Background: The minimal clinically important difference (MCID) for patient-reported outcome measures (PROMs) expresses both the extent of the improvement and the value that patients place on it. MCID use is becoming increasingly widespread to understand the clinical efficacy of a given treatment, define guidelines for clinical practice, and properly interpret trial results. However, there is still large heterogeneity in the different calculation methods. Purpose: To calculate and compare the MCID threshold values of a PROM by applying various methods and analyzing their effect on the study results interpretation. Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: The data set used to investigate the different MCID calculation approaches was based on a database of 312 patients affected by knee osteoarthritis and treated with intra-articular platelet-rich plasma. MCID values were calculated on the International Knee Documentation Committee (IKDC) subjective score at 6 months using 2 approaches: 9 methodologies referred to an anchor-based approach and 8 methodologies to a distribution-based approach. The obtained threshold values were applied to the same series of patients to understand the effect of using different MCID methods in evaluating patient response to treatment. Results: The different methods employed led to MCID values ranging from 1.8 to 25.9 points. The anchor-based methods ranged from 6.3 to 25.9, while the distribution-based ones were from 1.8 to 13.8 points, showing a 4.1× variation of the MCID values within the anchor-based methods and a 7.6× variation within the distribution-based methods. The percentage of patients who reached the MCID for the IKDC subjective score changed based on the specific calculation method used. Among the anchor-based methods, this value varied from 24.0% to 66.0%, while among the distribution-based methods, the percentage of patients reaching the MCID varied from 44.6% to 75.9%. Conclusion: This study proved that different MCID calculation methods lead to highly heterogeneous values, which significantly affect the percentage of patients achieving the MCID in a given population. The wide-ranging thresholds obtained with the different methodologies make it difficult to evaluate the real effectiveness of a given treatment questioning the usefulness of MCID, as currently available, in the clinical research.

Background: Platelet-rich plasma (PRP) is gaining large interest in clinical practice as a minimally invasive injective treatment for knee osteoarthritis (OA). Different preparation methods are available, and the presence of leukocytes, deemed detrimental in some preclinical studies, is one of the most debated aspects regarding PRP efficacy. Purpose: To compare the safety and effectiveness of leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) for the treatment of knee OA. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 192 patients with symptomatic knee OA (Kellgren-Lawrence grade 1-3) were randomly allocated to 3 weekly injections of LR-PRP or LP-PRP. LP-PRP was obtained with a filter for leukodepletion. LR-PRP and LP-PRP were divided into aliquots of 5 mL, with a mean platelet concentration of 1146.8 × 10 ⁹ /L and 1074.9 × 10 ⁹ /L and a mean leukocyte concentration of 7991.4 × 10 ⁶ /L and 0.1 × 10 ⁶ /L, respectively. Patients were evaluated at baseline and thereafter at 2, 6, and 12 months for the primary outcome, the International Knee Documentation Committee (IKDC) subjective score; and for secondary outcomes, the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol–visual analog scale (EQ-VAS), and Tegner score. Results: No differences between groups were observed in terms of absolute values or improvement of the clinical scores across all follow-up intervals. The mean IKDC subjective score at baseline and 12 months improved from 45.6 to 60.7 in the LR-PRP group as compared with 46.8 to 62.9 in the LP-PRP group ( P = .626). No severe adverse events were described in either group, although 15 mild adverse events (knee pain or swelling) were reported: 12.2% for LR-PRP and 4.7% for LP-PRP ( P = .101). No statistically significant difference was also found between LR-PRP and LP-PRP in terms of failures (7.8% vs 3.5%, P = .331). Conclusion: This double-blind randomized trial showed that 3 intra-articular LR-PRP or LP-PRP injections produced similar clinical improvement in the 12 months of follow-up in patients with symptomatic knee OA. Both treatment groups reported a low number of adverse events, without intergroup differences. The presence of leukocytes did not significantly affect the clinical results of PRP injections. Registration: NCT02923700 (ClinicalTrials.gov identifier).

Objective: The aim of this systematic review was to analyze the evidence about the efficacy of the several synovial fluid (SF) biomarkers proposed for knee osteoarthritis (OA), categorizing them by both molecular characteristics and clinical use according to the BIPEDs criteria, to provide a comprehensive and structured overview of the current literature. Design: A systematic review was performed in May 2020 on PubMed, Cochrane Library, and Embase databases about SF biomarkers in patients with knee OA. The search was limited to articles in the last 20 years on human studies, involving patients with knee OA, reporting SF biomarkers. The evidence for each selected SF biomarker was quantified according to the 6 categories of BIPEDs classification. Results: A total of 159 articles were included in the qualitative data synthesis and 201 different SF biomarkers were identified. Among these, several were investigated multiple times in different articles, for a total of 373 analyses. The studies included 13,557 patients with knee OA. The most promising SF biomarkers were C4S, IL-6, IL-8, Leptin, MMP-1/3, TIMP-1, TNF-α, and VEGF. The “burden of disease” and “diagnostic” categories were the most represented with 132 and 106 different biomarkers, respectively. Conclusions: The systematic review identified numerous SF biomarkers. However, despite the high number of studies on the plethora of identified molecules, the evidence about the efficacy of each biomarker is supported by limited and often conflicting findings. Further research efforts are needed to improve the understanding of SF biomarkers for a better management of patients with knee OA.

