Arthrofibrosis After Total Knee Arthroplasty: A Critical Analysis Review.

¼ Arthrofibrosis after total knee arthroplasty (TKA) is the new formation of excessive scar tissue that results in limited ROM, pain, and functional deficits.¼ The diagnosis of arthrofibrosis is based on the patient's history, clinical examination, absence of alternative diagnoses from diagnostic testing, and operative findings. Imaging is helpful in ruling out specific causes of stiffness after TKA. A biopsy is not indicated, and no biomarkers of arthrofibrosis exist.¼ Arthrofibrosis pathophysiology is multifactorial and related to aberrant activation and proliferation of myofibroblasts that primarily deposit type I collagen in response to a proinflammatory environment. Transforming growth factor-beta signaling is the best established pathway involved in arthrofibrosis after TKA.¼ Management includes both nonoperative and operative modalities. Physical therapy is most used while revision arthroplasty is typically reserved as a last resort. Additional investigation into specific pathophysiologic mechanisms can better inform targeted therapeutics.

Arthrofibrosis - a myth or true joint disorder?

Authors, mostly specialists on rehabilitation and orthopedic surgery prove that arthrofibrosis is a commonly overlooked phenomenon, which may lead to serious limitation in the range of movement, leading to limitation in patients quality of functioning. The main goal of this article is to emphasize the importance of understanding a such complex condition. Non typical patomechanism, lack of biomarkers dedicated to this dysfunction and general lack of understanding in this pathology causes that risk factors and the most effective strategies remain vastly unknown. Pathophysiology of the arthrofibrosis in the joints is definitely multifactorial, but intense production of collagen seems to be the main factor. Most modern pharmacological methods concentrate on the regulation of collagen fiber production and reducing the inflammation. Inflammation from joint contractures stimulates the proliferation of activated cells that results in the production of extracellular matrix macromolecules to form fibrotic tissue that is deposited into the capsule, thereby resulting in fibrosis. Lack of unified classification scale is caused by relatively high variation of the functions fulfilled by particular joints and each treatment plan should be constructed individually. Quality of surgical treatment and physical therapy play a major role in both prevention and treatment of such complex condition as arthrofibrosis. Both iatrogenic mistakes and overly aggressive manual therapy are some of main factors increasing the risk of this pathological condition. Introducing properly conducted physical therapy treatment in the early stage is crucial to main the range of movement and preventing this significant problem.

Efficacy of non-operative treatment of patients with knee arthrofibrosis using high-intensity home mechanical therapy: a retrospective review of 11,000+ patients.

BACKGROUND: Recovery from knee surgery or injury can be hindered by knee arthrofibrosis, which can lead to motion limitations, pain and delayed recovery. Surgery or prolonged physical therapy are often treatment options for arthrofibrosis, but they can result in increased costs and decreased quality of life. A treatment option that can regain lost motion without surgery would help minimize risks and costs for the patient. The purpose of this study was to determine treatment efficacy of high-intensity home mechanical stretch therapy in patients with knee arthrofibrosis. METHODS: Records were reviewed for 11,000+ patients who were prescribed a high-intensity stretch device to regain knee flexion. Initial and last recorded knee flexion and days between measurements were available for 9842 patients (Dataset 1). Dataset 2 was a subset of 966 patients from Dataset 1. These 966 patients had separate more rigorous measurements available from physical therapy notes (Dataset 3) in addition to data from the internal database (Dataset 2). Within and between dataset statistics were calculated using t tests for comparison of means and Cohen's d for determination of effect size. RESULTS: All dataset showed significant gains in flexion (p < 0.01). Mean initial flexion, last recorded flexion and flexion gain were 79.5°, 108.4°, and 29.9°, respectively in Dataset 1. Differences between Datasets 2 and 3 had small effect sizes (Cohen's d < 0.17). The were no significant differences when comparing workers' compensation and non-workers' compensation patients. The average last recorded flexion for all datasets was above the level required to perform activities of daily living. Motion gains were recorded in under 60 days from device delivery. CONCLUSIONS: High-intensity home mechanical stretch therapy was effective in restoring knee flexion, generally in 2 months or less, and in avoiding additional surgery in severe motion loss patients regardless of sex, age, or workers' compensation status. We believe high-intensity stretching should be considered in any patient who is at risk for a secondary motion loss surgery, because in over 90% of these patients, the complications and costs associated with surgery can be avoided.

