In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis.

Autologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). However, the clinical outcomes after PRP administration are often variable, and there is limited information about the specific characteristics of PRP that impact bioactivity and clinical responses. In this study, we aimed to develop an integrative workflow to evaluate responses to PRP in vitro, and to assess if the in vitro responses to PRP are associated with the PRP composition and clinical outcomes in patients with knee OA. To do this, we used a coculture system of macrophages and fibroblasts paired with transcriptomic analyses to comprehensively characterize the modulation of inflammatory responses by PRP in vitro. Relying on patient-reported outcomes and achievement of minimal clinically important differences in OA patients receiving PRP injections, we identified responders and non-responders to the treatment. Comparisons of PRP from these patient groups allowed us to identify differences in the composition and in vitro activity of PRP. We believe that our integrative workflow may enable the development of targeted approaches that rely on PRP and other orthobiologics to treat musculoskeletal pathologies.

Foot Pain in Relation to Ipsilateral and Contralateral Lower-Extremity Pain in a Population-Based Study.

BACKGROUND: Clinical observations note that foot pain can be linked to contralateral pain at the knee or hip, yet we are unaware of any community-based studies that have investigated the sidedness of pain. Because clinic-based patient samples are often different from the general population, the purpose of this study was to determine whether knee or hip pain is more prevalent with contralateral foot pain than with ipsilateral foot pain in a population-based cohort. METHODS: Framingham Foot Study participants (2002-2008) with information on foot, knee, and hip pain were included in this cross-sectional analysis. Foot pain was queried as pain, aching, or stiffness on most days. Using a manikin diagram, participants indicated whether they had experienced pain, aching, or stiffness at the hip or knee and specified the side of any reported pain. Sex-specific multinomial logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals for the association of foot pain with knee and hip pain, adjusting for age and body mass index. RESULTS: In the 2,181 participants, the mean ± SD age was 64 ± 9 years; 56% were women, and the mean body mass index was 28.6. For men and women, bilateral foot pain was associated with increased odds of knee pain on any side (ORs = 2-3; P < .02). Men with foot pain were more likely to have ipsilateral hip pain (ORs = 2-4; P<.03), whereas women with bilateral foot pain were more likely to have hip pain on any side (OR = 2-3; P < .02). CONCLUSIONS: Bilateral foot pain was associated with increased odds of knee and hip pain in men and women. For ipsilateral foot and hip pain, men had a stronger effect compared with women.

State-of-the-Art management of knee osteoarthritis.

Osteoarthritis (OA) is the most common type of arthritis found in the United States' population and is also the most common disease of joints in adults throughout the world with the knee being the most frequently affected of all joints. As the United States' population ages along with the increasing trends in obesity prevalence in other parts of the world, it is expected that the burden of OA on the population, healthcare system, and overall economy will continue to increase in the future without making major improvements in managing knee OA. Numerous therapies aim to reduce symptoms of knee OA and continued research has helped to further understand the complex pathophysiology of its disease mechanism attempting to uncover new potential targets for the treatment of OA. This review article seeks to evaluate the current practices for managing knee OA and discusses emerging therapies on the horizon. These practices include non-pharmacological treatments such as providing patient education and self-management strategies, advising weight loss, strengthening programs, and addressing biomechanical issues with bracing or foot orthoses. Oral analgesics and anti-inflammatories are pharmacologicals that are commonly used and the literature overall supports that some of these medications can be helpful for managing knee OA in the short-term but are less effective for long-term management. Additionally, more prolonged use significantly increases the risk of serious associated side effects that are not too uncommon. Disease-modifying osteoarthritis drugs are being researched as a treatment modality to potentially halt or slow disease progression but data at this time is limited and continued studies are being conducted to further investigate their effectiveness. Intra-articular injectables are also implemented to manage knee OA ranging from corticosteroids to hyaluronans to more recently platelet-rich plasma and even stem cells while several other injection therapies are presently being studied. The goal of developing new treatment strategies for knee OA is to prolong the need for total knee arthroplasty which should be utilized only if other strategies have failed. High tibial osteotomy and unicompartmental knee arthroplasty are potential alternatives if only a single compartment is involved with more data supporting unicompartmental knee arthroplasty as a good treatment option in this scenario. Arthroscopy has been commonly used for many years to treat knee OA to address degenerative articular cartilage and menisci, however, several high-quality studies have shown that it is not a very effective treatment for the majority of cases and should generally not be considered when managing knee OA. Improving the management of knee OA requires a multi-faceted treatment approach along with continuing to broaden our understanding of this complex disease so that therapeutic advancements can continue to be developed with the goal of preventing further disease progression and even potentially reversing the degenerative process.

