Abstract

BACKGROUND There has been an increase in interest in the use of biological therapies in orthopaedic conditions such as knee osteoarthritis. Platelet-rich plasma (PRP) is one of these therapies, but it still lacks consistent results. PURPOSE To evaluate the effects (benefits and harms) of PRP intra-articular injection compared with other nonsurgical methods for the treatment of knee osteoarthritis. STUDY DESIGN Systematic review and meta-analysis of randomized and quasi-randomized controlled trials; Level of evidence, 2. METHODS Three electronic databases were searched to identify relevant studies published before January 2021. The primary outcomes were pain, function, and failure of treatment. Risks of bias of all trials were assessed using a Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation System was used to assess the quality of evidence of included studies. RESULTS A total of 40 studies with 3035 participants were included. Analysis of this review focused on comparing PRP with hyaluronic acid, corticosteroid, and saline, as we believe they are the most relevant comparisons with the most studies available. At 6-month follow-up, PRP was as effective as and in some studies more effective than other therapies regarding pain, function, and stiffness. However, current evidence is of low or very low quality and is based on trials with high risk of bias and great heterogeneity among them. No significant difference among treatments was found concerning major adverse events and treatment failure. CONCLUSION Although studies suggest that PRP may be more effective than or at least as effective as other modalities of nonsurgical treatment for knee osteoarthritis in terms of pain, function, and adverse events, serious limitations and methodological flaws are considerable in the current literature. Therefore, the authors are not able to make recommendations for clinical practice regarding PRP for knee osteoarthritis.

Abstract

OBJECTIVES We aim to analyze the effectiveness of platelet-rich plasma (PRP) therapy in comparison to all the available treatments in the management of lateral epicondylitis. MATERIALS AND METHODS We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library till June 2021 for randomized controlled trials (RCTs), analyzing the efficacy and safety of PRP in the management of lateral epicondylitis. Visual Analog Score (VAS) for pain, Disabilities of the Arm, Shoulder and Hand (DASH) Score, Patient Reported Tennis-Elbow Evaluation (PRETEE) Score were the outcomes analyzed. Analysis was performed in R-platform using MetaInsight. Available treatment methods in the network were ranking based on the p-score approach. The quality of results from network analysis was appraised with Cochrane's CINeMA approach. RESULTS 25 RCTs with 2040 patients were included in the network analysis. Compared to saline control, only leucocyte-rich PRP resulted in significant pain relief (WMD -14.8 95% CI [-23.18,-6.39]; low confidence) on network analysis of VAS outcome compared to other treatment methods such as steroid, local anesthetic, laser, and surgery. Concerning functional outcome parameters such as DASH score or PRETEE score, none of the above-mentioned treatment methods were superior to saline control. On subgroup analysis of the outcomes at various time points, LR-PRP resulted in clinically significant improvement at all time points analyzed. Upon ranking the probabilities of being best of all the interventions analyzed in the network, leucocyte-rich PRP seems more promising with a p score of 0.415. CONCLUSION PRP therapy offers significant pain relief compared to saline control when employed in the management lateral epicondylitis. However, we did not note similar improvement in functional outcomes measures. With the available low-quality evidence, PRP is ranked to be the most promising therapy that needs further exploration. Further high-quality RCTs are needed to explore its usefulness in lateral epicondylitis.

Abstract

BACKGROUND Platelet-rich plasma (PRP) usage in orthopaedics continues to rise despite guidelines suggesting non-superiority to comparative cohorts. Therefore, we performed a systematic review and meta-analysis on PRP efficacy using two clinical assessments: (1) Visual Analog Scale (VAS) and (2) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We assessed consistency and clinical relevancy by determining study heterogeneity (e.g., sample sizes, ages, BMIs, arthritic severities, etc.). Comparative cohorts were: (A) hyaluronic acid (HA); (B) corticosteroid (CS); (C) normal saline (NS); and (D) exercise therapy. We performed sub-analyses of structural changes assessed on ultrasound, radiograph, or magnetic resonance imaging (MRI). METHODS We utilized PubMed, Cochrane Library, and Embase databases up to December 1, 2021, according to Preferred Reporting Items for Systematic-Reviews and Meta-Analyses guidelines. Twenty-four studies met criteria, with comparisons to: HA (n=11); CS (n=6); NS (n=5); and exercise therapy (n=3). Seven studies assessed structural changes. Evaluations utilized a methodological scoring system. I(2) statistics and forest plots pooled analyses and delineated study results. RESULTS PRP led to VAS and WOMAC improvements in most studies when compared to HA, CS, and NS (p≤0.05). Comparison to exercise therapy resulted in inconclusive findings (p≥0.05). However, substantial heterogeneity (I(2) ≥76%) was reported due to study variability. No differences were found when assessing structural changes or cartilage thickness by MRI (standardized mean difference -0.01 [-0.19, 0.18], p=0.91). CONCLUSIONS PRP may be associated with pain and functional improvements but was not clinically relevant (inconsistent study- and patient-metrics). Additionally, PRP did not confer superiority when assessing knee-related structural changes.

