Regenerative therapies for upper limb functional recovery after stroke: study protocol of a randomized clinical trial.

CORR Synthesis: What Is the Role of Platelet-rich Plasma Injection in the Treatment of Tendon Disorders?

To compare the effectiveness, after 3 months, of a single injection of platelet-rich plasma (PRP), glucocorticoid (GC), or saline in reducing pain in lateral epicondylitis. Randomized, controlled, 3-group trial (RCT). Patients and outcome assessors were blinded to intervention group. Sample size was calculated to show a clinically important difference in patient-reported pain intensity at 12 months with 17 patients per group. Tertiary study at the Rheumatology Unit at the Diagnostic Centre of the Region Hospital Silkeborg, Denmark. Patients were referred to the Rheumatology Unit by general practitioners or other rheumatology or orthopedic departments. Inclusion criteria (verified by 1 physician) were lateral epicondylitis symptoms for ≥3 months (pain on the lateral side of the elbow and at the lateral epicondyle on palpation and during resisted dorsiflexion of the wrist), an ultrasound (US) color Doppler flow of ≥ grade 2 (range, 0-4). Exclusion criteria were age <18 years, treatment with GC injection within 3 months, inflammatory diseases, and conditions causing chronic pain. The 60 included patients had a mean age of 45 years, 52% were women, 58% had ≥1 previous injection, and 58% used analgesics. The patients were randomized to a single US-guided injection of PRP, GC, or saline, administered by the 1 physician who had made the diagnosis. All patients were blindfolded during blood collection and injection. They all received an injection of 10 to 15 mL of lidocaine into the peritendon before the procedure. The PRP injection was of approximately 3.5 mL of autologous platelets (collected and centrifuged for 15 minutes from 27 mL of whole blood) buffered with 8.4% sodium bicarbonate, and immediately peppered into the common tendon origin. The GC injection (1 mL triamcinolon, 40 mg/mL + 2 mL lidocaine, 10 mg/mL) was delivered through 1 site. The saline injection (3 mL saline, 0.9%) was peppered in the same manner as the PRP injection. After treatment, the patients were asked to use the arm minimally for 3 days and then gradually to return to normal use. The pain intensity scale of the Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaire was the main outcome measure (least to most pain = 0-50 points). The secondary end points included changes in functional disability using the functional section of the PRTEE, (least to most disability = 0-100 points), US changes in color Doppler signal and tendon thickness, and adverse events, which included pain after the injection. After 3 months, if the patient was unsatisfied with the result of treatment, he or she could be released from the study to seek other management. Ten, 11, and 13 patients (58% of the total) dropped out of the PRP, GC, and saline groups, respectively, at the 3-month follow-up, thus evaluations were only made at 1 and 3 months. At 1 month, the mean reduction in pain for the PRP group versus the saline group was 1.2 (95% confidence interval [CI], -5.0 to 7.3); for the GC group versus the saline group was -8.1 (95% CI, -14.3 to -1.9); and for the GC group versus the PRP group, -9.3 (95% CI, -15.4 to -3.2). At 3 months, the mean reduction in pain for no group was significantly greater than for others (PRP vs the saline group, -2.7; 95% CI, -8.8 to 3.5; GC vs the saline group, -3.8; 95% CI, -9.9 to 2.4; GC vs the PRP group, -1.1; 95% CI, -7.2 to 5.0). The PRTEE disability scores at 1 month also favored the GC group versus saline, but no differences were found between any groups at 3 months. The improvement in Doppler grades at 3 months favored the GC group versus the saline group and the PRP group (P<0.0001 for both comparisons). Mean reduction in tendon thickness was greater for the GC group versus the saline group (P<0.0001) and the PRP group (P=0.002). PRP injections were found to be more painful than GC and saline injections. No adverse events leading to hospitalization, and no reports of infections resulting from the injections, occurred. The dropout rate of 58% at 3 months showed that none of PRP, glucocorticoid, or saline injections adequately reduced the pain and disability of lateral epicondylitis.

