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BackgroundObesity influences the development of osteoarthritis via low-grade inflammation. Progression of local inflammation (= synovitis) increased with weight gain in overweight and obese women compared to stable weight. Synovitis could be associated with subcutaneous fat (SCF) around the knee. Purpose of the study was to investigate the effect of weight loss on synovitis progression and to assess whether SCF around the knee mediates the relationship between weight loss and synovitis progression.MethodsWe included 234 overweight and obese participants (body mass index [BMI] ≥ 25 kg/m2) from the Osteoarthritis Initiative (OAI) with > 10% weight loss (n = 117) or stable overweight (

Objective: To investigate the clinical characteristics of patients who presented with concomitant carpal tunnel syndrome (CTS) at the initial diagnosis with rheumatoid arthritis (RA). Methods: We analyzed patients with newly diagnosed RA at a single institution between 2012 and 2021. Patient demographic and laboratory data, the 2010 ACR/EULAR classification criteria, and the duration from the initial visit to RA diagnosis were compared between RA patients with concomitant CTS (RA with CTS group) and those without CTS (RA without CTS group). Results: The study included 235 patients (157 females), of which 11 patients (4.7%) presented with CTS at the initial diagnosis with RA. In the RA with CTS group, the age was significantly higher (P = .033), all patients were female, and anti-cyclic citrullinated peptide antibody (ACPA) was negative, and the duration to RA diagnosis was longer than in the RA without CTS group. Among all RA with CTS patients, ultrasonography showed power Doppler signal-positive tenosynovitis in the carpal tunnel, which is not usually detected in idiopathic CTS. Conclusions: Patients with concomitant CTS at the initial diagnosis with RA were characterized by old age, female sex, and negative ACPA. Patients with symptoms of CTS should undergo ultrasonography for early diagnosis of RA. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis. RA is routinely treated by various systemic drugs; on the other hand, administration of intra-articular corticosteroids or different types of synovectomies can be used in case of systemic medication's failure. Chemical, radio isotopic, and surgical synovectomies are being used as therapeutic options for chronic synovitis to improve joint function. Chemical synovectomy is not well tolerated, and the long-term response is relatively low. Surgical synovectomy has a better success rate, but it recommends higher expenses. In radiation synovectomy, radioactive labeled particles are applied directly in the articular cavity, followed by homogeneous distribution in joint. Next, the radioactive particles are transported in the depth of synovia and phagocytized by inflammatory cells. Finally, the radiation leads to fibrosis and sclerosis of formerly inflamed synovial membrane; thus, it stops the inflammation and reduces the symptoms. It has a success rate of 40–100% and its effect can be similar to surgical synovectomy. Materials and methods: Thirty-one patients with resistant monoarthritis of the knee were enrolled in this study. One millicurie of phosphorus-32 was injected into patients' knee via US guide. Saline was injected afterwards to prevent leakage. Direct pressure was performed after removing the needle and the knee was flexed slowly to ensure homogenous distribution and fixed with a splint for 1 to 2 weeks. Patients were followed up after 2 weeks, 1 month, 2 months, and 6 months. The following variables were assessed by the treating rheumatologist: patients' pain, joint tenderness, effusion, and ROM. At the time of injection and after the first week, patients were investigated for any complication including infection, necrosis, pain, and swelling. The effect of clinical characteristics and demographic data on existing complications and the changes of pain, joint tenderness, effusion, and ROM was assessed. Results: Thirty-one patients with the mean age of 54.5 ± 12.2 years and the mean disease duration of 12 ± 6.5 years were enrolled in this study. Mean DAS-28 ESR score for our patients was 4 ± 0.7. The pain, effusion, and reduced ROM were decreased significantly after all follow-up intervals. Knee tenderness was not affected in the first 2 weeks, but it was reduced significantly after 1, 2, and 6 months. No serious complications like infection and necrosis were reported through our study. 51.6% and 54.8% of our patients reported pain and swelling in the administration site. Furthermore, 19.4% and 16.1% of patients reported deterioration of pain and effusion in the first week of injection. Conclusion: In our study, we demonstrated that pain, tenderness, effusion, and ROM are improved after radiation synovectomy with phosphorus-32. We also showed that there was no serious adverse effect like infection and necrosis. However, more than half of our patients experienced pain and swelling of injection site at the time of administration. Key points • We demonstrated the efficacy of radiation synovectomy as a medication for monoarthritis. • The results of our study can lead to a bigger clinical trial to assess the benefits and adverse effects of radiation synovectomy in comparison to treatment with local or systemic corticosteroids. [ABSTRACT FROM AUTHOR]

In the pathogenesis of osteoarthritis, various signaling pathways may influence the bone joint through a common terminal pathway, thereby contributing to the pathological remodeling of the joint. Semaphorins (SEMAs) are cell-surface proteins actively involved in and primarily responsible for regulating chondrocyte function in the pathophysiological process of osteoarthritis (OA). The significance of the SEMA family in OA is increasingly acknowledged as pivotal. This review aims to summarize the mechanisms through which different members of the SEMA family impact various structures within joints. The findings indicate that SEMA3A and SEMA4D are particularly relevant to OA, as they participate in cartilage injury, subchondral bone remodeling, or synovitis. Additionally, other elements such as SEMA4A and SEMA5A may also contribute to the onset and progression of OA by affecting different components of the bone and joint. The mentioned mechanisms demonstrate the indispensable role of SEMA family members in OA, although the detailed mechanisms still require further exploration. [ABSTRACT FROM AUTHOR]

