Intra-articular Tissue Research Articles

Quantification of temporomandibular joint space in patients with juvenile idiopathic arthritis assessed by cone beam computerized tomography.

To describe a method to calculate the total intra-articular volume (inter-osseous space) of the temporomandibular joint (TMJ) determined by cone-beam computed tomography (CBCT). This could be used as a marker of tissue proliferation and different degrees of soft tissue hyperplasia in juvenile idiopathic arthritis (JIA) patients. Axial single-slice CBCT images of cross-sections of the TMJs of 11 JIA patients and 11 controls were employed. From the top of the glenoid fossa, in the caudal direction, an average of 26 slices were defined in each joint (N = 44). The interosseous space was manually delimited from each slice by using dedicated software that includes a graphic interface. TMJ volumes were calculated by adding the areas measured in each slice. Two volumes were defined: Ve-i and Vi , where Ve-i is the inter-osseous space, volume defined by the borders of the fossa and Vi is the internal volume defined by the condyle. An intra-articular volume filling index (IF) was defined as Ve-i /Vi , which represents the filling of the space. The measured space of the intra-articular volume, corresponding to the intra-articular soft tissue and synovial fluid, was more than twice as large in the JIA group as in the control group. The presented method, based on CBCT, is feasible for assessing inter-osseus joint volume of the TMJ and delimits a threshold of intra-articular changes related to intra-articular soft tissue proliferation, based on differences in volumes. Intra-articular soft tissue is found to be enlarged in JIA patients.

Surgical Treatment of Juvenile Idiopathic Arthritis in the Era of Novel Drug Therapies.

Juvenile idiopathic arthritis is the most common chronic rheumatic disease encountered in children under the age of sixteen and causes significant impairments in daily life. Over the last two decades, the introduction of new drug treatments (including disease-modifying antirheumatic drugs and biologics) has changed the course of this disease, thus reducing the indication for surgery. However, some patients fail to respond to drug therapy and thus require personalized surgical management, e.g., the local reduction of joint effusion or a synovial pannus (via intra-articular corticosteroid injections, synovectomy, or soft tissue release), and management of the sequelae of arthritis (such as growth disorders and joint degeneration). Here, we provide an overview of the surgical indications and outcomes of the following interventions: intra-articular corticosteroid injections, synovectomy, soft tissue release, surgery for growth disorders, and arthroplasty.

Application of magnetic particle imaging to evaluate nanoparticle fate in rodent joints.

Nanoparticles are a promising approach for improving intra-articular drug delivery and tissue targeting. However, techniques to non-invasively track and quantify their concentration in vivo are limited, resulting in an inadequate understanding of their retention, clearance, and biodistribution in the joint. Currently, fluorescence imaging is often used to track nanoparticle fate in animal models; however, this approach has limitations that impede long-term quantitative assessment of nanoparticles over time. The goal of this work was to evaluate an emerging imaging modality, magnetic particle imaging (MPI), for intra-articular tracking of nanoparticles. MPI provides 3D visualization and depth-independent quantification of superparamagnetic iron oxide nanoparticle (SPION) tracers. Here, we developed and characterized a polymer-based magnetic nanoparticle system incorporated with SPION tracers and cartilage targeting properties. MPI was then used to longitudinally assess nanoparticle fate after intra-articular injection. Magnetic nanoparticles were injected into the joints of healthy mice, and evaluated for nanoparticle retention, biodistribution, and clearance over 6weeks using MPI. In parallel, the fate of fluorescently tagged nanoparticles was tracked using in vivo fluorescence imaging. The study was concluded at day 42, and MPI and fluorescence imaging demonstrated different profiles in nanoparticle retention and clearance from the joint. MPI signal was persistent over the study duration, suggesting NP retention of at least 42days, much longer than the 14days observed based on fluorescence signal. These data suggest that the type of tracer - SPIONs or fluorophores - and modality of imaging can affect interpretation of nanoparticle fate in the joint. Given that understanding particle fate over time is paramount for attaining insights about therapeutic profiles in vivo, our data suggest MPI may yield a quantitative and robust method to non-invasively track nanoparticles following intra-articular injection on an extended timeline.

Peri-procedural management and incidence of bleeding events following musculoskeletal injections or aspirations in people on oral anticoagulation and antiplatelet therapy.

