Progression Of Arthritis Research Articles

‘It surprised me a lot that there is a link’: a qualitative study of the acceptability of periodontal treatment for individuals at risk of rheumatoid arthritis

ObjectivesCurrent evidence suggests that periodontal disease could be a causal risk factor for rheumatoid arthritis (RA) onset and progression. Earlier periodontal intervention in individuals at risk of RA could provide...

Tillaux Fracture Associated with Adult Ankle Fracture Injury.

Tillaux fractures in adults are rare and, if unrecognized, can lead to ankle fracture healing complications, early progression of arthritis, and limited ankle movement caused by pain and degenerative changes. The Tillaux fracture was first described by Paul Tillaux as an external rotation injury of the ankle, involving an avulsion fracture of the distal anterolateral tibia. This fracture can be easily overlooked on plain radiographs in the adult. A high index of suspicion for this type of fracture pattern along with the use of computed tomographic scanning can help confirm the suspected diagnosis, rule out other tibial injuries, and provide more information on the best course of action. Historically, Tillaux fractures have been more common in adolescents because of the open tibial epiphyseal plate. Once the epiphyseal plate fully closes, skeletal maturity is achieved, thus making it extremely unusual for the anterior tibiofibular ligament to cause an avulsion fragment of the distal anterolateral tibia. Because of how uncommon this type of fracture is in adults, it has rarely been reported in our literature. We reviewed the literature and present a case report of this rare fracture injury.

Lonicerin alleviates the progression of experimental rheumatoid arthritis by downregulating M1 macrophages through the NF-κB signaling pathway.

The present study aimed to evaluate anti-rheumatoid arthritis (RA) effect of Lonicerin (LON), a safe compound with anti-inflammatory and immunomodulatory properties. Nevertheless, the exact role of LON in RA remains elusive. In this test, the anti-RA effect of LON was evaluated in collagen-induced arthritis (CIA) mouse model. Relevant parameters were measured during the experiment; ankle tissue and serum were collected at the end of the experiment for radiology, histopathology, and inflammation analysis. ELISA, qRT-PCR, immunofluorescence, and western blot were used to explore the effect of LON on the polarization of macrophages and related signal pathways. It was discovered that LON treatment attenuated the disease progression of CIA mice with lower paw swelling, clinical score, mobility, and inflammatory response. LON treatment significantly decreased M1 marker levels in CIA mice and LPS/IFN-γ-induced RAW264.7 cells, while slightly increasing M2 marker levels in CIA mice and IL-4-induced RAW264.7 cells. Mechanistically, LON attenuated the activation of the NF-κB signaling pathway, which contributes to M1 macrophage polarization and inflammasome activation. In addition, LON inhibited NLRP3 inflammasome activation in M1 macrophages, thereby reducing inflammation by inhibiting IL-1β and IL-18 release. These results indicated that LON might exert anti-RA effects by regulating the polarization of M1/M2 macrophage, especially by inhibiting macrophage polarization toward M1.

Serum substance P level as a marker for subclinical rheumatoid arthritis activity

ABSTRACT Background Regular assessments of disease activity are essential to prevent the progression of rheumatoid arthritis (RA). Aim of the work This study aimed to assess the utility of serum substance P (SP) level as a marker for RA activity and to establish the value of SP level for the diagnosis of subclinical RA activity. Patients and Methods The study included three groups each 30. subject Group 1 was with minimal or no disease, group 2 had moderate to severe disease activity and group 3 was healthy controls. RA patients were assessed using a Disease Activity Score-28 (DAS28) and power Doppler ultrasonography measurement of the synovitis total score. The serum substance P levels of study groups were assessed using ELISA technique. Results Statistically significant difference in serum SP level was detected in RA patients compared to controls (p ≤ 0.001) and between different disease activity groups (p ≤ 0.001). The best cut off SP value to distinguish patients in subclinical activity active disease patients was 555.5 pg/ml. This had a diagnostic sensitivity, specificity, and accuracy of 96.7%, 80% and 88.3 %, respectively. Conclusion Serum SP can be used as an indicator of RA disease activity even in those with subclinical activity.

