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.
Abstract The purpose of this article is to review the etiology, economic burden, treatment strategies, and future research directions of arthrofibrosis after total knee arthroplasty (TKA). ...Arthrofibrosis is a debilitating postoperative complication of TKA. This condition is one of the leading causes of hospital readmission and a predominant reason for TKA failure. The prevalence of arthrofibrosis will increase as the annual incidence of TKA in the United States rises into the millions. Characterized by the excessive proliferation of scar tissue during an impaired wound healing response, the resulting stiffness of arthrofibrosis causes functional deficits in activities of daily living, such as walking, stair climbing, and standing from a chair. Postoperative, supervised physiotherapy remains the first line of defense against the development of arthrofibrosis. Also, adjuncts to traditional physiotherapy such as splinting and augmented soft tissue mobilization can be beneficial. The effectiveness of rehabilitation on functional outcomes depends on the appropriate timing, intensity, and progression of the program, accounting for the patient’s ability and level of pain. Invasive treatments such as manipulation under anesthesia, debridement, and revision arthroplasty improve range of motion, but can be traumatic and costly. Future studies investigating novel treatments, early diagnosis, and potential preoperative screening for risk of arthrofibrosis will help target those patients who will need additional attention and tailored rehabilitation to improve TKA outcomes.
Haemarthroses cause major morbidity in patients with haemophilia. Blood has devastating effects on all joint components, resulting in synovitis, osteochondral degeneration and ultimately end‐stage ...haemophilic arthropathy. Key players in this process are iron and inflammation. Preventing joint bleeds is of utmost importance to maintain joint health as targeted therapies directed against blood‐induced inflammation and iron‐mediated processes are lacking. Joint bleeds result in acute pain as well as chronic pain due to synovitis or arthropathy. Acute pain originates from nociceptors activated by tissue damage. In chronic inflammation, central and peripheral sensitization of nociceptors might occur resulting in chronic pain. This also triggers a series of brain disorders such as emotional fear, anxiety, mood depression and impairment of cognitive functions. Treatment of haemophilia‐related pain not only consists of analgesics, but also of exercise, education and in selected cases antidepressants and anticonvulsants. For objective assessment of joint structural outcome and detecting earlier changes of haemophilic arthropathy, both ultrasound (US) and magnetic resonance (MR) imaging have shown valuable. Both can be considered equally able to reveal signs of disease activity. MR imaging is able to visualize haemosiderin deposition and is more comprehensive in depicting osteochondral changes. Disadvantages of MR imaging are the duration of the examination, evaluation of a single joint at a time, costs and may require sedation, and it may need intraarticular contrast injection to depict initial osteochondral changes with accuracy. As such, US is a more useful screening tool and can be used for repeated follow‐up examinations.
Exosomes are a subset of small, membrane-bound extracellular vesicles that are important for communication among cells. They originate from the cell membrane during endocytic internalization, and are ...stable in biological fluids, including blood and synovial fluids. Increasing knowledge is emerging about exosomes in joint diseases, including osteoarthritis, rheumatoid arthritis, osteonecrosis of the femoral head, and others. Exosomes in synovial fluid can lead to inflammation, degeneration of cartilage, and destruction of joints. Exosomes in blood have diagnostic value in the early disease stage or for complicated conditions of joint diseases. Exosomes from stem cells could delay diseases and repair joints. For a comprehensive understanding about the emerging role of exosomes in joint diseases, we introduced the isolation and verification of exosomes from synovial fluid, reviewed the physiological and pathological effects of exosomes on joints, and discussed the diagnostic value and therapeutic potential of exosomes in joint diseases. In the future, immunologically active exosomes and engineered exosomes will of interest in the joint diseases. Challenges in the field of exosomes in joint-disease research include complex and expensive isolation, detection of contributing molecular, effectiveness and safety evaluation. In summary, challenges remain, but the field of exosomes in joint diseases has potential, including in mechanisms, diagnoses and therapies.
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•Focus on disease-modifying approaches for intra-articular drug delivery.•Polymeric particles as platforms for sustained and controlled drug release.•In vivo delivery of nucleic acids ...for cartilage preservation and regeneration.•Stem cell-based tissue-engineered products for cartilage regeneration.
