Platelet-rich plasma injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios.

PURPOSE: The aim of this consensus was to develop evidence- and expert-based patient-focused recommendations on the appropriateness of intra-articular platelet-rich plasma (PRP) injections in different clinical scenarios of patients with knee osteoarthritis (OA). METHODS: The RAND/UCLA Appropriateness Method was used by the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), as well as the International Cartilage Regeneration and Joint Preservation Society (ICRS) to reach a consensus and produce recommendations for specific patient categories combining best available scientific evidence with the collective judgement of a panel of experts. RESULTS: Scenarios were defined based on first treatment vs first injective treatment vs second injective treatment, age (<50/50-65/66-80/>80), tibiofemoral vs patellofemoral involvement, OA level (Kellgren-Lawrence/KL 0-I/II-III/IV), and joint effusion (dry knee, minor-mild or major effusion). Out of 216 scenarios, in 84 (38.9%) the indication was considered appropriate, in 9 (4.2%) inappropriate and in 123 (56.9%) uncertain. The parameters associated with the highest consensus were PRP use after failed injective treatments (62.5%), followed by PRP after failed conservative treatments and KL 0-III scenarios (58.3%), while the highest uncertainty was found for PRP use as first treatment and KL IV OA (91.7% and 87.5% of uncertain scenarios, respectively). CONCLUSION: This ESSKA-ICRS consensus established recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee OA, providing a useful reference for clinical practice. PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0-III OA grade after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. LEVEL OF EVIDENCE: Level I.

Chitosan-based scaffold augmentation to microfractures: Stable results at mid-term follow-up in patients with patellar cartilage lesions.

Purpose: Patellar cartilage lesions are a frequent and challenging finding in orthopaedic clinical practice. This study aimed to evaluate a chitosan-based scaffold's mid-term clinical and imaging results patients with patellar cartilage lesions. Methods: Thirteen patients (nine men, four women, 31.3 ± 12.7 years old) were clinically evaluated prospectively at baseline, 12, 24 and at a final minimum follow-up of 60 months (80.2 ± 14.7) with International Knee Documentation Committee (IKDC) subjective, Knee Injury and Osteoarthritis Outcome Score and Tegner scores. A magnetic resonance analysis was performed at the last follow-up using the Magnetic resonance Observation of CArtilage Repair Tissue (MOCART) 2.0 score. Results: An overall significant clinical improvement in the scores was observed from baseline to all follow-ups, with stable clinical results from 24 months to the mid-term evaluation. The IKDC subjective score passed from 46.3 ± 20.0 at baseline to 70.1 ± 21.5 at the last follow-up (p = 0.029). Symptoms' duration before surgery negatively correlated with the clinical improvement from baseline to the final follow-up (p = 0.013) and sex influenced the improvement of activity level from the preoperative evaluation to the final follow-up, with better results in men (p = 0.049). In line with the clinical findings, positive results were documented in terms of cartilage repair quality with a mean MOCART 2.0 score of 72.4 ± 12.5. Conclusions: Overall, the use of this chitosan-based scaffold provided satisfactory results with a stable clinical improvement up to mid-term follow-up, which should be confirmed by further high-level studies to be considered a suitable surgical option to treat patients affected by patellar cartilage lesions. Level of Evidence: Level IV, prospective case series.

Unicompartmental osteoarthritis: High survival rate with a combined mechanical and biological salvage approach as alternative to metal resurfacing: Results at minimum 10 years of follow-up.

