Influence of Platelet Concentration on the Clinical Outcome of Platelet-Rich Plasma Injections in Knee Osteoarthritis.

BACKGROUND: Platelet-rich plasma (PRP) is one of the most frequently used orthobiologic products for the injection treatment of patients affected by knee osteoarthritis (OA). Some preliminary evidence supports the influence of platelet concentration on patients' clinical outcomes. PURPOSE: To analyze if platelet concentration can influence the safety and clinical efficacy of PRP injections for the treatment of patients with knee OA. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study consisted of 253 patients with knee OA (142 men, 111 women; mean ± SD age, 54.8 ± 11.4 years; Kellgren-Lawrence grades 1-3) who were treated with 3 intra-articular injections of 5 mL of autologous leukocyte-rich or leukocyte-poor PRP. All patients were prospectively evaluated at baseline and at 2, 6, and 12 months. Patients were clinically assessed thorough the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales and the International Knee Documentation Committee (IKDC) Subjective score. Platelet concentration was correlated with clinical outcome. Further analysis was performed by stratifying patients into 3 groups (homogeneous for OA severity) based on platelet concentration (high, medium, and low). All complications and adverse events were reported, as well as failures. RESULTS: An overall statistically significant improvement in all clinical scores was documented from baseline to each follow-up evaluation. Platelet concentration positively correlated with clinical outcome. KOOS Pain improved more with higher platelet concentration at 2 months (P = .036; rho = 0.132), 6 months (P = .009; rho = 0.165), and 12 months (P = .014; rho = 0.155). The same trend was shown by the other KOOS subscales and by the IKDC Subjective score, as well as by the comparison of the groups of high-, medium-, and low-platelet PRP. The highest failure rate (15.0%) was found in the low-platelet group as compared with the medium-platelet group (3.3%) and the high-platelet group (3.3%). No differences were observed among the 3 groups in terms of adverse events. CONCLUSION: This study demonstrated that platelet concentration influences the clinical outcome of PRP injections in knee OA treatment. PRP with a higher platelet concentration provides a lower failure rate and higher clinical improvement as compared with PRP with a lower platelet concentration, with overall better results up to 12 months of follow-up in patients with knee OA.

Leukocytes Do Not Influence the Safety and Efficacy of Platelet-Rich Plasma Injections for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Platelet-rich plasma (PRP) is increasingly used for the injection treatment of knee osteoarthritis (OA). However, the role of leukocytes contained in PRP is controversial, with some preclinical studies suggesting detrimental effects and others emphasizing their contribution in secreting bioactive molecules. 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. HYPOTHESIS: That leukocytes could influence results both in terms of adverse events and clinical outcomes. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This double-blind randomized controlled trial included 132 patients with Kellgren-Lawrence grade 1-3 knee OA who were randomized to a 3-injection cycle of either LR-PRP or LP-PRP. Patients were prospectively assessed at baseline and at 2, 6, and 12 months with subjective evaluations comprising the International Knee Documentation Committee (IKDC) subjective score, the KOOS (Knee injury and Osteoarthritis Outcome Score), the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), the visual analog scale for pain, the EuroQol-visual analog scale, the EuroQol-5 dimensions, and the Tegner activity scale. Objective evaluations consisted of the IKDC objective score, active/passive range of motion, and circumference of the index and contralateral knees. Patient judgment of the treatment was recorded as well as adverse reactions and failures. RESULTS: An overall improvement in subjective and objective outcomes was documented, with no differences between the 2 groups, except for the improvement in the IKDC subjective score at 2 months, which was greater for the LR-PRP group compared with the LP-PRP group (14.8 ± 14.8 vs 8.6 ± 13.3, respectively; P = .046), as well as for active (P = .021) and passive (P = .040) ROM of the index knee at 6 months, showing statistically significant higher values in the LP-PRP group; and for quadriceps circumference of the index (P = .042) and contralateral (P = .045) knees at 12 months, which were significantly greater in the LR-PRP group. The IKDC subjective score improved from 42.5 ± 17.6 at baseline to 55.6 ± 21.4 at 12 months for the LR-PRP group (P < .0005) and from 45.7 ± 16.4 to 55.3 ± 20.4 for the LP-PRP group (P = .001). No differences in terms of patient treatment judgment were observed at all follow-up time points. No severe adverse events related to the treatment were reported, but some mild adverse events related to the treatment were observed: 16 in the LR-PRP group and 17 in the LP-PRP group. Treatment failed in 5 patients in the LR-PRP group and 2 in the LP-PRP group. CONCLUSION: This double-blind randomized controlled trial demonstrated that leukocytes did not affect the safety and efficacy of intra-articular PRP injections for the treatment of patients with knee OA. Both LR-PRP and LP-PRP demonstrated comparable clinical outcomes at all follow-up time points, without showing differences in subjective and objective outcomes or in adverse events and treatment failures. REGISTRATION: NCT04187183 (ClinicalTrials.gov).