Intra-articular (IA) injections directly deliver high concentrations of therapeutics to the joint space and are routinely used in various musculoskeletal conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, current IA-injected drugs are rapidly cleared and do not significantly affect the course of joint disease. In this review, we highlight recent developments in IA therapy, with a special emphasis on current and emerging therapeutic carriers and their potential to deliver disease-modifying treatment modalities for arthritis. Recent IA approaches concentrate on platforms that are safe with efficient tissue penetration, and readily translatable for controlled and sustained delivery of therapeutic agents. Gene therapy delivered by viral or non-viral vectors and cell-based therapy for cartilage preservation and regeneration are being intensively explored.
The Hip-Spine Challenge Chavarria, Joseph C; Douleh, Diana G; York, Philip J
Journal of bone and joint surgery. American volume,
10/2021, Letnik:
103, Številka:
19
Journal Article
Recenzirano
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.
The Assessment of SpondyloArthritis international Society (ASAS) MRI working group (WG) was convened to generate a consensus update on standardised definitions for MRI lesions in the sacroiliac joint ...(SIJ) of patients with spondyloarthritis (SpA), and to conduct preliminary validation.
The literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC).
No revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83) . Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ICC:0.50/0.37 and 0.58/0.97).
The ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions.
Background Minimal clinically important differences (MCIDs) for the American Shoulder and Elbow Surgeons (ASES) score, the Simple Shoulder Test (SST), and a visual analog scale (VAS) measuring pain ...have not been previously described using an anchor-based method after shoulder arthroplasty. The purpose of this study was to determine the MCIDs for these measures after shoulder arthroplasty for glenohumeral arthritis or advanced rotator cuff disease. Methods Primary anatomic total shoulder arthroplasty (TSA), primary reverse TSA, or hemiarthroplasty was performed in 326 patients by 1 of 5 shoulder and elbow surgeons. The SST score, ASES score, and VAS pain score were collected preoperatively and at a minimum of 2 years postoperatively (mean, 3.5 years). The MCIDs were calculated for the ASES score, SST score, and VAS pain score using an anchor-based method. Results The MCIDs for the ASES score, SST score, and VAS pain score were 20.9 ( P < .001), 2.4 ( P < .0001), and 1.4 ( P = .0158), respectively. Duration of follow-up and type of arthroplasty (anatomic TSA vs reverse TSA) did not have a significant effect on the MCIDs ( P > .1) except shorter follow-up correlated with a larger MCID for the ASES score ( P = .0081). Younger age correlated with larger MCIDs for all scores ( P < .024). Female sex correlated with larger MCIDs for the VAS pain score ( P = .123) and ASES score ( P = .05). Conclusions Patients treated with a shoulder arthroplasty require a 1.4-point improvement in the VAS pain score, a 2.4-point improvement in the SST score, and a 21-point improvement in the ASES score to achieve a minimal clinical importance difference from the procedure.
Total knee arthroplasty (TKA) is one of the most successful orthopaedic procedures that alleviates pain and restores function in patients with degenerative knee joint diseases. Arthrofibrosis, ...abnormal scarring in which dense fibrous tissue prevents normal range of motion, develops in ~3-10% of TKA patients. No prophylactic intervention is available and treatment is restricted to aggressive physiotherapy or revision surgery. Tissue was collected from patients undergoing primary (n = 30) or revision (n = 27) TKA. Revision patients were stratified as non-arthrofibrotic and arthrofibrotic. Tissue was macroscopically and histologically compared to improve our understanding of the pathophysiology of arthrofibrosis. Macroscopically, tissue from primary TKA presents as homogenous, fatty tissue whereas tissue from revision TKA presents as dense, pigmented tissue. Histologically, there was dramatic tissue remodelling, increased collagen deposition and increased (myo)fibroblast staining in tissue from revision TKA. Significantly, tissue architecture was similar between revision patients regardless of clinically diagnosis. There are significant differences in architecture and composition of tissue from revision TKA over primary TKA. Surprisingly, whether revision TKA were clinically diagnosed as arthrofibrotic or non-arthrofibrotic there were still significant differences in fibrotic markers compared to primary TKA suggesting an ongoing fibrotic process in all revision knees.
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