BackgroundThere is no consensus on the frequency and timing of platelet-rich plasma (PRP) injection in tendon healing. We aimed to evaluate the effectiveness of single versus multiple PRP injections in the healing of patellar tendon defects in the experimental model, through histological and biomechanical investigation.MethodsForty-four male skeletally mature Dutch rabbits were randomly divided into the five study groups ( A, B,C, D,E). After creating a longitudinal acute patellar tendon defect on both knees (One-third the width of the patella tendon), the right legs of the rabbits were used as the intervention group and the left legs as the control groups. Animals in groups A, B, and C were euthanized on days 7, 14, and 28, respectively, after the first PRP injection. Animals in group D received the second PRP injection on day 10 and was euthanized on day 14. Animals in group D received the second and third PRP injections on days 10 and 20, respectively, and were euthanized on day 28. The outcomes were evaluated histologically (modification of Movin’s Grading) and biomechanically.ResultsThe inflammatory condition was exaggerated in groups D and E. Load at failure was higher in the non-injected side of groups D and E, while there was no significant difference between the right and left legs of the three groups A, B and C. In other word, groups with a single PRP injection were more resistant to the increasing load compared to the groups with multiple PRP injections.ConclusionsPRP improves tendon healing if injected early after injury, while its injection after the initial phase of injury hampers tendon healing. In addition, a single PRP injection seems to be more effective than multiple PRP injection. Therefore, in cases where PRP injection is indicated for tendon repair, such as acute tendon injury, we recommend using a single PRP injection during tendon repair surgery.

Regarding “Intra-Articular Mesenchymal Stromal Cell Injections Are No Different From Placebo in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials”

Platelet-rich plasma (PRP) or corticosteroid injections may be used to conservatively treat mild-to-moderate carpal tunnel syndrome (CTS). We evaluated the cost-effectiveness of PRP injections versus corticosteroid injections for the treatment of mild-to-moderate CTS. Markov modeling was used to analyze the base-case 45-year-old patient with mild-to-moderate CTS, unresponsive to conservative treatments, never previously treated with an injection or surgery, treated with a single injection of PRP, or methylprednisolone/triamcinolone 40 mg/mL. Transition probabilities were derived from level-I/II studies, utility values from the Tufts University Cost-Effectiveness Analysis Registry reported using visual analog scale (VAS), Boston Carpal Tunnel Questionnaire Symptom severity (BCTQ-S), and Boston Carpal Tunnel Questionnaire Functional status (BCTQ-F), and costs from Medicare, published studies, and industry. Analyses were performed from healthcare/societal perspectives. Outcomes were incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB). Willingness-to-pay thresholds were $50 000 and $100 000. Deterministic/probabilistic sensitivity analyses were performed. From a healthcare perspective, compared to PRP injections, the ICER for corticosteroid injections measured by VAS: -$13.52/quality-adjusted-life-years (QALY), BCTQ-S: -$11.88/QALY, and BCTQ-F: -$16.04/QALY. PRP versus corticosteroid injections provided a NMB measured by VAS: $428 941.12 versus $375 788.21, BCTQ-S: $417 115.09 versus $356 614.18, and BCTQ-F: $421 706.44 versus $376 908.45. From a societal perspective, compared to PRP injections, the ICER for corticosteroid injections measured by VAS: -$1024.40/QALY, BCTQ-S: -$899.95/QALY, and BCTQ-F: -$1215.51/QALY. PRP versus corticosteroid injections provided a NMB measured by VAS: $428 171.63 versus $373 944.39, BCTQ-S: $416 345.61 versus $354 770.36, and BCTQ-F: $420 936.95 versus $375 064.63. PRP injections were more cost-effective than methylprednisolone/triamcinolone injections from healthcare and societal perspectives for mild-to-moderate CTS.