Injection therapy in professional footballers.

BACKGROUND: Injection therapy offers a minimally invasive approach for symptomatic relief that allows concurrent training, limiting time loss and providing a faster recovery. However, there is a lack of scientific evidence to support it, and there are controversies about its use. The present narrative review aims to present the available scientific literature on injection therapies in professional footballers (PF), highlighting the advantages and disadvantages of its use in the most common injuries. METHODS: The authors searched and reviewed contemporary literature on injection therapies in PF in electronic databases, summarizing them in a narrative review. RESULTS: Injection therapies such as hyaluronic acid and PRP have shown an adequate safety profile that allows their use. Current evidence suggests that hyaluronic acid injections are a valid option for managing symptomatic cartilage injuries. At the same time, PRP injections have failed to prove beneficial in treating muscle injuries and should be avoided until further evidence proves the opposite. Yet, PRP may have potential use in partial ACL injuries, anterior inferior tibiofibular ligament injuries (ankle syndesmosis), and fifth metatarsal fractures and needs further study. Due to the long-term health repercussions, other injection therapies should be preferred over corticosteroids in PF. CONCLUSIONS: There is a paucity of evidence on the use and benefits of injection therapies in PF despite its extensive use among physicians. Viscosupplementation may have a role in improving symptomatic cartilage injuries. In contrast, PRP injection therapy needs further high-quality clinical trials to assess its role in PF sports injuries.

Placebo Effect in the Treatment of Patellar Tendinopathy and Its Influencing Factors: Systematic Review With Meta-analysis and Meta Regression of Randomized Controlled Trials.

Background: The effectiveness of nonsurgical treatment of patellar tendinopathy is questioned due to the conflicting results of placebo-controlled randomized controlled trials (RCTs) in which placebo arms often show impressive results. Purpose: To quantify the magnitude of placebo effect of the different nonsurgical treatments of patellar tendinopathy. We also evaluated the influence of patients and treatments characteristics on the response to the placebo. Study Design: Systematic review; Level of evidence, 1. Methods: We searched PubMed, Web of Science, Embase, Scopus, Cochrane Library, and gray literature databases on May 10, 2023, with no time limitation. RCTs on nonoperative treatment of patellar tendinopathy, including a placebo control arm reporting the evolution of symptoms after placebo administration, were included. A single-arm meta-analysis was performed with the Victorian Institute of Sport Assessment-Patella (VISA-P) at mid-term follow-up (3-6 months) as the primary outcome. The VISA-P score at short-term (1-3 months) and long-term (6-12 months) follow-ups, as well as visual analog scale (VAS) for pain at all 3 time points were also analyzed. A subanalysis based on the type of placebo and a meta-regression were conducted to look for potential determinants of the placebo effect. Risk of bias and level of evidence were also analyzed using the revised tool for risk of bias in randomized trials and Grading of Recommendations Assessment, Development and Evaluation. Results: In total, 14 studies (251 patients) were included. VISA-P score at mid-term follow-up (3-6 months) showed statistically significant improvements of 13 of 100 points (P = .001). The change at short-term follow-up (1-3 months) was not statistically significant, whereas at long-term follow-up (6-12 months) it was 27 of 100 points (P < .001). Regarding VAS, results were statistically significant only at mid-term (MD = -1.5/10; P = .02) and long-term (MD = -3.2/10; P < .001) follow-ups. The meta-regression showed positive correlations between the response to placebo and the follow-up length (P < .001) and the effect size in the experimental group (P = .006). The level of evidence was moderate for mid- and long-term results and low for short-term results. Conclusion: The placebo effect for nonsurgical treatments of patellar tendinopathy is long-lasting (up to 12 months) and statistically and clinically significant. It has a perceived and true component and differs among treatments. The duration of follow-up and the effect size of experimental groups correlate with the magnitude of the placebo component, underlining the importance of RCTs to determine the effectiveness of new treatments of patellar tendinopathy.

Cell-free biomimetic osteochondral scaffold for the treatment of knee articular surface lesions: Clinical outcomes differ based on patient and lesion characteristics.