Management of arthrofibrosis in neuromuscular disorders: a review.

Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism and severity of the precipitating neuromuscular disorder. Most neuromuscular disorders, whether spastic or hypotonic, culminate in decreased joint range of motion. Limited range of motion precipitates a cascade of pathophysiological changes in the muscle-tendon unit, the joint capsule, and the articular cartilage. Resulting joint contractures limit functional mobility, posing both physical and psychosocial burdens to patients, economic burdens on the healthcare system, and lost productivity to society. This article reviews the pathophysiology of arthrofibrosis in the setting of neuromuscular disorders. We describe current non-surgical and surgical interventions for treating arthrofibrosis of commonly affected joints. In addition, we preview several promising modalities under development to ameliorate arthrofibrosis non-surgically and discuss limitations in the field of arthrofibrosis secondary to neuromuscular disorders.

Role of exosomes in bone and joint disease metabolism, diagnosis, and therapy.

Bone and joint diseases are prevalent and often fatal conditions in elderly individuals. Additionally, bone-derived cells may release exosomes that package and distribute a range of active substances, such as proteins, miRNAs, and numerous active factors, thereby facilitating material and information interchange between cells. Exososmes generated from bone may be utilized to manage bone production and resorption balance or even as biological or gene therapy carriers, depending on their properties and composition. In this review, we will discuss the composition, secretion, and uptake theory of exososmes, the role of exososmes in bone metabolism regulation, the pathogenesis and diagnosis of bone and joint diseases, and the application of exososmes in regenerative medicine. The findings will expand our understanding of the potential research and application space regarding exososmes.

Advances in Engineered Three-Dimensional (3D) Body Articulation Unit Models.

Indeed, the body articulation units, commonly referred to as body joints, play significant roles in the musculoskeletal system, enabling body flexibility. Nevertheless, these articulation units suffer from several pathological conditions, such as osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, gout, and psoriatic arthritis. There exist several treatment modalities based on the utilization of anti-inflammatory and analgesic drugs, which can reduce or control the pathophysiological symptoms. Despite the success, these treatment modalities suffer from major shortcomings of enormous cost and poor recovery, limiting their applicability and requiring promising strategies. To address these limitations, several engineering strategies have been emerged as promising solutions in fabricating the body articulation as unit models towards local articulation repair for tissue regeneration and high-throughput screening for drug development. In this article, we present challenges related to the selection of biomaterials (natural and synthetic sources), construction of 3D articulation models (scaffold-free, scaffold-based, and organ-on-a-chip), architectural designs (microfluidics, bioprinting, electrospinning, and biomineralization), and the type of culture conditions (growth factors and active peptides). Then, we emphasize the applicability of these articulation units for emerging biomedical applications of drug screening and tissue repair/regeneration. In conclusion, we put forward the challenges and difficulties for the further clinical application of the in vitro 3D articulation unit models in terms of the long-term high activity of the models.

The use of LED therapy to treat synovial joints disorders: scoping review.

The aim of this scoping review was to assess the extent of the literature on the use of LED therapy to treat synovial joint disorders. The JBI methodology for scoping reviews was followed. The databases used were PUBMED, EMBASE, Scopus, Web of Science, LILACS, PEDro, Cochrane Database, Google Scholar and ProQuest. To be included, studies should have used LED as therapy, and include at least one measure related to the structures of any synovial joint. The search strategy included all keywords and indexed terms identified in the articles. Studies in any language and in any year, whether published or not, were included. The analysis of the studies was carried out by two independent reviewers. Data were extracted from articles using a data extraction tool developed by the reviewers. After carrying out the definitive search and selection, 47 publications were included: 15 clinical trials, 8 clinical protocols, 12 animal studies, 4 in vitro studies and 8 reviews on the topic. Studies have shown great variability from the device and number of diodes used, to the parameters and dosimetry chosen. Some positive effects were observed: on cell proliferation (in vitro); on anti-inflammatory biomarkers (murine models) and on pain scale (clinical trials - TMD). Although, the cause of non-significant results in clinical trials was rarely discussed: depth of penetration, dosimetry, follow-up time? Thus, future studies should focus on answering more elementary aspects about the LED effect when used alone in different synovial joints.