Background: Skeletal muscle injuries are the most common sports-related injury and a major concern in sports medicine. The effect of platelet-rich plasma (PRP) injections on muscle healing is still poorly understood, and current data are inconclusive. Purpose: To evaluate the effects of an ultrasound-guided intramuscular PRP injection, administered 24 hours after injury, and/or posttraumatic daily exercise training for 2 weeks on skeletal muscle healing in a recently established rat model of skeletal muscle injury that highly mimics the muscle trauma seen in human athletes. Study Design: Controlled laboratory study. Methods: A total of 40 rats were assigned to 5 groups. Injured rats (medial gastrocnemius injury) received a single PRP injection (PRP group), daily exercise training (Exer group), or a combination of a single PRP injection and daily exercise training (PRP-Exer group). Untreated and intramuscular saline–injected animals were used as controls. Muscle force was determined 2 weeks after muscle injury, and muscles were harvested and evaluated by means of histological assessment and immunofluorescence microscopy. Results: Both PRP (exhibiting 4.8-fold higher platelet concentration than whole blood) and exercise training improved muscle strength (maximum tetanus force, TetF) in approximately 18%, 20%, and 30% of rats in the PRP, PRP-Exer, and Exer groups, respectively. Specific markers of muscle regeneration (developmental myosin heavy chain, dMHC) and scar formation (collagen I) demonstrated the beneficial effect of the tested therapies in accelerating the muscle healing process in rats. PRP and exercise treatments stimulated the growth of newly formed regenerating muscle fibers (1.5-, 2-, and 2.5-fold increase in myofiber cross-sectional area in PRP, PRP-Exer, and Exer groups, respectively) and reduced scar formation in injured skeletal muscle (20%, 34%, and 41% of reduction in PRP, PRP-Exer, and Exer groups, respectively). Exercise-treated muscles (PRP-Exer and Exer groups) had significantly reduced percentage of dMHC-positive regenerating fibers (35% and 47% decrease in dMHC expression, respectively), indicating that exercise therapies accelerated the muscle healing process witnessed by the more rapid replacement of the embryonic-developmental myosin isoform by mature muscle myosin isoforms. Conclusion: Intramuscular PRP injection and, especially, treadmill exercise improve histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries in athletes. However, there was not a synergistic effect when both treatments were combined, suggesting that PRP does not add any beneficial effect to exercise-based therapy in the treatment of injured skeletal muscle. Clinical Relevance: This study demonstrates the efficacy of an early active rehabilitation protocol or single intramuscular PRP injection on muscle recovery. The data also reveal that the outcome of the early active rehabilitation is adversely affected by the PRP injection when the two therapies are combined, and this could explain why PRP therapies have failed in randomized clinical trials where the athletes have adhered to postinjection rehabilitation protocols based on the principle of early, active mobilization.

Poor ovarian response (POR) is a challenge in reproductive medicine, often leading to suboptimal outcomes in IVF/ICSI cycles. Autologous platelet-rich plasma (PRP) injections have emerged as a potential therapy to enhance ovarian function. This study aims to compare the efficacy of single versus double PRP ovarian injections in improving ovarian reserve, response to stimulation, and IVF/ICSI outcomes in women with POR. This before-and-after study was conducted at the Reproductive Center of the Sixth Affiliated Hospital of Sun Yat-sen University. Seventy-one women diagnosed with POR (POSEIDON group 3 or 4), characterized by anti-Müllerian hormone (AMH) levels below 1.2 ng/mL and fewer than five antral follicles, who had completed at least one IVF/ICSI cycle before and after PRP treatment were included. Participants received intraovarian injections of autologous PRP (2–2.5 mL per ovary) via transvaginal ultrasound guidance, either once or twice as determined clinically. We evaluated changes in ovarian reserve markers (AMH and antral follicle count [AFC]) and IVF/ICSI outcomes, such as the number of retrieved oocytes and quality embryos. Comparative analysis between single and double injections utilized the difference (Δ) between post- and pre-treatment values. PRP treatment resulted in significant improvements in AMH levels (from 0.33 ± 0.24 ng/mL to 0.43 ± 0.29 ng/mL, p = 0.005) and AFC (from 2.62 ± 1.09 to 3.80 ± 1.95, p < 0.001). Both single and double PRP injections significantly increased the number of retrieved oocytes (2.32 ± 1.80 vs. 3.59 ± 2.00, p < 0.001) and high-quality embryos (0.73 ± 1.08 vs. 1.28 ± 1.21, p = 0.002). Subgroup analysis indicated no significant differences in ΔAMH, ΔAFC, or IVF/ICSI outcomes between single and double treatments. However, the increase in AMH levels reached statistical significance only after double PRP injection, not after single injection. Autologous PRP ovarian injections significantly improve ovarian reserve parameters, the number of oocytes retrieved and high-quality embryos in women with POR. A single PRP injection is as effective as double injections, suggesting a more cost-effective and simpler protocol for clinical application.