Rice bodies (RBs) synovitis in the shoulder joints of systemic lupus erythematosus patients is a rare clinical condition that has not been previously reported. Despite the fact that the diagnosis of RBs synovitis has primarily relied on MRI imaging, ultrasound has been used less frequently. In this report, we discuss a 43-year-old female diagnosed with systemic lupus erythematosus who presented with pain and swelling in the right shoulder. The ultrasound findings were typical, and the patient was diagnosed with RBs synovitis, as she had no history of tuberculosis or rheumatoid arthritis. Subsequently, the patient underwent ultrasound-guided percutaneous biopsy and surgical excision, which led to a good postoperative outcome. Based on this case, a literature review of RBs synovitis over the past 2 decades indicates that rice bodies synovitis is rare in clinical presentation accompanied by SLE. Moreover, ultrasound has not been extensively employed for diagnosing this condition. It is important to note the pivotal role of ultrasound in detecting RBs synovitis, and it should be the preferred method for early detection. Therefore, ultrasound physicians should be well informed about this condition to enhance diagnostic precision. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a disease with sex-dependent prevalence and severity in both human and animal models. We sought to elucidate sex differences in synovitis, mechanical sensitization, structural damage, bone remodeling, and the synovial transcriptome in the anterior cruciate ligament rupture (ACLR) mouse model of post-traumatic OA (PTOA). Male and female 12-week-old C57/BL6J mice were randomized to Sham or noninvasive ACLR with harvests at 7d or 28d post-ACLR (n = 9 per sex in each group – Sham, 7d ACLR, 28d ACLR). Knee hyperalgesia, mechanical allodynia, and intra-articular matrix metalloproteinase (MMP) activity (via intravital imaging) were measured longitudinally. Trabecular and subchondral bone (SCB) remodeling and osteophyte formation were assessed by µCT. Histological scoring of PTOA, synovitis, and anti-MMP13 immunostaining were performed. Na V 1.8-Cre;tdTomato mice were used to document localization and sprouting of nociceptors. Bulk RNA-seq of synovium in Sham, 7d, and 28d post-ACLR, and contralateral joints (n = 6 per group per sex) assessed injury-induced and sex-dependent gene expression. Male mice exhibited more severe joint damage at 7d and 28d and more severe synovitis at 28d, accompanied by 19% greater MMP activity, 8% lower knee hyperalgesia threshold, and 43% lower hindpaw withdrawal threshold in injured limbs compared to female injured limbs. Females had injury-induced catabolic responses in trabecular and SCB, whereas males exhibited 133% greater normalized osteophyte volume relative to females and sclerotic remodeling of trabecular and SCB. Na V 1.8+ nociceptor sprouting in SCB and medial synovium was induced by injury and comparable between sexes. RNA-seq of synovium demonstrated similar injury-induced transcriptomic programs between the sexes at 7d, but only female mice exhibited a transcriptomic signature indicative of synovial inflammatory resolution by 28d, whereas males had persistent pro-inflammatory, pro-fibrotic, pro-neurogenic, and pro-angiogenic gene expression. Male mice exhibited more severe overall joint damage and pain behavior after ACLR, which was associated with persistent activation of synovial inflammatory, fibrotic, and neuroangiogenic processes, implicating persistent synovitis in driving sex differences in murine PTOA. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Pigmented villonodular synovitis is a rare clinical entity, with 2-3% of all PVNS cases affecting the shoulder. Diagnosis is challenging and can elude clinicians for years, with definitive treatment involving arthroscopic or open synovectomy. Case Report: A 50-year-old woman presented with left shoulder pain persisting for 2 years. She was initially conservatively treated by a rheumatologist, with corticosteroid schemes intra-articularly injected and per os, but no improvement of her symptoms was noted. Two years later, she was referred to the Orthopedics Department of our hospital with constant pain in her left shoulder, refractory to the conservative measures. Physical examination revealed tenderness of her shoulder on palpation and limited range of motion. The diagnosis of PVNS was established by preoperative magnetic resonance arthrography (MRA) and confirmed by biopsy from intra-operative tissue sampling. Arthroscopic debridement and synovectomy were performed, yielding good surgical results, and she now reports pain relief, improved function, and no recurrence of symptoms at 1-year follow-up. Conclusions: The diagnosis of PVNS can be elusive for years. MRI and clinical suspicion along with tissue biopsy can set the diagnosis. Shoulder PVNS follows a similar natural history as knee PVNS, with conservative treatment failing and arthroscopic excision providing definite relief. We report a rare case of shoulder PVNS, underscoring the importance of considering PVNS in cases of shoulder pain refractory to conservative treatment. [ABSTRACT FROM AUTHOR]

While conventional radiography and MRI have a well-established role in the assessment of patients with knee osteoarthritis, ultrasound is considered a complementary and additional tool. Moreover, the actual usefulness of ultrasound is still a matter of debate in knee osteoarthritis assessment. Despite that, ultrasound offers several advantages and interesting aspects for both current clinical practice and future perspectives. Ultrasound is potentially a helpful tool in the detection of anomalies such as cartilage degradation, osteophytes, and synovitis in cases of knee osteoarthritis. Furthermore, local diagnostic and minimally invasive therapeutic operations pertaining to knee osteoarthritis can be safely guided by real-time ultrasound imaging. We are constantly observing a growing knowledge and awareness among radiologists and other physicians, concerning ultrasound imaging. Ultrasound studies can be extremely useful to track the response to various therapies. For this specific aim, tele-ultrasonography may constitute an easy tool aiding precise and repeated follow-up controls. Moreover, raw radio-frequency data from US backscattering signals contain more information than B-mode imaging. This paves the way for quantitative in-depth analyses of cartilage, bone, and other articular structures. Overall, ultrasound technologies and their rapid evolution have the potential to make a difference at both the research and clinical levels. This narrative review article describes the potential of such technologies and their possible future implications. [ABSTRACT FROM AUTHOR]

Objective: Oxylipins are bioactive lipids derived from polyunsaturated fatty acids (PUFAs) that modulate inflammation and may remain overexpressed in refractory synovitis. In plasma, they could also be biomarkers of synovial pathology. The aim of this study is to determine if synovial oxylipins in inflamed joints correlate with plasma oxylipins and with synovial histologic patterns. Methods: Patients with established rheumatoid or psoriatic arthritis with active disease despite treatment were recruited, and paired synovial tissue (ST) and plasma were collected. Oxylipins were determined by liquid chromatography with tandem mass spectrometry and were classified into groups according to their PUFA precursor and enzyme. The expression of CD20, CD68, CD3, and CD138 was obtained to describe synovial histology. Cell‐specific expression of oxylipin‐related genes was identified by examining available synovial single‐cell RNA sequencing data. Results: We included a total of 32 ST and 26 paired‐plasma samples. A total of 71 oxylipins were identified in ST, but only 24 were identified in plasma. Only levels of 9,10‐dihydroxyoctadecenoic acid and tetranor‐Prostaglandin FM had a significant positive correlation between plasma and ST. Several oxylipins and oxylipin‐related genes were differentially expressed among synovial phenotypes. Specifically, several 5‐lipoxygenase (LOX)–derived oxylipins were statistically elevated in the lympho‐myeloid phenotype and associated with B cell expression in rheumatoid arthritis samples. Conclusion: The lack of correlation between ST and plasma oxylipins suggests that ST lipid profiling better characterizes active pathways in treated joints. Synovial 5‐LOX–derived oxylipins were highly expressed in lympho‐myeloid–enriched synovium. Combination therapy with 5‐LOX inhibitors to improve refractory inflammation may be needed in patients with this histologic group. [ABSTRACT FROM AUTHOR]

