High tibial osteotomy combined with cartilage restoration: A systematic review of clinical outcomes and prognostic factors.

Background: Focal chondral defects are often treated with cartilage restoration procedures. Malalignment often accompanies chondral defects. High tibial osteotomy (HTO), classically utilized to treat uni-compartmental knee osteoarthritis, corrects malalignment. HTO combined with cartilage restoration procedures can treat uni-compartmental osteoarthritis and focal chondral defects. Purpose: To assess outcomes of combined HTO and cartilage restoration procedures and review prognostic factors that may assist in preoperative planning and patient counseling. Study design: Systematic Review of published literature. Methods: A systematic review of PubMed and Scopus was performed following PRISMA guidelines. Thirty-four papers were included in qualitative considerations. Results: Thirty-four papers that reported the combined outcome of HTO and cartilage repair were included. Twenty of the 34 included papers reported prognostic factors that affected the success or failure of combined HTO and cartilage repair surgery for focal articular defect and uni-compartmental knee osteoarthritis. Cartilage repair techniques that were combined with HTO and included in this review are bone marrow stimulation, allograft transplantation, osteochondral autograft transplantation, autologous chondrocyte implantation, and mesenchymal stem cell implantation. Conclusions: HTO with adjunctive cartilage repair procedures improve clinical outcome scores and restore alignment in patients with medial compartment osteoarthritis and isolated focal chondral defects. HTO with adjunctive cartilage procedures produces optimal results in younger, non-obese patients with focal chondral defects and varus malalignment, without significant lateral compartment and patellofemoral involvement.

Experts Achieve Consensus on a Majority of Statements Regarding Platelet-Rich Plasma Treatments for Treatment of Musculoskeletal Pathology.

PURPOSE: To establish consensus statements on platelet-rich plasma (PRP) for the treatment of musculoskeletal pathologies. METHODS: A consensus process on the treatment of PRP using a modified Delphi technique was conducted. Thirty-five orthopaedic surgeons and sports medicine physicians participated in these consensus statements on PRP. The participants were composed of representatives of the Biologic Association, representing 9 international orthopaedic and musculoskeletal professional societies invited due to their active interest in the study of orthobiologics. Consensus was defined as achieving 80% to 89% agreement, strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: There was consensus on 62% of statements about PRP. CONCLUSIONS: (1) PRP should be classified based on platelet count, leukocyte count, red blood count, activation method, and pure-plasma versus fibrin matrix; (2) PRP characteristics for reporting in research studies are platelet count, leukocyte count, neutrophil count, red blood cell count, total volume, the volume of injection, delivery method, and the number of injections; (3) the prognostic factors for those undergoing PRP injections are age, body mass index, severity/grade of pathology, chronicity of pathology, prior injections and response, primary diagnosis (primary vs postsurgery vs post-trauma vs psoriatic), comorbidities, and smoking; (4) regarding age and body mass index, there is no minimum or maximum, but clinical judgment should be used at extremes of either; (5) the ideal dose of PRP is undetermined; and (6) the minimal volume required is unclear and may depend on the pathology. LEVEL OF EVIDENCE: Level V, expert opinion.

Aragonite-Based Scaffold Versus Microfracture and Debridement for the Treatment of Knee Chondral and Osteochondral Lesions: Results of a Multicenter Randomized Controlled Trial.

BACKGROUND: Lesions of the articular cartilage, with or without involvement of the subchondral bone, are a common cause of pain and dysfunction in the knee. Although several treatment options have been developed, the majority of previous clinical trials examined patients with isolated or focal midsized defects, which rarely represent the condition found in the general population. Rather, cartilage lesions are often associated with the presence of mild to moderate osteoarthritic changes. PURPOSE: The present multicenter randomized controlled trial compared the clinical and radiographic outcomes of an aragonite-based osteochondral implant with a control group (arthroscopic debridement/microfractures) in patients affected by joint surface lesions of the knee, including those with concurrent mild to moderate osteoarthritis. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 251 patients were enrolled in 26 medical centers according to the following criteria: age 21 to 75 years, up to 3 cartilage defects of International Cartilage Regeneration & Joint Preservation Society grade 3a or above located on the femoral condyles and/or trochlea, total treatable area from 1 to 7 cm2, bony defect depth ≤8 mm, and knee osteoarthritis grade 0 to 3 according to Kellgren-Lawrence score. Patients were randomized to the aragonite-based implant or debridement/microfracture control arm in a 2:1 ratio. Evaluation was performed at 6, 12, 18, and 24 months based on overall Knee injury and Osteoarthritis Outcome Score (KOOS) as the primary endpoint, and the KOOS subscales (Pain, Quality of Life, Activities of Daily Living), percentage of responders, and International Knee Documentation Committee (IKDC) subjective score as the secondary endpoints. Patients also underwent magnetic resonance imaging evaluation at 12 and 24 months to assess defect fill grade. Failures (ie, need for any secondary treatment) and adverse events were also recorded. RESULTS: The implant group showed a statistically superior outcome in the primary endpoint and all secondary endpoints at each follow-up. The magnitude of improvement in the implant group was twice as large as that in the control group in terms of mean KOOS improvement at 2 years. Responder rate (defined as at least a 30-point improvement in overall KOOS) was 77.8% in the implant group as opposed to 33.6% in the control (P < .0001). Statistically superior results were seen in the IKDC score as well. At 24 months, 88.5% of the implanted group had at least 75% defect fill on magnetic resonance imaging as compared with 30.9% of controls (P < .0001). The failure rate was 7.2% for the implant group versus 21.4% for control. CONCLUSION: This aragonite-based scaffold was safe and effective in the treatment of chondral and osteochondral lesions in the knee, including patients with mild to moderate osteoarthritis, and provided superior outcomes as compared with the control group. REGISTRATION: NCT03299959 (ClinicalTrials.gov identifier).

