Nicolás Fiz

A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

PURPOSE This multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis. METHODS We randomly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis). The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As secondary outcomes, we also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. RESULTS The mean age of the patients was 59.8 years, and 52% were women. Compared with the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher (95% confidence interval, 0.5 to 27.6; P = .044). Regarding the secondary outcome measures, the rate of response to PRGF-Endoret was higher in all cases, although no significant differences were reached. Adverse events were mild and evenly distributed between the groups. CONCLUSIONS Plasma rich in growth factors showed superior short-term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee. LEVEL OF EVIDENCE Level I, randomized controlled multicenter trial.

Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip

OBJECTIVE To assess the safety and symptomatic changes of IA injections of platelet-rich plasma (PRP) in patients with OA of the hip. METHODS Forty patients affected by monolateral severe hip OA were included in the study. Each joint received three IA injections of PRP, which were administered once a week. The primary end point was meaningful pain relief, which was described as a reduction in pain intensity of at least 30% from baseline levels as evaluated by the WOMAC subscale at 6-months post-treatment. The visual analogue scale (VAS) and Harris hip score subscale for pain were used to verify the results. Secondary end points included changes in the level of disability of at least 30% and the percentage of positive responders, i.e. the number of patients that achieved a >30% reduction in pain and disability. RESULTS Statistically significant reductions in VAS, WOMAC and Harris hip subscores for pain and function were reported at 7 weeks and 6 months (P < 0.05). Twenty-three (57.5%) patients reported a clinically relevant reduction of pain (45%, range 30-71%) as assessed by the WOMAC subscale. Sixteen (40%) of these patients were classified as excellent responders who showed an early pain reduction at 6-7 weeks, which was sustained at 6 months, and a parallel reduction of disability. Side effects were negligible and were limited to a sensation of heaviness in the injection site. CONCLUSIONS This preliminary non-controlled prospective study supported the safety, tolerability and efficacy of PRP injections for pain relief and improved function in a limited number of patients with OA of the hip.

Arthroscopic management and platelet-rich plasma therapy for avascular necrosis of the hip

PurposeThe purpose is to describe a noninvasive arthroscopic procedure as an alternative to open surgery for avascular necrosis of the hip.MethodsPatients with grade I or IIA avascular necrosis of the hip are treated by core decompression performed by drilling under fluoroscopic guidance. Liquid platelet-rich plasma (PRP) is delivered through a trocar, saturating the necrotic area. In more severe conditions, the necrotic bone is decompressed and debrided, through a cortical window at the head–neck junction. A composite graft made of autologous bone and PRP is delivered by impactation through the core decompression track. Fibrin membranes are applied to enhance healing of the head–neck window and arthroscopic portals. Platelet-rich plasma is infiltrated in the central compartment.ResultsThis arthroscopic approach aids in making diagnosis of the labrum and articular cartilage and permits intra-operative treatment decisions. Visual control permits the precise localization and treatment for the necrotic area allowing cartilage integrity to be preserved.ConclusionsArthroscopic management of avascular necrosis of the femoral head is viable and has significant advantages. Clinical studies should justify the theoretical additional benefits of this approach.

Ultrasound-guided plasma rich in growth factors injections and scaffolds hasten motor nerve functional recovery in an ovine model of nerve crush injury.