Nanoparticle based dnmt3b gene therapy attenuates arthritis progression in a murine injury model

Nanoparticle based dnmt3b gene therapy attenuates arthritis progression in a murine injury model

Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis

T regulatory cells (Tregs) are a potential therapeutic target in many autoimmune diseases including rheumatoid arthritis (RA). The mechanisms responsible for the maintenance of Tregs in chronic inflammatory conditions such as RA are poorly understood. We employed our mouse model of RA in which, the following deletion of Flice-like inhibitory protein in CD11c+ cells, CD11c-FLIP-KO (HUPO) mice develop spontaneous, progressive, erosive arthritis, with reduced Tregs, and the adoptive transfer of Tregs ameliorates the arthritis. HUPO thymic Treg development was normal, but peripheral of Treg Foxp3 was diminished mediated by reduction of dendritic cells and interleukin-2 (IL-2). During chronic inflammatory arthritis Tregs fail to maintain Foxp3, leading to non-apoptotic cell death and conversion to CD4+CD25+Foxp3- cells. Treatment with IL-2 increased Tregs and ameliorated the arthritis. In summary, reduced dendritic cells and IL-2 in the milieu of chronic inflammation, contribute to Treg instability, promoting HUPO arthritis progression, and suggesting a therapeutic approach in RA.

P141 Periodontal assessment and treatment among individuals at-risk of rheumatoid arthritis: a qualitative study

Abstract Background/Aims Periodontitis is a chronic inflammatory disease affecting almost half of adults in the UK and is a leading cause of tooth loss. Current evidence suggests that periodontitis could be a causal risk factor for rheumatoid arthritis (RA) onset and progression, and periodontal treatment may improve disease activity in patients with established RA. Earlier periodontal intervention in individuals at-risk of RA could provide a unique opportunity to delay progression or prevent it entirely. This study aimed to explore the perceptions of oral health among individuals at-risk of developing RA and the perceived acceptability of preventive periodontal treatment. Methods This was a qualitative interview study employing a phenomenological approach. Anti-CCP positive at-risk individuals with musculoskeletal symptoms but no synovitis were recruited from the Leeds CCP cohort. Periodontal assessments and treatment were delivered by a dentist and/or oral hygiene therapist. Individual semi-structured interviews were conducted via video or telephone between March-June 2022. Interviews were audio-recorded and transcribed verbatim. Data were analysed using reflexive thematic analysis. Results Nineteen participants (ten women; age range 35-70) were interviewed. All had been offered periodontal assessment and treatment; four declined and nine had periodontal treatment. Three themes were identified: i) understanding risk; ii) oral health perceptions and experiences; iii) oral health treatment and maintenance. The majority of participants lacked awareness of the association between oral health and the risk of developing RA, and perceived lack of knowledge of this link among dentists. Preference for information provision relating to oral health as a risk factor varied extensively between participants. Negative perceptions towards dental appointments were common. Many participants identified the cost of dental treatment as an issue and expressed difficulty in accessing NHS dentists. Participants discussed oral health issues such as bleeding and sore gums, chipped and weak teeth, infections, and missing teeth. However, oral health was less of a priority when compared to comorbidities that had a bigger impact on daily life. Participation in a clinical trial involving preventive periodontal treatment was perceived to be acceptable for most participants. Facilitators included the personal benefits of being able to reduce risk, access a dentist, and not having to pay for treatment. Participants with dental phobia highlighted that seeing the same dentist at every visit was important. Perceived barriers included the location and time of appointments. Conclusion The impact of poor oral health may not be well understood by individuals at-risk of RA. Information relating to this risk factor should be tailored to the individual. Whilst periodontal disease is common in individuals at-risk of RA, seeking dental treatment can be hindered by dental phobia, treatment cost, or shortage of NHS dentists. A clinical trial involving preventive periodontal treatment is potentially acceptable for individuals at-risk of RA. Disclosure L.S. Chapman: None. K.A. Vinall-Collier: None. H.J. Siddle: None. Z. Mustufvi: None. K. Mankia: None. S. Serban: None.

