Leukocyte- and platelet-rich fibrin in endoscopic endonasal skull base reconstruction: study protocol for a multicenter prospective, parallel-group, single-blinded randomized controlled non-inferiority trial
BACKGROUND Recent advances in endoscopic endonasal transsphenoidal approaches (EETA) for skull base lesions have resulted in a significant increase in extent and complexity of skull base defects, demanding more elaborate and novel reconstruction techniques to prevent cerebrospinal fluid (CSF) leakage and to improve healing. Currently, commercially available fibrin sealants are often used to reinforce the skull base reconstruction. However, problems have been reported regarding hypersensitivity reactions, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) membranes as an alternative for commercially available fibrin glues in EETA-related skull base reconstruction reinforcement. METHODS/DESIGN This multicenter, prospective randomized controlled trial aims to demonstrate non-inferiority of L-PRF membranes compared to commercially available fibrin sealants in EETA cases (1) without intra-operative CSF-leak as dural or sellar floor closure reinforcement and (2) in EETA cases with intra-operative CSF-leak (or very large defects) in which a classic multilayer reconstruction has been made, as an additional sealing. The trial includes patients undergoing EETA in three different centers in Belgium. Patients are randomized in a 1:1 fashion comparing L-PRF with commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage. Secondary endpoints are identification of risk factors for reconstruction failure, assessment of rhinological symptoms, and interference with postoperative imaging. Additionally, a cost-effectiveness analysis is performed. DISCUSSION With this trial, we will evaluate the safety and efficacy of L-PRF compared to commercially available fibrin sealants. TRIAL REGISTRATION ClinicalTrials.gov NCT03910374. Registered on 10 April 2019.
The Influence of Industry Affiliation on Randomized Controlled Trials of Platelet-Rich Plasma for Knee Osteoarthritis
The American journal of sports medicine. 2023;:3635465221140917
BACKGROUND Industry funding and corporate sponsorship have played a significant role in the advancement of orthopaedic research and technology. However, this relationship raises concerns for how industry association may bias research findings and influence clinical practice. PURPOSE To determine whether industry affiliation plays a role in the outcomes of randomized controlled trials (RCTs) investigating platelet-rich plasma (PRP). STUDY DESIGN Meta-analysis; Level of evidence, 2. METHODS A search of the PubMed, Cochrane, and MEDLINE databases for RCTs published between 2011 and the present comparing PRP versus hyaluronic acid, corticosteroid, or placebo for the treatment of knee osteoarthritis was performed. To determine industry affiliation, the conflict of interest, funding, and disclosure sections of publications were assessed, and all authors were assessed through the American Academy of Orthopaedic Surgeons disclosure database and the Centers for Medicare & Medicaid Services open payments database. Studies were classified as industry affiliated (IA) or non-industry affiliated (NIA). The outcomes of each study were rated as favorable, analogous, or unfavorable according to predefined criteria. RESULTS A total of 37 studies (6 IA and 31 NIA) were available for analysis. Overall, 19 studies (51.4%) reported PRP as favorable compared with other treatment options, while 18 studies (48.6%) showed no significant differences between PRP and other treatment methods. There was no significant difference in qualitative conclusions between the IA and NIA groups, with the IA group having 3 favorable studies and 3 analogous studies and the NIA group having 16 favorable studies and 15 analogous studies (P = .8881). When comparing IA versus NIA studies using 6- and 12-month Western Ontario and McMaster Universities Arthritis Index and International Knee Documentation Committee scores, there were no significant differences in outcomes. CONCLUSION The results of this study demonstrated that qualitative conclusions and outcome scores were found to not be associated with industry affiliation. Although the results of this study suggest that there is no influence of industry involvement on RCTs examining PRP, it is still necessary to carefully evaluate pertinent commercial affiliations when reviewing recommendations from studies before adopting new treatment approaches, such as the use of PRP for knee osteoarthritis.
Two-year outcomes following a randomised platelet transfusion trial in preterm infants
Archives of disease in childhood. Fetal and neonatal edition. 2023
OBJECTIVE Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. DESIGN Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. SETTING 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. PATIENTS 660 infants born at less than 34 weeks' gestation with platelet counts less than 50×10(9)/L. INTERVENTIONS Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×10(9)/L (higher threshold group) or 25×10(9)/L (lower threshold group). MAIN OUTCOMES MEASURES Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. RESULTS Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). CONCLUSIONS Infants randomised to a higher platelet transfusion threshold of 50×10(9)/L compared with 25×10(9)/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. TRIAL REGISTRATION NUMBER ISRCTN87736839.