Native joint infections in Iceland 2003-2017: an increase in postarthroscopic infections.

OBJECTIVES: Nationwide study on the epidemiology, clinical characteristics and outcomes among patients with native joint infection (NJI) in Iceland, 2003-2017. METHODS: All positive synovial fluid culture results in Iceland were identified and medical records reviewed. RESULTS: A total of 299 NJI (40 children and 259 adults) were diagnosed in Iceland in 2003-2017, with a stable incidence of 6.3 cases/100 000/year, but marked gender difference among adults (33% women vs 67% men, p<0.001). The knee joint was most commonly affected, and Staphylococcus aureus was the most common isolate in both adults and children, followed by various streptococcal species in adults and Kingella kingae in children. NJI was iatrogenic in 34% of adults (88/259) but comprised 45% among 18-65 years and a stable incidence. Incidence of infections following arthroscopic procedures in adults increased significantly compared with the previous decade (9/100 000/year in 1990-2002 vs 25/100 000/year in 2003-2017, p<0.01) with no significant increase seen in risk per procedure. The proportion of postarthroscopic NJI was 0.17% overall but 0.24% for knee arthroscopy. Patients with postarthroscopic infection were more likely to undergo subsequent arthroplasty when compared with other patients with NJI (p=0.008). CONCLUSIONS: The incidence of NJI in Iceland has remained stable. The proportion of iatrogenic infections is high, especially among young adults, with an increase seen in postarthroscopic infections when compared with the previous decade. Although rare, NJI following arthroscopy can be a devastating complication, with significant morbidity and these results, therefore, emphasise the need for firm indications when arthroscopic treatment is considered.

Past and Future of Phage Therapy and Phage-Derived Proteins in Patients with Bone and Joint Infection.

Phage-derived therapies comprise phage therapy and the use of phage-derived proteins as anti-bacterial therapy. Bacteriophages are natural viruses that target specific bacteria. They were proposed to be used to treat bacterial infections in the 1920s, before the discovery and widespread over-commercialized use of antibiotics. Phage therapy was totally abandoned in Western countries, whereas it is still used in Poland, Georgia and Russia. We review here the history of phage therapy by focusing on bone and joint infection, and on the development of phage therapy in France in this indication. We discuss the rationale of its use in bacterial infection and show the feasibility of phage therapy in the 2020s, based on several patients with complex bone and joint infection who recently received phages as compassionate therapy. Although the status of phage therapy remains to be clarified by health care authorities, obtaining pharmaceutical-grade therapeutic phages (i.e., following good manufacturing practice guidelines or being "GMP-like") targeting bacterial species of concern is essential. Moreover, multidisciplinary clinical expertise has to determine what could be the relevant indications to perform clinical trials. Finally "phage therapy 2.0" has to integrate the following steps: (i) follow the status of phage therapy, that is not settled and defined; (ii) develop in each country a close relationship with the national health care authority; (iii) develop industrial-academic partnerships; (iv) create academic reference centers; (v) identify relevant clinical indications; (vi) use GMP/GMP-like phages with guaranteed quality bioproduction; (vii) start as salvage therapy; (vii) combine with antibiotics and adequate surgery; and (viii) perform clinical trials, to finally (ix) demonstrate in which clinical settings phage therapy provides benefit. Phage-derived proteins such as peptidoglycan hydrolases, polysaccharide depolymerases or lysins are enzymes that also have anti-biofilm activity. In contrast to phages, their development has to follow the classical process of medicinal products. Phage therapy and phage-derived products also have a huge potential to treat biofilm-associated bacterial diseases, and this is of crucial importance in the worldwide spread of antimicrobial resistance.

The Hip-Spine Challenge.

