Deep learning-based classification of erosion, synovitis and osteitis in hand MRI of patients with inflammatory arthritis.

OBJECTIVES: To train, test and validate the performance of a convolutional neural network (CNN)-based approach for the automated assessment of bone erosions, osteitis and synovitis in hand MRI of patients with inflammatory arthritis. METHODS: Hand MRIs (coronal T1-weighted, T2-weighted fat-suppressed, T1-weighted fat-suppressed contrast-enhanced) of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients from the rheumatology department of the Erlangen University Hospital were assessed by two expert rheumatologists using the Outcome Measures in Rheumatology-validated RA MRI Scoring System and PsA MRI Scoring System scores and were used to train, validate and test CNNs to automatically score erosions, osteitis and synovitis. Scoring performance was compared with human annotations in terms of macro-area under the receiver operating characteristic curve (AUC) and balanced accuracy using fivefold cross-validation. Validation was performed on an independent dataset of MRIs from a second patient cohort. RESULTS: In total, 211 MRIs from 112 patients (14 906 region of interests (ROIs)) were included for training/internal validation using cross-validation and 220 MRIs from 75 patients (11 040 ROIs) for external validation of the networks. The networks achieved high mean (SD) macro-AUC of 92%±1% for erosions, 91%±2% for osteitis and 85%±2% for synovitis. Compared with human annotation, CNNs achieved a high mean Spearman correlation for erosions (90±2%), osteitis (78±8%) and synovitis (69±7%), which remained consistent in the validation dataset. CONCLUSIONS: We developed a CNN-based automated scoring system that allowed a rapid grading of erosions, osteitis and synovitis with good diagnostic accuracy and using less MRI sequences compared with conventional scoring. This CNN-based approach may help develop standardised cost-efficient and time-efficient assessments of hand MRIs for patients with arthritis.

Disease-Modifying Effects of Lenvatinib, a Multiple Receptor Tyrosine Kinase Inhibitor, on Posttraumatic Osteoarthritis of the Knee.

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.

MRI of shoulder girdle in polymyalgia rheumatica: inflammatory findings and their diagnostic value.

BACKGROUND: Non-synovial inflammation as detected by MRI is characteristic in polymyalgia rheumatica (PMR) with potentially high diagnostic value. OBJECTIVE: The objective is to describe inflammatory MRI findings in the shoulder girdle of patients with PMR and discriminate from other causes of shoulder girdle pain. METHODS: Retrospective study of 496 contrast-enhanced MRI scans of the shoulder girdle from 122 PMR patients and 374 non-PMR cases. Two radiologists blinded to clinical and demographic information evaluated inflammation at six non-synovial plus three synovial sites for the presence or absence of inflammation. The prevalence of synovial and non-synovial inflammation, both alone and together with clinical information, was tested for its ability to differentiate PMR from non-PMR. RESULTS: A high prevalence of non-synovial inflammation was identified as striking imaging finding in PMR, in average 3.4±1.7, mean (M)±SD, out of the six predefined sites were inflamed compared with 1.1±1.4 (M±SD) in non-PMR group, p<0.001, with excellent discriminatory effect between PMR patients and non-PMR cases. The prevalence of synovitis also differed significantly between PMR patients and non-PMR cases, 2.5±0.8 (M±SD) vs 1.9±1.1 (M±SD) out of three predefined synovial sites, but with an inferior discriminatory effect. The detection of inflammation at three out of six predefined non-synovial sites differentiated PMR patients from controls with a sensitivity/specificity of 73.8%/85.8% and overall better performance than detection of synovitis alone (sensitivity/specificity of 86.1%/36.1%, respectively). CONCLUSION: Contrast-enhanced MRI of the shoulder girdle is a reliable imaging tool with significant diagnostic value in the assessment of patients suffering from PMR and differentiation to other conditions for shoulder girdle pain.

Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, -19.9 [krill oil] vs -20.2 [placebo]; between-group mean difference, -0.3; 95% CI, -6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087.

Successful Treatment of Ultrasound-confirmed Synovitis in Anti-MDA5 Antibody-positive Clinically Amyopathic Dermatomyositis with Corticosteroid Therapy.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis without severe myositis but with characteristic cutaneous manifestations and severe interstitial lung disease. Joint symptoms can occur in patients with anti-MDA5 antibody-positive CADM. However, the treatment strategy and utility of ultrasound for treating joint symptoms remain unknown. We herein report an 85-year-old man with anti-MDA5 antibody-positive CADM who presented with ultrasound-confirmed synovitis that improved with medium-dose corticosteroid therapy.

Work-related physical strain and development of joint inflammation in the trajectory of emerging inflammatory and rheumatoid arthritis: a prospective cohort study.

OBJECTIVES: Rheumatoid arthritis (RA) mainly affects small joints. Despite the mechanical function of joints, the role of mechanical stress in the development of arthritis is insufficiently understood. We hypothesised that mechanical stress/physical strain is a risk factor for joint inflammation in RA. Therefore, we studied work-related physical strain in subjects with clinically suspected arthralgia (CSA) as a risk factor for the presence of imaging-detected subclinical joint inflammation and the development of clinical arthritis/RA. METHODS: In 501 CSA patients and 155 symptom-free persons' occupation-related physical strain was quantified using the International Standard Classification of Occupations. Contrast-enhanced hand-MRIs were made and evaluated for joint inflammation (sum of synovitis/tenosynovitis/osteitis). CSA patients were followed on RA development. Age relationship was studied using an interaction term of physical strain with age. RESULTS: The degree of physical strain in CSA is associated with the severity of joint inflammation, independent of educational-level/BMI/smoking (interaction physical strain-age p=0.007; indicating a stronger association with increasing age). Physical strain is associated with higher tenosynovitis scores, in particular. In symptom-free persons, physical strain was not associated with imaging-detected joint inflammation. Higher degrees of physical strain also associated with higher risks for RA development in an age-dependent manner (HR=1.20 (1.06-1.37)/10-year increase in age), independent of educational-level/BMI/smoking. This association was partly mediated by an effect via subclinical joint inflammation. CONCLUSIONS: Work-related physical strain increases the risk of subclinical joint inflammation and of developing RA. The age relationship suggests an effect of long-term stress or that tenosynovium is more sensitive to stress at older age. Together, the data indicate that mechanical stress contributes to the development of arthritis in RA.

Haemophilic arthropathy: Diagnosis, management, and aging patient considerations.

Gene therapy and universal use of safer, more effective, and personalised prophylactic regimens (factor, and nonfactor) are expected to prevent joint bleeding and promote joint health in persons with haemophilia (PwH). Growing evidence suggests that subclinical bleeding, with active and inactive synovial proliferation, continues and haemophilic arthropathy remains a major morbidity in PwH despite early institution of joint prophylaxis. Joint health assessment is evolving with physical examination scores complementing imaging scores. Point-of-care ultrasound is emerging as a safe, cost-effective, and readily available tool for acute determination of musculoskeletal abnormalities, serial evaluation of joints for sonographic markers of haemophilic arthropathy, and in providing objective insight into the efficacy of new therapies. In acute haemarthrosis, arthrocentesis expedites recovery and prevent the vicious cycle of bleed-synovitis-rebleed. When synovial proliferation develops, a multidisciplinary team approach is critical with haematology, orthopaedics, and physiotherapy involvement. Synovectomy is considered for patients with chronic synovitis that fail conservative management. Non-surgical and minimally invasive procedures should always be offered and considered first. Careful patient selection, screening and early intervention increase the success of these interventions in reducing bleeding, pain, and improving joint function and quality of life. Chemical synovectomy is practical in developing countries, but radioactive synovectomy appears to be more effective. When surgical synovectomy is considered, arthroscopic/minimally invasive approach should be attempted first. In advanced haemophilic arthropathy, joint replacement and arthrodesis can be considered. While excited about the future of haemophilia management, navigating musculoskeletal challenges in the aging haemophilia population is equally important.

