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Systematic review

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Journal Journal of vascular and interventional radiology
Year 2022
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ABSTRACT: PURPOSE: To review and indirectly compare the outcomes of genicular artery embolization (GAE), radiofrequency (RF) ablation, and intra-articular (IA) injection for the treatment of knee pain secondary to osteoarthritis (OA). MATERIALS AND METHODS: A literature review of the MEDLINE and Cochrane databases was conducted with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement in June 2020. The visual analog scale (VAS) was recorded at baseline and at all available time points for each therapy. Standard mean differences were calculated at each time point and compared between treatments to assess the magnitude of the treatment effect. RESULTS: All 3 treatments demonstrated significant differences in VAS scores after therapy. RF ablation produced the greatest significant mean reduction in relative VAS score from baseline at 1 year of follow-up (mean, 0.49; 95% confidence interval, 0.4-0.59; P = .03). GAE reported the most significant reductions in VAS scores across all measured time points. Overall, the comparison did not demonstrate a significant difference in VAS scores among patients receiving IA injections, RF ablation, and GAE. CONCLUSIONS: The current evidence does not suggest a significant difference in outcomes among IA injection, RF ablation, and GAE for knee pain secondary to OA.

Systematic review

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Authors Lee OS , Ahn S , Ahn JH , Teo SH , Lee YS
Journal Archives of orthopaedic and trauma surgery
Year 2018
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INTRODUCTION: The purpose of this systematic review and meta-analysis was to evaluate the efficacy of concurrent cartilage procedures during high tibial osteotomy (HTO) for medial compartment osteoarthritis (OA) by comparing the outcomes of studies that directly compared the use of HTO plus concurrent cartilage procedures versus HTO alone. MATERIALS AND METHODS: Results that are possible to be compared in more than two articles were presented as forest plots. A 95% confidence interval was calculated for each effect size, and we calculated the I (2) statistic, which presents the percentage of total variation attributable to the heterogeneity among studies. The random effects model was used to calculate the effect size. RESULTS: Seven articles were included to the final analysis. Case groups were composed of HTO without concurrent procedures and control groups were composed of HTO with concurrent procedures such as marrow stimulation procedure, mesenchymal stem cell transplantation, and injection. The case group showed a higher hospital for special surgery score and mean difference was 4.10 [I (2) 80.8%, 95% confidence interval (CI) - 9.02 to 4.82]. Mean difference of the mechanical femorotibial angle in five studies was 0.08° (I (2) 0%, 95% CI - 0.26 to 0.43). However, improved arthroscopic, histologic, and MRI results were reported in the control group. CONCLUSION: Our analysis support that concurrent procedures during HTO for medial compartment OA have little beneficial effect regarding clinical and radiological outcomes. However, they might have some beneficial effects in terms of arthroscopic, histologic, and MRI findings even though the quality of healed cartilage is not good as that of original cartilage. Therefore, until now, concurrent procedures for medial compartment OA have been considered optional. Nevertheless, no conclusions can be drawn for younger patients with focal cartilage defects and concomitant varus deformity. This question needs to be addressed separately.

Systematic review

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Journal NPJ Regenerative medicine
Year 2018
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This systematic review with a meta-analysis aimed to summarize the current evidence of the effectiveness of mesenchymal stem cell (MSC) treatment for knee osteoarthritis (OA) and to examine whether rehabilitation is an effect modifier of the effect estimate of MSC treatment. A literature search yielded 659 studies, of which 35 studies met the inclusion criteria (n = 2385 patients; mean age: 36.0–74.5 years). The meta-analysis results suggested that MSC treatment through intra-articular injection or arthroscopic implantation significantly improved knee pain (standardized mean difference [SMD]: −1.45, 95% confidence interval [CI]: −1.94, −0.96), self-reported physical function (SMD: 1.50, 95% CI: 1.09, 1.92), and cartilage quality (SMD: −1.99; 95% CI: −3.51, −0.47). However, the MSC treatment efficacy on cartilage volume was limited (SMD: 0.49; 95% CI: −0.19, 1.16). Minor adverse events (knee pain or swelling) were reported with a wide-ranging prevalence of 2–60%; however, no severe adverse events occurred. The evidence for these outcomes was “very low” to “low” according to the Grades of Recommendation, Assessment, Development and Evaluation system because of the poor study design, high risk of bias, large heterogeneity, and wide 95% CI of the effects estimate. Performing rehabilitation was significantly associated with better SMD for self-reported physical function (regression coefficient: 0.881, 95% CI: 0.049, 1.712; P = 0.039). We suggest that more high quality randomized controlled trials with consideration of the potential rehabilitation-driven clinical benefit would be needed to facilitate the foundation of effective MSC treatment and regenerative rehabilitation for patients with knee OA. © 2018, The Author(s).