PURPOSE: A cell-free biomimetic osteochondral scaffold was developed to treat cartilage knee lesions, with positive clinical results documented in small case series. However, clear evidence on patient and lesion characteristics that might affect the outcome is still lacking. The aim of this study is to analyse a large cohort of patients treated with this scaffold to investigate factors that could influence the clinical outcome. METHODS: Two hundred and three patients (mean age 30.7 ± 10.9 years) treated with this scaffold were prospectively evaluated at baseline, 6-, 12- and 24-month follow-up. The clinical outcome was analysed using the International Knee Documentation Committee (IKDC) score, and the activity level was assessed with the Tegner score. The influence of patient and lesion characteristics on clinical outcomes was analysed. RESULTS: Mild and severe adverse reactions were found in 39.0% and 1.5% of patients, respectively. The failure rate was 2.0%, increasing to 12.3% when including also clinical failures. The IKDC subjective score increased from 43.3 ± 15.9 to 61.0 ± 16.2 at 6 months, 68.3 ± 18.5 at 12 months and 73.8 ± 18.3 at 24 months (p < 0.0005). The Tegner improved from 2.5 ± 1.7 to 4.2 ± 1.7 at 24 months (p < 0.0005), without reaching the pre-injury level (6.0 ± 2.2) (p < 0.0005). The IKDC objective score changed from 68.5% normal and nearly normal knees before the treatment to 90.1% at 24 months. At 24 months, age showed a correlation with the IKDC subjective score (ρ = -0.247; p < 0.0005), women had a lower score (p < 0.0005), as well as patients with patellar lesions (p = 0.002). Previous surgery correlated with lower results (p = 0.003), while better results were found in osteochondritis dissecans (OCD) compared to degenerative lesions (p = 0.001). CONCLUSION: This cell-free biomimetic scaffold is a safe and effective treatment for cartilage knee lesions, offering positive clinical results at 2 years with a low failure rate. Better outcomes were observed in younger patients, in lesions of the femoral condyles and in OCD, while joints affected by patellar lesions, patients who underwent previous knee surgery, and women may expect lower results. LEVEL OF EVIDENCE: III, Cohort study.

10-Year Survival and Clinical Improvement of Meniscal Allograft Transplantation in Early to Moderate Knee Osteoarthritis.

BACKGROUND: Meniscal allograft transplantation (MAT) is a viable option for patients experiencing unicompartmental knee pain after total or subtotal meniscectomy. Nonetheless, caution is recommended when suggesting this procedure in the presence of knee osteoarthritis (OA) because of the higher risk of poor survival and outcomes. PURPOSE/HYPOTHESIS: The purpose was to document the long-term survival of MAT performed as a salvage procedure in patients with knee OA. The hypothesis was that MAT would significantly reduce pain and increase the function of the affected joint at a long-term follow-up compared with the preoperative condition, with a low number of failures and knee replacement surgeries. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 47 patients (37 men and 10 women) with symptomatic knee OA (Kellgren-Lawrence grades 2 or 3) treated with MAT were evaluated at baseline, 5 years, and a minimum 10-year final follow-up (11.1 ± 1 years) using the Lysholm score, the visual analog scale for pain, the Knee injury and Osteoarthritis Outcome Score subscales, and the Tegner score. A total of 44 patients had undergone previous surgeries. Patient satisfaction, revision surgeries, and failures were also recorded. RESULTS: A statistically significant improvement was observed in all clinical scores from the baseline assessment to the final follow-up. The Lysholm score improved significantly from 46.4 ± 17.2 at the preoperative assessment to 77.7 ± 20.4 at the intermediate follow-up (P < .001), with a significant decrease at the final follow-up (71 ± 23.3; P = .018). A similar trend was reported for the visual analog scale scale for pain, Knee injury and Osteoarthritis Outcome Score, and Tegner score, with no complete recovery to the previous sports activity level. A total of 33 patients required concurrent procedures, such as anterior cruciate ligament reconstructions, osteotomies, and cartilage procedures. Five patients underwent reoperation and were considered surgical failures, while 15 patients presented a clinical condition of <65 of the Lysholm score and were considered clinical failures. Among these, 4 patients were considered both surgical and clinical failures. CONCLUSION: MAT surgery has proven to be a valid option for improving pain and function even in OA joints (Kellgren-Lawrence grades 2 or 3), yielding satisfactory results despite a worsening clinical outcome in the long-term follow-up. Therefore, based on the data from this study, orthopaedic surgeons may consider recommending MAT as a salvage procedure even in knees affected by early to moderate OA, while advising patients that the need for combined interventions could potentially reduce graft survival.

Clinical Outcomes of Medial Meniscal Allograft Transplantation With or Without High Tibial Osteotomy: A Case-Control Study Up to 8 Years of Follow-up.