Subclinical synovitis impact on the progression of lupus joint disease: A 10-year longitudinal multicenter study.

OBJECTIVE: To determine the effect of subclinical synovitis on the progression of joint disease in a cohort of patients with systemic lupus erythematosus over a mean follow-up of 10 years. METHODS: A longitudinal follow-up of 96 patients diagnosed with lupus was performed. All patients were considered clinically free of joint disease or with minimal joint impairment at baseline and were studied through ultrasound study of their dominant hand to assess the prevalence of subclinical synovitis. Now, over 10 years after we contacted them and reviewed their evolution to determine the impact of had or had not been diagnosed with subclinical synovitis in their current joint condition. RESULTS: Thirty-one of the 91 reached patients developed clinical progression in their joint manifestations (at least one ordinal degree of worsening). Of these, 23 (74,9%) had demonstrated subclinical synovitis at baseline. In the group of patients who did not progress clinically, 46 (76,6%) did not have this finding at the start of follow-up (p < .01, OR 9,44 95%CI 3,46-25,74). The patients in whom clinical progression was demonstrated had worse combined ultrasound scores than the rest of the patients: 6,41 SD 1,45 vs. 1,15 SD 0,97 (p < .01). CONCLUSIONS: The finding of subclinical synovitis in patients with systemic lupus erythematosus is associated with the development of joint disease progression both clinically and ultrasonographically.

Radiosynovectomy in haemophilic synovitis and arthropathy of the knee: A scoping review.

INTRODUCTION: Radiosynovectomy is an established treatment for chronic synovitis in patients with haemophilia. Although its role in rheumatological diseases has diminished, it remains an accepted therapy for haemophilic synovitis. AIM: The aim of this scoping review was to map and summarise the evidence surrounding radiosynovectomy in haemophilic knees, identify gaps in the literature and inform future research. RESULTS: Forty-three manuscripts and abstracts were identified for this review. Evidence was limited to observational studies and Yttrium-90 was the most studied licensed radioisotope. Radiosynovectomy was associated with a reduction in bleeding frequency and pain, improvements in range of motion and a reduction in the use of factor replacement. CONCLUSION: The literature reviewed lacks studies of sufficient methodological quality to permit systematic review and meta-analysis. Systematic review using risk of bias assessment for observational studies should be undertaken to better evaluate the efficacy and safety of radiosynovectomy. A causal relationship between RSV and key clinical outcomes remains undetermined.

Validity of an ultrasonographic joint-specific scoring system in juvenile idiopathic arthritis: a cross-sectional study comparing ultrasound findings of synovitis with whole-body magnetic resonance imaging and clinical assessment.

OBJECTIVE: To assess the validity of an ultrasonographic scoring system in juvenile idiopathic arthritis (JIA) by comparing ultrasound detected synovitis with whole-body MRI and clinical assessment of disease activity. METHODS: In a cross-sectional study, 27 patients with active JIA underwent clinical 71-joints examination, non-contrast enhanced whole-body MRI and ultrasound evaluation of 28 joints (elbow, radiocarpal, midcarpal, metacarpophalangeal 2-3, proximal interphalangeal 2-3, hip, knee, tibiotalar, talonavicular, subtalar and metatarsophalangeal 2-3). One rheumatologist, blinded to clinical findings, performed ultrasound and scored synovitis (B-mode and power Doppler) findings using a semiquantitative joint-specific scoring system for synovitis in JIA. A radiologist scored effusion/synovial thickening on whole-body MRI using a scoring system for whole-body MRI in JIA. At patient level, associations between ultrasound synovitis sum scores, whole-body MRI effusion/synovial thickening sum scores, clinical arthritis sum scores, and the 71-joints Juvenile Arthritis Disease Activity Score (JADAS71) were calculated using Spearman's correlation coefficients (rs). To explore associations at joint level, sensitivity and specificity were calculated for ultrasound using whole-body MRI or clinical joint examination as reference. RESULTS: Ultrasound synovitis sum scores strongly correlated with whole-body MRI effusion/synovial thickening sum scores (rs=0.74,p<0.01) and the JADAS71 (rs=0.71,p<0.01), and moderately with clinical arthritis sum scores (rs=0.57,p<0.01). Sensitivity/specificity of ultrasound in detecting synovitis were 0.57/0.96 and 0.55/0.96 using whole-body MRI or clinical joint examination as reference, respectively. CONCLUSION: Our findings suggest that ultrasound is a valid instrument to detect synovitis, and that ultrasound synovitis sum scores can reflect disease activity and may be an outcome measure in JIA.

