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  • Comparison study between plasma rich in growth factors and platelet-rich plasma for osteoconduction in rat calvaria

    Abstract

    Objective: Plasma rich in growth factors (PRGF) and platelet-rich plasma (PRP) can be rapidly obtained from patient blood. They are a new and potentially useful adjunct in oral and maxillofacial bone repair or regenerative surgery. The aim of this study was to compare the possibility of new bone formation using PRGF and PRP.

    Methods: The osteogenic potential with transplantation of PRGF or PRP onto rat calvaria was evaluated by histologic examination and microCT. PRGF or PRP was prepared by centrifugation of rat whole blood (WB). First, the cells in the blood product were counted; there were no leukocytes in PRGF, and PRP included leukocytes. PRGF contained higher levels of TGF-β1 and PDGF-BB than PRP. Furthermore, PRGF or PRP was transplanted onto calvarial bone of rats.

    Results: MicroCT showed that PRGF promoted an increase in bone volume when compared to PRP. Histological observation demonstrated that the PRGF group showed newly formed bone in a wide range. In addition, the PRP group showed numerous inflammatory cells compared to the PRGF group in HE-stained specimens. This suggests that PRP might delay bone regeneration due to the inflammatory response.

    Conclusions: PRGF has more availability for bone regeneration than PRP, and PRGF may be useful in bone regeneration treatment.

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  • Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip

    Abstract

    Objective: To assess the safety and symptomatic changes of IA injections of platelet-rich plasma (PRP) in patients with OA of the hip.

    Methods: Forty patients affected by monolateral severe hip OA were included in the study. Each joint received three IA injections of PRP, which were administered once a week. The primary end point was meaningful pain relief, which was described as a reduction in pain intensity of at least 30% from baseline levels as evaluated by the WOMAC subscale at 6-months post-treatment. The visual analogue scale (VAS) and Harris hip score subscale for pain were used to verify the results. Secondary end points included changes in the level of disability of at least 30% and the percentage of positive responders, i.e. the number of patients that achieved a >30% reduction in pain and disability.

    Results: Statistically significant reductions in VAS, WOMAC and Harris hip subscores for pain and function were reported at 7 weeks and 6 months (P < 0.05). Twenty-three (57.5%) patients reported a clinically relevant reduction of pain (45%, range 30-71%) as assessed by the WOMAC subscale. Sixteen (40%) of these patients were classified as excellent responders who showed an early pain reduction at 6-7 weeks, which was sustained at 6 months, and a parallel reduction of disability. Side effects were negligible and were limited to a sensation of heaviness in the injection site.

    Conclusion: This preliminary non-controlled prospective study supported the safety, tolerability and efficacy of PRP injections for pain relief and improved function in a limited number of patients with OA of the hip.

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  • The contribution of leucocytes to the antimicrobial activity of platelet-rich plasma preparations: a systematic review

    Abstract

    The infection of a wound is one of the major contributors to delays in healing and tissue regeneration. As multi-drug resistance to antibiotics is becoming a serious threat, research in this field has focused on finding new agents and strategies to fight infection and additionally to reduce healing times. The topical use of autologous Platelet Rich Plasma (PRP) as a biological accelerator of the healing process, has been safely used as a form of treatment for wounds since the 1990s. Although the presence or absence of leucocytes in PRP preparation was previously neglected, in the last decade more attention has been paid to their role and several studies have been conducted to explore both their immuno-metabolic effects and their antimicrobial properties. In this review, we aim to summarise the literature on the contribution of leucocytes included in PRP preparations in terms of their antimicrobial properties. This should help to inform clinical practice and additional research in this promising field.

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  • Ultrasound-guided perineural injection with platelet-rich plasma improved the neurophysiological parameters of carpal tunnel syndrome: A case report

    Abstract

    Carpal tunnel syndrome (CTS) is a common and sometimes challenging condition, which causes pain; paresthesia; tingling of the thumb, index and long fingers; and even thenar weakness in the hands. The effectiveness of corticosteroid injections seems to be transient, and there is a lack of information around long-term effects in previous studies. In recent years, platelet-rich plasma (PRP) has proven to bean alternative as it encourages tissue regeneration. We hereby describe a patient with CTS showing significant improvements in electrophysiological parameters after receiving PRP injections. The results revealed significant improvements in the distal motor and sensory latencies as well as the sensory nerve action potential and compound muscle action potential amplitudes of the both median nerves. In summary, if patients are refractory to conservative treatments —such as splinting, oral medication, and corticosteroid injection —PRP may be used as an alternative before surgical intervention.