Corticosteroid injections and aspirations are common interventions for managing musculoskeletal and inflammatory conditions. However, there remains limited safety evidence to support injection decisions and peri-procedural management in people on anti-thrombotics, particularly for direct oral anticoagulants (DOACs). To investigate peri-procedural management and bleeding complications following musculoskeletal injections or aspirations with anti-thrombotic medication use. A prospective observational study was undertaken (October 2018-December 2020) in Orthopaedics, Rheumatology and Radiology specialities in two large UK healthcare providers. Data collection involved weekly identification of musculoskeletal procedures, emergency attendance or admission within 30days and follow-up questionnaires sent within 2weeks post-procedure. Descriptive statistics were used to analyse anticoagulant/anti-platelet use, peri-procedural management and bleeding complications. Of 5080 procedures, 237 of 1338 responses reported antithrombotic use: warfarin (n=36), DOACs (n=75) and antiplatelets (n=126). There were no self-report or electronic identification of clinically significant bleeding events/complications. Only local bruising was reported (8.6% vs. 0.2% with non-use), and only with medication continuation or international normalised ratio (INR) levels ≥3.8 or unknown. Only 3/72 DOAC use was interrupted. In this study, no clinically significant bleeding events or complications were reported or identified following musculoskeletal injections or aspirations, with only localised bruising reported. It was not universal practice to check INR levels and DOAC interruption was uncommon. Findings add evidence that musculoskeletal procedures appear to be low risk procedures for bleeding complications with antithrombotic continuation and when INR levels within lower target range. Research on intra-articular or soft tissue iatrogenic consequences would add to risk/benefit evaluations.

Joint and soft tissue injections in Irish primary care: a survey of GPs' attitudes and practices.

Musculoskeletal conditions are common in primary care, causing significant morbidity. Intra-articular and soft tissue corticosteroid injections are commonly performed by GPs internationally. It is unknown how commonly they are performed by GPs in the Republic of Ireland. To determine the frequency and type of joint and soft tissue injections performed by GPs in the Republic of Ireland and investigate factors affecting their use. A cross-sectional online questionnaire, which was based on previous international research, was devised for completion by GPs practising in the Republic of Ireland. GPs were invited to electronically complete a questionnaire on their practices and attitudes regarding joint and soft tissue injections. A total of 147 of 204 GPs (72.1%) had performed an intra-articular or soft tissue injection in the preceding year. GPs who were principals or partners, male, or worked in a rural or mixed urban and rural practice setting were more likely to perform these procedures. The most common injection sites were the shoulder and knee. Participants were confident about performing joint and soft tissue injections. It was found that 80.4% had received prior training in this treatment modality, most commonly during their GP training programme. A prolonged wait for secondary care intervention, symptom duration, and symptom severity were factors that increased the likelihood of performing injections. Difficulty maintaining skills and medicolegal concerns were common barriers to performing joint and soft tissue injections. Most GPs surveyed carried out joint and soft tissue injections, most commonly injecting the shoulder and knee. Irish GPs experience many of the same barriers to performing intra-articular injection as experienced internationally.

Outcomes of arthroscopic-assisted fixation of intra-articular proximal tibial fractures by circular external fixator

Abstract Background Fractures of the tibial plateau usually result from high-energy trauma. Motor vehicle accidents seem to be the predominant cause worldwide. The objective of treating displaced fractures is to restore the articular surface anatomy and repair soft tissue injuries. We aim to improve the functional and radiological results of the arthroscopically assisted fixation of the tibial plateau fractures using Ilizarov fixator. Methods The study was carried out on patients attending to Orthopedic Surgery Department at a major metropolitan hospital in Egypt, between March 2019 to September 2020. Forty-five patients with tibial plateau fractures of Schatzker classification type II to type VI were operated on. Results The results indicate that the Ilizarov method is a valuable alternative in treating Schatzker II-VI fracture types. The mean time from injury to partial weight bearing (PWB) and full weight bearing (FWB) were 12.75 and 22.73 weeks, respectively. The mean Knee Society Score was 75.42 ± 9.91. Over 70% of self-reported Overall Functional Grades were deemed ‘good’ (n=21, 47.6%) or ‘excellent’ (n=12, 26.7%) at the end of the follow-up period. Pin tract infection was reported in 31(68.9%) cases, and delayed union developed in 7 (15.6%) cases. Conclusion Early and definite fixation is achieved with the Ilizarov and arthroscopic technique, allowing intra-articular assessment of the reduction, and management of associated intra-articular soft tissue injuries with immediate PWB. It is believed that this minimally invasive method does not lead to the additional morbidity and the combined advantages of arthroscopy and Ilizarov allows successful fixation and early activity.