Systematic review

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Journal Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
Year 2018
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PURPOSE: The purpose of this systematic review is to evaluate the effects of adipose derived mesenchymal stem cells (ADSCs) in the treatment of osteoarthritis (OA) in the clinical setting. METHODS: A literature search was performed in the MEDLINE, EMBASE, and The Cochrane Library Database up to January 2017 for inclusion and exclusion criteria. Criteria for inclusion were clinical studies demonstrating the effects of ADSCs on OA, and written in English. The following variables were analyzed: donor site, volume of adipose tissue, preparation of ADSCs, clinical outcomes, and complication rate. RESULTS: Sixteen studies (knee: 14 studies, multiple joints: 1 study, ankle: 1 study) were included in this systematic review. All of the studies prepared ADSCs in the form of the stromal vascular fraction (SVF). Inconsistencies between studies were found with regards to reported clinical variability, donor sites of SVF, and reported clinical outcomes. Nine studies used either platelet-rich plasma (PRP) (7/16) or fibrin (4/16) or both PRP and Fibrin (1/16), as an adjunct at time of SVF injection. All of the studies reported an improvement in clinical outcomes with the use of SVF. Five studies reported a 90% satisfaction rate, and no study reported any complications with liposuction. Five studies reported on complications, with a 5% incidence of swelling and pain. CONCLUSIONS: This systematic review demonstrated that ADSCs are currently used in the form of SVF. While SVF may produce favorable clinical outcomes with minimal risk of side effects on osteoarthritis, the variability in the data and the use of biological adjuvants have confounded the effectiveness of ADSCs. This study will help surgeons understand the limitations in the literature on ADSCs. LEVEL OF EVIDENCE: Level IV, systematic review of level IV studies.

Systematic review

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Journal The American journal of sports medicine
Year 2018
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BACKGROUND: Stem cell therapy is emerging as a potential treatment of osteoarthritis (OA) and chondral defects (CDs). However, there is a great deal of heterogeneity in the literature. The indications for stem cell use, the ideal tissue source, and the preferred outcome measures for stem cell-based treatments have yet to be determined. PURPOSE: To provide clinicians with a comprehensive overview of the entire body of the current human literature investigating the safety and efficacy of intra-articular mesenchymal stem cell (MSC) therapy in all joints. METHODS: To provide a comprehensive overview of the current literature, all clinical studies investigating the safety and efficacy of intra-articular MSC therapy were included. PubMed, MEDLINE, and Cochrane Library databases were searched for published human clinical trials involving the use of MSCs for the treatment of OA and CDs in all joints. A total of 3867 publications were screened. RESULTS: Twenty-eight studies met the criteria to be included in this review. Fourteen studies treating osteoarthritis and 14 studies treating focal chondral defects were included. MSCs originating from bone marrow (13), adipose tissue (12), synovial tissue (2), or peripheral blood (2) were administered to 584 distinct individuals. MSCs were administered into the knee (523 knees), foot/ankle (61), and hip (5). The mean follow-up time was 24.4 months after MSC therapy. All studies reported improvement from baseline in at least 1 clinical outcome measure, and no study reported major adverse events attributable to MSC therapy. DISCUSSION: The studies included in this review suggest that intra-articular MSC therapy is safe. While clinical and, in some cases, radiological improvements were reported for both OA and CD trials, the overall quality of the literature was poor, and heterogeneity and lack of reproducibility limit firm conclusions regarding the efficacy of these treatments. CONCLUSION: This review provides strong evidence that autologous intra-articular MSC therapy is safe, with generally positive clinical outcomes.