BACKGROUND: Satisfactory clinical results of meniscal allograft transplantation (MAT) have been reported in recent years. However, it remains unclear whether the clinical outcomes of MAT when combined with an osteotomy are inferior to those of isolated MAT. PURPOSE: To compare the survival rates and clinical outcomes of patients who received isolated medial MAT with those of patients undergoing medial MAT combined with high tibial osteotomy (HTO). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 55 patients underwent arthroscopic medial MAT using the soft tissue technique and HTO (mean age, 41.3 ± 10.4 years; 9 female); after fuzzy case-control matching on demographics, 55 controls who underwent isolated medial MAT were also included. Survival analyses were performed using the Kaplan-Meier method with surgical failure, clinical failure (Lysholm score, <65), and reoperation as endpoints. Subjective clinical scores were collected preoperatively and at the final follow-up. RESULTS: The mean follow-up time was 5.4 years, up to 8 years. All outcomes significantly improved at the last follow-up (P < .001). No differences were identified between MAT and MAT + HTO groups preoperatively and at the last follow-up (P > .05). At the final follow-up, 8 of 55 (14.5%) of the MAT + HTO patients and 9 of 55 (16.4%) of the MAT patients had a Lysholm score <65 (P = .885). Overall, 90% of the patients declared they would repeat the surgery regardless of the combined procedure. Surgical failure was identified in 6 of 110 (5.5%) patients: 5 of 55 (9.1%) in the MAT + HTO group and 1 of 55 (1.8%) in the MAT group (P = .093). Clinical failure was identified in 19 of 110 (17.3%) patients: 11 of 55 (20%) in the MAT + HTO group and 8 of 55 (14.5%) in the MAT group (P = .447). A significantly lower survivorship from surgical failure was identified in the MAT + HTO group (hazard ratio, 5.1; P = .049), while no differences in survivorship from reoperation and clinical failure were identified (P > .05). CONCLUSION: Patients undergoing medial MAT + HTO showed similar clinical results to patients undergoing isolated medial MAT at midterm follow-up, and thus a surgically addressed malalignment does not represent a contraindication for medial MAT. However, the need for a concomitant HTO is associated with a slightly higher failure rate over time.

Meniscal allograft transplantation: A matched-pair analysis reveals worse sport activity level but similar clinical improvement and survival in women compared to men.

PURPOSE: The aim of this study was to assess how gender might affect the clinical outcome and survival of meniscal allograft transplantation (MAT). METHODS: A total of 358 patients (23.2% women, 76.8% men) were treated with fresh-frozen nonirradiated allografts implantated arthroscopically using a single- or double-tunnel technique without bone plugs and peripheral suture to the capsule with 'all-inside' stitches. RESULTS: Patients were evaluated at baseline and 2-year follow-up with the Lysholm score, visual analogue scale (VAS) pain, the Knee Osteoarthritis Outcome Score (KOOS) subscales and Tegner score. Women presented higher body mass index (p < 0.0005), poorer baseline VAS (p = 0.012), Lysholm score (p = 0.005), KOOS symptom (p = 0.034) and KOOS pain (p = 0.030),  Tegner score (preinjury and basal, p < 0.0001 and p = 0.002, respectively), a lower number of previous (p = 0.039) and concurrent (p = 0.001) anterior cruciate ligament reconstructions and a higher number of concurrent procedures (p = 0.032) and distal femoral osteotomies (p = 0.024). Worse results were documented in women at 2 years, with lower Lysholm score (p = 0.024) and Tegner score (p = 0.007) and a lower clinical survival rate (p = 0.03) (67.5% vs. 82.2%) in the overall patient cohort. However, the matched-pair analysis only confirmed a lower Tegner score value at 2 years (p = 0.016), while underlying the interplay of sex, age and concomitant cartilage lesions in determining the clinical outcome. The analysis of this large series of patients affected by postmeniscectomy syndrome and treated with MAT revealed gender differences. CONCLUSION: While both genders benefited from a significant improvement, the female population presents more often with older age, concomitant cartilage lesions and a lower activity level, all factors contributing towards a lower clinical success after MAT. LEVEL OF EVIDENCE: Level III, comparative study.

Patellar tendon angle is not elevated in ACL-injured subjects, suggesting methods to correct should focus on prehabilitation and rehabilitation rather than surgery.

Purpose: The aim of the study was to explore if the patellar tendon angles (PTAs) is an intrinsic risk factor for anterior cruciate ligament (ACL) rupture. We hypothesised that the PTAs will be increased in ACL rupture patients compared to matched controls. Methods: We performed a retrospective radiographic cohort study. A cohort of ACL-injured patients between 2019 and 2022 was utilised. The control population, from the same time period, was a consecutive series of 100 patients without ligament or meniscal injuries which were prospectively added to our institutional registry. Posterior tibial slope (PTS), static anterior tibial translation (SATT), patellar tendon to tibial plateau angle (PT-TPA), patellar tendon-tibial shaft angle (PT-TSA) were measured. Results: A total of 100 patients were included in the control cohort and 110 in the ACL cohort. The PT-TPA was significantly less in the ACL cohort compared to the control cohort, mean and SD of 15.33 (±5.74) versus 13.91 (±5.68), respectively (p = 0.01). PT-TSA was also less in the ACL cohort, mean and SD of 116.15 (±5.89) versus 114.27 (±4.81), however, this failed to reach statistical significance (p = 0.08). The PT-TPA was not correlated with PTS (p = 0.65) and the PT-TSA was inversely correlated with PTS; Pearson correlation coefficient of -0.28 (p < 0.01). The PT-TSA had a greater correlation -0.4 (p < 0.01) with SATT than PTS 0.37 (p < 0.01). Conclusion: PTAs are not elevated in ACL-injured subjects. While anteriorisation of the tibial tubercle is utilised in dogs to decrease the anterior thrust resulting from the anteriorly directed vector of the quadriceps, this treatment in the humans is not warranted and methods to reduce the PTAs should focus on prehabilitation and rehabilitation. Level of Evidence: Level III.

