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      Effectiveness of platelet-rich plasma in the treatment of Achilles tendon disease

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          Abstract

          BACKGROUND

          The effectiveness of Platelet-Rich Plasma (PRP) in the treatment of patients with Achilles tendon rupture (ATR) and Achilles tendinopathy (AT) has been controversial.

          AIM

          To assess PRP injections’ effectiveness in treating ATR and AT.

          METHODS

          A comprehensive review of relevant literature was conducted utilizing multiple databases such as Cochrane Library, PubMed, Web of Science, Chinese Science and Technology Journal, EMBASE, and China Biomedical CD-ROM. The present investigation integrated randomized controlled trials that assessed the effectiveness of platelet-rich plasma injections in managing individuals with Achilles tendon rupture and tendinopathy. The eligibility criteria for the trials encompassed publications that were published within the timeframe of January 1, 1966 to December 2022. The statistical analysis was performed utilizing the Review Manager 5.4.1, the visual analogue scale (VAS), Victorian Institute Ankle Function Scale (VISA-A), and Achilles Tendon Thickness were used to assess outcomes.

          RESULTS

          This meta-analysis included 13 randomized controlled trials, 8 of which were randomized controlled trials of PRP for AT and 5 of which were randomized controlled trials of PRP for ATR. PRP for AT at 6 wk [weighted mean difference (WMD) = 1.92, 95%CI: -0.54 to 4.38, I 2 = 34%], at 3 mo [WMD = 0.20, 95%CI: -2.65 to 3.05, I 2 = 60%], and 6 mo [WMD = 2.75, 95%CI: -2.76 to 8.26, I 2 = 87%) after which there was no significant difference in VISA-A scores between the PRP and control groups. There was no significant difference in VAS scores between the PRP group and the control group after 6 wk [WMD = 6.75, 95%CI: -6.12 to 19.62, I 2 = 69%] and 6 mo [WMD = 10.46, 95%CI: -2.44 to 23.37, I 2 = 69%] of treatment, and at mid-treatment at 3 mo [WMD = 11.30, 95%CI: 7.33 to 15.27, I 2 = 0%] after mid-treatment, the PRP group demonstrated better outcomes than the control group. Post-treatment patient satisfaction [WMD = 1.07, 95%CI: 0.84 to 1.35, I 2 = 0%], Achilles tendon thickness [WMD = 0.34, 95%CI: -0.04 to 0.71, I 2 = 61%] and return to sport [WMD = 1.11, 95%CI: 0.87 to 1.42, I 2 = 0%] were not significantly different between the PRP and control groups. The study did not find any statistically significant distinction between the groups that received PRP treatment and those that did not, regarding the Victorian Institute of Sport Assessment - Achilles scores at 3 mo [WMD = -1.49, 95%CI: -5.24 to 2.25, I 2 = 0%], 6 mo [WMD = -0.24, 95%CI: -3.80 to 3.32, I 2 = 0%], and 12 mo [WMD = -2.02, 95%CI: -5.34 to 1.29, I 2 = 87%] for ATR patients. Additionally, no significant difference was observed between the PRP and the control groups in improving Heel lift height respectively at 6 mo [WMD = -3.96, 95%CI: -8.61 to 0.69, I 2 = 0%] and 12 mo [WMD = -1.66, 95%CI: -11.15 to 7.83, I 2 = 0%] for ATR patients. There was no significant difference in calf circumference between the PRP group and the control group after 6 mo [WMD = 1.01, 95%CI: -0.78 to 2.80, I 2 = 54%] and 12 mo [WMD = -0.55, 95%CI: -2.2 to 1.09, I 2 = 0%] of treatment. There was no significant difference in ankle mobility between the PRP and control groups at 6 mo of treatment [WMD = -0.38, 95%CI: -2.34 to 1.58, I 2 = 82%] and after 12 mo of treatment [WMD = -0.98, 95%CI: -1.41 to -0.56, I 2 = 10%] there was a significant improvement in ankle mobility between the PRP and control groups. There was no significant difference in the rate of return to exercise after treatment [WMD = 1.20, 95%CI: 0.77 to 1.87, I 2 = 0%] and the rate of adverse events [WMD = 0.85, 95%CI: 0.50 to 1.45, I 2 = 0%] between the PRP group and the control group.