Background: Young patients with osteoarthritic knees are a challenging population because of a combination of high functional demands and limited indication for joint replacement. Purpose: To analyze the potential of the cartilage regenerative approach by documenting the results and failures of matrix-assisted autologous chondrocyte transplantation (MACT) at midterm follow-up. Study Design: Case series; Level of evidence, 4. Methods: Forty-four patients affected by cartilage lesions in osteoarthritic knees underwent MACT as a salvage procedure. The mean age at surgery was 42 years (range, 20-58 years), and the average defect size was 4 cm ² (range, 1.5-9 cm ² ). Patients were prospectively evaluated with the subjective International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores preoperatively; at 1, 2, and 5 years; and at a final assessment at 9 years’ mean follow-up. Adverse events and failures were also reported. Results: A statistically significant improvement was observed in all scores from the initial evaluation to the final follow-up. The mean ± standard deviation IKDC subjective score improved from 38.0 ± 15.8 to 67.0 ± 18.3 at 2 years ( P < .0005), with a subsequent decrease to 57.8 ± 20.6 at the final follow-up ( P = .012). The same trend was confirmed by the EQ-VAS score. The activity level revealed by the Tegner score improved at all follow-ups but without achieving the preinjury level. The analysis of the influencing factors showed the importance of the meniscus condition, revealing a significantly inferior outcome in knees with previous or combined partial meniscectomy procedures. During the study period, 12 patients had failed results, producing a cumulative failure rate of 27.3%. At the last evaluation, half of the patients considered their condition not better than before the treatment, and 39% would not repeat the treatment considering the results obtained. Conclusion: Despite a statistically significant improvement, the clinical outcome was poor. A higher improvement could be obtained in patients who had not undergone previous or combined meniscectomies, but this was limited over time. The failure rate was also high, regardless of the degree of osteoarthritis. Tissue-engineered cartilage implantation is questionable for this indication, and the limits of this scaffold-based procedure have to be considered if it is used as a salvage procedure for young patients affected by knee osteoarthritis.

Background: Matrix-assisted autologous chondrocyte transplantation (MACT) has been shown to offer good outcomes at midterm follow-up, but results are heterogeneous among different patients and lesion types. Being part of the same joint, both patellar and trochlear cartilage lesions are commonly considered to be affected by the same treatment issues, and therefore, it is common practice to report results obtained treating these lesions together. Purpose: To determine, in a large cohort of patients prospectively followed at midterm follow-up for patellofemoral chondral defects, if patellar and trochlear defects actually represent different clinical conditions with different healing potentials after cartilage treatment. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 49 consecutive patients with full-thickness patellofemoral chondral lesions of the knee were treated with MACT at the authors’ institute and followed prospectively for a minimum follow-up of 5 years. Among these 49 patients, 28 were affected by patellar lesions, 17 were affected by trochlear lesions, and 4 had both patellar and trochlear defects. The clinical outcome was analyzed with International Knee Documentation Committee (IKDC) subjective, EuroQol visual analogue scale (EQ-VAS), Kujala, and Tegner scores. Results: A statistically significant improvement in all scores was observed after treatment. Patellar lesions required more realignment procedures and were more common in women. The comparative analysis showed better results for trochlear lesions compared with patellar lesions at all follow-ups, with mean IKDC scores at 5-year follow-up of 89.6 ± 12.7 and 69.7 ± 17.6, respectively ( P < .0005). Better results were also shown for the mean Kujala score (92.4 ± 14.7 vs 81.5 ± 12.7, respectively; P = .012) and mean EQ-VAS score (90.0 ± 10.8 vs 81.9 ± 11.7, respectively; P = .027). Finally, the sport activity level evaluated with the Tegner score confirmed the same trend; even though neither patellar nor trochlear lesion groups reached the preinjury level, both improved after treatment, with a significantly higher improvement in the trochlear lesion group (5.9 ± 1.8 vs 3.9 ± 1.7, respectively; P < .0005). Conclusion: Patient characteristics differ between patellar and trochlear cartilage defects, and moreover, the results obtained are significantly different, with a markedly good outcome in cases with trochlear lesions and less satisfactory results for patients affected by cartilage lesions of the patella. Thus, patellar and trochlear defects should be considered separately when evaluating the outcome of cartilage treatments in this anatomic region.