A non-weight bearing protocol after ACL reconstruction improves static anterior tibial translation in patients with elevated slope and increased weight bearing tibial anterior translation.

PURPOSE: Aim of this study is to evaluate the impact of a non-weight bearing (NWB) protocol within 21 post-operative days after anterior cruciate ligament (ACL) reconstruction on static and dynamic anterior tibial translations (SATT and DATT, respectively). The hypothesis is that delayed WB would improve ATT at 9 months follow-up. METHODS: A series of patients treated with ACL reconstruction was retrospectively reviewed, comparing a group with immediate post-operative weight bearing (WB group) and a group without post-operative weight bearing (NWB group). The NWB protocol was applied to patients with posterior tibial slope (PTS) ≥ 12°, pre-operative SATT ≥ 5 mm, and/or meniscal lesions of root or radial type. SATT, and PTS were measured on 20° flexion monopodal lateral x-rays, while DATT on Telos™ x-rays at pre-operative and 9-months follow-up. RESULTS: One hundred seventy-nine patients were included (50 NWB group, 129 WB group). The SATT worsened in the WB group with a mean increase of 0.7 mm (SD 3.1 mm), while in the NWB group, the SATT improved with a mean decrease of 1.4 mm (SD 3.1 mm) from the pre-operative to 9 months' follow-up (p < 0.001). The side-to-side Telos™ evaluation showed a significant improvement in DATT within both the groups (p < 0.001), but there was no difference between the two groups (p = 0.99). CONCLUSION: The post-operative protocol of 21 days without WB led to an improvement in SATT at 9 months without an influence on DATT, and it is recommended for patients with a SATT ≥ 5 mm and/or a PTS ≥ 12° as part of an "à la carte" approach to ACL reconstruction. LEVEL OF EVIDENCE: Level IV, Retrospective case series.

Meniscal allograft transplantation, anterior cruciate ligament reconstruction, and valgus high tibial osteotomy for meniscal-deficient, unstable, and varus knees: surgical technique and clinical outcomes.

PURPOSE: The aim of this study was to determine the clinical and functional outcome of a salvage surgical approach with the combined procedures meniscal allograft transplantation (MAT), anterior cruciate ligament reconstruction (ACLR), and high tibial osteotomy (HTO), in a cohort of patients treated for complex knee lesions evaluated up to a mid-term follow-up. METHODS: Eight patients (38.8 ± 4.6 years, 88% males) were treated arthroscopically with MAT without bone plugs combined with primary or revision ACLR and HTO and evaluated at basal, at a minimum of two years (short follow-up), and at a mean follow-up of 5.1 years (mid-term follow-up) with the VAS score for pain, Lysholm score, IKDC subjective score, WOMAC Osteoarthritis index, and Tegner score. Physical examination (Lachman and pivot-shift tests, arthrometer assessment) and radiographic evaluation (pre- and post-operative x-rays) were obtained. Complications and failures were also recorded. RESULTS: A statistically significant improvement was observed from baseline to five years in all clinical scores. In particular, the IKDC subjective score improved from 33.3 ± 20.7 to 73.1 ± 18.4 at short follow-up (p < 0.05), up to 78.3 ± 9.8 at the final follow-up (p < 0.05). A similar trend was demonstrated with the Lysholm, VAS, WOMAC, and Tegner score, even though only one patient reached the pre-injury activity level. Two patients had a worsening of the Kellgren-Lawrence (KL) grade from preoperative (grade 1) to final follow-up (grade 2). No major complications and surgical failures were documented. CONCLUSION: The combined procedure of MAT, ACLR, and HTO presents few complications and failures and showed to be a valid option to reduce pain, recover knee function, and slow down the osteoarthritis process even in complex patients, with good and stable results up to a mid-term follow-up.

Survivorship and Reoperation of 324 Consecutive Isolated or Combined Arthroscopic Meniscal Allograft Transplants Using Soft Tissue Fixation.