P130 Transcriptomic analysis of synovitis identifies inhibition of CXCL1 as a mechanism contributing to resolution of inflammatory arthritis under IL-27 control

Abstract Background/Aims Interleukin-27 (IL-27) regulates adaptive immune responses and is critical for the timely resolution of inflammation to restore tissue homeostasis. Studies have highlighted roles for IL-27 in limiting immune cell effector function, stromal cell responses and erosive joint pathology in clinical rheumatoid arthritis and experimental models of the disease. In the murine antigen-induced arthritis (AIA) model, IL-27 receptor-deficient (Il27ra-/-) mice develop severe synovitis associated with increased infiltration of synovial CD4+ T cells, development of synovial ectopic lymphoid-like structures and exacerbated cartilage and bone erosion. Similarly, mice with collagen-induced arthritis (CIA) administered IL-27 show improved joint pathology and reduced serum IFN-γ and IL-17 levels. Identifying mechanisms by which IL-27 regulates arthritis progression is key to understanding its therapeutic potential. Using RNA-sequencing of synovial tissue and joint-infiltrating CD4+ T cells we reveal that IL-27 regulates the magnitude of synovitis and genes in CD4+ T cells central to neutrophil recruitment. Methods Antigen-induced arthritis (AIA) was established in Il27ra-/- and wild-type control mice. RNA-sequencing was performed on whole synovial tissue and joint-infiltrating CD4+ T cells during the peak of joint inflammation and during the resolution of synovitis. Differentially expressed genes were interrogated by molecular pathway analysis and gene set enrichment analysis. CD4+ T cell culture assays, qPCR and ELISA were used to test and validate genes under IL-27 regulation. Results RNA-sequencing of whole synovial tissue revealed that pathways relating to CD4+ T cell and Th17 biology were significantly overrepresented in Il27ra-/- mice with AIA, consistent with a pathogenic role for these cells in inflammatory arthritis. Genes associated with neutrophil effector function (e.g. Elane, Padi4, Prtn3) and recruitment (e.g. Cxcl1, Cxcr2) were also highly expressed in Il27ra-/- synovium and was reflected in the increased number of Ly6G+CD11b+ neutrophils recovered from the joints of Il27ra-/- mice. In contrast to the transcriptomic analysis of inflamed synovial tissue, surprisingly RNA-sequencing of joint-infiltrating CD4+ T cells revealed that the expression of signature Th17 genes (e.g. Il17a, Il17f, Rorc) was comparable between WT and Il27ra-/- T cells. This implies that IL-27 predominantly regulates the magnitude of the joint CD4+ T cell infiltrate more than the effector characteristics of the infiltrating T cells. Differential gene expression analysis revealed heightened Cxcl1 expression in both whole synovial tissue and joint-infiltrating CD4+ T cells recovered from Il27ra-/- mice with AIA. CD4+ T cell differentiation cultures confirmed upregulation of Cxcl1 following T cell receptor activation and under Th1 polarizing conditions. Here, IL-27 suppressed the expression of CXCL1 at the mRNA and protein level. Conclusion Together, our data reveals a role for IL-27 in limiting CXCL1 expression in activated and joint-infiltrating CD4+ T cells, highlighting a novel mechanism by which IL-27 may integrate innate and adaptive arms of the immune response to regulate arthritis progression. Disclosure I. Burridge: None. S. Eastham: None. D.G. Hill: None. R. Andrews: None. B. Szomolay: None. N. Williams: None. S.A. Jones: None. G.W. Jones: None.

Humeral Head Three-Part Posterior Fracture-Dislocation Reduced through a Posterior Approach and Fixed with Blocked Threaded Wires: A Consecutive Case Series.