Management for Arthrofibrosis Following ACL Reconstruction

Introduction: Arthrofibrosis following ACL reconstruction is a debilitating complication. The incidence range from 2% to as high 35%. This Loss of motion not only cause of anterior knee pain but also inability to return to sports, and persistent weakness. The emergence of intra-articular scar tissue adhesions, or post-traumatic arthrofibrosis, may restrict the patient’s knee motion in the early postoperative period even though many factors may contribute to the development of motion loss. It might be difficult to manage motion loss once it has been diagnosed as a condition. Better understanding of the time of surgery, surgical technique improvement, and rehabilitation protocols showed less incidence of motion loss after ACL reconstruction. Case Presentation: A 46-year-old female complains of pain, stiffness, and decreased range of motion following arthroscopy ACL reconstruction of her left knee. Local examination showed diffused firm swelling over the anteromedial aspect of the knee and limitation of motion to mobilize the patella in all directions. Her bad rehabilitation program after surgery caused the main loss of her knee motion and the development of pain. Arthroscopic lysis of adhesions with manipulation under anesthesia was conducted. Following the surgery, graft observation was normal. A cyclops located between the infrapatellar pouch and medial gutter was observed and excised. Passive range of motion was also checked intra-operatively. Immediately after surgery, intensive physiotherapy was begun. The patient was very compliant with the rehabilitation program and the clinic follow-up schedule. Gradually, the patient started to regain her active full extension and flexion. Result: The functional outcome score showed improvement at the time of final follow-up, as did the average pain scores. Conclusion: Arthrofibrosis is multifactorial etiology. Knee joint ROM is better maximized by arthroscopic debridement and lysis of adhesions following arthrofibrosis after ACLR in conjunction with an intensive post-operative physical therapy plan.

An observational study evaluating the efficacy of microfragmented adipose tissue in the treatment of osteoarthritis.

Aim: Osteoarthritis(OA) prevalence is increased in ageing and obese populations. This prospective single-arm cohort study aimed to investigate the efficacy of autologous microfragmented adipose tissuetreatment of severe knee or shoulder OA. Materials & methods: Participants received an intra-articular microfragmented adipose tissue injection to the affected joint(s). Multiple patient reported outcome measures (PROMS) were recorded from 0 to 52weeks for 63 consecutive joints. Results: Compared with baseline, there were significant improvements in all PROMS from 2 to12weeks and maintained at 52weeks. Regression analysis revealed an inverse correlation with BMI and change in PROMS for knee joints. Conclusion: Our observed findings suggest this approach represents a safe, effective treatment for moderate-to-severe knee and shoulder OA, although efficacy may be reduced with increasing obesity.

Sample preparation for lipid analysis of intra-articular adipose tissue by using matrix-assisted laser desorption/ionization imaging

Mass spectrometry imaging (MSI) is a powerful technique enabling the visualization of the spatial distribution of different molecules in tissue biopsies with different pathologies. Sample handling and preparing adipose tissue for MSI is challenging and prone to molecular delocalization due to tissue melting. In this work, we developed a method for matrix-assisted laser desorption/ionization (MALDI)-MSI to study lipids in human infrapatellar fat pad (IPFP), a biomarker source in musculoskeletal pathologies, while preserving molecular spatial distribution. Cryosectioning at 15 μm with a temperature below −30 °C, thaw-mounting, and sublimation, was demonstrated to preserve IPFP's heterogeneous appearance and spatial distribution of lipids.

Intra-articular Soft Tissue Pathology of the Postpartum Hip: A Systematic Review.

Pregnancy-related lumbopelvic and hip pain affects over half of postpartum females and has multiple aetiologies. The relative contribution of intra-articular soft tissue pathology to pregnancy-related hip pain is unknown. The current review investigates the available evidence regarding underlying intra-articular soft tissue aetiologies of hip pain in females during pregnancy and in the acute postpartum period. Three online databases (Embase, PubMed and Ovid [MEDLINE]) were searched from database inception until 11 April 2021. All titles, relevant abstracts and full-text articles were screened by two reviewers independently. The methodological quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) instrument. Descriptive study characteristics are presented in a narrative summary. Five level IV evidence articles were eligible for inclusion. Twenty-two females were included. Twenty patients presented with labral pathology, 15 of which necessitated hip arthroscopy with labral debridement or repair with or without acetabuloplasty and/or femoroplasty. One patient presented with an incidental labral tear in the context of osteitis condensans illi. One patient presented with posttraumatic osteoarthritis necessitating a hip arthroplasty. The contribution of intra-articular soft tissue injury is a documented, albeit sparse, aetiology contributing to pregnancy-related hip pain. Further research to better delineate the prevalence, natural history and optimal management options for females who sustained these injuries at a life-altering juncture is necessary to advance the care of these patients.