BACKGROUND: Meniscal allograft transplant (MAT) is an effective treatment for relieving symptoms and improving knee function in patients who experience symptomatic unicompartmental knee pain after a previous meniscectomy. However, the literature contains a paucity of studies assessing the survival rate and prognostic factors of soft tissue MAT. PURPOSE: To report the survivorship of a large, single-center cohort of consecutive patients treated with arthroscopic MAT using soft tissue technique and to investigate variables that could potentially influence failures and outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Consecutive MAT procedures totaling 364 performed in a single institution between June 2004 and April 2019 were screened and assessed for eligibility. Subjective clinical scores (Lysholm score, Tegner activity scale, and visual analog score) were collected preoperatively and at 2, 5, 7, and 10 years of follow-up. Two survival analyses were performed using Kaplan-Meier curves, with surgical failure (defined as any graft revision) and clinical failure (defined as a Lysholm score <65 points) used as endpoints. Univariate analyses were performed using reoperations, surgical failure, clinical failure, and different demographic and surgical characteristics as endpoints. RESULTS: A total of 324 consecutive patients were evaluated at a mean follow-up 5.7 ± 3.0 years. Of these, 189 (58%) underwent an associated surgical procedure. A total of 22 patients (6.8%) were considered to have experienced surgical failure, and no predictors of surgical failure were identified based on the relevant variables. When all patients were considered, a significant improvement in all of the patient-reported outcome measures was present between the preoperative assessment and the last follow-up (P < .001), with no significant decrease over time. Moreover, 70 (21.6%) patients were considered to have experienced clinical failure; the need for concurrent cartilage procedures (odds ratio, 0.16; P = .001) and anterior cruciate ligament (ACL) reconstruction (odds ratio, 0.40; P = .059) were predictors of failure. Finally, a lower survival rate was reported in female patients compared with male patients (49% vs 69%, respectively; P = .007) and in patients who required cartilage surgery (P = .014). In particular, patients who required cartilage surgery showed nearly half the survival rate compared with those with required no cartilage procedures at 10-year follow-up (36.4% vs 71%, respectively; P = .029). CONCLUSION: Female sex and the need to combine MAT with a cartilage procedure or ACL reconstruction could result in an increased rate of clinical failure at midterm follow-up.

Does Bone Marrow Edema Influence the Clinical Results of Intra-Articular Platelet-Rich Plasma Injections for Knee Osteoarthritis?

Platelet-rich plasma (PRP) is increasingly used for the intra-articular treatment of knee osteoarthritis (OA). However, clinical studies on PRP injections reported controversial results. Bone marrow edema (BME) can cause symptoms by affecting the subchondral bone and it is not targeted by intra-articular treatments. The aim of this study was to investigate if the presence of BME can influence the outcome of intra-articular PRP injections in knee OA patients. A total of 201 patients were included in the study, 80 with and 121 without BME at the baseline MRI. BME area and site were evaluated, and BME was graded using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Patients were assessed with International Knee Documentation Committee (IKDC) score Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, the EuroQol-Visual Analogue Scale (EQ-VAS), and the Tegner score at baseline, 2, 6, and 12 months. Overall, the presence of BME did not influence the clinical results of intra-articular PRP injections in these patients treated for knee OA. Patients with BME presented a similar failure rate and clinical improvement after PRP treatment compared to patients without BME. The area and site of BME did not affect clinical outcomes. However, patients with a higher BME grade had a higher failure rate.

Leukocyte-Rich versus Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Trial.

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 × 109/L and 1074.9 × 109/L and a mean leukocyte concentration of 7991.4 × 106/L and 0.1 × 106/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).

Autologous Protein Solution Effect on Chondrogenic Differentiation of Mesenchymal Stem Cells from Adipose Tissue and Bone Marrow in an Osteoarthritic Environment.

OBJECTIVE: Osteoarthritis (OA) is an inflammatory and degenerative disease, and the numerous treatments currently used are not fully effective. Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) are proposed for OA treatment as biologic therapies. The aim of the study was to observe the role of autologous protein solution (APS), a type of PRP, on chondrogenic differentiation of 2 types of MSCs, from bone marrow (BMSCs) and adipose tissue (ADSCs), in an in vitro osteoarthritic microenvironment. DESIGN: Inflammatory culture conditions, mimicking OA, were obtained by adding interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNFα), or synovial fluid from patient osteoarthritic knees (OSF), to the culture medium. MSCs were then treated with APS. RESULTS: After 1 month of culture, both cell types formed mature micromasses, partially altered in the presence of IL-1ß and TNFα but quite preserved with OSF. Inflammatory conditions hindered differentiation in terms of gene expression, not counterbalanced by APS. APS triggered type I collagen deposition and above all contributed to decrease the expression of metalloproteinases in the most aggressive conditions (IL-1ß and TNFα in the culture medium). ADSCs originated micromasses more mature and less prone toward osteogenic lineage than BMSCs, thus showing to better adapt in an aggressive environment than BMSC. CONCLUSIONS: APS seems to act better on inflammation front and, between cell types, ADSCs respond better to the inflammatory microenvironment of OA and to the treatment with APS than BMSCs.