Improving our understanding of the paradoxical protective effect of obesity on radiographic damage: a large magnetic resonance imaging-study in early arthritis.

OBJECTIVE: Obesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in detail from MRI-detected synovitis and osteitis to MRI-detected erosive progression, which precedes radiographic progression. Previous research suggested obesity associates with less osteitis and synovitis. We therefore aimed to (i) validate the previously suggested association between BMI and MRI-detected osteitis/synovitis; (ii) study whether this is specific for ACPA-positive or ACPA-negative RA or also present in other arthritides; (iii) study whether MRI-detected osteitis associates with MRI-detected erosive progression; and (iv) study whether obesity associates with MRI-detected erosive progression. METHODS: We studied 1029 early arthritis patients (454 RA, 575 other arthritides), consecutively included in Leiden Early Arthritis Clinic. At baseline patients underwent hand-and-foot MRI that were RAMRIS-scored, and 149 RA patients underwent follow-up MRIs. We studied associations between baseline BMI and MRI-detected osteitis/synovitis (using linear regression), and erosive progression (using Poisson mixed models). RESULTS: In RA, higher BMI associated with less osteitis at disease onset (ß = 0.94; 95% CI: 0.93, 0.96) but not with synovitis. Higher BMI associated with less osteitis in ACPA-positive RA (ß = 0.95; 95% CI: 0.93, 0.97), ACPA-negative RA (ß = 0.97; 95% CI: 0.95, 0.99) and other arthritides (ß = 0.98; 95% CI: 0.96, 0.99). Over 2 years, overweight and obesity associated with less MRI-detected erosive progression (P = 0.02 and 0.03, respectively). Osteitis also associated with erosive progression over 2 years (P < 0.001). CONCLUSIONS: High BMI relates to less osteitis at disease onset, which is not confined to RA. Within RA, high BMI and less osteitis associated with less MRI-detected erosive progression. This suggests that the protective effect of obesity on radiographic progression is exerted via a path of less osteitis and subsequently fewer MRI-detected erosions.

Three-dimensional ultrasound to investigate synovitis in first carpometacarpal osteoarthritis: A feasibility study.