Recent Advances in Animal Models, Diagnosis, and Treatment of Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a gradual degenerative jaw joint condition. Until recent years, TMJOA is still relatively unrecognized and ineffective to be treated. Appropriate animal models with reliable detection methods can help researchers understand the pathophysiology of TMJOA and find therapeutic options. In this study, we summarized common animal models of TMJOA created by chemical, surgical, mechanical, and genetical approaches. The relevant pathological symptoms and induction mechanisms were outlined. In addition, different pathological indicators, furthermore, emerging therapeutic regimens, such as intra-articular drug delivery and tissue engineering-based approaches to treat TMJOA based on these animal models, were summarized and updated. Understanding the physiology and pathogenesis of the TMJOA, together using various ways to diagnose the TMJOA, were elaborated, including imaging techniques, molecular techniques for detecting inflammatory cytokines, histochemical staining, and histomorphometry measures. A more reliable diagnosis will enable the development of new prevention and more effective treatment strategies and thereby improve the quality of life of TMJOA patients. Impact statement Temporomandibular joint osteoarthritis (TMJOA) affects 8 to 16 percent of the population worldwide. However, TMJOA is still relatively unrecognized and ineffective to be treated in the clinic. Appropriate animal models with reliable diagnostic methods can help researchers understand the pathophysiology of TMJOA and find therapeutic options. We herein summarized common animal models of TMJOA and various ways to diagnose the TMJOA. More importantly, emerging therapeutic regimens to treat TMJOA based on these animal models were summarized. With the aid of strategies listed, more effective treatment strategies will be developed and thereby improve the life quality of TMJOA patients.

Intra-Articular Biomechanical Changes of the Meniscus and Ligaments During Stance Phase of Gait Circle after Different Anterior Cruciate Ligament Reconstruction Surgical Procedures: A Finite Element Analysis.

The debate on the superiority of single- or double-bundle for anterior cruciate ligament reconstruction has not ceased. The comparative studies on intra-articular biomechanics after different surgical reconstructions are rare. This study is to evaluate the biomechanical stress distribution intra-knee after single- and double-bundle anterior cruciate ligament reconstruction by three-dimensional finite element analysis, and to observe the change of stress concentration under the condition of vertical gradient loads. In this study, magnetic resonance imaging data were extracted from patients and healthy controls for biomechanical analysis. Patients included in the three models were matched in age and sex. The strength and distribution of induced stresses were analyzed in two frequently used procedures, anatomical single-bundle anterior cruciate ligament reconstruction and anatomical double-bundle anterior cruciate ligament reconstruction, using femoral-graft-tibial system under different loads, to mimic a post-operation mechanical motion. The three-dimensional finite-element models for normal ligament and two surgical methods were applied. A vertical force simulating daily walking was performed on the models to assess the interfacial stresses and displacements of intra-articular tissues and ligaments. The evaluation results mainly included the stress of each part of ligament and meniscus. The stress values of different parts of three models were extracted and compared. The stress of ligament/graft at femoral side of three finite-element models was significantly higher than at tibial side, while the highest level was observed in single-bundle reconstruction finite-element model. With the increase of force, the maximum stress in the medial (7.1-7.1 MPa) and lateral (4.9-7.4 MPa) meniscus of single-bundle reconstruction finite-element model shifted from the anterior horn to the central area (p=0.0161, 0.0479, respectively). The stress was shown to be at a lower level at femoral side and posterior cruciate ligament of intra-knee in two reconstruction finite-element models than that in normal finite-element models, while presented higher level at the tibial side than normal knee (p=0.3528). The displacement of the femoral side and intra-knee areas in reconstruction finite-element models was greater than that in normal finite-element model (p=0.0855). Compared with the single-bundle technique, the graft of double-bundle anterior cruciate ligament reconstruction has better stress dissipation effect and can prevent postoperative meniscus tear more effectively.