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  • High-resolution ultrasound and magnetic resonance imaging to document tissue repair after prolotherapy: a report of 3 cases

    Abstract

    High-resolution ultrasound imaging of musculoskeletal tissue is increasing in popularity because of patient tolerability, low cost, ability to visualize tissue in real-time motion, and superior resolution of highly organized tissue such as a tendon. Prolotherapy, defined as the injection of growth factors or growth factor production stimulants to grow normal cells or tissue, has been a controversial procedure for decades; it is currently gaining in popularity among physiatrists and other musculoskeletal physicians. This report describes imaging of tendons, ligaments, and medial meniscus disease (from trauma or degeneration). Although these tissues have been poorly responsive to nonsurgical treatment, it is proposed that tissue growth and repair after prolotherapy in these structures can be documented with ultrasound and confirmed with magnetic resonance imaging. Directions for future research application are discussed.

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  • Platelet-Rich Plasma Augmentation for Hip Arthroscopy

    Abstract

    Biological augmentation and therapeutics are being increasingly used in musculoskeletal and orthopaedic care. Platelet-rich plasma (PRP) is produced from centrifugation of peripheral blood, a process that concentrates platelets within autologous plasma. The process of PRP preparation is fundamental in controlling the contents, and it influences its therapeutic potential. Platelets contain alpha granules that store and release a variety of growth factors and other proteins that may augment the healing environment; PRP also has the added benefit of promoting postsurgical hemostasis. The purpose of this report was to detail our institutional preparation protocol and method of administration of PRP during hip arthroscopy.

    Biological augmentation and therapeutics are being increasingly used in musculoskeletal and orthopaedic care1,2,3 Platelet-rich plasma (PRP) has been used by orthopaedic surgeons and other health practitioners to enhance healing and modulate the environment of tendinopathy, surgical repair of tendons, ligament reconstruction, diffuse arthritis, and focal chondral defects4,5,6.

    PRP is produced from centrifugation of peripheral blood, a process that concentrates platelets within autologous plasma.2 Platelets contain alpha granules that store and release a variety of growth factors, such as cytokines and chemokines, as well as other proteins including insulin growth factor 1, transforming growth factor β1, and vascular endothelial growth factor.1 These biological factors can be modulated by the preparation method used to produce the PRP. For example, leukocyte-rich PRP may increase inflammation and catabolic pathways, whereas leukocyte-poor PRP may decrease inflammation and anabolic pathways.7, 8 In addition, PRP can be prepared as a fibrinous product with adhesive hemostatic properties through endogenous or exogenous activation. The PRP-fibrin preparation can enhance endothelial, epithelial, and epidermal regeneration, by stimulating angiogenesis, improving collagen synthesis, and decreasing scarring.9

    PRP has been historically described as \"a volume of plasma with a platelet count above baseline,\"10 but a more recent quantitative definition requires PRP to contain more than 1 million platelets per milliliter of serum or a 5-fold increase from the baseline platelet concentration.11 The preparation of PRP is essential in determining the therapeutic potential for biological augmentation. The purpose of this report was to detail our institutional PRP preparation protocol and method of administration during hip arthroscopy.

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  • Prolotherapy Induces an Inflammatory Response in Human Tenocytes In Vitro

    Abstract

    Background: Proliferative therapy, or prolotherapy, is a controversial treatment method for many connective tissue injuries and disorders. It involves the injection of a proliferant, or irritant solution, into the site of injury, which causes small-scale cell death. This therapeutic trauma is theorized to initiate the body\'s wound-healing cascade, perhaps leading to tissue repair. The immediate effects of many of these proliferants are poorly characterized, as are the cellular responses to them; here, we sought to evaluate the immediate effects of two common proliferants (dextrose and P2G, a combination of phenol, glucose, and glycerin) on the cellular response of human tenocytes, and begin to explicate the mechanisms with which each proliferant functions.

    QUESTIONS/PURPOSES: We asked: What are the effects of treating cultured tenocytes with proliferative treatment agents on their (1) cellular metabolic activity, (2) RNA expression, (3) protein secretion, and (4) cell migration?