In the present study we evaluated the motor recovery process of peripheral nerve injury (PNI), based on electrophysiological and histomorphometric criteria, after treatment with plasma rich in growth factors (PRGF) injections and scaffolds in an ovine model. Three groups of sheep underwent a nerve crush lesion: the first group (n = 3) was left to recover spontaneously (SR); the second group was administered saline injections (SI; n = 5) and a third group (n = 6) received PRGF injections and scaffolds immediately after the crush injury. At post‐intervention week 8, 70% of sheep in the PRGF group were CMAP‐positive, with no electrophysiological response in the rest of the groups. Histomorphometric analysis 12 weeks after the surgical intervention revealed that the average axonal density of the SR (1184 ± 864 axons/µm2) and SI (3109 ± 2450 axons/µm2) groups was significantly inferior to the control (8427 ± 2433 axons/µm2) and also inferior to the PRGF group (5276 ± 4148 axons/µm2), showing no significant differences between the control and PRGF groups. The axonal size of the SR and SI groups was significantly smaller compared with the control group (18 ± 4 µm2), whereas the axonal size of the PRGF group (6 ± 5 µm2) did not show statistical differences from the control. Morphometry of the target muscles indicated that the PRGF group had the lowest percentage volume reduction 12 weeks after the crush injury. The PRGF group had larger muscle fibre areas than the SI and SR groups, although the differences did not reach statistical significance. Overall, these data suggest that the PRGF injections and scaffolds hastened functional axon recovery and dampened atrophy of the target muscles in an ovine model. Copyright

Platelet rich plasma and knee surgery.

In orthopaedic surgery and sports medicine, the knee joint has traditionally been considered the workhorse. The reconstruction of every damaged element in this joint is crucial in achieving the surgeons goal to restore the knee function and prevent degeneration towards osteoarthritis. In the last fifteen years, the field of regenerative medicine is witnessing a boost of autologous blood-derived platelet rich plasma products (PRPs) application to effectively mimic and accelerate the tissue healing process. The scientific rationale behind PRPs is the delivery of growth factors, cytokines, and adhesive proteins present in platelets and plasma, as well as other biologically active proteins conveyed by the plasma such as fibrinogen, prothrombin, and fibronectin; with this biological engineering approach, new perspectives in knee surgery were opened. This work describes the use of PRP to construct and repair every single anatomical structure involved in knee surgery, detailing the process conducted in ligament, meniscal, and chondral surgery.

Intraosseous Infiltration of Platelet-Rich Plasma for Severe Knee Osteoarthritis

We describe a new technique of platelet-rich plasma (PRP) infiltration for the treatment of severe knee osteoarthritis. PRP intra-articular infiltration is a promising treatment for knee osteoarthritis, but it still has some limitations in high-degree osteoarthritis. Diagnosis of osteoarthritis is based on clinical and radiographic findings, and patients with grade III or IV knee tibiofemoral osteoarthritis based on the Ahlbäck scale are considered candidates for this technique. The technique consists of performing intraosseous infiltration of PRP into the subchondral bone, which acts on this tissue and consequently on cartilage-bone communication. Although the intraosseous injection hinders the conventional knee intra-articular infiltration, it allows an extension of the range of action of the PRP, which acts directly on the subchondral bone, which is involved in the progression of osteoarthritis. Thus this technique involves a new administration of PRP that can delay knee arthroplasty; moreover, it can be applied for not only severe osteoarthritis but also other pathologies in which the subchondral bone is critical in the etiology, such as necrosis and osteochondral lesions.

Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee Osteoarthritis: A Pilot Study

The aim of this study was to assess a novel approach to treating severe knee osteoarthritis by targeting synovial membrane, superficial articular cartilage, synovial fluid, and subchondral bone by combining intra-articular injections and intraosseous infiltrations of platelet rich plasma. We explored a new strategy consisting of intraosseous infiltrations of platelet rich plasma into the subchondral bone in combination with the conventional intra-articular injection in order to tackle several knee joint tissues simultaneously. We assessed the clinical outcomes through osteoarthritis outcome score (KOOS) and the inflammatory response by quantifying mesenchymal stem cells in synovial fluid. There was a significant pain reduction in the KOOS from baseline (61.55 ± 14.11) to week 24 (74.60 ± 19.19), after treatment (p = 0.008), in the secondary outcomes (symptoms, p = 0.004; ADL, p = 0.022; sport/rec., p = 0.017; QOL, p = 0.012), as well as VAS score (p < 0.001) and Lequesne Index (p = 0.008). The presence of mesenchymal stem cells in synovial fluid and colony-forming cells one week after treatment decreased substantially from 7.98 ± 8.21 MSC/μL to 4.04 ± 5.36 MSC/μL (p = 0.019) and from 601.75 ± 312.30 to 139.19 ± 123.61  (p = 0.012), respectively. Intra-articular injections combined with intraosseous infiltrations of platelet rich plasma reduce pain and mesenchymal stem cells in synovial fluid, besides significantly improving knee joint function in patients with severe knee osteoarthritis. This trial is registered on EudraCT with the number 2013-003982-32.