PURPOSE: The aim of this study was to prospectively evaluate the long-term clinical results and failure rate of patients treated with complex salvage procedures using a combined mechanical and biological approach to address unicompartmental knee osteoarthritis (OA) and postpone the need for joint replacement. METHODS: Thirty-nine patients (40.3 ± 10.9 years old) affected by unicompartmental OA (Kellgren-Lawrence 3) in stable joints underwent a personalized surgical treatment depending on the specific requirements of the affected compartment, including high tibial osteotomy, osteochondral scaffold, meniscal scaffold and meniscal allograft transplantation. Patients were evaluated with the International Knee Documentation Committee (IKDC), Visual Analogue Scale (VAS) and Tegner scores before surgery, at 3 years and a minimum of 10 years of follow-up. RESULTS: A significant improvement was observed over time in all scores but worsened at the final follow-up. The IKDC subjective score improved from 46.9 ± 16.2 to 79.8 ± 16.4 at 3 years (p < 0.0005) and then decreased to 64.5 ± 21.4 (p = 0.001) at 12 years. A similar trend was confirmed for VAS and Tegner scores. Only two patients subsequently underwent knee arthroplasty, and nine more patients were considered clinical failure, for a cumulative surgical and clinical failure rate of 28.2% at the final follow-up. CONCLUSION: A personalized, joint-preserving, combined mechanical and biological approach, addressing alignment as well as meniscal and cartilage lesions, is safe and effective, providing a clinical benefit and delaying the need for arthroplasty in young patients affected by unicompartmental knee OA. At the final evaluation, the clinical improvement decreased, but more than two-thirds of the patients still benefited from this treatment at a long-term follow-up. LEVEL OF EVIDENCE: Level IV case series.

The reimbursement system can influence the treatment choice and favor joint replacement versus other less invasive solutions in patients affected by osteoarthritis.

PURPOSE: The aim of this study was to assess how physicians perceive the role of the reimbursement system and its potential influence in affecting their treatment choice in the management of patients affected by osteoarthritis (OA). METHODS: A survey was administered to 283 members of SIAGASCOT (Italian Society of Arthroscopy, Knee, Upper Limb, Sport, Cartilage and Orthopaedic Technologies), a National scientific orthopaedic society. The survey presented multiple choice questions on the access allowed by the current Diagnosis-Related Groups (DRG) system to all necessary options to treat patients affected by OA and on the influence toward prosthetic solutions versus other less invasive options. RESULTS: Almost 70% of the participants consider that the current DRG system does not allow access to all necessary options to best treat patients affected by OA. More than half of the participants thought that the current DRG system favors the choice of prosthetic solutions (55%) and that it can contribute to the increase in prosthetic implantation at the expense of less invasive solutions (54%). The sub-analyses based on different age groups, professional roles, and places of work allowed to evaluate the response in each specific category, confirming the findings for all investigated aspects. CONCLUSIONS: This survey documented that the majority of physicians consider that the reimbursement system can influence the treatment choice when managing OA patients. The current DRG system was perceived as unbalanced in favor of the choice of the prosthetic solution, which could contribute to the increase in prosthetic implantation at the expense of other less invasive options for OA management.

Joint Response to Exercise Is Affected by Knee Osteoarthritis: An Infrared Thermography Analysis.

Infrared thermography can be used to evaluate the inflammation characterizing the joint environment of OA knees, but there is limited evidence on the response to physical exercise. Identifying the response to exercise of OA knees and the influencing variables could provide important information to better profile patients with different knee OA patterns. Sixty consecutive patients (38 men/22 women, 61.4 ± 9.2 years) with symptomatic knee OA were enrolled. Patients were evaluated with a standardized protocol using a thermographic camera (FLIR-T1020) positioned at 1 m with image acquisition of an anterior view at baseline, immediately after, and at 5 min after a 2-min knee flexion-extension exercise with a 2 kg anklet. Patients' demographic and clinical characteristics were documented and correlated with the thermographic changes. This study demonstrated that the temperature response to exercise in symptomatic knee OA was affected by some demographic and clinical characteristics of the assessed patients. Patients with a poor clinical knee status presented with a lower response to exercise, and women showed a greater temperature decrease than men. Not all evaluated ROIs showed the same trend, which underlines the need to specifically study the different joint subareas to identify the inflammatory component and joint response while investigating knee OA patterns.

Infrared Thermography in Symptomatic Knee Osteoarthritis: Joint Temperature Differs Based on Patient and Pain Characteristics.