Background: Gluteus medius/minimus tendinopathy is a common cause of lateral hip pain or greater trochanteric pain syndrome. Hypothesis: There would be no difference in the modified Harris Hip Score (mHHS) between a single platelet-rich plasma (PRP) injection compared with a corticosteroid injection in the treatment of gluteal tendinopathy. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: There were 228 consecutive patients referred with gluteal tendinopathy who were screened to enroll 80 participants; 148 were excluded (refusal: n = 42; previous surgery or sciatica: n = 50; osteoarthritis, n = 17; full-thickness tendon tear, n = 17; other: n = 22). Participants were randomized (1:1) to receive either a blinded glucocorticoid or PRP injection intratendinously under ultrasound guidance. A pain and functional assessment was performed using the mHHS questionnaire at 0, 2, 6, and 12 weeks and the patient acceptable symptom state (PASS) and minimal clinically important difference (MCID) at 12 weeks. Results: Participants had a mean age of 60 years, a ratio of female to male of 9:1, and mean duration of symptoms of >14 months. Pain and function measured by the mean mHHS showed no difference at 2 weeks (corticosteroid: 66.95 ± 15.14 vs PRP: 65.23 ± 11.60) or 6 weeks (corticosteroid: 69.51 ± 14.78 vs PRP: 68.79 ± 13.33). The mean mHHS was significantly improved at 12 weeks in the PRP group (74.05 ± 13.92) compared with the corticosteroid group (67.13 ± 16.04) (P = .048). The proportion of participants who achieved an outcome score of ≥74 at 12 weeks was 17 of 37 (45.9%) in the corticosteroid group and 25 of 39 (64.1%) in the PRP group. The proportion of participants who achieved the MCID of more than 8 points at 12 weeks was 21 of 37 (56.7%) in the corticosteroid group and 32 of 39 (82%) in the PRP group (P = .016). Conclusion: Patients with chronic gluteal tendinopathy >4 months, diagnosed with both clinical and radiological examinations, achieved greater clinical improvement at 12 weeks when treated with a single PRP injection than those treated with a single corticosteroid injection. Registration: ACTRN12613000677707 (Australian New Zealand Clinical Trials Registry).

Background: Lateral epicondylitis is seen more commonly in non-athletes than athletes. Non-operative methods are the mainstay of treatment being effective in more than 95% of cases. Platelet rich plasma (PRP) has shown promising results in many studies as compared to steroid injection & other modes of conservative management. Hence, this study was done to compare the efficacy of PRP and triamcinolone injection in tennis elbow. Material &Methods: This randomized study was conducted at our center, for a period of two years from Aug 2015 to Sep 2017 on 60 consenting patients diagnosed as lateral epicondylitis. Patients were randomized into Group –1 (30 patients) receiving 2 ml of PRP injection and group –2 (30 patients) receiving 2 ml of Triamcinolone injection. Post therapy assessment was done using with Oxford elbow score. Results: Average age at presentation was 31.11 year (range 20 to 40). Mean Oxford Elbow Score for both PRP injection group and in triamcinolone group at 6 weeks, 3 month and 6 month improved from pre injection score with p-value less than 0.001, thus stating that both PRP and triamcinolone injections works very well. On comparing PRP with triamcinolone, we found that PRP was slight better than the triamcinolone injection and was better maintained in long term in PRP group. Conclusion: Lateral epicondylitis or Tennis elbow is a painful debilitating condition of elbow, which creates disturbance in functional activities. A single injection of PRP at the site of the elbow pain resulted in relief of pain in patients with longer duration as compared to local steroids to other conservative treatments.

Platelet-rich plasma vs. corticosteroid injections for the treatment of recalcitrant lateral epicondylitis: a cost-effectiveness Markov decision analysis.

Average bone healing times of common fractures in adults ranges from 3 to 12weeks and is location dependent. Platelet Rich Plasma (PRP) stimulates natural healing process through growth factors contained in platelets and has been employed for the same in delayed unions. All patients > 18years and documented delayed union were included in the study. Patients were followed up monthly after each Leucocyte-rich PRP (LR-PRP) injection and a decision for repeat PRP injection was taken on basis of visible impression in radiograph after previous injection. Total 36 patients were studied in which 5 patients were lost to follow-up. Union was achieved in 28/31 (90.3%). 20 (71.4%) patients required only single PRP injections. 4 (14.3%) patients required 2 PRP injections, 3 (10.7%) patients required 3 PRP injections and 1 (3.6%) patient required 4 PRP injection. There was no significant correlation of number of PRPs to time from 1st PRP-union or time from last PPR- union. Single/multiple dose percutaneously administered LR-PRP can be used as a fruitful alternative to catalyze union in patients having delayed union irrespective of site of injury.