    Methods: Using human hamstring and Achilles tendon cells, we attempted to answer our research questions. We used a colorimetric metabolic assay to assess the effect of dextrose and P2G proliferant treatment on cell mitochondrial activity compared with nontreated tenocytes. Next, using quantitative PCR, ELISA, and a reporter cell line, we assessed the expression of several key markers involved in tendon development and inflammation. In addition, we used a scratch wound-healing assay to evaluate the effect of proliferant treatment on tenocyte migration.

    Results: Results showed that exposure to both solutions led to decreased metabolic activity of tenocytes, with P2G having the more pronounced effect (75% ± 7% versus 95% ± 7% of untreated control cell metabolic levels) (ANOVA; p < 0.01; mean difference, 0.202; 95% CI, 0.052-0.35). Next, gene expression analysis confirmed that treatment led to the upregulation of key proinflammatory markers including interleukin-8 and cyclooxygenase-2 and downregulation of the matrix marker collagen type I. Furthermore, using a reporter cell line for transforming growth factor-β (TGF-β), a prominent antiinflammatory marker, we showed that treatments led to decreased TGF-β bioactivity. Analysis of soluble proteins using ELISA revealed elevated levels of soluble prostaglandin E2 (PGE2), a prominent inducer of inflammation. Finally, both solutions led to decreased cellular migration in the tenocytes.

    Conclusion: Taken together, these results suggest that prolotherapy, more so with P2G, may work by decreasing cellular function and eliciting an inflammatory response in tenocytes. Additional studies are needed to confirm the cellular signaling mechanisms involved and the resulting immediate response in vivo.

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  • Single Platelet-Rich Plasma Injection for Early Stage of Osteoarthritis of the Knee

    Abstract

    Purpose: The purpose of this study was to determine the safety efficacy and outcomes of platelet-rich plasma (PRP) intra-articular injections for early stages of knee osteoarthritis (OA).

    Methods: Twenty-five patients affected by grade I and II knee primary OA according to the Kellgren-Lawrence scale received a single intra-articular PRP injection. Patients were prospectively evaluated for 6 months. Visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee injury and Osteoarthritis Outcome Score (KOOS) scoring scales were used to evaluate clinical outcomes. Wilcoxon signed rank test was used to evaluate significance of improvement of WOMAC, KOOS, and VAS scores.

    Results: Twenty-one patients completed 6-months follow-up. The median WOMAC score improved from 29.1 points (range: 17.4-60.4; standard deviation [SD] = 13.0) at baseline to 42.41 (range: 24.3-71.2; SD = 12.5) at final follow-up. Improvements in median KOOS and VAS score have been also found, from 37.49 points and 64.2 mm before injection to 59.71 points and 42.8 mm, respectively. All these improvements were statistically significant (p < 0.05). No adverse reactions have been observed.

    Conclusion: Treating knee OA with PRP injection is safe. A single dose of PRP seems to be effective in managing pain and improving quality of life in patients with low-grade knee OA.

    Level of Evidence: Level IV, therapeutic case series.

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  • Dr Weglein and Dr Garcia teaching at TOBI ( the Orthobiologic institute)

    Dr Weglein and Dr Garcia teaching at TOBI ( the Orthobiologic institute)

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  • TOBI Faculty for 2017

    Abstract

    Over the years, TOBI has become best known for world-renowned faculty. TOBI annual events bring together field experts publishing the research in orthopedic biologics and regenerative medicine. This event has enjoyed consistent annual growth, as global thought-leaders return for annual updates and the year\'s best networking opportunities to collaborate on projects and advance the field. Newcomers to the field come to learn from the best.

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  • Effect of High-Volume Injection, Platelet-Rich Plasma, and Sham Treatment in Chronic Midportion Achilles Tendinopathy: A Randomized Double-Blinded Prospective Study

    Abstract

    Background: Injection therapies are often considered alongside exercise for chronic midportion Achilles tendinopathy (AT), although evidence of their efficacy is sparse.

    Purpose: To determine whether eccentric training in combination with high-volume injection (HVI) or platelet-rich plasma (PRP) injections improves outcomes in AT.

    Study Design: Randomized controlled trial; Level of evidence, 1.