➤: The proper diagnosis and treatment of patients with concurrent hip and spine pathological processes can be challenging because of the substantial overlap in symptomatology. ➤: There is no consensus on which pathological condition should be addressed first. ➤: Factors such as advanced spinal degeneration, deformity, and prior fusion alter the biomechanics of the spinopelvic unit. Attention should be paid to recognizing these issues during the work-up for a total hip arthroplasty as they can result in an increased risk of dislocation. ➤: In patients with concurrent spine and hip degeneration, the surgeon must pay close attention to appropriate implant positioning and have consideration for implants with enhanced stability to minimize the risk of dislocation. ➤: A proper understanding of sagittal balance and restoration of this balance is integral to improving patient outcomes following spinal surgery. ➤: The advent of new imaging modalities, increased awareness of spinopelvic mobility, as well as a better understanding of sagittal alignment will hopefully improve our treatment of patients with hip-spine syndrome.

Iron homeostasis in arthropathies: From pathogenesis to therapeutic potential.

Iron is an essential element for proper functioning of cells within mammalian organ systems; in particular, iron homeostasis is critical for joint health. Excess iron can induce oxidative stress damage, associated with the pathogenesis of iron-storage and ageing-related diseases. Therefore, iron levels in body tissues and cells must be tightly regulated. In the past decades, excess iron content within joints has been found in some patients with joint diseases including hemophilic arthropathy, hemochromatosis arthropathy, and osteoarthritis (OA). Currently, increased evidence has shown that iron accumulation is closely associated with multiple pathological changes of these arthropathies. This review summarizes system-level and intracellular regulation of iron homeostasis, and emphasizes the role of iron in synovial alterations, cartilage degeneration, and subchondral bone of several arthropathies. Of note, we discuss the potential link between iron homeostasis and OA pathogenesis. Finally, we discuss the therapeutic potential of maintaining iron homeostasis in these arthropathies.

Use of autologous products for the treatment of joint and soft tissue disease in horses: A systematic review.

BACKGROUND: Soft tissue injuries and joint disease are the predominate causes of lameness in the equine athlete and these pathologies carry a guarded prognosis for a return to previous performance. Recently the use of autologous products has become more widespread as a treatment in equine sports medicine. However, the efficacy of these products is yet to be fully established. OBJECTIVE: To evaluate the current published evidence base regarding the efficacy of autologous products in soft tissue injuries and joint disease. METHODS: A systematic review of English articles using MEDLINE, EMBASE and Web of Science databases from 1980 to 2017. The search strategy identified 1594 papers for review. RESULTS: Fifty-eight papers were included in this review, 28 of which were randomised controlled trials. Significant benefit was reported under several parameters, most notably in the use of autologous chondrocytes in artificially induced cartilage defects on histology. One paper documented a significant clinical response under lameness examination. CONCLUSION: The current literature shows that the treatment of soft tissue injury and cartilage disease with autologous products is safe and that the use of some products can give significant benefit on some outcome measures. True clinical significance is yet to be demonstrated with any product.

The non-coding RNA interactome in joint health and disease.

Non-coding RNAs have distinct regulatory roles in the pathogenesis of joint diseases including osteoarthritis (OA) and rheumatoid arthritis (RA). As the amount of high-throughput profiling studies and mechanistic investigations of microRNAs, long non-coding RNAs and circular RNAs in joint tissues and biofluids has increased, data have emerged that suggest complex interactions among non-coding RNAs that are often overlooked as critical regulators of gene expression. Identifying these non-coding RNAs and their interactions is useful for understanding both joint health and disease. Non-coding RNAs regulate signalling pathways and biological processes that are important for normal joint development but, when dysregulated, can contribute to disease. The specific expression profiles of non-coding RNAs in various disease states support their roles as promising candidate biomarkers, mediators of pathogenic mechanisms and potential therapeutic targets. This Review synthesizes literature published in the past 2 years on the role of non-coding RNAs in OA and RA with a focus on inflammation, cell death, cell proliferation and extracellular matrix dysregulation. Research to date makes it apparent that 'non-coding' does not mean 'non-essential' and that non-coding RNAs are important parts of a complex interactome that underlies OA and RA.

Current Clinical Concepts: Synthesizing the Available Evidence for Improved Clinical Outcomes in Iliotibial Band Impingement Syndrome.