          CONCLUSION

          The use of PRP for AT improved the patient’s immediate VAS scores but not VISA-A scores, changes in Achilles tendon thickness, patient satisfaction, or return to sport. Treatment of ATR with PRP injections alone improved long-term ankle mobility but had no significant effect on VISA-A scores, single heel lift height, calf circumference or return to sport. Additional research employing more extensive sampling sizes, more strict experimental methods, and standard methodologies may be necessary to yield more dependable and precise findings.

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          Most cited references53

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          Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial.

          Tendon disorders comprise 30% to 50% of all activity-related injuries; chronic degenerative tendon disorders (tendinopathy) occur frequently and are difficult to treat. Tendon regeneration might be improved by injecting platelet-rich plasma (PRP), an increasingly used treatment for releasing growth factors into the degenerative tendon. To examine whether a PRP injection would improve outcome in chronic midportion Achilles tendinopathy. A stratified, block-randomized, double-blind, placebo-controlled trial at a single center (The Hague Medical Center, Leidschendam, The Netherlands) of 54 randomized patients aged 18 to 70 years with chronic tendinopathy 2 to 7 cm above the Achilles tendon insertion. The trial was conducted between August 28, 2008, and January 29, 2009, with follow-up until July 16, 2009. Eccentric exercises (usual care) with either a PRP injection (PRP group) or saline injection (placebo group). Randomization was stratified by activity level. The validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire, which evaluated pain score and activity level, was completed at baseline and 6, 12, and 24 weeks. The VISA-A score ranged from 0 to 100, with higher scores corresponding with less pain and increased activity. Treatment group effects were evaluated using general linear models on the basis of intention-to-treat. After randomization into the PRP group (n = 27) or placebo group (n = 27), there was complete follow-up of all patients. The mean VISA-A score improved significantly after 24 weeks in the PRP group by 21.7 points (95% confidence interval [CI], 13.0-30.5) and in the placebo group by 20.5 points (95% CI, 11.6-29.4). The increase was not significantly different between both groups (adjusted between-group difference from baseline to 24 weeks, -0.9; 95% CI, -12.4 to 10.6). This CI did not include the predefined relevant difference of 12 points in favor of PRP treatment. Among patients with chronic Achilles tendinopathy who were treated with eccentric exercises, a PRP injection compared with a saline injection did not result in greater improvement in pain and activity. clinicaltrials.gov Identifier: NCT00761423.
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            Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma.

            Previous studies of bioactive molecules in platelet-rich plasma (PRP) have documented growth factor concentrations that promote tissue healing. However, the effects of leukocytes and inflammatory molecules in PRP have not been defined. The hypothesis for this study was that the concentration of growth factors and catabolic cytokines would be dependent on the cellular composition of PRP. Controlled laboratory study. Platelet-rich plasma was made from 11 human volunteers using 2 commercial systems: Arthrex ACP (Autologous Conditioned Plasma) Double Syringe System (PRP-1), which concentrates platelets and minimizes leukocytes, and Biomet GPS III Mini Platelet Concentrate System (PRP-2), which concentrates both platelets and leukocytes. Transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-AB (PDGF-AB), matrix metalloproteinase-9 (MMP-9), and interleukin-1β (IL-1β) were measured with enzyme-linked immunosorbent assay (ELISA). The PRP-1 system consisted of concentrated platelets (1.99×) and diminished leukocytes (0.13×) compared with blood, while PRP-2 contained concentrated platelets (4.69×) and leukocytes (4.26×) compared with blood. Growth factors were significantly increased in PRP-2 compared with PRP-1 (TGF-β1: PRP-2 = 89 ng/mL, PRP-1 = 20 ng/mL, P < .05; PDGF-AB: PRP-2 = 22 ng/mL, PRP-1 = 6.4 ng/mL, P < .05). The PRP-1 system did not have a higher concentration of PDGF-AB compared with whole blood. Catabolic cytokines were significantly increased in PRP-2 compared with PRP-1 (MMP-9: PRP-2 = 222 ng/mL, PRP-1 = 40 ng/mL, P < .05; IL-1β: PRP-2 = 3.67 pg/mL, PRP-1 = 0.31 pg/mL, P < .05). Significant, positive correlations were found between TGF-β1 and platelets (r(2) = .75, P < .001), PDGF-AB and platelets (r(2) = .60, P < .001), MMP-9 and neutrophils (r(2) = .37, P < .001), IL-1β and neutrophils (r(2) = .73, P < .001), and IL-1β and monocytes (r(2) = .75, P < .001). Growth factor and catabolic cytokine concentrations were influenced by the cellular composition of PRP. Platelets increased anabolic signaling and, in contrast, leukocytes increased catabolic signaling molecules. Platelet-rich plasma products should be analyzed for content of platelets and leukocytes as both can influence the biologic effects of PRP. Depending on the clinical application, preparations of PRP should be considered based on their ability to concentrate platelets and leukocytes with sensitivity to pathologic conditions that will benefit most from increased platelet or reduced leukocyte concentration.
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              One-year follow-up of platelet-rich plasma treatment in chronic Achilles tendinopathy: a double-blind randomized placebo-controlled trial.