    Methods: A total of 60 men (age, 18-59 years) with chronic (>3 months) AT were included and followed for 6 months (n = 57). All participants performed eccentric training combined with either (1) one HVI (steroid, saline, and local anesthetic), (2) four PRP injections each 14 days apart, or (3) placebo (a few drops of saline under the skin). Randomization was stratified for age, function, and symptom severity (Victorian Institute of Sports Assessment-Achilles [VISA-A]). Outcomes included function and symptoms (VISA-A), self-reported tendon pain during activity (visual analog pain scale [VAS]), tendon thickness and intratendinous vascularity (ultrasonographic imaging and Doppler signal), and muscle function (heel-rise test). Outcomes were assessed at baseline and at 6, 12, and 24 weeks of follow-up.

    Conclusion: Treatment with HVI or PRP in combination with eccentric training in chronic AT seems more effective in reducing pain, improving activity level, and reducing tendon thickness and intratendinous vascularity than eccentric training alone. HVI may be more effective in improving outcomes of chronic AT than PRP in the short term.

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  • Prolotherapy: An effective therapy for Tietze syndrome

    Abstract

    Purpose: To compare the short-term effect of prolotherapy and conservative terapy for the Tietze synrome.

    Patients And Methods: From 2013 to 2014, twenty-one patients underwent prolotherapy (group 1) and thirteen underwent conservative therapy with analgesics (group 2). A visual analogue score (VAS) was recorded for measurement of pain intensity in all patients before (Pre VAS) and after injection first day (VAS1), first week (VAS2) and fourth week (VAS3). Group 2 were received systemic nonsteroidal anti-inflammatory drug. VAS score was recorded similarly at the same times (Pre VAS, VAS1, VAS2, VAS3), and clinical affects were compared between the two groups.

    Results: The mean VAS score (mm) before prolotherapy was 7.10 in patients who received prolotherapy, and 7.14 mm in patients who treated nonsteroidal anti-inflammatory drug. The mean VAS after the fist injection was 2.19 mm and dropped to 1.52 mm after the third injection. The mean VAS after the nonsteroidal anti-inflammatory drug treatment dropped 2.62 mm and during the same scores to 3 weeks later. There was no significant difference between the group 1 and group 2 in the age, sex and comorbidity. Also there was no significant difference between the group 1 and group 2 in clinical and radiological evidence. The prolotherapy group showed a faster recovery, including significantly reduced clinic findings (p: 0.001). Third VAS is significant finding for the prolotherapy group.

    Conclusion: Prolotherapy could be performed safely and is a method with a favorable long term treatments for t he Tietze Syndrome. It may be the ideal procedure for patients with drugs side effects and advers events especially for those with limited liver and kidney reserve or significant comorbidities.

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  • Houston researchers use stem cells to treat traumatic brain injuries

    Abstract

    A Houston research team has uncovered a possible treatment for severe brain injuries that could dramatically improve the outlook for tens of thousands of trauma patients - from those injured on Houston highways, to soldiers wounded on faraway battlefields.

    About 275,000 people across the country each year are wheeled into emergency rooms with severe traumatic brain injuries; about a fourth don\'t survive. Those who do often suffer permanent disabilities, in part because swelling in the brain in the days and weeks after the injury cuts off blood flow, killing neurons.

    In a new clinical trial conducted at Memorial Hermann Hospital, researchers from UTHealth have shown it\'s possible to reduce brain inflammation by harvesting stem cells from a trauma patient\'s bone marrow and re-infusing them into the bloodstream within 48 hours of injury. The results are promising, said Dr. Charles Cox, who\'s been working on the experimental treatment for more than 15 years.

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  • Functional outcomes of platelet rich plasma injections in plantar fascitis

    Abstract

    Background: The study was conducted to analyse the clinical outcomes following a single injection of platelet rich plasma, produced using autologous blood by standard double centrifugation technique in patients with plantar fasciitis who have not had relief using conservative methods.

    Methods: Between June 2013 and June 2015, 26 consecutive patients (Mean age 45.92) (11 males/15 females) who had symptoms for a minimum of 3 months and had failed conservative management options such as rest, anti-inflammatories and physiotherapy were given a single injection of PRP in the medial calcaneal tubercle.