Abstract

BACKGROUND Platelet-rich plasma (PRP) is reported as an effective treatment for lateral epicondylitis (LE). Theoretically, different types of PRP have different therapeutic effects. However, there is controversy on the effects of different types of PRP in the treatment of LE. PURPOSE To systematically compare the pain relief, functional improvement and successful rates on treatment of two different types of PRP, by reviewing and summarizing the data available in the current literature on LE after PRP injection. METHODS The PubMed, Medline, Embase, Cochrane Library and Web of science were reviewed. A computerized literature search was performed for related studies published from inception to August 2021 by terms of lateral epicondylitis, tennis elbow, tendinopathy, lateral elbow pain, PRP. PRP involved in present study were divided into leukocyte-poor PRP and leukocyte-rich PRP groups according to different preparation methods. Outcomes of interest included characteristics of the subjects, types and preparations of PRP, clinical outcomes, successful rate and safety of treatment of short-term and long-term follow-up. RESULTS A total of 33 studies included 2420 LE patients. There were 19 studies with LP-PRP, 13 studies with LR-PRP and 1 study involved both LP-PRP and LR-PRP. Patients had significant improved clinical outcomes post-treatment compared to pre-treatment in both groups of PRP. The mean of VAS was ranged from 6.1 to 8.0 before the treatment, 1.5 to 4.0 at short-term and 0.6 to 3.3 at the long-term follow-up in LR-PRP group. The mean of VAS was ranged from 4.2 to 8.4 before the treatment, 1.6 to 5.9 at short-term and 0.7 to 2.7 in the long-term follow-up in LP-PRP group. The DASH score of LR-PRP and LP-PRP were ranged from 47.0 to 54.3 and 30.0 to 67.7 separately before the treatment and 20.0 to 22.0 and 5.5 to 19.0 separately at long-term follow-up. LR-PRP and LP-PRP groups reflected successful rate ranged from 70%-100% and 36%-100% respectively. The complication rate lower in LP-PRP group (3.9%) than LR-PRP group (6.4%), with the major complication was temporary pain after PRP treatment (P = 0.029). CONCLUSION PRP treatment demonstrated a significant improvement with pain relief and functional improvement on lateral epicondylitis regardless types of PRP. There was no significant difference between LR-PRP and LP-PRP in pain relief and functional improvement. The major complication was temporary pain after PRP injection and the complication rate in LP-PRP was lower than LR-PRP.

Abstract

INTRODUCTION Reports have concluded that platelet-rich plasma (PRP) is an effective and safe biological approach to treating knee osteoarthritis (OA). However, the effectiveness of PRP in advanced stages of the disease is not entirely clear. The purpose of this study was to evaluate whether the use of PRP would be as effective in studies with early-moderate knee OA patients compared to studies including patients with end-stage OA, based on the Kellgren-Lawrence classification. MATERIALS AND METHODS A comprehensive search in MEDLINE, EMBASE, Scopus, and Web of Science databases was conducted to identify randomized controlled trials (RCTs) comparing the effect of PRP injections versus other intra-articular treatments on pain and functionality. A meta-analysis was conducted using a random-effects model and the generic inverse variance method. RESULTS We included 31 clinical trials that reported data of 2705 subjects. Meta-analysis revealed an overall significant improvement of both pain [MD, - 1.05 (95% CI - 1.41 to - 0.68); I(2) = 86%; P ≤ 0.00001] and function [SMD, - 1.00 (95% CI - 1.33, to - 0.66); I(2) = 94%; P ≤ 0.00001], favoring PRP. Subanalysis for pain and functional improvement showed a significant pain relief in studies with 1-3 and 1-4 Kellgren-Lawrence OA stages and a significant functional improvement in studies with 1-2, 1-3 and 1-4 knee OA stages, favoring PRP. CONCLUSION Our results indicate that including patients with advanced knee OA does not seem to affect the outcomes of clinical trials in which the effectiveness of the PRP in knee OA is assessed.