The aim of this study was to evaluate osteoarthritis (OA) patients with infrared thermography to investigate imaging patterns as well as demographic and clinical characteristics that influence knee inflammation. Forty patients with one-sided symptomatic knee OA were included and evaluated through knee-specific PROMs and the PainDETECT Questionnaire for neuropathic pain evaluation. Thermograms were captured using a thermographic camera FLIR-T1020 and temperatures were extracted using the software ResearchIR for the overall knee and the five ROIs: medial, lateral, medial patella, lateral patella, and suprapatellar. The mean temperature of the total knee was 31.9 ± 1.6 °C. It negatively correlated with age (rho = -0.380, p = 0.016) and positively correlated with BMI (rho = 0.421, p = 0.007) and the IKDC objective score (tau = 0.294, p = 0.016). Men had higher temperatures in the knee medial, lateral, and suprapatellar areas (p = 0.017, p = 0.019, p = 0.025, respectively). Patients with neuropathic pain had a lower temperature of the medial knee area (31.5 ± 1.0 vs. 32.3 ± 1.1, p = 0.042), with the total knee negatively correlating with PainDETECT (p = 0.045). This study demonstrated that the skin temperature of OA symptomatic knees is influenced by demographic and clinical characteristics of patients, with higher joint temperatures in younger male patients with higher BMI and worst objective knee scores and lower temperatures in patients affected by neuropathic pain.

Pure Platelet and Leukocyte-Platelet-Rich Plasma for Regenerative Medicine in Orthopedics-Time- and Preparation-Dependent Release of Growth Factors and Effects on Synovial Fibroblasts: A Comparative Analysis.

Intra-articular injections of autologous platelet concentrates are considered capable to enhance the healing of cartilage lesions, alleviate joint inflammation, and relieve other musculoskeletal pathological conditions. The aim of this study was to analyze the soluble fractions obtained from platelet-rich plasma (pure- and leukocyte-PRP) to compare time- and preparation-dependent modifications of growth factor concentrations and the supporting activity of the two preparations on synovial fibroblast growth and hyaluronic acid (HA) production in vitro. The release kinetics of FGF-2, SDF-1, VEGF, HGF, EGF, PD GF-AB/BB, IGF-1, VCAM-1, and TGF-ß isoforms were followed up to 168 h after PRP activation, and their amounts were determined by multiplex-beads immunoassay. Synovial cell growth and supernatant HA production were respectively analyzed by Alamar Blue assay and ELISA. Time-dependent modifications grouped molecules in three peculiar patterns: one reaching the highest concentrations within 18 h and decreasing afterwards, another progressively increasing up to 168 h, and the last peaking at the central time points. Synovial fibroblast growth in response to L-PRP and P-PRP revealed differences over time and among added concentrations. Both preparations displayed a preserved supporting capacity of HA synthesis.

Chitosan based scaffold applied in patellar cartilage lesions showed positive clinical and MRI results at minimum 2 years of follow up.

PURPOSE: New scaffold-based cartilage regeneration techniques have been developed to improve the results of microfractures also in complex locations like the patello-femoral joint. The aim of this study was to analyse the results obtained in patellar lesions treated with a bioscaffold,  a mixture composed by a chitosan solution, a buffer, and the patient's whole blood  which forms a stable clot into the lesion. METHODS: Fifteen patients with ICRS grade 3-4 cartilage lesions of the patellar surface were treated with a chitosan bioscaffold. Fourteen patients were clinically and radiologically evaluated prospectively for a minimum follow-up of 2 years with IKDC, KOOS, Tegner score, and MRI. The mean age of patients at the time of surgery was 31.8 ± 11.9 and nine patients presented degenerative aetiology, four patients with previous trauma, and 1 patient with osteochondritis dissecans.  RESULTS: The IKDC subjective score improved from 46.2 ± 19.3 preoperatively to 69.5 ± 20.3 (p < 0.05) and 74.1 ± 23.2 (p < 0.05) at 12 and 24 months, respectively. Also KOOS Pain, KOOS Sport/Rec and KOOS QOL showed a significant improvement from baseline to 12 months and to the final follow-up. MRI evaluation showed a complete filling of the cartilage defect at the final follow-up in 70% of the lesions, obtaining a total MOCART 2.0 score of 71.5 ± 13.6 at 24 months after surgery. CONCLUSION: Chondral patellar lesions represent a complex pathology, with lower results compared to other sites. This bioscaffold represents a safe surgical treatment providing a significant clinical improvement at 24 months in the treatment of patellar cartilage lesions. LEVEL OF EVIDENCE: IV.