Background and Objectives: Posterior fracture dislocations are rare. There is currently no uniformity regarding treatment. Therefore, outcomes are difficult to compare. We evaluated clinical and radiological outcomes of patients with humeral head posterior fracture dislocation treated with an open posterior reduction and then fixed with a biomechanically validated configuration of blocked threaded wires. Materials and Methods: 11 consecutive patients with humeral head three-part posterior fracture dislocation were treated by reduction through a posterior approach and fixed with blocked threaded wires. All patients were clinically and radiographically evaluated after a mean follow-up of 50 months. Results: The mean irCS was 86.1% (range: 70.5-95.3%). No significant difference was found between irCS at 6 and 12 months postoperatively and the final follow-up. Six patients noted their pain intensity as 0/10, three as 1/10, and two as 2/10. The postoperative reduction was considered as excellent in eight patients (Bahr's criteria) and good in the remaining three; at the final follow-up, reduction was excellent and good in seven and four patients, respectively. The mean neck-shaft angles at FU 0 and at the final FU were 137° and 132°, respectively. No signs of avascular necrosis, non-union, and arthritis progression were seen. No recurrence of dislocation or posterior instability symptoms were reported. Conclusions: We believe that our very satisfactory results stem from: (1) the manual reduction of the dislocation through a vertical posterior surgical approach, which does not produce further osteocartilaginous damage of the humeral head; (2) no multiple perforations of the humeral head are performed; (3) the threaded wires have a smaller diameter than the screws, therefore they preserve the bone tissue of the humeral head; (4) deperiostization or further detachment of soft tissues are not expected; (5) the adopted and validated system is stable and limits translation, torsion, and the collapse of the humeral head.

Vascularized Bone Grafts from the Lateral Femoral Condyle for the Treatment of Avascular Lunate Necrosis (Kienböck's).

Avascular necrosis of the lunate (Kienböck's disease) is rare and one of the main causes of progressive painful arthritis, requiring surgical intervention. Various approaches have shown benefits in treating Kienbock's disease but with limitations. The article aims to analyze the functional outcome using lateral femoral condyle free vascularized bone grafts (VBGs) as the first choice of treatment for Kienböck`s. This was a retrospective analysis of 31 patients with Kienbock's who had microsurgical revascularization or reconstruction of the lunate between 2016 and 2021 using either corticocancellous or osteochondral VBGs from the lateral femoral condyle. The characteristics of lunate necrosis, choice of VBG and postoperative functional outcome were reviewed. Corticocancellous VBGs were used in 20 patients (64.5%), while osteochondral VBGs in 11 patients (35.4%). The lunate was reconstructed in 11 patients, revascularized in 19 patients, and one patient received augmentation of a luno-capitate arthrodesis with a corticocancellous graft. We noted postoperative irritation of the median nerve (n = 3) and screw loosening requiring removal (n = 1) as minor complications. All patients had complete graft healing at eight-month follow-up and acceptable functional outcomes. Free VBG from the lateral femoral condyle represent a reliable method of lunate revascularisation or reconstruction in advanced Kienböck's. Their main advantages are the constant vascular anatomy, straightforward graft harvesting technique and possibility to harvest several graft types according to the requirements at the donor site. Postoperatively, the patients become pain-free and have an acceptable functional outcome.

The Utility of Peptide Ligand-Functionalized Liposomes for Subcutaneous Drug Delivery for Arthritis Therapy.

Liposomes and other types of nanoparticles are increasingly being explored for drug delivery in a variety of diseases. There is an impetus in the field to exploit different types of ligands to functionalize nanoparticles to guide them to the diseased site. Most of this work has been conducted in the cancer field, with relatively much less information from autoimmune diseases, such as rheumatoid arthritis (RA). Furthermore, in RA, many drugs are self-administered by patients subcutaneously (SC). In this context, we have examined the attributes of liposomes functionalized with a novel joint-homing peptide (denoted ART-1) for arthritis therapy using the SC route. This peptide was previously identified following phage peptide library screening in the rat adjuvant arthritis (AA) model. Our results show a distinct effect of this peptide ligand on increasing the zeta potential of liposomes. Furthermore, liposomes injected SC into arthritic rats showed preferential homing to arthritic joints, following a migration profile in vivo similar to that of intravenously injected liposomes, except for a less steep decline after the peak. Finally, liposomal dexamethasone administered SC was more effective than the unpackaged (free) drug in suppressing arthritis progression in rats. We suggest that with suitable modifications, this SC liposomal treatment modality can be adapted for human RA therapy.