The burden of osteoarthritis (OA) is rapidly increasing with population aging, but there are still no approved disease-modifying drugs available. Accumulating evidence has shown that OA is a heterogeneous disease with multiple phenotypes, and it is unlikely to respond to one-size-fits-all treatments. Inflammation is recognized as an important phenotype of OA and is associated with worse pain and joint deterioration. Therefore, it is believed that anti-inflammatory treatments may be more effective for OA with an inflammatory phenotype. In this review, we summarized clinical trials that evaluated anti-inflammatory treatments for OA and discussed whether these treatments are more effective in inflammatory OA phenotypes compared to general OA patients. [ABSTRACT FROM AUTHOR]

Objectives To investigate, in anti-CCP antibody–positive individuals with musculoskeletal symptoms but no clinical synovitis (CCP+ at-risk), the additional value of US for the prediction of inflammatory arthritis. Furthermore, to define a concise US protocol for feasible risk prediction. Methods Demographic and clinical data were collected in 417 CCP+ at-risk (Leeds CCP cohort) with a baseline US scan assessing synovitis and bone erosions in 36 joints, and a follow-up duration ≥24 months. Multivariable binary regression models for inflammatory arthritis development at 24 months evaluated routine clinical variables associated with inflammatory arthritis alone ('clinical' model) and combined with a 36-joint US scanning protocol ('clinical-US extended' model). A 'clinical-US short' model was also developed. Results At 24 months, 92/417 (22.1%) CCP+ at-risk developed inflammatory arthritis (median time 7 months, interquartile range 3–12). The 'clinical-US extended' model performed better than the 'clinical' model [area under the curve (AUC) 0.788 vs AUC 0.731, respectively, P  < 0.001] with an odds ratio for inflammatory arthritis development of 3.18 (95% CI 1.80–5.63) for US synovitis and 2.54 (95% CI 1.21–5.37) for bone erosions. The 'clinical-US short' model, which retained the wrists, knees and MTP5 joints, performed better (AUC 0.782) than the 'clinical' model (P  < 0.001) and similarly (difference in Akaike information criteria <2) to the 'clinical-US extended' model. Conclusions US provides valuable information for predicting progression to inflammatory arthritis in CCP+ individuals both alone and in addition to clinical variables. US synovitis was associated with a 3-fold increase risk of inflammatory arthritis development. A concise US protocol of six joints provides clinically feasible risk prediction in CCP+ at-risk. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic, inflammatory systemic disorder of synovial joints and results in polyarthritis, chronical degeneration, and finally deformities and ankylosis in severe cases. Synovitis and pannus formation are results of inflammatory changes and lead into restriction in joint movement. Shoulders are among the later affected and larger joints and formation of synovitis in early active stages and pannus in later stages might be concluded with frozen shoulder and severe impairment in functionality. These late-term changes cannot be controlled with systemic or local anti-inflammatory agents and synovectomy is chosen in some cases. However, the results are not satisfactory and recurrence is common. In this case report, we presented a case of RA with severe shoulder pain, restricted movement due to synovial hypertrophy, and pannus formation which are resistant to local and systemic interventions and not suitable for surgical or chemical synovectomy. Microwave ablation (MWA) was performed successfully without any complication and she well responded in terms of DAS-28, functional, and pain scores. Range of motion and funcitonal restriction were recovered. This case report describes the use and promising results of MWA in RA with severe synovial hypertrophy and pannus formation even in the absence of active arthritis and effusion. MWA is a safe and minimally invasive technique that can be easily performed in coordinance of rheumatologists and interventional radiologists in proper cases. [ABSTRACT FROM AUTHOR]

Knee popping is a frequent symptom among knee disorders which requires further investigation in case of a recent evolution of the symptom or pathological associated ones. This article reports a rare presentation of pigmented villonodular synovitis (PVNS), identified as the cause of knee popping symptoms, by performing MRI sequences at various degrees of knee flexion for a patient complaining from a gradual onset of knee popping, occurring when bending the knee over 120° of flexion. MRI sequences were performed just before the popping occurs (flexion 90°) and right after it had occurred (flexion 120°). The latter confirmed the origin of the symptom as the lesion moved forward, passing brutally through the interstice between the PCL and the ACL at 120° of flexion, explaining the popping. Treatment decision was to perform an arthroscopic resection of the lesion. Diagnosis of isolated PVNS was confirmed after anatomopathological analysis. [ABSTRACT FROM AUTHOR]

The malignant cycle of synovitis considerably impacts the progression of osteoarthritis (OA). Therefore, the precise localization of synovitis, targeted disruption of the inflammatory cycle, and real‐time monitoring of its dynamics are crucial for the effective diagnosis and management of OA. Here, porous HAMA/GelMA microspheres are synthesized using microfluidic technology. Interleukin‐10 (IL‐10) nanobubbles, prepared via double emulsification, are grafted with folic acid (FA) via an amide reaction and subsequently impregnated and adsorbed onto the microspheres, thereby constructing an ultrasonic contrast microsphere system. This system facilitates not only ultrasonic imaging for accurate localization of synovitis but also the targeted and controlled delivery of IL‐10 under ultrasound conditions. In vitro, under ultrasound intensities of 0, 0.5, and 1.5 W, the system effectively releases IL‐10 at the rates of 19.95%, 30.95%, and 40.67%, respectively. In vivo, the biodegradability of the system facilitates real‐time tracking and monitoring of synovitis for at least 14 days. In summary, ultrasonic contrast microspheres enable precise localization and real‐time monitoring of synovitis. Under ultrasound conditions, these microspheres enable targeted and controlled drug delivery, effectively disrupting vicious inflammatory cycles. This strategy pioneers new pathways for the management and precise treatment of OA. [ABSTRACT FROM AUTHOR]