Editorial Commentary: Amniotic Orthopaedic Biologics: There's Hope If We Avoid Hype.

Amniotic products donated from mothers having live births have been in use for wound care and other medical uses for many years. Recent developments in regenerative sciences have suggested these products in solution or lyophilized forms may be useful for the treatment of inflammatory diseases such as chronic tendinopathies and osteoarthritis of joints. These products for these indications, however, are deemed human cells, tissues, or cellular or tissue-based products (otherwise known as HCTPs) in the "351" category, meaning that they need to have a biologic license to be marketed and sold in the United States, and to gain this license, one needs to go through the usual rigor of investigational new drug filing and phase 1, 2, and 3 trials to prove safety and efficacy. Although current clinical use of amniotic solution and lyophilized products is on hold through this study period, both basic science and clinical trial studies are building a convincing set of data that suggest broad possibilities for their uses in the future. To date, both animal and human studies have shown that a single injection of amniotic suspension allograft is safe, has not elicited any significant immune response, and has been shown to be effective in several prospective studies and at least one well-controlled randomized controlled human study for knee osteoarthritis when compared with both hyaluronic acid and placebo saline. Proteins in these harvested and processed tissue allografts are anti-inflammatory, anticatabolic, and proanabolic. Appropriate caution by the Food and Drug Administration in granting licenses for these indications should not dissuade basic scientists and physicians from pursuing further research into these interesting products.

Treatment of post-meniscectomy knee symptoms with medial meniscus replacement results in greater pain reduction and functional improvement than non-surgical care.

PURPOSE: Partial meniscectomy is a common orthopedic procedure intended to improve knee pain and function in patients with irreparable meniscal tears. However, 6-25% of partial meniscectomy patients experience persistent knee pain after surgery. In this randomized controlled trial (RCT) involving subjects with knee pain following partial meniscectomy, it was hypothesized that treatment with a synthetic medial meniscus replacement (MMR) implant provides significantly greater improvements in knee pain and function compared to non-surgical care alone. METHODS: In this prospective, multicenter RCT, subjects with persistent knee pain following one or more previous partial meniscectomies were randomized to receive either MMR or non-surgical care. This analysis evaluated the 1-year outcomes of this 2-year clinical trial. Patient-reported knee pain, function, and quality of life were measured using nine separate patient-reported outcomes. The primary outcomes were the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) and the average of all five KOOS subscales (KOOS Overall). Treatment cessation was defined as permanent device removal in the MMR group and any surgical procedure to the index knee in the non-surgical care group. RESULTS: Treated subjects had a median age of 52 years old (range 30-69 years) and one or more previous partial meniscectomies at a median of 34 months (range 5-430 months) before trial entry. Among 127 subjects treated with either MMR (n = 61) or non-surgical care (n = 66), 11 withdrew from the trial or were lost to follow-up (MMR, n = 0; non-surgical care, n = 11). The magnitude of improvement from baseline to 1 year was significantly greater in subjects who received MMR in both primary outcomes of KOOS Pain (P = 0.013) and KOOS Overall (P = 0.027). Treatment cessation was reported in 14.5% of non-surgical care subjects and only 4.9% of MMR subjects (n.s.). CONCLUSION: Treatment with the synthetic MMR implant resulted in significantly greater improvements in knee pain, function, and quality of life at 1 year of follow-up compared to treatment with non-surgical care alone. LEVEL OF EVIDENCE: I.

Biologic Association Annual Summit: 2020 Report.