Incidence and progression of osteoarthritis following curettage and cementation of giant cell tumor of bone around the knee: long-term follow-up

BackgroundGiant cell tumor of bone (GCTB) is a benign locally aggressive tumor frequently treated with intralesional curettage and cementation. The aim of this study was to investigate the long-term incidence of arthritic changes following curettage and cementation of GCTB around the knee.Materials and methodsThis study was a retrospective review of patients with GCTB around the knee treated with curettage and cementation with a minimum follow-up of 10 years. The functional results were assessed using the Musculoskeletal Tumor Society (MSTS) score. The arthritic changes were classified using the Kellgren–Lawrence (KL) classification system of osteoarthritis.ResultsThis study included 119 patients, 54 males and 65 females, with a mean age of 29.4 ± 9.2 years. There were 35 (29.4%) patients with pathological fractures. There were 84 (70.6%) patients with de novo lesions and 35 (29.4%) with recurrent lesions. The mean follow-up period was 13.2 ± 3.16 years. The mean MSTS score was 28.5 ± 1.9. Overall, 25 (21%) patients developed variable degrees of arthritis of KL grade 1 (n = 7), KL grade 2 (n = 11), KL grade 3 (n = 4), and KL grade 4 (n = 3). Ten patients showed progression of arthritis during the follow-up period. Age at presentation, gender, presence of pathological fracture, whether the tumor was de novo or recurrent, and tumor location were not associated with arthritis incidence.ConclusionsCurettage and cementation can be used safely to treat GCTB around the knee. Arthritis of the knee is a possible complication, but mild grades are expected in most cases. There was no association between arthritis incidence and age, gender, pathological fractures, tumor location, or recurrent tumors.Level of evidenceLevel IV.

Evaluation of 18F-FAPI-04 Imaging in Assessing the Therapeutic Response of Rheumatoid Arthritis.

Fibroblast activating protein (FAP) is highly expressed in the synovial tissues of rheumatoid arthritis (RA) patients. The aim of this study was to determine the feasibility of PET imaging with an Al[18F] F-NOTA-labeled FAP inhibitor 04(18F-FAPI-04) for the evaluation of arthritic progression and therapeutic response in experimental arthritis. Fibroblast-like synoviocytes (FLSs) were obtained from patients with RA or osteoarthritis (OA), and the relationship between 18F-FAPI-04 uptake and the inflammatory activity of RA FLSs was investigated. Collagen-induce arthritis (CIA) mice models were established and treated with methotrexate (MTX) or etanercept (ETC). Then, PET imaging was performed 24h following 18F-FAPI-04 injection. The imaging results were compared by assessing macroscopic arthritis scores and histological staining. 18F-FAPI-04 uptake was obvious in RA FLSs that characterizing FAP activation. The higher the uptake of 18F-FAPI-04, the more severity of the inflammatory phenotype in RA FLS. Furthermore, the uptake of 18F-FAPI-04 in inflamed joints could be found even before the deformity of the parental joints could be observed by histological examination. Both MTX and ETC were effective in inhibiting the progression of arthritis in CIA mice was confirmed by macroscopic, histological, and radiographic pathology scores. Importantly, 18F-FAPI-04 uptake declined accordingly in CIA models following MTX and ETC treatment. These findings suggest that PET imaging of 18F-FAPI-04 can be used to monitor treatment response in RA, and is more sensitive in disease speculation than macroscopic arthritis scoring.

Evaluation of articular changes using a rat mono-iodoacetate-induced shoulder arthritis model by histology and radiology.