First Stage Revision of Infected TKR: A Technique of Handcrafted Articulating Spacers and Cement Pancake Soft Tissue Spacers.

This is a study to see if improvised 'articulating antibiotic cement spacers' work in two-stage revisions for infected TKRs with bone defects in the condyles. The second objective is to see if adhesions can be prevented between intra-articular bone and soft tissue around it after the first stage to make exposure of the joint easy and quick in the second stage. Six cases were selected which had moderate defects of femoral or tibial condyles and a modified technique was used to prepare articulating cement spacers. Antibiotic cement moulded like pancakes was placed on the exposed raw areas of the femur and tibia. Patients were mobilised with protected weight-bearing after the surgery and active knee flexion was encouraged. Patients regained a mean of 80 degrees of knee flexion during the interval between the stages and a mean of 100 degrees of flexion following the second stage. There was no bone loss while removing the modified cement spacers. Patients had no significant intra-articular adhesions and hence the exposure of the knee joint during the second stage did not require further intra-articular dissection. Standard articulating spacers are not suitable in the cases with bone loss of the condyles. Our modified technique allowed us to use it in cases with moderate bone loss also where static spacers are used otherwise. This helped to mobilise these knees between the two stages of revision instead of keeping immobilised with static spacers. Antibiotic cement pancakes prevented intra-articular adhesions and carried an extra dose of antibiotic into the joint.

Morphology of the rat knee joint after intraarticular injection of hydroxymethyl-quinoxaline dioxide

Topical antiseptics are widely used in orthopedics and traumatology. However, studies highlighting the effects of antiseptics during long-term use on joint tissues are limited. In the performed work, the peculiarities of the structure of intra-articular tissues of the knee joint and muscles in rats in two series of experiments were noted: control group (saline injection into the joint) and experimental group (hydroxymethyl-quinoxaline dioxide injection into the joint) daily for 5 days. Histological methods with semi-quantitative assessment of articular cartilage and synovial membrane were used. During the first day after the drug administration, similar reactive changes to the injection of saline and hydroxymethyl-quinoxaline dioxide were observed in the joint tissues of the two groups of rats. The synovial membrane of the capsule was thickened, and synoviocytes were hypertrophied. The articular cartilage contains single cells with dense nuclei only in the superficial parts, but in general, the cytoarchitectonics of articular cartilage was preserved. In 5 days after injection, no statistically significant differences between saline and hydroxymethyl-quinoxaline dioxide were observed for the study periods. According to the studies the safety of long-term use of the drug as an antiseptic for articular tissues was confirmed.

Osteoarthritis

Extreme interest in the problem of osteoarthritis (osteoarthrosis, OA) is due to the significant spread of this form of joint pathology. Research in recent years has made it possible to revise our ideas about the pathogenesis of this process with confirmation of the leading role of inflammation in the development of functional and structural damage in the specified pathology. The review article discusses the features of the pathogenesis of OA. It is noted that OA is a complex disease that affects not only cartilage tissue, but also intra-articular and peri-articular tissues. Clinical classification of OA, classification criteria for OA of hand, knee and hip joints are presented. Considered phenotypes of pain in OA, methods of pain assessment. It is noted that the diagnosis of OA of the knee and hand joints in the practice of the doctor is based mainly on the data of the clinical picture; an exception is OA of the hip joints. Presented Consensus for the development of criteria for primary care physicians for the diagnosis of OA using the methodology of red flags, which allows the examination to identify exactly those patients who should be immediately referred to narrow specialists.

Microfragmented Adipose Tissue Versus Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Prospective Randomized Controlled Trial at 2-Year Follow-up