Preterm infants enrolled in the PlaNeT-2/MATISSE trial, at 43 neonatal intensive care units across UK, Netherlands and Ireland (n= 660).
Higher platelet transfusion threshold (n= 296).
Lower platelet transfusion threshold (n= 305).
The prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR: 1.54, 95% CI: 1.09 to 2.17).
Three doses of PRP therapy may be more effective than one dose of Platelet-Rich Plasma (PRP) in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2023
PURPOSE This study aims to compare the efficacy of a single dose of Platelet-Rich Plasma (PRP) with multiple doses of PRP therapy in the treatment of knee osteoarthritis (KOA). METHODS PubMed, Embase, CINAHL, SCOPUS, Cochrane Library, grey literature and bibliographic references were searched from inception to May 2022. Only randomized controlled trials (RCTs) comparing the effect of single versus multiple doses of PRP for KOA were included. Literature retrieval and data extraction were conducted by three independent reviewers. Inclusion and exclusion criteria were based on type of study, research subjects, intervention, outcome, language and availability of data. Pooled analysis of Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and adverse events were conducted. RESULTS Seven studies (all RCTs) of high methodological quality involving 575 patients were included. Age of patients included in this study ranged from 20 to 80, with a balanced gender ratio. Single dose PRP therapy resulted in significantly better VAS scores compared to triple dose PRP therapy at 12 months (P<0. 0001), with no significant change in VAS scores between double and single dose PRP at 12 months. Regarding adverse events, double dose (P=0.28) and triple dose (P=0.24) therapy had no significant differences in safety from single dose therapy. CONCLUSION While there is a paucity of large high-quality Level I studies, current best evidence suggests that two or three doses of PRP for KOA are as effective as one dose of PRP at providing pain relief and improvement in function up to 1 year following administration.
Clinical evaluation of autologous platelet-rich plasma therapy for intrauterine adhesions: a systematic review and meta-analysis
Frontiers in endocrinology. 2023;14:1183209
OBJECTIVE This meta-analysis aims to evaluate the efficacy and safety of autologous platelet-rich plasma (PRP) administration in reducing adhesion recurrence and improving pregnancy outcomes in patients with intrauterine adhesion (IUA). METHODS We conducted a comprehensive search of Pubmed, Embase, the Cochrane Library, Web of Science, Scopus, and China National Knowledge Internet (CNKI) from inception to February 10, 2023, without any language or regional restrictions. We used random-effects models to assess odds ratios (OR) and weight mean differences (WMD) with 95% confidence intervals (CI). RESULTS Our meta-analysis included a total of 730 patients from 10 clinical studies (6 RCTs and 4 non-RCTs). The results showed that PRP administration significantly increased endometrial thickness (WMD = 0.79, 95% CI: 0.40-1.19; P < 0.001; I(2) = 0.0%), menstrual volume (WMD = 2.96, 95% CI = 2.30-3.61; P < 0.001; I(2) = 0.0%), and days of menstruation (WMD = 1.13, 95% CI = 0.86-1.41; P < 0.001; I(2) = 0.0%). Additionally, the clinical pregnancy rate was also improved (OR = 1.82, 95% CI: 1.19-2.78; P = 0.006; I(2) = 0.0%). However, there was insufficient evidence to reach a conclusion regarding the effects of PRP on the recurrence rate of moderate to severe IUA, changes in AFS scores, miscarriage rate, and live birth rate. CONCLUSIONS Our analysis confirms that autologous PRP is an effective treatment for IUA. However, the limited sample size suggests that the results should be interpreted with caution. Therefore, larger and well-designed studies are necessary in the future to confirm these findings and explore the optimal PRP dosing regimens further. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023391115.