Abstract

Background: Recently, there was a series of clinical studies focusing on local injection of platelet-rich plasma (PRP) for treatment of patients with carpal tunnel syndrome (CTS). However, the safety and efficacy of PRP in these CTS patients remains controversial. Therefore, we performed a systematic review to compare PRP with other conservative treatments in treatment of CTS patients. Methods: We systematically searched from electronic databases (Cochrane, PubMed, Web of Science, and EMBASE) up to 10 December 2021. The data of clinical results were extracted and analyzed by RevMan Manager 5.4. Results: Finally, eight randomized controlled studies, involving 220 CTS patients undergoing local injection of PRP were enrolled in this systematic review. All enrolled trials were considered to be of high quality. In the short-term efficacy, the PRP group was significantly lower in symptom severity scale (SSS) compared with the control group (MD = -2.00; 95% CI, -3.15 to -0.85; p = 0.0007; I(2) = 0%). In the mid-term efficacy, the PRP group was significantly effective than the control group in the visual analogue scale (MD = -0.63; 95% CI, -1.22 to -0.04; p = 0.04; I(2) = 61%), SSS (MD = -3.56; 95% CI, -4.93 to -2.18; p < 0.00001; I(2) = 0%), functional status scale (MD = -2.29; 95% CI, -3.03 to -1.56; p < 0.00001; I(2) = 45%), sensory peak latency (MD = -0.39; 95% CI, -0.58 to -0.19; p = 0.0001; I(2) = 0%) and cross-sectional area of median nerve (MD = -0.20; 95% CI, -0.31 to -0.10; p = 0.0002; I(2) = 0%). In the mid-long-term efficacy, the PRP group was only significantly lower in SSS compared with the control group (MD = -2.71; 95% CI, -4.33 to -1.10; p = 0.001; I(2) = 38%). Conclusion: Local PRP injection is more effective than other conservative treatments in terms of mid-term efficacy in relieving pain, improving wrist function and symptoms, reducing MN swelling, and partially improving electrophysiological indicators. However, the long-term adverse side and consensus on standardization of PRP in CTS patients still need further large-scale trials.

Abstract

PURPOSE The objective of the study was to assess the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of patellar tendinopathy. METHODS The PubMed, MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases were searched for clinical trials which compared PRP injection with other 'active treatment' interventions ('Non-PRP' injection and 'No-injection' treatments) or 'No-active treatment' interventions. Randomized and non-randomized clinical trials that had been published up to 15 November 2021, were included in the meta-analysis. The primary outcome, pain relief, was measured on a 'visual analog scale.' Secondary outcomes were knee functional activities and quality of life (QoL). The PRISMA guidelines were followed throughout the study. RESULTS Eight comparative studies were identified for inclusion in the meta-analysis. Assessment of these studies revealed that there were no significant differences in pain relief, functional outcomes, and QoL in the short, medium, and long term between PRP injection and Non-PRP injection interventions. Similarly, comparison of PRP injection to the No-active treatment intervention showed no differences in short- and medium-term pain relief. However, when PRP injection was compared to the No-injection treatment intervention extracorporeal shock wave therapy (ECWT), the former was found to be more effective in terms of pain relief in the medium term (mean difference [MD] - 1.50; 95% confidence interval [CI] - 2.72 to - 0.28) and long term (MD - 1.70; 95% CI, - 2.90 to - 0.50) and functional outcomes in the medium term (MD 13.0; 95% CI 3.01-22.99) and long term (MD 13.70; 95% CI 4.62-22.78). CONCLUSIONS In terms of pain relief and functional outcomes, the PRP injection did not provide significantly greater clinical benefit than Non-PRP injections in the treatment of patellar tendinopathy. However, in comparison with ESWT, there was a significant benefit in favor of PRP injection.