Background: Intra-articular microfragmented adipose tissue (MF-AT) injections have been proposed for the treatment of knee osteoarthritis (OA). Purpose: To compare a single injection of MF-AT or platelet-rich plasma (PRP) in terms of clinical outcomes and OA progression. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 118 patients with symptomatic knee OA were randomized to receive a single intra-articular injection of MF-AT or PRP. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the International Knee Documentation Committee (IKDC) subjective score, Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol visual analogue scale (EQ-VAS), EuroQol 5 dimensions (EQ-5D), and visual analogue scale (VAS) for pain. Primary outcomes were the IKDC subjective score and the KOOS pain subscore at 6 months. Knees were evaluated at baseline and at 6, 12, and 24 months with radiography and high-resolution magnetic resonance imaging (MRI) using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Results: Both MF-AT and PRP provided a statistically and clinically significant improvement up to 24 months. The improvement in the IKDC subjective score from baseline to 6 months was similar in both MF-AT (41.1 ± 16.3 to 57.3 ± 18.8) and PRP (44.8 ± 17.3 to 58.4 ± 18.1) groups (P < .0005). The improvement in the KOOS pain subscore from baseline to 6 months was similar in both the MF-AT (58.4 ± 15.9 to 75.8 ± 17.4) and PRP (63.5 ± 17.8 to 75.5 ± 16.1) groups (P < .0005). Overall, no differences were found between the MF-AT and PRP groups in terms of clinical outcomes, adverse events (18.9% and 10.9%, respectively), and failures (15.1% and 25.5%, respectively). Radiographic and MRI findings did not show changes after the injection. As a secondary outcome, more patients in the MF-AT group with moderate/severe OA reached the minimal clinically important difference for the IKDC score at 6 months compared with the PRP group (75.0% vs 34.6%, respectively; P = .005). Conclusion: A single intra-articular injection of MF-AT was not superior to PRP, with comparable low numbers of failures and adverse events and without disease progression. No differences were found in clinical and imaging results between the 2 biological approaches.

Osteoarthritis: management strategies depending on the location of lesions

Osteoarthritis (OA) is a multifactorial disease that can be caused by genetic factors, obesity, joint microtrauma, and excessive physical exercises. The key features of OA include gradual loss of articular cartilage, bone tissue remodeling, development of osteophytes, and subchondral sclerosis. The pathogenesis of OA is based on the loss of glycosaminoglycans, collagen disorganization, and inflammation mediated by a cytokine cascade. OA is a complex disease affecting not only cartilage, but also intraarticular and periarticular tissues. Together, these changes compromise joint function and cause chronic pain. Considerable attention has beer recently paid to OA phenotyping in order to introduce a tailored approach into patient management. Phenotypes are applicable to the three most common peripheral OA locations: gonarthrosis, coxarthrosis, and hand OA. An international group of experts of primary care has developed algorithms for OA patient management, including diagnostic criteria, treatment options, and criteria for referring the patient to a specialist (rheumatologist). Current guidelines recommend non-drug therapy, pharmacotherapy, and surgery. There is a growing interest in phytopharmaceuticals, a heterogeneous group of molecules with a high capacity of suppressing inflammation, oxidative stress, and pain, as well as improving joint function. Mucosate® in capsules (DIAMED-pharma, Russia) is one of currently available complex products with phytocompounds. It contains the NEM® complex (natural eggshell membrane), Harpagophytum root extract, glucosamine sulfate, chondroitin sulfate, and manganese sulfate monohydrate.

Paper 15: Micro-Fragmented Adipose Tissue versus Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Prospective Randomized Controlled Trial at 2-year follow-up

Objectives:Pre-clinical and clinical studies supported the use of intra-articular micro-fragmented adipose tissue (MF-AT) injections to address knee osteoarthritis (OA), suggesting their safety and clinical benefits. Nevertheless, no high-level studies investigated the potential of MF-AT over other biological products like platelet-rich plasma (PRP). The aim of this randomized controlled trial (RCT) was to compare a single injection of MF-AT to PRP in terms of clinical outcome and disease-modifying properties in patients with symptomatic knee OA.Methods:A total of 118 patients with symptomatic knee OA were randomly assigned to: single intra-articular MF-AT vs single intra-articular PRP injection. All patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the International Knee Documentation Committee (IKDC) subjective score, the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscales, the EuroQol-Visual Analogue Scale (EQ-VAS) and EuroQol-5D (EQ-5D), and the Visual Analogue Scale (VAS). The treated knees were evaluated at baseline and at 6, 12, and 24 months of follow-up with radiographs and high-resolution (1.5 T) magnetic resonance imaging (MRI) with the Whole-Organ Magnetic Resonance Imaging Score (WORMS).Results:Both MF-AT and PRP provided a statistically and clinically significant improvement up to the last follow-up of 24 months. No differences were found between MF-AT and PRP groups in terms of adverse events (18.9% vs 10.9%), failures (15.1% vs 25.5%), and all clinical outcomes at all follow-ups. Radiographs and MRI findings did not show significant changes after the injection, neither as improvement, nor as disease progression, with no intergroup difference. Patients with moderate/severe OA treated with MF-AT showed a significantly higher IKDC improvement at 6 months compared to PRP (15.7±19.0 vs 8.6±14.2, p=0.041). Similarly, more patients with moderate/severe OA treated with MF-AT reached the minimal clinically important difference (MCID) for the IKDC subjective score at 6 months compared to the PRP group (75.0% vs 34.6%, p=0.005).Conclusions:A single intra-articular injection of both MF-AT and PRP provided a significant clinical improvement up to 24 months in patients with symptomatic knee OA. Both treatments showed a comparable low number of failures and adverse events, without signs of disease progression. Overall, no differences could be documented in both clinical and imaging results between the two biological approaches. Compared with PRP, MF-AT provided a higher clinical improvement at 6 months in moderate-severe OA.