BACKGROUND: Synovitis is one of the defining characteristics of osteoarthritis (OA) in the carpometacarpal (CMC1) joint of the thumb. Quantitative characterization of synovial volume is important for furthering our understanding of CMC1 OA disease progression, treatment response, and monitoring strategies. In previous studies, three-dimensional ultrasound (3-D US) has demonstrated the feasibility of being a point-of-care system for monitoring knee OA. However, 3-D US has not been tested on the smaller joints of the hand, which presents unique physiological and imaging challenges. PURPOSE: To develop and validate a novel application of 3-D US to monitor soft-tissue characteristics of OA in a CMC1 OA patient population compared to the current gold standard, magnetic resonance imaging (MRI). METHODS: A motorized submerged transducer moving assembly was designed for this device specifically for imaging the joints of the hands and wrist. The device used a linear 3-D scanning approach, where a 14L5 2-D transducer was translated over the region of interest. Two imaging phantoms were used to test the linear and volumetric measurement accuracy of the 3-D US device. To evaluate the accuracy of the reconstructed 3-D US geometry, a multilayer monofilament string-grid phantom (10 mm square grid) was scanned. To validate the volumetric measurement capabilities of the system, a simulated synovial tissue phantom with an embedded synovial effusion was fabricated and imaged. Ten CMC1 OA patients were imaged by our 3-D US and a 3.0 T MRI system to compare synovial volumes. The synovial volumes were manually segmented by two raters on the 2D slices of the 3D US reconstruction and MR images, to assess the accuracy and precision of the device for determining synovial tissue volumes. The Standard Error of Measurement and Minimal Detectable Change was used to assess the precision and sensitivity of the volume measurements. Paired sample t-tests were used to assess statistical significance. Additionally, rater reliability was assessed using Intra-Class Correlation (ICC) coefficients. RESULTS: The largest percent difference observed between the known physical volume of synovial extrusion in the phantom and the volume measured by our 3D US was 1.1% (p-value = 0.03). The mean volume difference between the 3-D US and the gold standard MRI was 1.78% (p-value = 0.48). The 3-D US synovial tissue volume measurements had a Standard Error Measurement (SEm ) of 11.21 mm3 and a Minimal Detectible Change (MDC) of 31.06 mm3 , while the MRI synovial tissue volume measurements had an SEM of 16.82 mm3 and an MDC of 46.63 mm3 . Excellent inter- and intra-rater reliability (ICCs = 0.94-0.99) observed across all imaging modalities and raters. CONCLUSION: Our results indicate the feasibility of applying 3-D US technology to provide accurate and precise CMC1 synovial tissue volume measurements, similar to MRI volume measurements. Lower MDC and SEm values for 3-D US volume measurements indicate that it is a precise measurement tool to assess synovial volume and that it is sensitive to variation between volume segmentations. The application of this imaging technique to monitor OA pathogenesis and treatment response over time at the patient's bedside should be thoroughly investigated in future studies.

Particulate synovitis granuloma complication following a first metatarsophalangeal joint silastic implant.

This case presents a known complication of particulate synovitis granuloma associated with a first metatarsophalangeal joint silastic implant. However, the degree of soft tissue granuloma enlargement is quite unique in size and its proliferative effect-invading the medulla cavity and infiltrating the outer cortex of bone. This case study aims to demonstrate its clinical presentation, imaging investigations, surgical excision and histopathology findings. The learning points emphasised within this manuscript draw attention to the procedure selection for a silastic implant, as well as its proposed mode of action and various potential associated complications. Surgery was based on careful analysis of overall function, prior surgery conducted and patient expectations to achieve a shared decision-making process.

Advanced Magnetic Resonance Imaging and Molecular Imaging of the Painful Knee.

Chronic knee pain is a common condition. Causes of knee pain include trauma, inflammation, and degeneration, but in many patients the pathophysiology remains unknown. Recent developments in advanced magnetic resonance imaging (MRI) techniques and molecular imaging facilitate more in-depth research focused on the pathophysiology of chronic musculoskeletal pain and more specifically inflammation. The forthcoming new insights can help develop better targeted treatment, and some imaging techniques may even serve as imaging biomarkers for predicting and assessing treatment response in the future. This review highlights the latest developments in perfusion MRI, diffusion MRI, and molecular imaging with positron emission tomography/MRI and their application in the painful knee. The primary focus is synovial inflammation, also known as synovitis. Bone perfusion and bone metabolism are also addressed.

Arthroscopic debridement of the ankle in synovitis.

