Assessment of disease activity in patients with rheumatoid arthritis using plasma tumour M2-pyruvate kinase test.

Background: Pyruvate kinase M2 (PKM2) is an enzyme that regulates the final process of glycolysis and exists in tetrameric and dimeric forms. The dimeric form of PKM2, also known as tumour M2-PK, increases when aerobic glycolysis is augmented, a feature observed in rheumatoid arthritis (RA). We investigated whether plasma tumour M2-PK is elevated in patients with RA and whether its levels correlate with disease activity. Methods: Plasma levels of tumour M2-PK were measured for patients with RA (n=151), those with osteoarthritis (OA) (n=37), and controls (n=37). We evaluated the association between plasma tumour M2-PK and continuous variables using Pearson's correlation analysis, and multivariate logistic regression analysis to determine the association between plasma tumour M2-PK and disease activity status. Knee synovial tissue blocks from patients with RA and OA were subjected to real-time quantitative PCR (qPCR) using two different primers for PKM2 and tumour M2-PK immunohistochemical (IHC) staining. Results: The tumour M2-PK level significantly correlated with the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) (r=0.546, p<0.001) and DAS28-C-reactive protein (CRP) (r=0.589, p<0.001). Moreover, repeat testing of tumour M2-PK levels in 20 patients revealed a significant decline in tumour M2-PK levels after reduction in inflammation (p<0.001). Area under the receiver operating characteristic curve (AUROC) analysis demonstrated that upon incorporation of tumour M2-PK, ESR, and CRP, the area under the curve was 0.962 for distinguishing moderate/high from remission/low disease activity. Adjusted logistic regression also revealed that a tumour M2-PK >43.9 U/mL (OR 3.672, p=0.042) independently predicted moderate/high disease activity status. Furthermore, tumour M2-PK levels in patients with RA were significantly higher than in those with OA and controls (all p<0.001). However, no differences were found in PKM2 expression in RA and OA synovial tissues as assessed by qPCR, and IHC analysis revealed negligible tumour M2-PK expression in the synovial tissues. Conclusion: Circulating plasma tumour M2-PK levels may be a clinically useful indicator for evaluating disease activity and RA diagnosis.

Application of Ultrasound in the Assessment of Oligoarticular Psoriatic Arthritis Subset: Results from Patients Treated with Apremilast.

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by different phenotypes in terms of joint involvement. The so-called oligoarticular pattern involves fewer than five active joints at a different time points. The evaluation of disease activity in this subset of patients is an unmet need due to the lack of specific indices able to capture modifications over time. OBJECTIVES: To evaluate the ability of musculoskeletal ultrasound to monitor the response to apremilast treatment in oligoarticular PsA patients. METHODS: We evaluated 24 oligoarticular patients (19 women, 5 men; median age 56 years, interquartile range (IQR) 19; median disease duration 5 years, IQR 5.75). All patients were assessed at baseline (T0), and after 6 (T1), 12 (T2), and 24 (T3) weeks. Clinical assessment included evaluation of 66 swollen joints and patient global health assessment. All the patients underwent ultrasound assessment of the clinically involved joints. Synovial effusion/hypertrophy and power Doppler were scored with a semi-quantitative scale (0-3). The total inflammatory score was the sum of the scores. RESULTS: We found a reduction in the ultrasound inflammatory score at all time points, with a significant improvement at 6 and 12 weeks of treatment compared with baseline: T0 median 8.5 (IQR 5.0); T1 3.5 (3.0); T2 2.0 (3.5); P = 0.01. We observed a significant reduction of patient global health assessment after 24 weeks (T0 median 50 (32.5); T3 40 (57.5); P = 0.01). CONCLUSIONS: Musculoskeletal ultrasound could be useful in the assessment of treatment response in PsA patients with oligoarticular subset.

Atomic force microscopy technique used for assessment of the anti-arthritic effect of licochalcone A via suppressing NF-κB activation.