The current paradigm of insidious lateral knee pain involving the iliotibial band (ITB) in repetitive knee-flexion activities has been termed ITB friction syndrome since 1975. The original model for ITB pain was based on a limited or incorrect understanding of the relevant anatomy, biomechanics, and tissue science, which gradually led to a plethora of frustrating and ineffective interventional strategies. Mounting evidence from arthroscopic, cadaveric, and biomechanical studies, as well as from diagnostic imaging and histologic reports, has helped deconstruct this long-held paradigm for ITB-related pathology and treatment. By outlining the historical paradigm for our understanding of ITB pain and gathering newer evidence through extensive research, I will synthesize the available data in this clinical update to present an updated, more informed model for understanding insidious-onset ITB-related pathology and treating patients. The result is called ITB impingement syndrome.

Relationship between hospital specialization and health outcomes in patients with nonsurgical spinal joint disease in South Korea: A nationwide evidence-based study using national health insurance data.

ABSTRACT: Previous studies on hospital specialization in spinal joint disease have been limited to patients requiring surgical treatment. The lack of similar research on the nonsurgical spinal joint disease in specialized hospitals provides limited information to hospital executives.To analyze the relationship between hospital specialization and health outcomes (length of stay and medical expenses) with a focus on nonsurgical spinal joint diseases.The data of 56,516 patients, which were obtained from the 2018 National Inpatient Sample, provided by the Health Insurance Review and Assessment Service, were utilized. The study focused on inpatients with nonsurgical spinal joint disease and used a generalized linear mixed model with specialization status as the independent variable. Hospital specialization was measured using the Inner Herfindahl-Hirschman Index (IHI). The IHI (value ≤1) was calculated as the proportion of hospital discharges accounted for by each service category out of the hospital's total discharges. Patient and hospital characteristics were the control variables, and the mean length of hospital stay and medical expenses were the dependent variables.The majority of the patients with the nonsurgical spinal joint disease were female. More than half of all patients were middle-aged (40-64 years old). The majority did not undergo surgery and had mild disease, with Charlson Comorbidity Index score ≤1. The mean inpatient expense was 1265.22 USD per patient, and the mean length of stay was 9.2 days. The specialization status of a hospital had a negative correlation with the length of stay, as well as with medical expenses. An increase in specialization status, that is, IHI, was associated with a decrease in medical expenses and the length of stay, after adjusting for patient and hospital characteristics.Hospital specialization had a positive effect on hospital efficiency. The results of this study could inform decision-making by hospital executives and specialty hospital-related medical policymakers.

A survey on Koreans' preferred type of collaboration between conventional medical and traditional Korean medicine doctors.

ABSTRACT: Although collaborative treatment by traditional Korean medicine doctors (KMDs) and medical doctors occurs, it is mainly done by referral. As no survey of the general public's preference for the type of collaboration has ever been conducted, we aimed to investigate Koreans' preferences for a collaborative treatment type.The responders were extracted by random digit dialing and then reextracted using the proportional quota sampling method by sex and age. From July to October 2017, telephone interviews were conducted and the participant responses regarding treatment history for spinal or joint diseases, experiences with collaborative treatment, and preferred type of collaborative treatment were recorded.Of the 1008 respondents, 44.64% reported a history of treatment for spinal or joint diseases at a medical institution. The concurrent collaborative treatment system, in which both KMDs and medical doctors are present in one location participating in the treatment concurrently, was the most preferred system among the respondents. Respondents who reported experience with traditional Korean medicine hospitals were more likely to prefer a one-stop treatment approach than those who did not have experience with traditional Korean medicine hospitals (adjusted odds ratio: 1.73; 95% confidence interval: 1.12-2.68). Respondents who were familiar with collaborative treatment but did not report any personal experience with it were more likely to prefer a one-stop treatment approach than those who were not familiar with collaborative treatment (adjusted odds ratio: 1.82; 95% confidence interval: 1.37-2.44).Koreans prefer a concurrent type of collaborative treatment system by KMDs and medical doctors. Therefore, efforts and support are needed to increase the application of the concurrent type of collaborative system.