Inflammation and hypertrophy of the ankle joint's synovial lining can occur due to various causes. Chronic pain and degenerative changes may be due to synovitis causing clinical manifestations through traction on the joint capsule. The failure of conservative treatment for at least six months indicates arthroscopic debridement, which can provide significant pain relief without the morbidity of extensive surgical exposures. This study was therefore conducted to establish the functional results of arthroscopic debridement of the ankle joint in synovitis. Fifteen patients with chronic ankle pain who had not responded to conservative treatment for approximately six months were included in the study. Arthroscopic debridement was performed using a shaver blade, followed by a postoperative ankle physiotherapy regimen. Patients were assessed preoperatively and postoperatively using the AOFAS, FADI, and VAS scores, with a mean follow-up period of 26 months. There was a significant improvement in the final clinical outcomes of the patients. The post-operative VAS score improved to 2.20±0.56 (2-4) (p-value=0.001), the AOFAS score was 86±8.25 (65-98) (p-value-0.001), and the FADI Score was 86.93±7.35(70-96) (p-value=0.001). Thirteen patients (86.67%) achieved outstanding or good results, while two had fair results, according to Meislin's criterion. One patient reported a superficial wound infection, which subsided with antibiotic therapy. The study findings indicate that arthroscopic ankle debridement is an efficient method to treat persistent ankle discomfort induced by synovitis, and it has a low postsurgical complications rate, quicker recovery, and less joint stiffness.

Hemophilic arthropathy: how to diagnose subclinical bleeding early and how to orthopedically treat a damaged joint.

INTRODUCTION: It is important to know the current status of hemophilic arthropathy diagnoses, treatments, complications, and outcomes in developed countries. AREAS COVERED: A bibliographic search in PubMed for articles published from 1 January 2019 through 12 June 2023 was performed. EXPERT OPINION: In developed countries with specialized hemophilia treatment centers, primary hematological prophylaxis (started before the age of 2 years and after no more than one joint bleed) has almost completely eliminated the joint-related problems of the disease. The ideal goal of zero hemarthroses can be achieved only with intense and well-dosed prophylaxis: intravenous infusion of coagulation factor - standard half-life or extended half-life; periodic or subcutaneous injections of nonfactor products (emicizumab or fitusiran). However, hemophilic arthropathy continues to occur due to subclinical joint hemorrhages. In one study, 16% of the joints without reported hemarthroses showed signs of previous subclinical bleeding (hemosiderin deposits with/without synovial hypertrophy on magnetic resonance imaging were deemed signs of previous subclinical bleeding), rendering evidence for subclinical bleeding in people with severe hemophilia with lifelong prophylaxis treatment. Subclinical joint hemorrhages can be averted only by employing accurate and tailored prophylaxis.

Clinical examination, ultrasound assessment and aspiration of knee effusion in primary knee osteoarthritis patients.

BACKGROUND: To assess the diagnostic performance of clinical examination and ultrasound (US) assessment of knee effusion in primary knee osteoarthritis (KOA) patients. Furthermore, the success rate for effusion aspiration and the factors related to it were investigated. METHODS: This cross-sectional study included patients diagnosed with primary KOA-induced knee effusion clinically or sonographically. The affected knee of each patient was subjected to clinical examination and US assessment using the ZAGAZIG effusion and synovitis ultrasonographic score. Patients with confirmed effusion and consented to aspiration were prepared for direct US-guided aspiration under complete aseptic techniques. RESULTS: One hundred and nine knees were examined. During visual inspection, swelling was detected in 80.7% of knees and effusion was confirmed by US in 67.8% of knees. Visual inspection was the most sensitive at 90.54% while bulge sign was the most specific at 65.71%. Only 48 patients (61 knees) consented to aspiration procedure; 47.5% had grade III effusion, and 45.9% had grade III synovitis. Successful aspiration was achieved in 77% of knees. Two needle types were used; a 22 gauge / 3.5-inch spinal needle in 44 knees and an 18 gauge/ 1.5-inch needle in 17 knees, with a success rate of 90.9% and 41.2%, respectively. Aspirated amount of synovial fluid correlated positively with effusion grade (rs=0.455, p < 0.001) and negatively with synovitis grade on US (rs = - 0.329, p = 0.01). CONCLUSIONS: The superiority of the US over clinical examination in detecting knee effusion suggests that US should be used routinely to confirm the presence of effusion. Long needles (spinal needle) may have a higher success rate of aspiration than shorter needles.