Abstract

Cell therapy strategies using mesenchymal stem cells (MSCs) carried in fibrin glue have shown promising results in regenerative medicine. MSCs are crucial for tissue healing because they have angiogenic, anti-apoptotic and immunomodulatory properties, in addition to the ability to differentiate into several specialized cell lines. Fibrin sealant or fibrin glue is a natural polymer involved in the coagulation process. Fibrin glue provides a temporary structure that favors angiogenesis, extracellular matrix deposition and cell-matrix interactions. Additionally, fibrin glue maintains the local and paracrine functions of MSCs, providing tissue regeneration through less invasive clinical procedures. Thus, the objective of this systematic review was to assess the potential of fibrin glue combined with MSCs in bone or cartilage regeneration. The bibliographic search was performed in the PubMed/MEDLINE, LILACS and Embase databases, using the descriptors ("fibrin sealant" OR "fibrin glue") AND "stem cells" AND "bone regeneration", considering articles published until 2021. In this case, 12 preclinical and five clinical studies were selected to compose this review, according to the eligibility criteria. In preclinical studies, fibrin glue loaded with MSCs, alone or associated with bone substitute, significantly favored bone defects regeneration compared to scaffold without cells. Similarly, fibrin glue loaded with MSCs presented considerable potential to regenerate joint cartilage injuries and multiple bone fractures, with significant improvement in clinical parameters and absence of postoperative complications. Therefore, there is clear evidence in the literature that fibrin glue loaded with MSCs, alone or combined with bone substitute, is a promising strategy for treating lesions in bone or cartilaginous tissue.

Abstract

INTRODUCTION Prolotherapy and other injections, primarily acting on pathways associated with maladaptive tissue repair, are recommended for recalcitrant chronic soft tissue injuries (CSTI). However, selection of injection is challenging due to mixed results. This network meta-analysis (NMA) aimed to compare prolotherapy with other therapies, particularly injections, for CSTI and establish robustness of the results. METHODOLOGY Pubmed, Medline, SPORTDiscus and Google scholar were searched from inception to 4th January 2021 for randomised controlled trials (RCTs) involving injection therapies (e.g. blood derivatives, corticosteroid, hyaluronic acid, botulinum toxin) for CSTI. The primary and secondary outcomes were pain and function, respectively, at (or nearest to) 6 months. Effect size (ES) was presented as standardised mean difference with 95% confidence interval (CI). Frequentist random effect NMA was used to generate the overall estimates, subgroup estimates (by region and measurement time point) and sensitivity analyses. RESULTS A total of 91 articles (87 RCTs; 5859 participants) involving upper limb (74%), lower limb (23%) and truncal/hip (3%) injuries were included. At all time points, prolotherapy had no statistically significant pain benefits over other therapies. This observation remained unchanged when tested under various assumptions and with exclusion of studies with high risk of bias. Although prolotherapy did not offer statistically significant functional improvement compared to most therapies, its ES was consistently better than non-injections and corticosteroid injection for both outcomes. At selected time points and for selected injuries, prolotherapy demonstrated potentially better pain improvement over placebo (<4 months: shoulder [ES 0.65; 95% CI 0.00 to 1.30]; 4-8 months: elbow [ES 0.91; 95% CI 0.12 to 1.70]; >8 months: shoulder [ES 2.08; 95% CI 1.49, to 2.68]). Injections generally produced greater ES when combined with non-injection therapy. CONCLUSION While clinical outcomes were generally comparable across types of injection therapy, prolotherapy may be used preferentially for selected conditions at selected times.

Abstract

STUDY DESIGN Systematic review and meta-analysis. OBJECTIVES We performed this meta-analysis to evaluate whether intradiscal Platelet Rich Plasma(PRP) injection has any beneficial role in the management of lumbar disc disease. METHODS We conducted independent and duplicate electronic database searches including PubMed, Embase, and Cochrane Library till September 2020 for studies investigating the role of intradiscal PRP in the management of lumbar disc disease. The analysis was performed in the R platform using OpenMeta[Analyst] software. RESULTS 13 studies including 2 RCTs, 5 prospective, and 6 retrospective studies involving 319 patients were included in the meta-analysis. A single-arm meta-analysis of the included studies showed a beneficial effect of the intervention in terms of pain relief outcomes like VAS score (p < 0.001), pain component of SF-36 (p = 0.003) while such improvement was not seen in functional outcome measures like ODI score (p = 0.071), the physical component of SF-36 (p = 0.130) with significant heterogeneity noted among the included studies. No structural improvement in magnetic resonance imaging was observed (p = 0.106). No additional procedure-related adverse events were noted in the included studies (p = 0.662). CONCLUSION There is a paucity of high-quality studies to give conclusive evidence on the benefits of intradiscal PRP for lumbar disc disease. Although intradiscal PRP injection has shown some beneficial effect in controlling pain for lumbar disc disease, we could not find structural or functional improvement from the included studies. Hence, we recommend large double-blind double-arm randomized controlled studies to analyze the benefits of the intervention being analyzed.