Lateral elbow pain and tennis elbow have been considered almost synonymous, in that historically all patients with lateral elbow pain were assumed to have tennis elbow. With the evolution of diagnostic imaging, elbow arthroscopy and further understanding of the pathological processes, alongside analysis of failed tennis elbow treatment, a whole host of possible differential diagnoses that might cause lateral elbow pain became recognized. In addition to tendinopathies (tennis and golfers elbow), these include intraarticular mechanical issues (radiocapitellar plica and snapping annular ligament), elbow instability, nerve compression syndromes, osteochondral defects and degenerative joint disease (radiocapitellar joint arthritis). Accurate clinical assessment and diagnosis is key, alongside selective use of investigations that can confirm or refute diagnoses and guide ongoing management. This article serves to provide an overview of the history, examination findings, investigations and management options for lateral elbow pain. Whilst we will cover the whole scope of possible diagnoses responsible for lateral elbow pain, we will not be considering in detail those covered in other articles in this issue (tennis elbow, osteochondritis dissecans, elbow instability). The focus of this article will be to elaborate on the tips and tricks within the clinical assessment, and how to properly assess the lateral side of the elbow. We will mention the rarer conditions encountered (posterior interosseous nerve entrapment, synovial plica syndrome and snapping annular ligament) and discuss the reconstructive ladder for lateral sided degenerative joint disease. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the use of high‐frequency sonography as a tool for detecting inflammatory and destructive changes in the hand and foot joints of patients with early and long‐term RA. Methods: This study employs a prospective cohort design involving 162 patients diagnosed with Rheumatoid arthritis (RA) who meet the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Patients were divided into two groups based on disease duration: Group 1 (n = 74) included patients with a disease duration of up to 2 years, or early РА (ERA;), Group 2 (n = 88) consisted of patients with a disease duration exceeding 2 years, or long‐term persistent РА (LtRA). All patients underwent a clinical assessment of their joints, as well as radiography and arthrosonography, at the beginning of the study and again at 6 and 12 months later. Results: In the general group of patients, ultrasound examination revealed signs of synovitis in the joints of the hands more frequently (66%) compared with clinical examination (56% by a number of swollen joints [NSJ] and 55% by a number of painful joints [NPJ], P <.01). After 6 months of treatment, 12% of the patients achieved full US remission and 24% achieved partial US remission. Conclusions: Within the scope of comprehensive RA diagnostics, arthrosonography of the joints of the hands and feet, utilizing a combination of greyscale and power Doppler, may surpass radiography in detecting early RA. This method allows for a more accurate assessment of disease activity and progression rates. Access the CME test here and search by article title. [ABSTRACT FROM AUTHOR]

Objective: Although hand synovitis is prevalent in the older population, the etiology remains unclear. Hyperuricemia, a modifiable metabolic disorder, may serve as an underlying mechanism of hand synovitis, but little is known about their relationship. We assessed the association between hyperuricemia and hand synovitis in a large population‐based sample. Methods: We performed a cross‐sectional study in Longshan County, Hunan Province, China. Hyperuricemia was defined as a serum urate level >420 μmol/L in men and >360 μmol/L in women. Ultrasound examinations were performed on both hands of 4,080 participants, and both gray‐scale synovitis and the Power Doppler signal (PDS) were assessed using semiquantitative scores (grades 0–3). We evaluated the association of hyperuricemia with hand gray‐scale synovitis (grade ≥2) and PDS (grade ≥1), respectively, adjusting for age, sex, and body mass index. Results: All required assessments for analysis were available for 3,286 participants. The prevalence of hand gray‐scale synovitis was higher among participants with hyperuricemia (30.0%) than those with normouricemia (23.3%), with an adjusted odds ratio (aOR) of 1.28 (95% confidence interval [CI] 1.00–1.62). Participants with hyperuricemia also had a higher prevalence of PDS (aOR 2.36; 95% CI 1.15–4.81). Furthermore, hyperuricemia positively associated, both at the hand and joint levels, with the presence of gray‐scale synovitis (aOR 1.27; 95% CI 1.00–1.60 and adjusted prevalence ratio [aPR] 1.26; 95% CI 1.10–1.44, respectively) and PDS (aOR 2.35; 95% CI 1.15–4.79 and aPR 2.34; 95% CI 1.28–4.30, respectively). Conclusion: This population‐based study provides more evidence for a positive association between hyperuricemia and prevalent hand synovitis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovial membrane that leads to the destruction of cartilage and bone. Currently, pharmacological targeting of ion channels is being increasingly recognized as an attractive and feasible strategy for the treatment of RA. The present work employs a network analysis approach to predict the most promising ion channel target for potential RA‐treating drugs. A protein–protein interaction map was generated for 343 genes associated with inflammation in RA and ion channel genes using Search Tool for the Retrieval of Interacting Genes and visualized using Cytoscape. Based on the betweenness centrality and traffic values as key topological parameters, 17 hub nodes were identified, including FOS (9800.85), tumor necrosis factor (3654.60), TGFB1 (3305.75), and VEGFA (3052.88). The backbone network constructed with these 17 hub genes was intensely analyzed to identify the most promising ion channel target using network analyzer. Calcium permeating ion channels, especially store‐operated calcium entry channels, and their associated regulatory proteins were found to highly interact with RA inflammatory hub genes. This significant ion channel target for RA identified by theoretical and statistical studies was further validated by a pilot case–control gene expression study. Experimental verification of the above findings in 75 RA cases and 25 controls showed increased ORAI1 expression. Thus, with a combination of network analysis approach and gene expression studies, we have explored potential targets for RA treatment. [ABSTRACT FROM AUTHOR]