Objectives: Plantar fasciitis (PF) is not an uncommon cause of heel pain whose treatment is not yet standardized. Although platelet-rich plasma (PRP) and corticosteroid (CS) injections are the two commonly used modalities, yet not much importance has been given to the comparison of their roles in sustained functional improvement. We aimed to study the effect of PRP and CS injections in PF and compare their effectiveness with respect to pain relief and improvement of functional and patient satisfaction. Methods: Seventy-three cases were randomized into two groups: 39 patients (Group A) received a single injection of autologous PRP and 34 in Group B received a single injection of CS (40 mg of methylprednisolone) by the random selection. A structured home exercise program was demonstrated to both the groups, as baseline management. The effectiveness was assessed and compared in preinjection and postinjection at 3- and 6-months follow-up. Visual Analog Scale (VAS), Roles and Maudsley (RM), and Foot Function Index (FFI) scoring systems were used as outcome measures. Results: CSs had an early effect, reducing pain to a moderate level in 82.4% of patients compared to PRP (P = 0.000). However, the effect was not sustainable over a long period. On the other hand, PRP was found to have better pain relief over 3 months and 6 months follow-up with a mean VAS score of 2.0 ± 0.9 and 0.8 ± 0.8, respectively (P = 0.000). There was a significant improvement of FFI and RM score as well as at 6 months follow-up (P = 0.000). Conclusion: Injection of CS had an early effect, which is not sustainable, whereas PRP was found to have a prolonged impact on pain relief and better patient satisfaction with treatment outcomes. Therefore, PRP can be advised for sustained and prolonged improvement in PF.

Calcaneocuboid syndrome is a common yet underdiagnosed condition. It has been noted as a FADI scores complication of plantar flexion and inversion ankle injuries which are one of the most common athletic injuries. It is common in ballet dancers and athletes. Presentation of this condition is lateral foot pain which is exaggerated on inversion. To determine the outcomes of a single platelet-rich plasma (PRP) injection combined with rehabilitation for calcaneocuboid syndrome. Six patients (3 non-sportsperson, 2 footballers, 1 basketball player) who presented with complaints of chronic lateral ankle pain were evaluated clinically and radiologically and identified to have calcaneocuboid syndrome. Ultrasound-guided PRP injection was done. Preinjection and one and three months postinjection visual analog scale (VAS) and foot and ankle disability index (FADI) scores were noted. They also underwent a rehabilitation program. One patient was lost to follow-up after 1 month. Five patients showed significant improvement in VAS and FADI at 3 months. The use of PRP has shown proven benefits in the literature. Our study combined PRP along with a rehabilitation program for the subjects. Single PRP injection along with a rehabilitation program has shown to be effective in the management of calcaneocuboid syndrome. Rao V, Anand K, Jaganathan P, et al. Effectiveness of Single Platelet-rich Plasma Injection and Rehabilitation in the Management of Calcaneocuboid Syndrome: A Case Series. J Foot Ankle Surg (Asia Pacific) 2021;8(1):16–18.

A Single Injection of Platelet-rich Plasma Injection for the Treatment of Stress Urinary Incontinence in Females: A Randomized Placebo-controlled Trial

BackgroundCarpal tunnel syndrome is the most common peripheral entrapment neuropathy, for which conservative treatments are the first measures taken. However, these measures are not usually sufficient. Recently major attention has been drawn to platelet-rich plasma for its possible effects on axon regeneration and neurological recovery. Although few studies have evaluated the effects of this treatment in carpal tunnel syndrome, further investigation is required to reach concrete conclusion.MethodsIn this randomized controlled trial, women referring to the physical medicine and rehabilitation clinic at Shahid Modarres Hospital during 2016 with a diagnosis of mild and moderate idiopathic carpal tunnel syndrome were chosen. They were randomly assigned to two groups: (i) a control group using only a wrist splint, and (ii) a platelet-rich plasma group that received wrist splints along with a single local injection of platelet-rich plasma. The outcome measures were assessed via Visual Analogue Scale, the Boston Carpal Tunnel Syndrome Questionnaire and electrophysiological findings including the peak latency of sensory nerve action potential and the onset latency of the compound muscle action potential.ResultsA total of 41 women were included (20 wrists as control group) and (21 wrists as platelet-rich plasma group). Before treatment there were no significant differences between the two groups except for the median peak latency of sensory nerve action potential which was significantly higher among the patients in the platelet-rich plasma group (p = 0.03). All the measured variables significantly decreased in both groups after 10 weeks of treatment except for the median onset latency of the compound muscle action potential (p = 0.472). Finally, the changes in neither of the evaluated outcome measures were found to significantly differ between the two groups, even when the analyses were adjusted for age of the patients.ConclusionThe findings of this study showed that in a relatively short period of time after treatment, a single injection of platelet-rich plasma in the wrist does not significantly add to the effects of conservative treatment with wrist splints, in regards to the women pain and symptom severity, functional status and electrophysiological parameters.Trial registrationThe trial has been retrospectively registered with an ID: IRCT2017041513442N13 (Date of registration: 2017–06-19).