Correlation of systemic metabolic inflammation with knee osteoarthritis.

The aim of this study was to analyze local and systematic inflammatory status in knee osteoarthritis (KOA), focusing on intra-articular and remote adipose tissue depots, and to explore its potential association with metabolic syndrome (MetS). Patients (n = 27) with end-stage KOA were enrolled in the study and samples from infrapatellar fat pad (IFP), synovium, subcutaneous adipose tissue (SAT), synovial fluid (SF), and serum were collected. In homogenates from the tissues, mRNA expression of developmental endothelial locus-1 (DEL-1) was determined. Interleukin 6 (IL-6) and interleukin 8 (IL-8) were measured in tissues and SF and serum samples by enzyme-linked immunosorbent assay. Fifteen patients fulfilled MetS criteria (w-MetS group) and 12 did not (non-MetS). In the entire population, IL-6 levels were significantly higher in IFP compared to synovium (median (interquartile range), 26.05 (26.16) vs. 15.75 (14.8) pg/mg of total protein, p = 0.043), but not to SAT (17.89 (17.9) pg/mg); IL-8 levels were significantly higher in IFP (17.3 (19.3) pg/mg) and SAT (24.2 (26) pg/mg) when compared to synovium (8.45 (6.17) pg/mg) (p = 0.029 and < 0.001, respectively). Significantly higher IL-6 concentrations in SF were detected in w-MetS patients compared to non-MetS (194.8 (299) vs. 64.1 (86.9) pg/ml, p = 0.027). Finally, DEL-1 mRNA expression was higher in IFP compared to synovium (eightfold, p = 0.019). Our findings support the critical role of IFP in knee joint homeostasis and progression of KOA. Furthermore, in KOA patients w-MetS, SAT is thought to play an important role in intra-knee inflammation via secretion of soluble inflammatory mediators, such as IL-6.

Platelet-Rich Plasma for Musculoskeletal Disorders: No Infection Reported in Daily Practice

Background: Platelet-rich plasma is an autologous blood product defined by a concentration of platelets higher than baseline. Enough evidence supports its application for the treatment of orthopedic disorders. Objectives: The aim of this study was to report the absence of infection and/or complication events related to platelet-rich plasma treatment in patients with musculoskeletal disorders of diverse etiologies. Methods: This transversal and descriptive study included a total of 513 patients, presenting either common orthopedic disorders or hemophilic synovitis/arthropathy. Peripheral whole blood was collected in the presence of anticoagulant and centrifuged. Platelet-rich fraction was separated under sterile conditions. Before injection, the affected area was sanitized and covered with sterile field drapes. Injections were performed in the procedure room under ultrasound image. No anesthesia or antibiotics were administered. Data were analyzed using Pearson’s chi-square test and Cramer’s V test. Results: Of the 923 procedures, 63.2% were intra-articular, and 36.8% were performed in soft tissues. Intra-articular injections were more common in patients with hemophilia, compared with patients without hemophilia (P &lt; 0.001). The most commonly affected anatomical sites were: the knee, the ankle, the hip, and the elbow, with a higher prevalence of ankle and elbow disorders in patients with hemophilia, compared with patients without hemophilia (P &lt; 0.001). Among patients with hemophilia, 13 presented HCV infection, one presented HIV infection, and three were coinfected with HCV and HIV. Twelve patients presented inhibitors. No complications were observed during blood extraction or after platelet-rich plasma injection. No infections occurred at the site of injection. Conclusions: Our platelet-rich plasma preparation and administration protocol under sterile conditions considerably reduce the chances of contamination and further complications associated with it. The occurrence of infection after intra-articular or soft tissue injection was nil in this study, even in patients with hemophilia.