Treatment of Juvenile Knee Osteochondritis Dissecans with a Cell-Free Biomimetic Osteochondral Scaffold: Clinical and MRI Results at Mid-Term Follow-up.

OBJECTIVE: Osteochondral surgical procedures have been described for the treatment of unfixable osteochondritis dissecans (OCD), but only few of them have been studied for juvenile OCD (JOCD) lesions. A cell-free biomimetic osteochondral scaffold showed positive results in adult patients. The aim of this study was to evaluate the results of this scaffold for the treatment of knee JOCD at mid-term follow-up. DESIGN: Twenty patients (14 males, 6 females) were included in this study. Mean age was 16.2 ± 1.4 years, average defect size was 3.2 ± 1.8 cm2, and mean symptoms duration was 20.2 ± 17.9 months. After the implantation of the osteochondral collagen-hydroxyapatite scaffold (Maioregen, Fin-Ceramica, Faenza, Italy), patients were evaluated preoperatively and prospectively at 1, 2, and at final mean follow-up of 6 years (range 5-7 years) with International Knee Documentation Committee (IKDC) subjective and objective, Tegner, and EuroQol visual analogue scale (VAS) scores. MRI evaluation was performed with the MOCART 2.0 score. RESULTS: All scores showed a significant improvement. IKDC subjective score went from 50.3 ± 17.4 preoperative score to 75.3 ± 14.6 at 1 year (P = 0.002), 80.8 ± 14.6 at 2 years and 85.0 ± 9.3 at 6 years. The Tegner score improved from the preoperative evaluation of 2.6 ± 1.4 to 5.5 ± 2.0 at 6 years (P < 0.0005), although without reaching the level registered before the onset of symptoms. A longer symptoms duration influenced negatively IKDC subjective and Tegner scores up to 2 years (P = 0.003 and P = 0.002, respectively) but did not affect the final outcome. Lesion size did not affect the final result. The MOCART 2.0 score showed a significant improvement between 1-year and final follow-up, but with persisting subchondral alterations. CONCLUSIONS: This study demonstrated a clinical improvement stable over time with a high survival rate, although with persisting abnormal MRI findings, especially at subchondral bone level. This procedure can be considered a suitable option for the treatment of young patients affected by knee OCD. Level of evidence. Case series, level IV.

Long-term Outcomes and Survivorship of Fresh-Frozen Meniscal Allograft Transplant With Soft Tissue Fixation: Minimum 10-Year Follow-up Study.

BACKGROUND: Meniscal allograft transplant (MAT) is considered an effective procedure for reducing pain and improving knee function. Nevertheless, the current knowledge regarding the results of MAT is limited to short- to mid-term follow-up studies, especially for arthroscopic techniques. PURPOSE: To evaluate the long-term clinical outcomes, reoperations, and failures with a minimum follow-up of 10 years after fresh-frozen MAT performed arthroscopically with soft tissue fixation. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 46 patients (age, 36.6 ± 10.6 years; 36 male, 10 female) who underwent medial MAT (n = 27) or lateral MAT (n = 19) with a minimum 10-year follow-up were evaluated with the Lysholm score, Knee injury and Osteoarthritis Outcome Score (KOOS), visual analog scale for pain, and Tegner score. Surgical failure was defined as the need for partial or total graft removal (meniscectomy or knee replacement), and clinical failure was defined as the need for partial or total graft removal in addition to a poor Lysholm score (<65 points) at final follow-up. Survival analysis was performed with Kaplan-Meier curve, and clinical scores were analyzed based on the Patient Acceptable Symptom State (PASS) for MAT. RESULTS: 10-year survival and clinical data were available for 38 patients. Because 6 meniscectomies were required, the rate of survival free from surgical failure was 91% at 5 years and 86% at 10 years. Lower survival was reported in lateral MAT (73%) compared with medial MAT (96%). Because a further 4 patients had poor Lysholm scores, the rate of survival free from surgical and clinical failure was 87% at 5 years and 70% at 10 years. The average Lysholm score at final follow-up was 82 ± 20, and 60% to 82% of patients achieved PASS of the various KOOS subscales. The Tegner score and the KOOS Sport score significantly decreased from mid-term to long-term evaluation (P < .001 and P < .05, respectively). Other KOOS subscales and the Lysholm score remained stable at long-term evaluation. No significant differences were found between isolated MAT or combined MAT regarding subjective scores, surgical failures, or clinical failures. CONCLUSION: Up to 10 years after surgery, 86% of fresh-frozen MATs with soft tissue fixation were still in situ, and satisfactory clinical results were present for about 70% of patients. Decline of clinical outcomes from midterm to long term was noted only in sports-related scores. A higher number of overall reoperations was noted in female patients, whereas a higher risk of failure was present in the patients with lateral MAT.