The main pathogenesis of the frozen shoulder is thought to be the inflammation of the intra‐articular synovium and subsequent fibrosis of the shoulder joint capsule. However, the molecular pathogenesis of the frozen shoulder is still unknown. A class of noncoding RNAs, microRNAs contribute to various diseases including musculoskeletal diseases. MicroRNA‐26a (miR‐26a) has been reported to be associated with fibrosis in several organs. This study aims to reveal the role of miR‐26a on fibrosis in the shoulder capsule using a frozen shoulder model in miR‐26a deficient (miR‐26a KO) mice. MiR‐26a KO and wild‐type (WT) mice were investigated using a frozen shoulder model. The range of motion (ROM) of the shoulder, histopathological changes such as synovitis, and fibrosis‐related gene expression in the model mice were evaluated to determine the role of miR‐26a. In WT mice, both inflammatory cell infiltration and thickening of the inferior shoulder joint capsule were observed after 1 week of immobilization, and this thickening further progressed over the subsequent 6 weeks. However, the immobilized shoulder in miR‐26a KO mice consistently exhibited significantly better ROM compared with WT mice at 1 and 6 weeks, and histological changes were significantly less severe. The expression of inflammation‐ and fibrosis‐related genes was decreased in the miR‐26a KO mice compared with WT mice at 1 and 6 weeks. Together, miR‐26a deficiency attenuated the severity of frozen shoulder in the immobilization model mouse. The present study suggests that miR‐26a has the potential to be a target miRNA for therapeutic approach to frozen shoulder. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative whole‐joint disease in which the synovium and joint cartilage become inflamed and damaged. The essential role of inflammation in the development of OA has been recognized recently. Accordingly, simultaneous regulation of local inflammation and tissue degeneration is proposed as a promising therapeutic strategy. Herein, multifunctional biomimetic apoptotic nanovesicles (Apo‐NVs) are constructed with plasma membrane derived from apoptotic T cells. The anti‐inflammatory microRNA‐124 is further encapsulated into Apo‐NVs in the hope of achieving an enhanced immunomodulatory effect. It is found that apoptotic nanovesicles, including Apo‐NVs and Apo‐NVs‐miR‐124, both efficiently promote the M2 repolarization of M1 macrophages and inhibit the degenerative phenotype of chondrocytes. Further in vivo studies show that Apo‐NVs and Apo‐NVs‐miR‐124 alleviate synovial inflammation and protect cartilage tissue from degeneration in OA mice. The study highlights the potential of Apo‐NVs in treating OA and other inflammation‐related diseases. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the small joints of the hands and feet, characterized by pain, inflammation, and joint damage. In this context, magnetic resonance imaging (MRI) is useful to identify and monitor joint/tendon inflammation and the evolution of joint damage, playing a key role in treatment response evaluation, in addition to clinical measurements. Various methods to quantify joint inflammation and damage with MRI in RA have been developed, such as RA-MRI Score (RAMRIS), Early RA-MRI Score (ERAMRS), and Simplified RA-MRI Score (SAMIS). RAMRIS, introduced in 2002, offers an objective means to assess inflammation and damage via MRI in RA trials, encompassing findings such as synovitis, bone erosion, and edema/osteitis. Recently, an updated RAMRIS version was developed, which also includes the evaluation of joint space narrowing and tenosynovitis. The RAMRIS-5, which is a condensed RAMSIS version focusing on five hand joints only, has been proven to be a valuable resource for the semi-quantitative evaluation of RA joint damage, both in early and established disease. This narrative literature review will provide an overview of the MRI scoring systems that have been developed for the assessment of joint inflammation and structural damage in RA patients. [ABSTRACT FROM AUTHOR]

Recurrent bleeding in the synovial joint, such as the knee, can give rise to chronic synovitis and degenerative arthritis, which are major causes of morbidity. Whereas chronic arthropathy affects one-fifth of hemophiliacs, conditions such as rheumatoid arthritis (RA), periarticular and articular fractures, osteochondral autograft transplantation surgery, and anterior cruciate ligament (ACL) injury are also associated with joint bleeding. Synovial joint trauma is associated with inflammation, acute pain, bloody joint effusion, and knee instability. Clinically, some physicians have advocated for blood aspiration from the joint post-injury to mitigate the harmful effects of bleeding. Despite the significant potential clinical impact of joint bleeding, the mechanism(s) by which joint bleeding, acute or microbleeds, leads to deleterious changes to the synovial joint remains understudied. This review will address the impact of blood on synovial joint tissues observed from in vitro and in vivo studies. While the deleterious effects of blood on cartilage and synovium are well-described, there are much fewer reports describing the negative effects of blood on the meniscus, cruciate ligaments, and subchondral bone. Based on our studies of blood in co-culture with chondrocytes/cartilage, we raise the possibility that ferroptosis, an iron-dependent, nonapoptotic form of regulated cell death, plays a contributing role in mediating hemophilic arthropathy (HA) and may represent a therapeutic target in reducing the negative impact of joint bleeds. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common autoimmune rheumatic disease that causes chronic synovitis, bone erosion, and joint destruction. The autoantigens in RA include a wide array of posttranslational modified proteins, such as citrullinated proteins catalyzed by peptidyl arginine deiminase4a. Pathogenic anti-citrullinated protein antibodies (ACPAs) directed against a variety of citrullinated epitopes are abundant both in plasma and synovial fluid of RA patients. ACPAs play an important role in the onset and progression of RA. Intensive and extensive studies are being conducted to unveil the mechanisms of RA pathogenesis and evaluate the efficacy of some investigative drugs. In this review, we focus on the formation and pathogenic function of ACPAs. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease. [ABSTRACT FROM AUTHOR]

Background: The synovium, a soft tissue lining diarthrodial joints, tendon sheaths, and bursae, plays a pivotal role in various arthritides. This study aims to evaluate the histopathological spectrum of synovectomy and synovial biopsies, assessing their diagnostic value in neoplastic, granulomatous diseases, and infections. Materials and Methods: This cross-sectional descriptive study was conducted in the Department of Pathology at Siddhartha Medical College, Vijayawada, from January 2021 to January 2023. A total of 100 synovectomies and synovial biopsies, obtained via open or arthroscopic methods, were included. Samples were fixed in 10% buffered formalin, processed, and stained using hematoxylin and eosin and special stains as necessary. Clinical, demographic, histopathological, radiological, and serological data were reviewed. Results: The study revealed a higher prevalence of synovial lesions in individuals aged 51-70 years (38%) and 71-90 years (32%), with females predominantly affected (60%). Inflammatory joint diseases comprised 40% of cases, with chronic nonspecific synovitis (18%) being the most common. Septic arthritis (10%), tuberculous synovitis (6%), and rheumatoid arthritis (6%) were also notable. Degenerative joint diseases accounted for 22% of cases, including osteoarthritis (10%), gout (3%), pseudogout (3%), ochronosis (2%), and avascular necrosis (5%). Tumor and tumor-like lesions constituted 37% of cases, with giant cell tumor of the tendon sheath (15%) and synovial chondromatosis (8%) being prominent. Conclusion: The study emphasizes the diagnostic value of histopathological examination in early and ambiguous cases of synovial pathology. The prevalence of inflammatory, degenerative, and tumor-like conditions reflects the necessity for comprehensive evaluation in managing joint diseases. [ABSTRACT FROM AUTHOR]