Combined subchondral and intra-articular injections of bone marrow aspirate concentrate provide stable results up to 24 months.

PURPOSE: The aim of this study was to evaluate the clinical and imaging findings up to 24 months of follow-up in patients treated with combined subchondral and intra-articular bone marrow aspirate concentrate (BMAC) injections for the treatment of knee osteoarthritis (OA). METHODS: Thirty consecutive patients (19 males, 11 females) aged between 40 and 75 years (mean age 56.4 ± 8.1 years) with unilateral symptomatic knee OA (Kellgren-Lawrence 2-3) were included in the study. Patients were treated with combined intra-articular and subchondral bone BMAC injections (total 9 ml) under fluoroscopic control. IKDC subjective score, VAS for pain, KOOS, and EQ-VAS were prospectively evaluated up to 24 months. Radiographs were performed at baseline and at 24 months after the procedure. MRI was evaluated with the WORMS score at baseline, 6-12 months, and 24 months of follow-up. The statistical analysis was performed using SPSS v.19.0 and for all tests p < 0.05 was considered significant. RESULTS: No major complications and a 13% failure rate were reported. The IKDC subjective score remained stable from 62.6 ± 19.4 at 12 months to 63.4 ± 17.1 at 24 months (both p < 0.0005 compared to baseline, 40.5 ± 12.5). Similar improvements were reported for all KOOS subscales, while EQ-VAS did not report any significant improvement. VAS pain worsened from 3.0 ± 1.9 at 12 months to 4.4 ± 1.8 at the final follow-up (p = 0.0001), although remaining lower compared to the baseline value of 6.3 ± 1.8 (p = 0.002). The radiographic evaluation did not reveal signs of improvement or deterioration of the OA grade. The MRI findings showed a worsening in marginal osteophytes and synovitis, but a significant reduction of bone marrow edema at 24 months (p < 0.0005). CONCLUSION: Combined intra-articular and subchondral BMAC injections provided clinical and imaging benefits up to 24 months for the treatment of symptomatic knee OA, with durable clinical results, a low failure rate, and a significant reduction of bone marrow edema.

Prospective double-blind randomised controlled trial protocol comparing bone marrow aspirate concentrate intra-articular injection combined with subchondral injection versus intra-articular injection alone for the treatment of symptomatic knee osteoarthritis.

INTRODUCTION: Subchondral and intra-articular injections of bone marrow aspirate concentrate (BMAC) showed promising results for knee osteoarthritis (OA) patients. To date, there is no evidence to demonstrate whether the combination of these treatments provides higher benefits than the intra-articular injection alone. METHODS AND ANALYSIS: Eighty-six patients with symptomatic knee OA (aged between 40 and 70 years) are randomised to BMAC intra-articular injection combined with subchondral BMAC injection or BMAC intra-articular injection alone in a ratio of 1:1. The primary outcome is the total Western Ontario and McMaster Universities Osteoarthritis Index, the secondary outcomes are the International Knee Documentation Committee Subjective and Objective Knee Evaluation Form, the Tegner activity scale, the EuroQol-Visual Analogue Scale, and the health questionnaire European Quality of Life Five Dimension score. Additional CT and MRI evaluations are performed at the baseline assessment and at the final 12-month follow-up. The hypothesis is that the combined injections provide higher knee pain and function improvement compared with BMAC intra-articular injection alone. The primary analysis follows an intention to treat principle. ETHICS AND DISSEMINATION: The study protocol has been approved by the Emilia Wide Area Ethical Committee of the Emilia-Romagna Region (CE-AVEC), Bologna, Italy. Written informed consent is obtained from all the participants. Findings of this study will be disseminated through peer-reviewed publications and conference presentations. PROTOCOL VERSION: Version 1 (14 May 2018). TRIAL REGISTRATION NUMBER: NCT03876795.

Recall Bias Affects Pain Assessment in Knee Osteoarthritis: A Pilot Study.