Cell-Free Osteochondral Scaffold for the Treatment of Focal Articular Cartilage Defects in Early Knee OA: 5 Years' Follow-Up Results.

The purpose of this study was to investigate the clinical results at five years' follow-up of a tri-layered nanostructured biomimetic osteochondral scaffold used for focal articular cartilage defects in patients meeting the criteria of early osteoarthritis (EOA). The study population comprised 22 patients (mean age: 39 years), prospectively assessed before surgery, at 24 and 60 months' follow-up. Inclusion criteria were: at least two episodes of knee pain for more than 10 days in the last year, Kellgren-Lawrence OA grade 0, I or II and arthroscopic or MRI findings according to the European Society of Sports Traumatology, Knee Surgery & Arthroscopy (ESSKA) criteria. Clinical results demonstrated significant improvement in International Knee Documentation Committee (IKDC) subjective and objective scores and in Tegner score, although activity level never reached the pre-injury level. The complication rate of this study was 8.3%. Two patients underwent re-operation (8.3%), while a comprehensive definition of failure (including both surgical and clinical criteria) identified four failed patients (16.6%) at this mid-term follow-up evaluation. The use of a free-cell osteochondral scaffold represented a safe and valid alternative for the treatment of focal articular cartilage defects in the setting of an EOA, and was able to permit a significant clinical improvement and stable outcome with low complication and failure rates.

Total Knee Arthroplasty in Patients With Knee Osteoarthritis: Effects on Proprioception. A Systematic Review and Best Evidence Synthesis.

BACKGROUND: Impact of total knee arthroplasty (TKA) on proprioception remains to be determined. The aim of this systematic review is to analyze factors influencing proprioception in patients with knee osteoarthritis (OA) undergoing TKA. METHODS: A systematic literature search was conducted on 3 medical electronic databases: PubMed, PeDRO, and Cochrane Collaboration. The Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were used. Risk of bias analysis and best evidence synthesis were performed. Three main aspects were investigated: the presence of preoperative, surgical, and postoperative factors influencing proprioception in OA patients undergoing TKA. RESULTS: Search identified 1601 records. After screening, 19 papers were used for the analysis of 676 patients. Proprioception generally improved but often remained impaired after surgery. Strong evidence was found for no influence of prosthesis design on proprioception. Moderate evidence was found for patellar resurfacing not affecting proprioception, varus deformity negatively influencing proprioception, and time elapsed from surgery positively influencing proprioception. Limited evidence was found for valgus deformity, OA grade, intact anterior cruciate ligament, and anteroposterior joint laxity negatively affecting knee proprioception, and for muscle strength and sensorimotor training not affecting proprioception. Finally, conflicting evidence was found for better postoperative proprioception vs preoperative level. CONCLUSION: Proprioception in OA patients undergoing TKA improves but remains impaired after surgery. The best evidence synthesis demonstrated no influence of prosthetic design, while the role of the treatment remains unclear. This warrants for further research efforts to study proprioceptive impairment to better manage OA patients undergoing TKA.

Meniscal allograft transplantation combined with anterior cruciate ligament reconstruction provides good mid-term clinical outcome.

PURPOSE: Aim of this study is to document if combined meniscal allograft transplantation (MAT) and ACL reconstruction can improve knee function, reduce pain and allow patients with meniscal defect and ACL lesion to resume sport activities. METHODS: Fifty MAT, arthroscopically performed without bone plugs and combined with one-stage primary or revision ACL reconstruction, with or without high tibial osteotomy (HTO), were included. Patients (aged 38.2 ± 10.6 years, 87% males) were evaluated at a mean follow-up of 5 years with Lysholm, Tegner and VAS scores. Patient satisfaction was also recorded, together with complications and failures. RESULTS: VAS and Lysholm scores improved significantly (from 63.7 to 24.5 and from 60.6 to 82.7, respectively, p < 0.001), while the Tegner score did not reach pre-injury values (p < 0.001), but it improved significantly compared to pre-surgery values (from 2.8 to 4.6, p < 0.001). Medial MAT reported significantly better results compared to lateral MAT. Patients undergoing concomitant HTO reported a significantly higher decrease of VAS. Younger patients with higher pre-operative pain and lower activity level presented higher satisfaction. Eight patients needed a reoperation. Three patients were considered surgical failures while four were considered clinical failures, for a total of 15% failures. CONCLUSIONS: Meniscal allograft transplantation combined with ACL reconstruction represents a safe and suitable treatment, which should be considered as a suitable option in the clinical practice. All evaluated patient profiles, ACL injury in a patient with post-meniscectomy syndrome, failed ACL reconstruction in patients with a meniscus defect, and ACL reconstruction in patients with malalignment due to meniscal defect, benefited from the combined MAT procedure at medium-term follow-up. LEVEL OF EVIDENCE: IV.