Clinical and MRI outcomes after platelet-rich plasma treatment for knee osteoarthritis.

The purpose of this study was to investigate whether platelet-rich plasma therapy for early knee osteoarthritis is associated with good clinical outcomes and a change in magnetic resonance imaging (MRI) structural appearances. The design was a prospective cohort study following patients 1 year after platelet-rich plasma therapy for knee osteoarthritis. Twenty-two patients were treated with platelet-rich plasma for early osteoarthritis, confirmed with a baseline MRI. Inclusion criteria were Kellgren grade 0-II with knee pain in patients aged 30 to 70 years. All the patients received a 6-mL platelet-rich plasma injection using the Cascade system. Fifteen subjects underwent clinical assessments at baseline, 1 week, and 1, 3, 6, and 12 months, and MRIs at 1 year. Pain scores significantly decreased, whereas functional and clinical scores increased at 6 months and 1 year from baseline. Qualitative MRIs demonstrated no change per compartment in at least 73% of cases at 1 year.

The role of platelet-rich plasma in inducing musculoskeletal tissue healing.

BACKGROUND: Platelet-rich plasma [PRP] has received increasing interest across many musculoskeletal disciplines and has been widely applied clinically to stimulate tissue healing in numerous anatomical regions. The known actions of platelet-derived factors suggest that PRP may have significant potential in the treatment of pathological conditions of cartilage, tendon, ligament, and muscle. PURPOSE: The aim of this manuscript is to review current literature regarding the biology of PRP and the efficacy of using PRP to augment healing of tendon ligament and muscle injuries, as well as early osteoarthritis. METHODS: A comprehensive literature review of musculoskeletal applications of PRP was performed, including basic science and clinical studies such as randomized controlled trials, case controlled series, and case series. RESULTS: The most compelling evidence to support the efficacy of PRP is for its application to tendon damage associated with lateral and medial epicondylitis. Although some promising studies have been reported supporting the use of PRP in osteoarthritis and ligament and muscle injuries, it currently remains unknown whether PRP effectively alters the progression of osteoarthritis or aids the healing of ligament and muscle tissues. CONCLUSION: The rationale for the use of PRP to improve tissue healing is strong, but the efficacy for many musculoskeletal applications remains unproven. PRP has been shown to be a safe treatment. A number of questions regarding PRP remain unanswered, including the optimal concentration of platelets, what cell types should be present, the ideal frequency of application, or the optimal rehabilitation regimen for tissue repair and return to full function.

ASRA checklist improves trainee performance during a simulated episode of local anesthetic systemic toxicity.

OBJECTIVE: Severe local anesthetic systemic toxicity (LAST) is a rare event, the management of which might best be learned using high-fidelity simulation. In its 2010 Practice Advisory, the American Society of Regional Anesthesia and Pain Medicine (ASRA) created a medical checklist to aid in the management of LAST. We hypothesized that trainees provided with this checklist would manage a simulated episode of LAST more effectively than those without it. A secondary aim of the study was to assess the ASRA Checklist's usability and readability. METHODS: Trainees undergoing a simulated LAST event were randomized to the checklist group (n = 12) or the no-checklist group (n = 13). Our primary outcome was the number of medical management tasks completed correctly. Secondary outcomes included assessment of the anesthesiologists' nontechnical skills and posttest performance. RESULTS: Trainees receiving the checklist demonstrated superior medical management of the simulated LAST event: the checklist group correctly performed 16.0 (2.6) tasks versus the no-checklist group's 8.8 (3.0) tasks (mean [SD], P < 0.001). The checklist group had higher decision making scores on the anesthesiologists' nontechnical skills assessment (5.2 [1.8] versus 4.0 [1.35] summed rater score, P = 0.037) and had higher knowledge retention 2 months later (P = 0.031). Of those trainees randomized to receive the checklist, 7 of 12 used it fully (versus partially), which was reflected in higher medical and nontechnical performance scores. CONCLUSIONS: Use of the ASRA Checklist significantly improved the trainees' medical management and nontechnical performance during a simulated episode of severe LAST. Partial use of the checklist correlated with lower overall performance.