Systematic review

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Journal Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
Year 2018
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PURPOSE: To assess whether the combination of HTO and cartilage treatment produced an additional clinical benefit compared to HTO alone. The secondary aim was to identify if there was any difference among different cartilage procedures in terms of healing potential and clinical outcome. METHODS: A systematic review of the literature was performed on PubMed database by three independent observers according to the following inclusion criteria: clinical reports of any level of evidence, written in the English language, with no time limitation, about HTO associated with cartilage surgical and injective treatment, including surveys reporting clinical, radiological, or second-look outcomes at any follow-up time. RESULTS: The database search identified 1956 records: 21 studies were included for the final analysis, for a total of 1068 patients; 10 case series and 11 comparative studies. While overall good results were reported in the case series, the analysis of the comparative studies showed less uniform results. Among the eight studies investigating HTO with cartilage surgical procedures, improved tissue regeneration was found in 5/8 studies, whereas a clinical improvement was reported only in two studies. Three studies on HTO combination with injective treatment showed better tissue regeneration and clinical benefit. CONCLUSIONS: Literature presents low-quality studies, with only few heterogeneous comparative papers. While surgical treatments targeting only the cartilage layer did not achieve clinical improvements, injective treatments targeting the overall joint environment showed promising findings. This prompts further research towards the development of treatments able to improve knee osteotomies outcomes. However, until new evidence will prove otherwise, there is no indication for a combined cartilage treatment in routine clinical practice. LEVEL OF EVIDENCE: Level IV.

Systematic review

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Journal Open access rheumatology : research and reviews
Year 2018
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BACKGROUND: Pain and limitations in joint mobility associated with knee osteoarthritis (OA) are clinically challenging to manage, and advanced progression of disease can often lead to total knee arthroplasty. Intra-articular injection of hyaluronic acid (HA), also referred to as viscosupplementation, is a non-surgical treatment approach for OA, the effectiveness of which may depend on the HA composition, and the length of time over which it resides in the joint. One of the available options for such therapies includes NASHA (Durolane HA), a non-animal, biofermentation-derived product, which is manufactured using a process that stabilizes the HA molecules to slow down their rate of degradation and produce a unique formulation with a terminal half-life of ~1 month. The objectives of the current review were to assess, in patients with OA of the knee, the efficacy and safety of intra-articular treatment with NASHA relative to control (saline) injections, other HA products, and other injectables (corticosteroids, platelet-rich plasma, mesenchymal stem cells). METHODS: This systematic evidence review examines patient outcomes following NASHA treatment as described in published data from studies conducted in subjects with knee OA. A Preferred Reporting Items for Systematic Reviews and Meta-analyses-compliant literature search strategy yielded 11 eligible clinical studies with a variety of comparator arms. Outcomes assessed at various time points following intra-articular treatment included measures of pain, function, quality of life, and incidence of treatment-related adverse events (AEs). RESULTS: The available evidence reported for the clinical studies assessed demonstrates sustained and effective relief of knee OA symptoms following a single injection of NASHA. In addition, an excellent biocompatibility profile is observed for NASHA as an intra-articular therapy for OA, as reflected by the low rate of AEs associated with treatment. CONCLUSION: Treatment with NASHA is an effective and safe single-injection procedure, which can be beneficial in the clinical management of knee OA.