L-carnitine alleviates synovitis in knee osteoarthritis by regulating lipid accumulation and mitochondrial function through the AMPK-ACC-CPT1 signaling pathway.

BACKGROUND: Knee osteoarthritis (KOA) is a disability-associated condition that is rapidly growing with the increase in obesity rates worldwide. There is a pressing need for precise management and timely intervention in the development of KOA. L-carnitine has been frequently recommended as a supplement to increase physical activity in obese individuals due to its role in fatty acid metabolism, immune disorders, and in maintaining the mitochondrial acetyl-CoA/CoA ratio. In this study, we aimed to investigate the anti-inflammatory effects of L-carnitine on KOA and delineate a potential molecular mechanism. METHODS: Lipopolysaccharide-stimulated primary rat fibroblast-like synoviocytes (FLS) were treated with an AMP-activated protein kinase (AMPK) inhibitor or siRNA and carnitine palmitoyltransferase 1 (CPT1) siRNA to examine the synovial protective effects of L-carnitine. An anterior cruciate ligament transection model of rats was treated with an AMPK agonist (metformin) and CPT1 inhibitor (etomoxir) to define the therapeutic effects of L-carnitine. RESULTS: L-carnitine displayed a protective effect against synovitis of KOA in vitro and in vivo experiments. Specifically, L-carnitine treatment can reduce synovitis by inhibiting AMPK-ACC-CPT1 pathway activation and showed an increase in fatty acid ß-oxidation, a lower lipid accumulation, and a noticeable improvement in mitochondrial function. CONCLUSIONS: Our data suggested that L-carnitine can mitigate synovitis in FLS and synovial tissue, and the underlying mechanism may be related to improving mitochondrial function and reducing lipid accumulation via the AMPK-ACC-CPT1 signaling pathway. Therefore, L-carnitine may be a potential treatment strategy for KOA.

Associations between markers of inflammation and altered pain perception mechanisms in people with knee osteoarthritis: a systematic review.

To provide an extensive review on the associations between knee inflammation and altered pain perception mechanisms in people with knee osteoarthritis (OA). MEDLINE, Web of Science, EMBASE and Scopus were searched up to 13 December 2022. We included articles reporting associations between knee inflammation (measured by effusion, synovitis, bone marrow lesions (BMLs) and cytokines) and signs of altered pain processing (assessed by quantitative sensory testing and/or questionnaire for neuropathic-like pain) in people with knee OA. Methodological quality was evaluated using the National Heart, Lung and Blood Institute Study Quality Assessment Tool. Level of evidence and strength of conclusion were determined using the Evidence-Based Guideline Development method. Nine studies were included, comprising of 1889 people with knee OA. Signs of greater effusion/synovitis may be positively associated with lower knee pain pressure threshold (PPT) and neuropathic-like pain. Current evidence could not establish an association between BMLs and pain sensitivity. Evidence on associations between inflammatory cytokines and pain sensitivity or neuropathic-like pain was conflicting. There are indications of a positive association between higher serum C reactive protein (CRP) levels and lower PPT and presence of temporal summation. Methodological quality varied from level C to A2. Signs of effusion/synovitis may be positively associated with neuropathic-like pain and pain sensitivity. There are indications of a possible positive association between serum CRP levels and pain sensitivity. Given the quality and the small amount of included studies, uncertainty remains. Future studies with adequate sample size and follow-up are needed to strengthen the level of evidence.PROSPERO registration number: CRD42022329245.