    Results: The outcomes were measured using Visual analogue scale and Foot function index at pre injection, and at 1, 6 and 12 months post injection and results tabulated. All patients reported an improvement in VAS and FFI scores consistently. One superficial infection was encountered.

    Conclusions: Single injection of platelet rich plasma improves pain and function in the foot in patients suffering from plantar fasciitis when conservative management has failed. The synergism between various autologous growth factors may play a role in tendon healing.

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  • Effect of Intraarticular injection of ozone on inflammatory cytokines in knee osteoarthritis

    Abstract

    Introduction: Knee Osteoarthrosis is one of the most debilitating diseases. Prolotherapy includes intraarticular injection of various drugs to decrease inflammation. Injection of Intradiscal O2-O3 has reduced pain and disability of patients with low back pain due to prolapsed lumbar disk.

    Objective: To compare the effect of intraarticular injection of Ozone and steroids in improvement of clinical and cellular healing of knee osteoarthritis.

    Methods:in a randomized clinical trial, 70 patients with knee osteoarthrosis were included in the study. In Ozone group, 5 ml (35 μg/ml) of Ozone and in steroid group 5ml (50 mg) Triamcinolone were injected intraarticular. At 1,2,and 6 month patients were followed for pain scale, disability index and IL-1β and TNF-α serum levels were measured.

    Results: At 1 month after injection pain scale and disability index and IL-1β and TNF-α were decreased in both groups. However, at 2 and 6 month pain scale and disability index were significantly lower in Ozone group compare to steroid group (p<0.05). Besides, serum level of IL-1β and TNF-α were also significantly lower at 2 and 6 month in Ozone group compare to steroid group (p<0.05).

    Conclusion: Intraarticular Ozone induces significantly longer improvement of pain and disability in knee osteoartherosis compare to steroid injection. In addition, serum inflammatory cytokines are also lower in Ozone group compared to steroid group along with clinical improvements.

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  • Autologous platelet-rich plasma versus corticosteroid in the management of elbow epicondylitis: A randomized study

    Abstract

    Introduction: Elbow epicondylar tendinitis is a common problem for patients whose activities require strong gripping or repetitive wrist movements in the day-to-day activities of life. Histologic specimens from chronic cases confirm that tendinitis is not an acute inflammatory condition but rather a failure of the normal tendon repair mechanism associated with angiofibroblastic degeneration. Tendon regeneration may be improved by injecting autologous growth factors obtained from the patient\'s own blood. Autologous growth factors can be injected with autologous whole blood or platelet-rich plasma (PRP).

    Materials and Methods: A randomized study with 83 patients was done. The study population comprised two groups. Group A (n = 50) treated with local steroid injection and Group B (n = 33) treated with autologous PRP. Patients were allocated randomly using computer-generated random number table. The base-line evaluation was done using visual analog score (VAS) and modified Mayo performance index for elbow (MAYO). Re-evaluation was after 1, 2, and 6 months of the procedure. Statistical analysis was done using independent t-test.

    Results: Six months after treatment with PRP, patient\'s with elbow epicondylitis had a significant improvement in their VAS (P < 0.05) and MAYO (P < 0.05) in contrast to steroid, whereas no statistical difference was found between the two groups at 1 and 2 months after intervention.

    Conclusion: Treatment of patients with epicondylitis with PRP reduces pain and significantly increases function, exceeding the effect of corticosteroid injection.

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  • Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review

    Abstract

    Purpose of Review: Osteoarthritis and overuse tendinopathy are common chronic conditions of high societal and patient burden. The precise etiology of pain and disability in both conditions is multifactorial and not well understood. Patients are often refractory to conservative therapy. The development of new therapeutic options in both conditions is a public health priority. Prolotherapy is an injection-based outpatient regenerative therapy for chronic musculoskeletal conditions, including osteoarthritis and tendinopathy. The authors reviewed the basic science and clinical literature associated with prolotherapy for these conditions.

    Recent Findings: Systematic review, including meta-analysis, and randomized controlled trials suggest that prolotherapy may be associated with symptom improvement in mild to moderate symptomatic knee osteoarthritis and overuse tendinopathy.