Systematic review

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Journal Osteoarthritis and cartilage
Year 2018
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OBJECTIVE: Osteoarthritis (OA) is a leading cause of disability in the world. Mesenchymal stem cells (MSCs) have been studied to treat OA. This review was performed to systematically assess the quality of literature and compare the procedural specifics surrounding MSC therapy for osteoarthritis. DESIGN: PubMed, CINAHL, EMBASE and Cochrane Central Register of Controlled Trials were searched for studies using MSCs for OA treatment (final search December 2017). Outcomes of interest included study evidence level, patient demographics, MSC protocol, treatment results and adverse events. Level I and II evidence articles were further analyzed. RESULTS: Sixty-one of 3,172 articles were identified. These studies treated 2,390 patients with osteoarthritis. Most used adipose-derived stem cells (ADSCs) (n = 29) or bone marrow-derived stem cells (BMSCs) (n = 30) though the preparation varied within group. 57% of the sixty-one studies were level IV evidence, leaving five level I and nine level II studies containing 288 patients to be further analyzed. Eight studies used BMSCs, five ADSCs and one peripheral blood stem cells (PBSCs). The risk of bias in these studies showed five level I studies at low risk with seven level II at moderate and two at high risk. CONCLUSION: While studies support the notion that MSC therapy has a positive effect on OA patients, there is limited high quality evidence and long-term follow-up. The present study summarizes the specifics of high level evidence studies and identifies a lack of consistency, including a diversity of MSC preparations, and thus a lack of reproducibility amongst these articles' methods.

Systematic review

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Thesis California State University
Year 2018
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PURPOSE: The purpose of this meta-analysis was to evaluate if stem cell injection is more effective than PT intervention on WOMAC scores for persons with knee OA at 6 months or at a 1-year follow-up. It was hypothesized that MSC injections have a greater effect on WOMAC scores for patients with knee OA than physical therapy interventions at long-term follow-up. METHODS: This study utilized PRIZMA guidelines for the procedure and searches of the U.S. National Library of Medicine National Institute s of Health (PubMed), Elsevier, the Journal of American Medical Association, MEDLINE, EBSCOhost and Wiley online library search engines beginning in August of 2017. RESULTS: Six studies were identified that fit the PICO. PEDro scale scores ranged from 5--10. Both MSC injections and PT interventions had large effect sizes at 1 year, with MSCs having greater effects than PT interventions. However, all findings were heterogenous resulting in acceptance of the null hypothesis. CONCLUSIONS: MSC injection appears to be more effective than PT interventions at 1 year on total WOMAC score, but further studies need to be conducted to verify this result. Future research needs to be conducted to improve the quality and quantity of studies for both PT interventions and MSC interventions on knee OA, and the additive benefits of PT in patients who underwent MSC injection needs to be explored.

Systematic review

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Journal British journal of sports medicine
Year 2017
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OBJECTIVE: Stem cell injection for knee osteoarthritis (KOA) is an emerging new therapy, and we aimed to review its evidence of efficacy. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Criteria for eligibility were randomised controlled trials (RCTs) and non-RCT on the efficacy of stem cell injections in KOA. All references were checked for missed articles. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane Library, PEDro and SPORTDiscus were searched. A grey literature search was performed. No restrictions were imposed to our search strategy. RISK OF BIAS AND DATA SYNTHESIS: Risk of bias was assessed using the Cochrane risk of bias tool. Descriptive synthesis was performed using the levels of evidence according to the Oxford Levels of Evidence. RESULTS: Five RCTs and one non-RCT were found. Bone-marrow-derived stem cells, adipose-derived mesenchymal stem cells and peripheral blood stem cells were used. All trials were at high risk of bias, resulting in level-3 evidence. All five RCTs reported superior efficacy for patient-reported outcomes (Visual Analogue Scale, Western Ontario and McMaster Universities Arthritis Index, Tegner, Lysolm, International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Lequesne) compared with controls at final follow-up (range 24-48 months). Superior radiological outcomes were found favouring stem cell injection. Superior histological outcomes and/or improved arthroscopically scored healing rates were reported in two trials. No serious adverse events were reported. CONCLUSION: Six trials with high risk of bias showed level-3 or level-4 evidence in favour of stem cell injections in KOA. In the absence of high-level evidence, we do not recommend stem cell therapy for KOA.