OBJECTIVE: The objective of this study was to evaluate the recall bias of symptoms evaluation in knee osteoarthritis (OA). DESIGN: In this multicentric pilot study, 50 patients with knee OA used a mobile App (Ecological Momentary Assessment [EMA]) to collect pain and function on two 0 to 10 numerical rating scales (NRS) 2 times a day for 2 months. At the 1-month and at the 2-month follow-up visits, patients retrospectively evaluated the mean level of pain/function of the last month. Recall bias was computed as the difference between the mean level of pain/function reported using the App and the level reported with the retrospective assessment. The correlation between the recall bias and patients' characteristics, as well as pain/function trajectories, was analyzed. RESULTS: A statistically significant recall bias was documented with higher pain reported at 1-month with the retrospective assessment (P < 0.001). These results were confirmed also at the 2-month follow-up (P = 0.002). For function, no significant recall bias was documented. During the first and second months, 47 and 31 patients showed pain peaks, respectively. The number of pain peaks during the first month was correlated with the magnitude of the recall bias (P = 0.02). CONCLUSIONS: The recall bias influences the retrospective self-assessment of pain at the follow-up visits and the presence of pain peaks, a common event in the patients with OA, increases the magnitude of recall bias. The EMA performed with a mobile App is a useful tool to limit the influence of recall bias in the clinical and research setting evaluation of knee OA.

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.

Microfragmented Adipose Tissue Versus Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Prospective Randomized Controlled Trial at 2-Year Follow-up.

BACKGROUND: Intra-articular microfragmented adipose tissue (MF-AT) injections have been proposed for the treatment of knee osteoarthritis (OA). PURPOSE: To compare a single injection of MF-AT or platelet-rich plasma (PRP) in terms of clinical outcomes and OA progression. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 118 patients with symptomatic knee OA were randomized to receive a single intra-articular injection of MF-AT or PRP. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the International Knee Documentation Committee (IKDC) subjective score, Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol visual analogue scale (EQ-VAS), EuroQol 5 dimensions (EQ-5D), and visual analogue scale (VAS) for pain. Primary outcomes were the IKDC subjective score and the KOOS pain subscore at 6 months. Knees were evaluated at baseline and at 6, 12, and 24 months with radiography and high-resolution magnetic resonance imaging (MRI) using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). RESULTS: Both MF-AT and PRP provided a statistically and clinically significant improvement up to 24 months. The improvement in the IKDC subjective score from baseline to 6 months was similar in both MF-AT (41.1 ± 16.3 to 57.3 ± 18.8) and PRP (44.8 ± 17.3 to 58.4 ± 18.1) groups (P < .0005). The improvement in the KOOS pain subscore from baseline to 6 months was similar in both the MF-AT (58.4 ± 15.9 to 75.8 ± 17.4) and PRP (63.5 ± 17.8 to 75.5 ± 16.1) groups (P < .0005). Overall, no differences were found between the MF-AT and PRP groups in terms of clinical outcomes, adverse events (18.9% and 10.9%, respectively), and failures (15.1% and 25.5%, respectively). Radiographic and MRI findings did not show changes after the injection. As a secondary outcome, more patients in the MF-AT group with moderate/severe OA reached the minimal clinically important difference for the IKDC score at 6 months compared with the PRP group (75.0% vs 34.6%, respectively; P = .005). CONCLUSION: A single intra-articular injection of MF-AT was not superior to PRP, with comparable low numbers of failures and adverse events and without disease progression. No differences were found in clinical and imaging results between the 2 biological approaches.

Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis.

The last decade has seen exponentially growing efforts to exploit the effects of adipose derived stromal cells (ADSC) in the treatment of a wide range of chronic degenerative diseases, including osteoarthritis (OA), the most prevalent joint disorder. In the perspective of developing a cell-free advanced therapy medicinal product, a focus has been recently addressed to the ADSC secretome that lends itself to an allogeneic use and can be further dissected for the selective purification of small extracellular vesicles (sEVs). sEVs can act as "biological drug carriers" to transfer information that mirror the pathophysiology of the providing cells. This is important in the clinical perspective where many OA patients are also affected by the metabolic syndrome (MetS). ADSC from MetS OA patients are dysfunctional and "inflammatory" primed within the adipose tissue. To mimic this condition, we exposed ADSC to IL-1ß, and then we investigated the effects of the isolated sEVs on chondrocytes and synoviocytes, either cultured separately or in co-culture, to tease out the effects of these "IL-1ß primed sEVs" on gene and protein expression of major inflammatory and catabolic OA markers. In comparison with sEVs isolated from unstimulated ADSC, the IL-1ß primed sEVs were able to propagate NF-κB activation in bystander joint cells. The effects were more prominent on synoviocytes, possibly because of a higher expression of binding molecules such as CD44. These findings call upon a careful characterization of the "inflammatory fingerprint" of ADSC to avoid the transfer of an unwanted message as well as the development of in vitro "preconditioning" strategies able to rescue the antiinflammatory/anticatabolic potential of ADSC-derived sEVs.