Potential of Exosomes for Diagnosis and Treatment of Joint Disease: Towards a Point-of-Care Therapy for Osteoarthritis of the Knee.

In the knee joint, articular cartilage injury can often lead to osteoarthritis of the knee (OAK). Currently, no point-of-care treatment can completely address OAK symptoms and regenerate articular cartilage to restore original functions. While various cell-based therapies are being developed to address OAK, exosomes containing various components derived from their cells of origin have attracted attention as a cell-free alternative. The potential for exosomes as a novel point-of-care treatment for OAK has been studied extensively, especially in the context of intra-articular treatments. Specific exosomal microRNAs have been identified as possibly effective in treating cartilage defects. Additionally, exosomes have been studied as biomarkers through their differences in body fluid composition between joint disease patients and healthy subjects. Exosomes themselves can be utilized as a drug delivery system through their manipulation and encapsulation of specific contents to be delivered to specific cells. Through the combination of exosomes with tissue engineering, novel sustained release drug delivery systems are being developed. On the other hand, many of the functions and activities of exosomes are unknown and challenges remain for clinical applications. In this review, the possibilities of intra-articular treatments utilizing exosomes and the challenges in using exosomes in therapy are discussed.

The Prognosis of Arthrofibroses: Prevalence, Clinical Shortcomings, and Future Prospects.

Fibrosis is the dysregulated biosynthesis of connective tissue that results from persistent infection, high serum cholesterol, surgery, trauma, or prolonged joint immobilization. As a disease that impacts connective tissue, it is prevalent across the body and disrupts normal extracellular and tissue organization. Ultimately, fibrosis impairs the tissue structural, mechanical, or biochemical function. This review describes the clinical landscape of joint fibrosis, that is, arthrofibrosis, including the risk factors and causes, as well as current clinical treatments and their shortcomings. Because treating arthrofibrosis remains an unmet clinical challenge, we present several animal models used for exploration of the physiopathology of arthrofibrosis and summarize their use for testing novel treatments. We then discuss therapeutics for the prevention or treatment of arthrofibrosis that are in preclinical development and in ongoing clinical trials. We conclude with recent findings from molecular biological studies of arthrofibroses that shed insight on future areas of research for improved treatments.

Biologic Therapy in Chronic Pain Management: a Review of the Clinical Data and Future Investigations.

PURPOSE: With the aging population, it is clear that the demand for future chronic pain treatment modalities is at an all-time high. One of the newest treatment modalities that is gaining popularity with both practitioners and patients alike is that of regenerative medicine and the use of stem cells to treat chronic painful conditions. This article aims to distill the most recent, available data from both laboratory research and clinical trials to better illuminate the potentials for these therapies in the treatment of chronic pain. RECENT FINDINGS: There are numerous investigations underway using mesenchymal stem cells (MSCs) to treat painful, largely degenerative conditions. A large majority of these investigations focus on osteoarthritis of the knee and have demonstrated significantly improved pain scores. Some of these investigations have demonstrated significantly increased articular cartilage and meniscus growth as well as improved function. These studies have been smaller (n, 18) and need to be corroborated on a macrolevel. Platelet-rich plasma (PRP)-based therapies have been most extensively studied in the treatment of knee osteoarthritis. Multiple prospective and randomized trials and meta-analyses have afforded level I evidence in support of PRP's safety and efficacy in chronic knee pain demonstrating both decreased pain (via VAS) and increased functional status (via WOMAC and IKDC). There have been randomized controlled trials examining PRP therapies in treatment degenerative disc disease (intradiscal treatment), facet arthropathy (intra-facet injections), and sacroiliitis (SIJ) which have all yielded similar positive results. Each RTC demonstrated decreased pain scores and increased function but lacks the scale to derive concrete guidelines. Newer investigations are underway examining modified PRP formulas with increased fibrin (PRF) or various growth factors (PRGF) and have shown positive outcomes with respect to osteoarthritic conditions in small trials. Animal trials are underway further investigating these therapies as well as specific gene modulation therapies. This review of the most recent investigations into the application and uses of biologic stem cell-derived treatments for chronic painful conditions should act to illustrate the growing, favorable data for these types of modalities both with respect to pain control and functional improvement.