The rat mono-iodoacetate (MIA) arthritis model has been used in studies on the hip, knee, and ankle joints. Few studies have explored its utility in shoulder arthritis research, and none have evaluated the effects of time and different MIA doses on arthritis progression. Therefore, we developed a rat MIA shoulder arthritis model to evaluate articular changes through radiological and histological analyses. Sprague-Dawley rats (n = 108) were equally divided into groups that were intra-articularly injected with 0.5 mg of MIA (in 50 µL of purified water), 2.0 mg of MIA (in 50 µL of purified water), or purified water (50 µL; sham group). Throughout the study period, 18 rats (six per group) were evaluated by computed tomography and assessed using the Larsen's classification system; 90 rats were further evaluated histologically using the Osteoarthritis Research Society International scoring system. Computed tomography revealed that the groups injected with MIA developed arthritis and osteophytes 14 days after injection, which progressed temporally. The Larsen's grades worsened over time; at all time points, the scores were higher in the group injected with 2.0 mg of MIA than in the group injected with 0.5 mg of MIA. Furthermore, concurrent with the worsening Larsen's grades, the Osteoarthritis Research Society International scores also significantly increased over time; at all time points, they were higher in the group injected with 2.0 mg of MIA than in the group injected with 0.5 mg of MIA. Our rat MIA shoulder arthritis model revealed radiologically and histologically confirmed temporal and MIA dose-dependent arthritic changes.

Treg-targeted efficient-inducible platform for collagen-induced arthritis treatment.

Regulatory T cells (Tregs) display great promise in rheumatoid arthritis (RA) therapy. However, their low number and differentiation rate limit their further application in the clinics. In the present study, we first optimized a combination of IL-2, TGF-β and cyclin dependent kinase inhibitor AS2863619 (IL-2/TGF-β/AS), which could induce Tregs with high efficiency in vitro. After the induced Tregs (iTregs) were confirmed to suppress lymphocyte proliferation and pro-inflammatory T help cells (Th1 and Th17) activation, a chitosan-stabilized nanoparticle drug delivery system (NDDS) was developed according to the optimized formula of IL-2/TGF-β/AS. In vivo study, the NDDS was injected into the knees of mice with collagen-induced arthritis (CIA). As a result, the NDDS remarkably reduced the pathological score of the CIA, alleviated the inflammatory cell infiltration and synovial hyperplasia, and minimized cartilage tissue damage in the knee joint of the CIA mice. Mechanically, the NDDS administration promoted Treg differentiation and decreased Th17 production, consequently reversing the ratio of Treg/Th17, and reducing the secretion of TNF-α in the sera, which facilitated to relieve the severity and progression of arthritis. In sum, NDDS capable of efficiently inducing Tregs were constructed successfully and provided a potential platform for treating RA by restoring the equilibrium of Treg/Th17 destroyed in RA.

An Efficient CNN for Hand X-Ray Classification of Rheumatoid Arthritis

Hand radiography is the initial imaging test for the monitoring of rheumatoid arthritis (RA) progress. Identifying the exact stage of RA is a complex task, as human capabilities often limit the methods of diagnosis involved.Convolutional Neural Network(CNN) is the core for hand detection for identifying intricate patterns. The human brain functions in an advanced manner, so CNN has been designed based on biological neural networks in the human brain for mimicking its complex functions.This paper therefore introduces the Convolutional Neural Network (CNN) that can automatically learn the characteristics and predict the class of hand radiographs from a broad data set.The simulation of the CNN intermediate layers, which describes the dynamics of the current network, is also shown. For model preparation, the 290 hand x-ray dataset is used. The result indicates that hand x-rays are rated with an accuracy of 94.46% by the proposed methodology. The network sensitivity is 0.95 and 0.82 is the specificity.

Apelin-13, a regulator of autophagy, apoptosis and inflammation in multifaceted bone protection.

Apelin/APJ is widely distributed in various tissues in the body and participates in the regulation of physiological and pathological mechanisms such as autophagy, apoptosis, inflammation, and oxidative stress. Apelin-13 is an adipokine family member with multiple biological roles and has been shown to be involved in the development and progression of bone diseases. In the process of osteoporosis and fracture healing, Apelin-13 plays an osteoprotective role by regulating the autophagy and apoptosis of BMSCs, and promotes the osteogenic differentiation of BMSCs. In addition, Apelin-13 also attenuates the progression of arthritis by regulating the inflammatory response of macrophages. In conclusion, Apelin-13 has an important connection with bone protection, which provides a new strategy for the clinical treatment of bone-related diseases.

Celastrol suppresses humoral immune responses and autoimmunity by targeting the COMMD3/8 complex.