Interest and research in biologic approaches for tissue healing are exponentially growing for a variety of musculoskeletal conditions. The recent hype concerning musculoskeletal biological therapies (including viscosupplementation, platelet-rich plasma, and cellular therapies, or "stem cells") is driven by several factors, including demand by patients promising regenerative evidence supported by substantial basic and translational work, as well as commercial endeavors that complicate the scientific and lay understanding of biological therapy outcomes. While significant improvements have been made in the field, further basic and preclinical research and well-designed randomized clinical trials are needed to better elucidate the optimal indications, processing techniques, delivery, and outcome assessment. Furthermore, biologic treatments may have potential devastating complications when proper methods or techniques are ignored. For these reasons, an association comprising several scientific societies, named the Biologic Association (BA), was created to foster coordinated efforts and speak with a unified voice, advocating for the responsible use of biologics in the musculoskeletal environment in clinical practice, spearheading the development of standards for treatment and outcomes assessment, and reporting on the safety and efficacy of biologic interventions. This article will introduce the BA and its purpose, provide a summary of the 2020 first annual Biologic Association Summit, and outline the future strategic plan for the BA.

Safety and Efficacy of an Amniotic Suspension Allograft Injection Over 12 Months in a Single-Blinded, Randomized Controlled Trial for Symptomatic Osteoarthritis of the Knee.

PURPOSE: The purpose of this study is to determine the efficacy of amniotic suspension allograft (ASA) compared to hyaluronic acid (HA) and saline at up to 12 months of follow-up through the use of patient-reported outcomes, immunoglobulin levels, and anti-human leukocyte antigen (HLA) levels. METHODS: Within this multicenter study, 200 patients were randomized 1:1:1 to a single intra-articular injection of saline, HA, or ASA. Patient-reported outcomes, including Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS) score, were collected at multiple time points (baseline, 1 week, 6 weeks, 3 months, 6 months) out to 12 months to assess improvements in pain and function. Radiographs at baseline and 12 months were taken to determine radiographic changes, while blood was collected at baseline, 6 weeks, and 6 months to determine changes in immunoglobulins and anti-HLA levels. Statistical analyses were performed using last observation carried forward and mixed effects model for repeated measures. RESULTS: Treatment with ASA resulted in significant improvements in KOOS and VAS scores that were maintained through 12 months (P < .05). Treatment with ASA resulted in a 63.2% responder rate at 12 months using the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International simplified definition. There were no significant differences between groups for radiographic measures in the index knee, immunoglobulins, C-reactive protein, or anti-HLA serum levels (P > .05). The number and type of adverse events (AEs) reported for ASA were comparable to the HA injection group, while no treatment-emergent AEs were reported for the saline group. CONCLUSIONS: This randomized controlled trial of ASA vs HA and saline for the treatment of symptomatic knee osteoarthritis demonstrated clinically meaningful improved outcomes with ASA over the controls out to 12 months postinjection. No concerning immunologic or adverse reactions to the ASA injection were identified with regards to severe AEs, immunoglobulin, or anti-HLA levels. LEVEL OF EVIDENCE: Level I, randomized controlled multicenter trial.

Preliminary Results From a US Clinical Trial of a Novel Synthetic Polymer Meniscal Implant.

BACKGROUND: At least 760,000 outpatient meniscectomies are performed in the United States each year, making this the most common musculoskeletal procedure. However, meniscal resection can alter the joint biomechanics and overload the articular cartilage, which may contribute to degenerative changes and the need for knee replacement. Avoiding or delaying knee replacement is particularly important in younger or more active patients. Synthetic meniscal implants have been developed in an attempt to restore the natural joint biomechanics, alleviate pain and disability, and potentially minimize degenerative changes in patients who require meniscectomy. PURPOSE: To evaluate the preliminary results from 2 ongoing trials that are evaluating the safety and effectiveness of a synthetic polymer meniscal implant (NUsurface; Active Implants, LLC). STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This was a preliminary analysis of the first 100 patients enrolled across 2 studies for 12 months: a single-arm, intervention-only study and a randomized controlled trial comparing the investigational meniscal implant with nonsurgical therapy. There were 65 patients in the implant group (30 randomized) and 35 in the control group. Outcomes included Knee injury and Osteoarthritis Outcome Score (KOOS) and adverse events (AEs) collected at baseline and follow-up visits of 6 weeks, 6 months, and 12 months. RESULTS: No statistically significant differences were found in baseline characteristics between the implant and control groups. At 12 months, follow-up KOOS data were available for 87% of the 100 included patients. Significantly greater improvements from baseline were observed in the implant group compared with controls in all KOOS subcomponents, except for symptoms (119%-177% greater improvement at 12 months). AEs were reported at similar rates between the 2 groups, with 12 AEs among 11 patients in the implant group (16.9%) versus 5 AEs among 5 patients (14.3%) in the control group (P = .99). CONCLUSION: These preliminary results suggest significant improvements in pain and function scores with the implant over nonsurgical therapy and a similar adverse event rate.