A Less-Invasive Technique for Capsular Management During Hip Arthroscopy for Femoroacetabular Impingement

The aim of this work is to describe a new arthroscopic technique for the treatment of femoroacetabular impingement that allows a complete articular joint view with maximum protection of the capsuloligamentous complex. This arthroscopic technique avoids injury to the capsuloligamentous complex, preventing the risk of postoperative instability. The diagnosis of femoroacetabular impingement was based on clinical and radiographic grounds. An alpha angle greater than 50° was considered pathologic. In this technique, the use of intra-articular devices (retractors) allows us to separate the capsular tissue from the femoral head-neck junction and mobilize the capsule, achieving an adequate joint view without performing a capsulotomy and, consequently, avoiding the complications of capsular damage.

Modulation of Synovial Fluid-Derived Mesenchymal Stem Cells by Intra-Articular and Intraosseous Platelet Rich Plasma Administration

The aim of this study was to evaluate the effect of intra-articular (IA) or a combination of intra-articular and intraosseous (IO) infiltration of Platelet Rich Plasma (PRP) on the cellular content of synovial fluid (SF) of osteoarthritic patients. Thirty-one patients received a single infiltration of PRP either in the IA space (n = 14) or in the IA space together with two IO infiltrations, one in the medial femoral condyle and one in the tibial plateau (n = 17). SF was collected before and after one week of the infiltration. The presence in the SF of mesenchymal stem cells (MSCs), monocytes, and lymphocytes was determined and quantified by flow cytometry. The number and identity of the MSCs were further confirmed by colony-forming and differentiation assays. PRP infiltration into the subchondral bone (SB) and the IA space induced a reduction in the population of MSCs in the SF. This reduction in MSCs was further confirmed by colony-forming (CFU-F) assay. On the contrary, IA infiltration alone did not cause variations in any of the cellular populations by flow cytometry or CFU-F assay. The SF of osteoarthritic patients contains a population of MSCs that can be modulated by PRP infiltration of the SB compartment.

Treating Severe Knee Osteoarthritis with Combination of Intra-Osseous and Intra-Articular Infiltrations of Platelet-Rich Plasma: An Observational Study

Objective Assessing the therapeutic effects of a combination of intra-articular and intra-osseous infiltrations of platelet-rich plasma (PRP) to treat severe knee osteoarthritis (KOA) using intra-articular injections of PRP as the control group. Design In this observational study, 60 patients suffering from severe KOA were treated with intra-articular infiltrations of PRP (IA group) or with a combination of intra-osseous and intra-articular infiltrations of PRP (IO group). Both groups were matched for sex, age, body mass index, and radiographic severity (III and IV degree according to Ahlbäck scale). Clinical outcome was evaluated at 2, 6, and 12 months, using the Knee injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires. Results At 2, 6 and 12 months after treatment, IO group had a significant improvement in all KOOS and WOMAC subscales (P < 0.05). On the contrary, patients of the IA group did not improve in any of the scores. Sixteen out of 30 IO group patients showed minimal clinically important improvement (MCII) whereas 8 out of 30 IA group patients showed this response at 6 months (26.7%; 95% CI −0.4 to 49.9; P = 0.037). At 12 months, 14 patients of IO group and 5 patients of the IA group showed MCII (30%; 95% CI 4.3 to 51.9; P = 0.013). No differences between groups were observed at 2 months. Conclusions PRP intra-articular injections in severe KOA were not effective and did not provide any benefit. Combination of intra-articular and intra-osseous infiltrations of PRP was not clinically superior at 2 months, but it showed superior clinical outcomes at 6 and 12 months when compared with intra-articular injections of PRP.