Pulsed electromagnetic field stimulation (PEMF) is gaining more attention as a non-invasive arthritis treatment. In our study, immortalized synovial fibroblasts (K4IM) derived from a non-arthritic donor were exposed to MAGCELL® ARTHRO, a PEMF device, with 105 mT intensity, 8 Hz frequency, and 2 × 2.5 min sessions conducted thrice with a 1 h interval, to understand the underlying mechanism in regard to the complement system. Additionally, tumor necrosis factor (TNFα, 10 ng/mL) pre-treatment prior to PEMF stimulation, as well as 3-day versus 6-day stimulation, were compared. Gene expression of C4b binding protein-alpha and -beta (C4BPα, C4BPβ), complement factor (CF)-H, CFI, CD55, CD59, Interleukin (IL-6) and TNFα was analyzed. Immunofluorescence staining of CD55, CD59, and Ki67 was conducted. Results showed the absence of C4BPα gene expression, but C4BPβ was present. One and three days of PEMF stimulation caused no significant changes. However, after six days, there was a significant increase in CD55, CFH, and CD59 gene expression, indicating cytoprotective effects. Conversely, IL-6 gene expression increased after six days of stimulation and even after a single session in TNFα pre-stimulated cells, indicating a pro-inflammatory effect. PEMF's ambivalent, i.e., enhancing complement regulatory proteins and pro-inflammatory cytokines, highlights its complexity at the molecular level. [ABSTRACT FROM AUTHOR]

Inflammation of the synovium, known as synovitis, plays an important role in the pathogenesis of osteoarthritis (OA). Synovitis involves the release of a wide variety of pro‐inflammatory mediators in synovial fluid (SF) that damage the articular cartilage extracellular matrix and induce death and apoptosis in chondrocytes. The composition of synovial fluid is dramatically altered by inflammation in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. However, the relationship between key biochemical markers of joint inflammation and mechanical function of SF is not well understood. Here, we demonstrate the application of a novel analytical framework to measure the effective viscosity for SF lubrication of cartilage, which is distinct from conventional rheological viscosity. Notably, in a well‐established equine model of synovitis, this effective lubricating viscosity decreased by up to 10,000‐fold for synovitis SF compared to a ~4 fold change in conventional viscosity measurements. Further, the effective lubricating viscosity was strongly inversely correlated (r = −0.6 to −0.8) to multiple established biochemical markers of SF inflammation, including white blood cell count, prostaglandin E2 (PGE2), and chemokine ligand (CCLs) concentrations, while conventional measurements of viscosity were poorly correlated to these markers. These findings demonstrate the importance of experimental and analytical approaches to characterize functional lubricating properties of synovial fluid and their relationships to soluble biomarkers to better understand the progression of OA. [ABSTRACT FROM AUTHOR]

Background: Animal models that use open surgical transection of the anterior cruciate ligament (ACL) do not accurately simulate the clinical condition regarding the pivot-shift mechanism and the associated inflammatory response that occurs before reconstruction. Purpose/Hypothesis: The purpose was to characterize a reproducible manual, nonsurgical method to mimic an isolated ACL tear in a clinically relevant model and to evaluate the development of progressive posttraumatic osteoarthritis due to ACL injury. It was hypothesized that the ACL could be reproducibly torn with minimal damage to other ligaments and that there would be progressive development of degenerative joint disease after ACL injury. Study Design: Controlled laboratory study. Methods: A total of 37 mice (strain C57BL/6) were used to compare the manual procedure with sham surgery (sham group; n = 10) and with the established surgical ACL transection (ACLT) procedure (surgical group; n = 27). In the sham group, a closed manual procedure was performed on the right knee and sham surgery on the left knee. In the surgical group, the closed manual procedure was performed on the right knee and surgical ACLT on the left knee. Dissection using India ink, histological assessment with safranin O and hematoxylin-eosin staining, radiological evaluation through radiographs and microfocus computed tomography scans, and gait analyses were performed to assess cartilage/ligament status. Osteoarthritis Research Society International (OARSI) and synovitis scores, anterior tibial translation, range of motion, bone microstructure, osteophyte volume, and pain were assessed at 2, 4, and 8 weeks postoperatively. Results: The manual procedure successfully resulted in an ACL rupture and associated meniscal injury. The posterior cruciate, lateral collateral, and medial collateral ligaments were intact in all dissected knees. Two weeks after ACL tear, the surgical group showed a significantly higher synovitis score, whereas 8 weeks after ACL tear, the manual group showed a significantly higher volume of osteophytes. No significant differences were found between the groups in terms of OARSI score, anterior tibial translation, range of motion, bone microstructure computed tomography values, and stride distance/irregularity. Conclusion: This procedure can be used to create an ACL tear model without causing grossly evident injuries to other ligaments and avoiding the risk of cartilage damage from surgical instruments. Clinical Relevance: This procedure offers a more clinically relevant ACL tear model and facilitates simple, inexpensive, and reproducible development of posttraumatic osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Unilateral presentation of sacroiliitis is a diagnostic dilemma, especially between infection and inflammatory sacroiliitis associated with spondyloarthritis, requiring an early and accurate diagnosis. Objective: To assess the utility of magnetic resonance imaging (MRI) in differentiating infective versus inflammatory etiology in unilateral sacroiliitis. Materials and Methods: Retrospective review of the MRI of 90 patients with unilateral sacroiliitis, having an established final diagnosis. MR images were evaluated for various bone and soft tissue changes using predefined criteria and analyzed using univariate and multivariate regression analysis. Results: Among the 90 patients, infective etiology was diagnosed in 66 (73.3%) and inflammatory etiology in 24 (26.7%). Large erosions, both iliac and sacral‐sided edema, joint space involvement with effusion or synovitis, soft tissue edema, elevated ESR/CRP, and absence of capsulitis and enthesitis were associated with infection (p <.001). The independently differentiating variables favoring infection on multivariate analysis were—both iliac and sacral‐sided edema (OR 4.79, 95% CI: 0.96–23.81, p =.05), large erosions (OR 17.96, 95% CI: 2.66–121.02, p =.003), and joint space involvement (OR 9.9, 95% CI: 1.36–72.06, p =.02). Exclusive features of infection were osteomyelitis, sequestra, abscesses, sinus tracts, large erosions, and multifocality. All infective cases had soft tissue edema, joint space involvement, elevated ESR, and no capsulitis. Conclusion: MRI evaluation for the presence and pattern of bone and joint space involvement, soft tissue involvement, and careful attention to certain exclusive features will aid in differentiating infectious sacroiliitis from inflammatory sacroiliitis. [ABSTRACT FROM AUTHOR]