Celastrol, a bioactive molecule extracted from the Tripterygium wilfordii plant, has been shown to exhibit anti-inflammatory properties. However, its mechanism of action has not been fully elucidated. Here, we show that celastrol suppresses humoral immune responses and autoimmunity by disabling a protein complex consisting of copper metabolism MURR1 domain-containing (COMMD) 3 and COMMD8 (COMMD3/8 complex), a signaling adaptor for chemoattractant receptors. Having demonstrated the involvement of the COMMD3/8 complex in a mouse model of rheumatoid arthritis, we identified celastrol as a compound that covalently bound to and dissociated the COMMD3/8 complex. Celastrol inhibited B cell migration, reduced antibody responses, and blocked arthritis progression, recapitulating deficiency of the COMMD3/8 complex. These effects of celastrol were abolished in mice expressing a celastrol-resistant mutant of the COMMD3/8 complex. These findings establish that celastrol exerts immunosuppressive activity by targeting the COMMD3/8 complex. Our study suggests that the COMMD3/8 complex is a potentially druggable target in autoimmune diseases and points to celastrol as a lead pharmacologic candidate in this capacity.

Assessing the potential of epigenetic targets as biomarkers in the diagnosis and treatment of rheumatoid arthritis

ABSTRACT Introduction Although there are gold-standard diagnostic guidelines and effective treatments to slow the disease progression of rheumatoid arthritis (RA), approximately 40% of patients still do not respond adequately to their initial treatment. The identification of specific and sensitive biomarkers for early and accurate diagnosis and response to treatment is a clinical priority and could reduce the time to effective therapy to mitigate the severity of tissue damage. Emerging studies show that epigenetic biomarkers play a role in RA-related pathways and are worthy targets that warrant further characterization. Areas covered In this review, the current significant literature around epigenetic studies of RA will be discussed, specifically, DNA methylation and histone modifications, being the most extensively studied. The pitfalls of biomarker studies in RA and how to potentially overcome barriers to their clinical application will be discussed. Expert opinion Epigenetic studies have shed light on mechanisms that mediate RA pathogenesis and potential roles as biomarkers of diagnosis and treatment response in conjunction with other biomarkers. Although these biomarkers are informative, limitations lie in their ease of use in clinical management and the requirement to ensure that the data are robust in large and diverse populations.

Treatment of Sports Injuries in Orthopedic Surgery: Recent Advances

This article reviews the most recent advances in the literature regarding orthopedic surgery for sports injuries. For large-to-massive rotator cuff tears, non-surgical treatment yielded superior results at three months to surgical treatment, although surgical treatment provided better results over time. Arthroscopic partial repair without a posterior interval slide yielded superior results to complete arthroscopic rotator cuff repair with a posterior interval slide. Graft bridging yielded superior results to superior capsular reconstruction. In first-time shoulder dislocations, arthroscopic Bankart repair has yielded superior results to arthroscopic washout. In high-grade acromioclavicular separation, a single clavicle tunnel tendon graft construct is preferable to a double tunnel construct. In femoroacetabular impingement, patients treated with hip arthroscopy had superior short-term results to those treated with physiotherapy alone. The odds of needing anterior cruciate ligament (ACL) graft revision were 2.1-fold higher for patients using a hamstring autograft than those using a patellar bone-tendon-bone (BTB) autograft. The use of a patellar tendon graft reduced the risk of graft rupture. The return-to-sports rate was higher for patients who underwent surgery with a BTB autograft than those with an autograft hamstring. The combination of lateral extra-articular tenodesis and ACL reconstruction-ACLR (single-bundle hamstring autograft) decreased the risk of ACLR failure after two years of follow-up. In complete mid-substance ACL injuries, the bridge-enhanced ACL repair technique resulted in similar outcomes to autograft ACLR. Fresh-frozen allografts have been a good alternative to autografts in ACLR. In posterior medial meniscal root tears, root repair was associated with less arthritic progression than non-surgical treatment and partial meniscectomy. Medial patellofemoral ligament (MPFL) reconstruction has provided better results than MPFL repair in patellofemoral instability.