    Summary: Although the mechanism of action is not well understood and is likely multifactorial, a growing body of literature suggests that prolotherapy for knee osteoarthritis may be appropriate for the treatment of symptoms associated with knee osteoarthritis in carefully selected patients who are refractory to conservative therapy and deserves further basic and clinical science investigation for the treatment of osteoarthritis and tendinopathy.

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  • Platelet-rich plasma versus dry needling of myofascial meridian trigger points in the treatment of plantar fasciitis

    Abstract

    Background: Plantar fasciitis (PF) is the most common cause of heel pain, which results from repetitive trauma with degenerative changes in the plantar tissue. Platelet-rich plasma (PRP) and dry needling showed promising results as regards pain resolution and healing effect, and hence our aim was to compare their efficacy in the treatment of chronic PF.

    Patients and methods : Thirty patients diagnosed with unilateral PF were subjected to full clinical assessment for foot function using the foot function index (FFI) and assessment of trigger points along the meridians. Ultrasonographic examination of plantar fascia thickness, echogenicity, and power Doppler was carried out. Patients were divided randomly into two groups of 15 each: group A received a single injection of PRP at the plantar fascia, and group B was treated with dry needling protocol in myofascial meridians trigger points along the superficial back line. Follow-up after 6 and 12 weeks included clinical re-evaluation, FFI determination, and ultrasonography. Our results showed a significant improvement in the clinical outcome of the FFI in group B (P<0.03) and a highly significant improvement in the clinical outcome within the PRP group by the 12th week (P<0.009). A significant decrease in thickness, heterogeneity, and Doppler signals (P<0.04, P<0.003, and P<0.03, respectively) was observed within the PRP group at the 12th week.

    Conclusion: PRP injection is a promising line of treatment for chronic PF with documented ultrasonographic healing effect. Dry needling is a simple and safe technique for treating pain associated with PF, yet it is more invasive and less effective compared with PRP injection.

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  • Short-term clinical results of intra-articular PRP injections for early osteoarthritis of the knee

    Abstract

    Purpose: To assess the short-term results of repeated intra-articular platelet rich plasma (PRP) injections into the knee in patients with early osteoarthritis (OA) and to determine a better treatment protocol.

    Methods: This is a retrospective study in 191 knees (127 patients) with minimum of 12 months follow-up. We compared the clinical results of three types of injection method, once a month, twice monthly, and three injections at monthly interval. The outcomes were assessed using Visual Rating Scale (VRS), functional score, knee score, range of motion (ROM), WOMAC Stiffness/Pain/Function score, IKDC score, before the first injection and at 12 months post treatment.

    Results: There were significant improvements in all scores after treatment as compared to the pre-treatment values (p < 0.05), except Knee score after 1st and 2nd injection and ROM in three groups. The parameters of Visual Rating Scale (VRS), functional score, and WOMAC Stiffness/Pain/Function score showed significant differences among the three groups in favour of the three injections group (p < 0.05). At 12 months, the effects began to decline in one injection and two injections groups, and the data in one injection group showed significant difference compared to two injection group (p < 0.001). Three injections group had higher scores and more improvement at 12 months after treatment when compared to the other two groups.

    Conclusion: PRP injection appears to be effective in early symptomatic OA knees. The results after treatment are encouraging with significant reduction in pain and improvement in knee function at 12 months after treatment when compared to the pre-treatment status. Three injections per month yielded significantly better results in short-term follow-up.

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  • Increased risk for knee replacement surgery after arthroscopic surgery for degenerative meniscal tears: a multi-center longitudinal observational study using data from the osteoarthritis initiative.

    Abstract

    Objective: The primary objective was to assess whether patients with knee osteoarthritis and whom undergo arthroscopic meniscectomy have an increased risk for future knee replacement surgery.

    Results: 335 participants underwent arthroscopic meniscectomy during follow up, of which 63 (18.8%) underwent knee replacement surgery in the same knee. Of the 335 propensity score matched participants 38 (11.1%) underwent knee replacement surgery during follow up. Results from the Cox-proportional hazards model demonstrated that the hazard ratio of knee replacement surgery was 3.03 (95% CI (1.67-5.26)) for participants who underwent arthroscopic meniscectomy relative to the propensity score matched participants who did not undergo arthroscopic meniscectomy.

    Conclusions: In patients with knee osteoarthritis arthroscopic knee surgery with meniscectomy is associated with a three fold increase in the risk for future knee replacement surgery.

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