Impact of autologous platelet concentrates on wound area reduction: A meta-analysis of randomized controlled trials
International wound journal. 2023
This meta-analysis aimed to evaluate the impact of autologous platelet concentrates (APCs) on wound area reduction based on randomized controlled trials (RCTs). A comprehensive search was conducted in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Web of Science, and the Cochrane Library to identify relevant literature. The primary outcome measure was the percentage of wound area reduction. Secondary outcome measures included wound healing time and the incidence of infection. A total of 14 studies were included in the meta-analysis. The results showed that the percentage of wound area reduction was significantly greater in the APCs group compared to conventional treatments (standardized mean difference [SMD] 1.98, 95% confidence interval [CI]: 1.27-2.68, p < 0.001). Subgroup analysis revealed that the percentage of wound area reduction varied based on wound location, follow-up duration, and type of APCs used. The healing time and incidence of infection presented no significant difference between the two groups. The findings suggest that APCs can effectively reduce wound areas when compared to conventional treatments, without increasing the risk of infection. In addition, the effectiveness of APCs in wound area reduction may vary depending on factors such as wound location, type of APCs used, and follow-up duration.
Comparative Investigation of Anti-Inflammatory Effect of Platelet-Rich Fibrin after Mandibular Wisdom Tooth Surgery: A Randomized Controlled Study
Journal of clinical medicine. 2023;12(13)
This study evaluated the anti-inflammatory effect of platelet-rich fibrin (PRF) applied to the extraction socket after impacted mandibular third molar surgery with subjective and objective parameters. Forty-eight patients with impacted wisdom teeth in bilateral and similar positions were included in the study. The control group was formed with the standard surgery and the PRF group was formed with local PRF application in addition to standard procedure (n = 96). The anti-inflammatory activity of PRF on postoperative 2nd and 7th days was evaluated subjectively by clinical parameters and objectively by biochemical parameters. Postoperative 2nd- and 7th-day follow-up data of pain, edema, and trismus in the PRF group were found to be statistically significantly lower. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were found to be statistically significantly lower in the PRF group than the control in the postoperative 2nd-day follow-up period (p < 0.001). There was no statistically significant difference in interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) parameters when the PRF group and the control group were compared in both follow-up periods (p > 0.05). The study has demonstrated the effectiveness of locally applied PRF after ITM surgery via clinical parameters and objective data. The quantitative analysis of CRP and ERS can be an effective parameter in determining the amount of inflammation after ITM surgery.
Autologous Concentrated Growth Factor Increases Skin Thickness and Area during Tissue Expansion: A Randomized Clinical Trial
Plastic and reconstructive surgery. 2023;152(2):281e-292e
BACKGROUND Mechanical stretching of the skin (ie, tissue expansion) could generate additional skin, but it is limited by the intrinsic growth capacity. The authors conducted a study of autologous concentrated growth factor (CGF) to promote skin regeneration by increasing skin thickness and area during tissue expansion. METHODS A single-center randomized controlled trial was conducted from 2016 to 2019. Participants undergoing skin expansion received either CGF or saline by means of intradermal injection on the expanded skin (0.02 mL/cm 2 ), for a total of three treatments at 4-week intervals. The primary endpoint was the expanded skin thickness at 12 weeks, which was measured by ultrasound. The secondary endpoints included skin thickness at 4 and 8 weeks and surface area, expansion index, and skin texture score of the expanded skin at 12 weeks. Safety assessments, for infection symptoms and nodule formation, were assessed at 24 weeks. RESULTS In total, 26 patients were enrolled and assigned to the CGF or control group. Compared with the control group, the CGF group had significantly increased skin thickness at 8 (control, 1.1 ± 0.1 mm; CGF, 1.4 ± 0.1 mm; -0.6 to 0.0 mm; P = 0.047) and 12 weeks (control, 1.0 ± 0.1 mm; CGF, 1.3 ± 0.1 mm; -0.6 to 0.0 mm; P = 0.047). Compared with the baseline thickness (control, 1.6 ± 0.1 mm; CGF, 1.5 ± 0.1 mm; -0.3 to 0.5 mm; P = 0.987), skin thickness was sustained in the CGF group at 8 weeks after treatment (-0.1 to 0.3 mm; P = 0.711) but decreased in the control group (0.3 to 0.7 mm; P < 0.001). At 12 weeks, the CGF group showed greater increases in surface area (control, 77.7 ± 18.5 cm 2 ; CGF, 135.0 ± 15.7 cm 2 ; 7.2 cm 2 to 107.4 cm 2 ; P = 0.027) and expansion index (control, 0.9 ± 0.1; CGF, 1.4 ± 0.2; 0.0 to 0.8; P = 0.030) than the control group. In addition, CGF-treated skin showed an improvement in texture [CGF: grade 3, n = 2 (15.8%), grade 2, n = 4 (30.7%); control: grade 3, n = 0 (0.0%), grade 2, n = 3 (23.0%)]. No severe adverse events occurred. CONCLUSION CGF treatment increases skin thickness and area during tissue expansion, and represents a safe and effective strategy for managing skin expansion. CLINICAL RELEVANCE STATEMENT The findings of this study indicate that it is practically feasible to improve skin regeneration by applying autologous platelet concentrate therapy for skin expansion management. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, II.