Introduction: Early diagnosis of joint damage is pivotal in haemophilia to prevent the occurrence and progression of haemophilic arthropathy thus providing optimal personalised management. The haemophilia joint health score version 2.1 (HJHS) is based on a physical examination of the mainly affected joints. Musculoskeletal ultrasound has demonstrated the capability to detect early changes in terms of synovitis and osteochondral damage. The haemophilia early detection with ultrasound (HEAD‐US) score has been proposed as a simple and reliable evaluation tool. Aim: This study aims to investigate the correlation between the HJHS and the HEAD‐US scores performed by two independent operators (physical therapist and musculoskeletal ultrasound expert) for the evaluation of the joint health status of patients with haemophilia. Methods: Consecutive adult patients independent of the severity degree were included. Elbows, knees and ankles were evaluated by a physical therapist by HJHS and by a musculoskeletal ultrasound expert following the HEAD‐US protocol. Results: We observed a good positive correlation between HJHS and HEAD‐US (Spearman's rho 0.72). The main discrepancy in conceptually similar domains was found between the HJHS swelling and the HEAD‐US synovitis (rho 0.17), as ultrasound was able to detect even mild synovitis when HJHS swelling was scored 0 in up to 40% of cases. Conclusions: The HJHS and HEAD‐US correlate well even when performed by two independent operators. Musculoskeletal ultrasound is particularly useful for the early detection of synovitis. The routine assessment of both scores helps clinicians define the stage and extension of joint involvement and set up a personalised treatment. [ABSTRACT FROM AUTHOR]

Background Diffuse-type tenosynovial giant-cell tumor (D-TGCT), formerly known as pigmented villonodular synovitis, is a rare, locally aggressive, invasive soft tissue tumor that primarily occurs in the knee. Surgical excision is the main treatment option, but there is a high recurrence rate. Arthroscopic surgical techniques are emphasized because they are less traumatic and offer faster postoperative recovery, but detailed reports on arthroscopic techniques and outcomes of D-TGCT in large cohorts are still lacking. Questions/purposes (1) What is the recurrence rate of knee D-TGCT after multiportal arthroscopic synovectomy? (2) What are the complications, knee ROM, pain score, and patient-reported outcomes for patients, and do they differ between patients with and without recurrence? (3) What factors are associated with recurrence after arthroscopic treatment in patients with D-TGCT? Methods In this single-center, retrospective study conducted between January 2010 and April 2021, we treated 295 patients with knee D-TGCTs. We considered patients undergoing initial surgical treatment with multiportal arthroscopic synovectomy as potentially eligible. Based on that, 27% (81 of 295) of patients were excluded because of recurrence after synovectomy performed at another institution. Of the 214 patients who met the inclusion criteria, 17% (36 of 214) were lost to follow-up, leaving 83% (178 of 214) of patients in the analysis. Twenty-eight percent (50 of 178) of patients were men and 72% (128 of 178) were women, with a median (range) age of 36 years (7 to 69). The median follow-up duration was 80 months (26 to 149). All patients underwent multiportal (anterior and posterior approaches) arthroscopic synovectomy, and all surgical protocols were determined by discussion among four surgeons after preoperative MRI. A combined open posterior incision was used for patients with lesions that invaded or surrounded the blood vessels and nerves or invaded the muscle space extraarticularly. Standard postoperative adjuvant radiotherapy was recommended for all patients with D-TGCT who had extraarticular and posterior compartment invasion; for patients with only anterior compartment invasion, radiotherapy was recommended for severe cases as assessed by the surgeons and radiologists based on preoperative MRI and intraoperative descriptions. Postoperative recurrence at 5 years was calculated using a Kaplan-Meier survivorship estimator. The WOMAC score (0 to 96, with higher scores representing a worse outcome; minimum clinically important difference [MCID] 8.5), the Lysholm knee score (0 to 100, with higher scores being better knee function; MCID 25.4), the VAS for pain (0 to 10, with higher scores representing more pain; MCID 2.46), and knee ROM were used to evaluate functional outcomes. Because we did not have preoperative patientreported outcomes scores, we present data on the proportion of patients who achieved the patient-acceptable symptom state (PASS) for each of those outcome metrics, which were 14.6 of 96 points on theWOMAC, 52.5 of 100 points on the Lysholm, and 2.32 of 10 points on the VAS. Results The symptomatic or radiographically documented recurrence at 5 years was 12% (95% confidence interval [CI] 7% to 17%) using the Kaplan-Meier estimator, with a mean recurrence time of 33 ± 19 months. Of these, three were asymptomatic recurrences found during regular MRI reviews, and the remaining 19 underwent repeat surgery. There was one intraoperative complication (vascular injury) with no effect on postoperative limb function and eight patients with postoperative joint stiffness, seven of whom improved with prolonged rehabilitation and one with manipulation under anesthesia. No postradiotherapy complications were found. The proportion of patients who achieved the preestablished PASS was 99% (176 of 178) for the VAS pain score, 97% (173 of 178) for theWOMAC score, and 100% (178 of 178) for the Lysholm score. A lower percentage of patients with recurrence achieved the PASS for WOMAC score than patients without recurrence (86% [19] versus 99% [154], OR 0.08 [95% CI 0.01 to 0.52]; p = 0.01), whereas no difference was found in the percentage of VAS score (95% [21] versus 99% [155], OR 0.14 [95% CI 0.01 to 2.25]; p = 0.23) or Lysholm score (100% [22] versus 100% [156], OR 1 [95% CI 1 to 1]; p = 0.99). Moreover, patients in the recurrence group showed worse knee flexion (median 135° [100° to 135°] versus median 135° [80° to 135°]; difference of medians 0°; p = 0.03), worse WOMAC score (median 3.5 [0 to 19] versus median 1 [0 to 29]; difference of medians 2.5; p = 0.01), and higher VAS pain score (median 1 [0 to 4] versus median 0 [0 to 4]; difference of medians 1; p < 0.01) than those in the nonrecurrence group, although no differences reached the MCID. No factors were associated with D-TGCT recurrence, including the use of postoperative radiotherapy, surgical technique, and invasion extent. Conclusion This single-center, large-cohort retrospective study confirmed that multiportal arthroscopic surgery can be used to treat knee D-TGCTs with a low recurrence rate, few complications, and satisfactory postoperative outcomes. Surgeons should conduct a thorough preoperative evaluation, meticulous arthroscopic synovectomy, and regular postoperative follow-up when treating patients with D-TGCT to reduce postoperative recurrence. Because the available evidence does not appear to fully support the use of postoperative adjuvant radiotherapy in all patients with D-TGCTs and our study design is inadequate to resolve this controversial issue, future studies should look for more appropriate indications for radiotherapy, such as planning based on a more precise classification of lesion invasion. Level of Evidence Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Native joint septic arthritis (NJSA) is a severe and rapidly progressing joint infection, predominantly bacterial but also potentially fungal or viral, characterized by synovial membrane inflammation and joint damage, necessitating urgent and multidisciplinary management to prevent permanent joint damage and systemic sepsis. Common in large joints like knees, hips, shoulders, and elbows, NJSA's incidence is elevated in individuals with conditions like rheumatoid arthritis, diabetes, immunosuppression, joint replacement history, or intravenous drug use. This review provides a comprehensive overview of NJSA, encompassing its diagnosis, treatment, antibiotic therapy duration, and surgical interventions, as well as the comparison between arthroscopic and open debridement approaches. Additionally, it explores the unique challenges of managing NJSA in patients who have undergone graft anterior cruciate ligament (ACL) reconstruction. The epidemiology, risk factors, pathogenesis, microbiology, clinical manifestations, diagnosis, differential diagnosis, antibiotic treatment, surgical intervention, prevention, and prophylaxis of NJSA are discussed, highlighting the need for prompt diagnosis, aggressive treatment, and ongoing research to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the effectiveness of the Global OMERACT–EULAR Synovitis Score (GLOESS) of bilateral second to fifth metacarpophalangeal joints (MCP 2–5) in evaluating rheumatoid arthritis (RA) activity in a real‐life setting. Methods: This cross‐sectional study included consecutive RA patients without hyperalgesia. Clinical data were extracted from electronic medical records. Evaluations were conducted on bilateral MCP 2–5 by two independent experts in musculoskeletal ultrasound (MSUS). Correlation between clinical and ultrasonographic parameters was analyzed, aiming to define a cutoff value for detecting disease activity. Results: Sixty‐nine patients were included. The mean DAS28‐ESR was 4.3 (±1.4), and the median GLOESS was 7 (13). The correlation between GLOESS and DAS28 was moderate (r =.62; P <.05). A total GLOESS score of ≤3 and all joints with both GS and PD ≤1 showed good sensitivity and specificity for detecting disease activity (remission/low vs moderate/high, P = 0). Conclusion: In a real‐life scenario, GLOESS for MCP 2–5 emerges as a valuable measure of RA activity. The optimal cutoff distinguishing remission/low from moderate/high disease activity was determined to be GLOESS ≤3, with all MCP joints exhibiting both GS and PD scores of ≤1. [ABSTRACT FROM AUTHOR]