Union, complication, reintervention and failure rates of surgical techniques for large diaphyseal defects: a systematic review and meta-analysis.

To understand the potential and limitations of the different available surgical techniques used to treat large, long-bone diaphyseal defects by focusing on union, complication, re-intervention, and failure rates, summarizing the pros and cons of each technique. A literature search was performed on PubMed, Web of Science, and Cochrane databases up to March 16th, 2022; Inclusion criteria were clinical studies written in English, of any level of evidence, with more than five patients, describing the treatment of diaphyseal bone defects. The primary outcome was the analysis of results in terms of primary union, complication, reintervention, and failure rate of the four major groups of techniques: bone allograft and autograft, bone transport, vascularized and non-vascularized fibular graft, and endoprosthesis. The statistical analysis was carried out according to Neyeloff et al., and the Mantel-Haenszel method was used to provide pooled rates across the studies. The influence of the various techniques on union rates, complication rates, and reintervention rates was assessed by a z test on the pooled rates with their corresponding 95% CIs. Assessment of risk of bias and quality of evidence was based on Downs and Black's "Checklist for Measuring Quality" and Rob 2.0 tool. Certainty of yielded evidence was evaluated with the GRADE system. Seventy-four articles were included on 1781 patients treated for the reconstruction of diaphyseal bone defects, 1496 cases in the inferior limb, and 285 in the upper limb, with trauma being the main cause of bone defect. The meta-analysis identified different outcomes in terms of results and risks. Primary union, complications, and reinterventions were 75%, 26% and 23% for bone allografts and autografts, 91%, 62% and 19% for the bone transport group, and 78%, 38% and 23% for fibular grafts; mean time to union was between 7.8 and 8.9 months in all these groups. Results varied according to the different aetiologies, endoprosthesis was the best solution for tumour, although with a 22% failure rate, while trauma presented a more composite outcome, with fibular grafts providing a faster time to union (6.9 months), while cancellous and cortical-cancellous grafts caused less complications, reinterventions, and failures. The literature about this topic has overall limited quality. However, important conclusions can be made: Many options are available to treat critical-size defects of the diaphysis, but no one appears to be an optimal solution in terms of a safe, satisfactory, and long-lasting outcome. Regardless of the bone defect cause, bone transport techniques showed a better primary union rate, but bone allograft and autograft had fewer complication, reintervention, and failure rates than the other techniques. The specific lesion aetiology represents a critical aspect influencing potential and limitations and therefore the choice of the most suitable technique to address the challenging large diaphyseal defects.

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).

The 50 most-cited clinical articles in cartilage surgery research: a bibliometric analysis.

PURPOSE: Articular cartilage lesions remain a challenge for orthopedic surgeons. The identification of the most important articles can help identifying the most influential techniques of the past, the current prevalent focus, and emerging strategies. The aim of this study was to identify milestones and trends in cartilage research. METHODS: This study is a bibliometric analysis based on published articles. All citation count data included in the "Scopus database" were used to identify eligible studies up to December 2020. The 50 most-cited articles on cartilage surgery were ranked based on the citation count and analyzed regarding citation density and quality (Coleman score and RoB 2.0 tool). A further search was performed to identify the most promising clinical studies among the latest publications on cartilage surgery. RESULTS: Different kinds of cartilage treatments were investigated in the 50 most-cited clinical articles. Regenerative techniques with chondrocytes were the most reported with a total of 23 articles, followed by microfracture technique in 17 articles and mosaicplasty or osteochondral autograft transplantation (OAT) in 11. Forty-five articles focused on the knee. A higher citation density was found in the most recent articles (p = 0.004). The study of the most promising landmarks of the most recent articles showed new cell-free or tissue engineering-based procedures and an overall increasing quality of the published studies. CONCLUSION: This bibliometric analysis documented an increasing interest in cartilage surgery, with efforts toward high-quality studies. Over the years, the focus switched from reconstructive toward regenerative techniques, with emerging options including cell-free and tissue-engineering strategies to restore the cartilage surface. LEVEL OF EVIDENCE: IV.