Platelet-rich Plasma for the Treatment of Erectile Dysfunction: A Prospective, Randomized, Double-blind, Placebo-controlled Clinical Trial
The Journal of urology. 2023;:101097ju0000000000003481
PURPOSE We assessed the safety and efficacy of 2 injections of platelet-rich plasma for treating mild to moderate erectile dysfunction by conducting a prospective, randomized, double-blind, placebo-controlled clinical trial. MATERIALS AND METHODS Men with mild to moderate erectile dysfunction (International Index of Erectile Function scores 11-25) were randomized to receive either 2 injections of platelet-rich plasma or placebo separated by 1 month. Primary outcome was percentage of men meeting minimum clinically important difference at 1 month after the second injection. Secondary outcomes were change in International Index of Erectile Function at 1, 3, and 6 months, and changes in penile vascular parameters and adverse events at 6 months. RESULTS We randomized 61 men: 28 into platelet-rich plasma and 33 into placebo. There was no difference between groups in percentage of men meeting minimum clinically important difference at 1 month: 14 (58.3%) in platelet-rich plasma vs 15 (53.6%) in placebo (P = .730). Mean International Index of Erectile Function-Erectile Function domain changed from 17.4 (95% CI 15.8-19.0) to 21 (17.9-24.0) at 1 month in men receiving platelet-rich plasma, vs 18.6 (17.3-19.8) to 21.6 (19.1-24.1) in the placebo group; however, there was no significant difference between groups (P = .756). There were no major adverse events and only 1 minor adverse event in each group. There were no changes in penile Doppler parameters from baseline to 6 months. CONCLUSIONS The results of our prospective, double-blind, randomized, placebo-controlled clinical trial suggest that 2 injections of intracavernosal platelet-rich plasma separated by 1 month in men with mild to moderate erectile dysfunction is safe, but we found no difference in efficacy between platelet-rich plasma and placebo.
Effects of Platelet-Rich Plasma in Tear Size Reduction in Partial-Thickness Tear of the Supraspinatus Tendon Compared to Corticosteroids Injection
Sports medicine - open. 2023;9(1):11
OBJECTIVES Corticosteroid (CS) injection is commonly used in partial-thickness rotator cuff tears to decrease pain. However, this could result in unwanted side effects, such as tendon rupture. Alternatively, platelet-rich plasma (PRP) injection is frequently used to treat tendinopathies because it enhances healing. This study aimed to compare the differences in tear size and functional scores between intralesional PRP and subacromial CS injections. METHODS Patients with symptomatic partial-thickness tears of the supraspinatus tendon who underwent conservative treatment for ≥ 3 months were enrolled. All patients underwent magnetic resonance imaging (MRI) to confirm the diagnosis. Fourteen and 15 patients were randomized to receive intralesional PRP and subacromial CS injections, respectively. Tears were measured in the coronal and sagittal planes. The patients underwent another MRI 6 months after the injection. Tear size was compared between the two MRI results. The American Shoulder and Elbow Surgeons Shoulder score (ASES) and Constant-Murley score (CMS) were also obtained. RESULTS The baseline data were similar between the groups. In the coronal plane, PRP and CS showed tear size reductions of 3.39 mm (P = 0.003) and 1.10 mm (P = 0.18), respectively. In the sagittal plane, PRP and CS showed tear size reductions of 2.97 mm (P = 0.001) and 0.76 mm (P = 0.29), respectively. Functional scores improved 6 months after injection in both groups, but PRP showed better functional scores than CS (P = 0.002 for ASES, P = 0.02 for CS). CONCLUSION Intralesional PRP injection can reduce the tear size in partial-thickness tears of the supraspinatus tendon. Subacromial steroid injection did not significantly affect the tear size. While CS improved functional scores compared with baseline, PRP resulted in better improvement 6 months post-injection. Trial registration Thai Clinical Trials Registry, TCTR20210428004. Registered 28 April 2021-retrospectively registered, TCTR20210428004 .