              Achilles tendinopathy is a common disease among both athletes and in the general population in which the use of platelet-rich plasma has recently been increasing. Good evidence for the use of this autologous product in tendinopathy is limited, and data on longer-term results are lacking. To study the effects of a platelet-rich plasma injection in patients with chronic midportion Achilles tendinopathy at 1-year follow-up. Randomized controlled trial; Level of evidence, 1. Fifty-four patients, aged 18 to 70 years, with chronic tendinopathy 2 to 7 cm proximal to the Achilles tendon insertion were randomized to receive either a blinded injection containing platelet-rich plasma or saline (placebo group) in addition to an eccentric training program. The main outcome was the validated Victorian Institute of Sports Assessment-Achilles score. Patient satisfaction was recorded and ultrasound examination performed at baseline and follow-up. The mean Victorian Institute of Sports Assessment-Achilles score improved in both the platelet-rich plasma group and the placebo group after 1 year. There was no significant difference in increase between both groups (adjusted between-group difference, 5.5; 95% confidence interval, -4.9 to 15.8, P = .292). In both groups, 59% of the patients were satisfied with the received treatment. Ultrasonographic tendon structure improved significantly in both groups but was not significantly different between groups (adjusted between-group difference, 1.2%; 95% confidence interval, -4.1 to 6.6, P = .647). This randomized controlled trial showed no clinical and ultrasonographic superiority of platelet-rich plasma injection over a placebo injection in chronic Achilles tendinopathy at 1 year combined with an eccentric training program.
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                Author and article information

                Contributors
                Journal
                World J Orthop
                WJO
                World Journal of Orthopedics
                Baishideng Publishing Group Inc
                2218-5836
                18 June 2023
                18 June 2023
                : 14
                : 6
                : 485-501
                Affiliations
                Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
                Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
                Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
                Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
                Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
                Department of Physiology, Hunan Normal University School of Medicine, Changsha 410005, Hunan Province, China
                Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
                Department of Anatomy, Hunan Normal University School of Medicine, Changsha 410005, Hunan Province, China. cashwj@ 123456qq.com
                Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
                Author notes

                Author contributions: Huang D, Arthur Vithran DT and Gong HL contribute equally to this study, they share co-first author; Wen J conceived and coordinated the study, designed; Xiao S performed and analyzed the experiments; Tang ZW wrote the paper; Zeng M, Arthur Vithran DT and Gong HL did the data analysis and carried out the data collection; Zeng M revised the paper; and all authors approved the final version of the manuscript.

                Supported by Scientific Research Project of Hunan Education Department, No. 21B0031 and No. 21B0042.

                Corresponding author: Jie Wen, PhD, Associate Professor, Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61 West Jiefang Road, Changsha 410013, Hunan Province, China. cashwj@ 123456qq.com

                Article
                jWJO.v14.i6.pg485
                10.5312/wjo.v14.i6.485
                10292057
                37377997
                0c6ccb58-8a82-40b4-a834-670d9fb5583b
                ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 24 December 2022
                : 28 March 2023
                : 20 April 2023
                Categories
                Meta-Analysis

                platelet-rich plasma,achilles tendon rupture,achilles tendinopathy,systematic evaluation,randomized controlled trial

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