ameliorate and to ensure the continued high quality of cytotherapeutic care in view of further clinical investigations, based on the synthetic analyses of existing GMP records. Therefore, a renewed risk analysis-based process definition was performed, with specific focus set on process parameters, controls, targets, and acceptance criteria. Overall, high importance of the interdisciplinary collaboration and of the manufacturing process robustness was underlined, considering the high variability (i.e., quantitative, functional) existing between the treated patients and between the derived primary HAC cell types.