Background: Although normal acute phase reactants (APRs) play an important role in assessing disease activity of rheumatoid arthritis (RA), some studies pointed out the discordance between disease activity and APR level. Neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs) and lymphocyte-to-monocyte ratios (LMRs) have been reported to be sensitive measures of inflammatory reaction. This study aims to explore the value of these haematological makers in assessment of APR-negative RA patients. Methods: Out of a cohort of 418 consecutive patients with RA, we enrolled 135 patients with normal APR for this study. We performed ultrasound assessments to evaluate synovitis and bone erosion in the affected joints. Synovitis was evaluated by ultrasound grey scale (GS) and power Doppler (PD) with semi-quantitative scoring (0-3). Demographic, clinical and laboratory data were collected from the patients. Disease Activity Score-28 joints (DAS28), NLR, MLR and PLR were calculated. Results: In RA patients with normal APR, PLR exhibited a positive correlation with ultrasound-detected synovitis and bone erosion, whereas NLR, MLR showed no significant correlation with ultrasonography parameters. The area under the ROC curve (AUC) for identifying synovitis with a GS grade ≥2 based on a PLR cutoff value of ≥159.6 was 0.7868 (sensitivity: 80.95%, specificity: 74.24%). For synovitis with a PD grade ≥2, the AUC was 0.7690, using a PLR cutoff value of ≥166.1 (sensitivity: 68.0%, specificity: 83.87%). Conclusions: Our findings suggested that PLR might be a reliable and cost-effective marker for identifying moderate-to-severe synovitis in RA patients with normal APR. [ABSTRACT FROM AUTHOR]

Konstantinos Mantantzis,1 Billy Franks,2 Preeti Kachroo,1 Mila Boncheva Bettex1 1R&D, Haleon CH SARL, Nyon, Switzerland; 2R&D, Haleon Netherlands B.V., Amersfoort, the NetherlandsCorrespondence: Mila Boncheva Bettex, Email mila.x.bonchevabettex@haleon.comPurpose: Synovitis, the inflammation of joint synovia, is a prominent feature of osteoarthritis (OA) manifested by enhanced synovial vascularity, endothelial leakage, and perivascular oedema. In this pilot study, we assessed the effect of topical diclofenac in hand OA (HOA) using the established semi-quantitative methods Magnetic Resonance Imaging (MRI) and Ultrasonography (US), and compared them with Fluorescent Optical Imaging (FOI), an emerging imaging modality.Patients and Methods: Ten patients with symptomatic and diagnosed HOA used topical diclofenac for 14 days, with FOI, MRI, US, and subjective pain assessed at Baseline and after 7 (Day 8), and 14 (Day 15) days of treatment. Changes in synovitis were assessed for all 10 joints of the hand (via sum scores), and separately for the two joints most affected by synovitis. A new, fully quantitative approach for objective synovitis assessment based on the FOI images was also developed and applied.Results: The semi-quantitative analysis of the sum scores showed a small decrease in synovitis throughout the treatment duration across the different imaging modalities. The effect of the treatment was more prominent on the two most affected joints, with a synovitis reduction vs Baseline of 21.1% and 34.2% on Day 8 and Day 15, respectively, in the FOI. The quantitative FOI pixel analysis further strengthened the evidence for this effect, with observed reduction of 17.8% and 42.4% for Days 8 and 15, respectively. A similar trend was observed for subjective pain perception, with a reduction of 7.2 and 13.3 mm on Days 8 and 15.Conclusion: This pilot study evidenced the effect of topical diclofenac on reducing synovitis in hand OA in semi- and fully quantitative analyses, with the effect being stronger in the most affected joints. Further, supporting studies are needed to probe the accuracy of the quantitative pixel analysis of FOI images. Keywords: fluorescent optical imaging, hand osteoarthritis, synovitis, topical diclofenac