Bone marrow aspirate concentrate injections provide similar results versus viscosupplementation up to 24 months of follow-up in patients with symptomatic knee osteoarthritis. A randomized controlled trial.

PURPOSE: The purpose of this double-blind randomized controlled trial (RCT) was to compare clinical improvement and radiographic findings up to 2 years of follow-up of a single intra-articular injection of bone marrow aspirate concentrate (BMAC) versus hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA). The hypothesis was that BMAC injection could lead to better clinical and radiographic results compared to viscosupplementation. METHODS: Patients with bilateral knee OA were randomized to one intra-articular injection of tibial-derived BMAC in one knee and one HA injection in the contralateral knee. Sixty patients were enrolled, and 56 were studied up to the final follow-up (35 men, 21 women, mean age 57.8 ± 8.9 years), for a total of 112 knees. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the IKDC subjective score, VAS for pain, and the KOOS score. Minimal clinically important difference (MCID), patient treatment judgement, and adverse events were documented, as well as bilateral X-Rays (Rosenberg view) before and after treatment. RESULTS: No severe adverse events nor differences were reported in terms of mild adverse events (7.1% vs 5.4%, p = ns) and treatment failures (10.7% vs 12.5%, p = ns) in BMAC and HA groups, respectively. The IKDC subjective score improved from baseline to all follow-ups for BMAC (p < 0.0005), while it improved up to 12 months (p < 0.0005) and then decreased at 24 months (p = 0.030) for HA. Compared to HA, BMAC showed a higher improvement for VAS pain at 12 (2.2 ± 2.6 vs 1.7 ± 2.5, p = 0.041) and 24 months (2.2 ± 2.6 vs 1.4 ± 2.8, p = 0.002). The analysis based on OA severity confirmed this difference only in Kellgren-Lawrence 1-2 knees, while comparable results were observed in moderate/severe OA. Radiographic evaluation did not show knee OA deterioration for both treatment groups, without intergroup differences. CONCLUSION: BMAC did not demonstrate a clinically significant superiority at short-term compared to viscosupplementation, reporting overall comparable results in terms of clinical scores, failures, adverse events, radiographic evaluation, MCID achievement, and patient treatment judgment. However, while HA results decreased over time, BMAC presented more durable results in mild OA knees. LEVEL OF EVIDENCE: Level I.

Meniscus treatment: biological augmentation strategies: a narrative review.

Objective: An up-to-date description on the biological augmentation strategies for meniscal repair procedures was performed to highlight the main preclinical and clinical evidence available in the literature. Background: Meniscal repair is a key surgical procedure to preserve as much meniscal tissue as possible to limit the development of knee osteoarthritis (OA). Unfortunately, the results of meniscal repair procedures are not always satisfactory, reporting an overall risk of failure of 25%, likely conditioned due to the poor vascularization of the meniscal tissue. For this reason, several biologic augmentation techniques have been developed to improve the meniscal healing process, ranging from mechanical stimulations to biological products. Methods: A literature review was conducted on the main biological augmentation procedures combined to the meniscal repair process. A description of the rationale, surgical technique, and preclinical and clinical evidence was performed. Conclusions: Mechanical stimulations and fibrin clot were the first techniques applied showing several limitations and not exciting results. Recently, platelet-rich plasma (PRP) augmentation to meniscal repair is slowly spreading in the clinical practice. Early evidence from comparative studies showed a significantly lower failure rate in patients treated with PRP augmentation compared with controls. Conversely, the current few and low-level data on mesenchymal stem/stromal cells (MSCs) for meniscal augmentation repair make this a promising but anecdotal topic. Further high-quality clinical studies are needed to support and guide the use of biological strategies for the augmentation of meniscus repair, PRP.