Atomic force microscopy (AFM) is appropriately applied to the examination of hard surfaces and soft samples with extremely high resolution and ultrasensitive force, which cannot be obtained by other imaging techniques, including optical and electron microscopy. In the current study, AFM was employed to evaluate the anti-arthritic effect of licochalcone A (LCA), a flavonoid isolated from the root of Chinese medicinal herb Glycyrrhiza inflate, on rheumatoid arthritis synovial fibroblasts (RASFs) at the nanoscale for the first time. The morphology, ultrastructure and stiffness of RASFs was modified by LCA as determined by AFM, suggesting that LCA most likely exerts an anti-arthritic effect based on the key role of RASFs in the progression of RA. Further studies showed that the inhibitory effect of LCA on IκBα phosphorylation and degradation as well as on p65 nuclear translocation and phosphorylation contributed to altering the morphology, ultrastructure and stiffness of the RASF membrane. Interestingly, IKKß phosphorylation was not detectable in RASFs, indicating that LCA altered the morphology, ultrastructure and stiffness of the RASF membrane by inhibiting NF-κB activation independent of IKKß phosphorylation. Antigen-induced arthritis (AIA) was established in Sprague Dawley (SD) rats to validate the anti-arthritic effect of LCA, and LCA significantly decreased both the arthritis scores and paw swelling in the AIA rats, suggesting that LCA inhibits the progression and development of arthritis in vivo. Collectively, AFM provides evidence at the nanoscale to predict the anti-arthritic effect of drugs on RASFs, and LCA should be further investigated as a candidate agent for the treatment of arthritis.

Burden of Illness Associated with Tenosynovial Giant Cell Tumors.

PURPOSE: Little is known about the burden of illness in patients with tenosynovial giant cell tumors (TGCT), which are rare, typically benign, lesions of the synovial tissue including giant cell tumor of the tendon sheath (GCT-TS) and pigmented villonodular synovitis (PVNS). The objective of this study was to describe health care resource use and costs for patients with GCT-TS and PVNS, which are rare and typically benign TGCT. METHODS: A retrospective cohort study design was used to analyze administrative claims for adult commercial and Medicare Advantage health plan enrollees with evidence of GCT-TS and PVNS from January 1, 2006 through March 31, 2015. Participants were continuously enrolled for 12 months before (pre-index period) and 12 months after (post-index period) the date of the first tenosynovial giant cell tumor (TGCT) claim (index date). Preindex and postindex measures were compared using the McNemar test and Wilcoxon signed-rank test. Results were stratified by TGCT type. FINDINGS: The study identified 4664 patients with TGCT, 284 with GCT-TS, and 4380 with PVNS. Mean age (GCT-TS group: 50 years; PVNS group: 51 years) and sex distributions (GCT-TS group: 60.2% female; PVNS group: 59.5% female) were similar for each group. Most patients with GCT-TS (78.2%) had at least one postindex surgery, compared with 38.7% of patients with PVNS. Mean total health care costs increased from $8943 in the preindex period to $14,880 in the postindex period (P < 0.001) for GCT-TS and from $13,221 in the preindex period to $17,728 in the postindex period (P < 0.001) for PVNS. Preindex to postindex ambulatory costs increased nearly 120% for patients with GCT-TS ($4340 to $9570, P < 0.001) and 50% for patients with PVNS ($6782 to $10,278, P < 0.001), and physical therapy use increased significantly during the same period (GCT-TS: 18% to 40%, P < 0.001; PVNS: 38% to 60%, P < 0.001). IMPLICATIONS: Costs increased substantially 1 year after the first TGCT claim, with more than half the costs covering ambulatory care. These results suggest a high health care burden once TGCT is identified.

Dosimetry in Radiosynoviorthesis: 90Y VS. 153Sm.

Although there are several radionuclides suitable for radiosynoviorthesis (RSO), not all of them can irradiate deeper synovium. Yttrium-90 (Y) is the beta radionuclide with more penetration range; therefore, it is predominantly used to treat knees. The aim of this paper is to highlight several dosimetry concepts to compare Y and Sm, also discussing the feasibility of implementing a dose planning methodology for both in RSO. The MCNPX Monte Carlo nuclear code version 2.6 was used for calculating S-values from which the activity to be injected into the joint was obtained. This activity is considered sufficient to deliver a 100-Gy absorbed dose in 1 mm of synovial tissue. The simulated mathematical model consisted of a system formed by several cylindrical slabs of 1-mm thickness, aligned consecutively. The different areas of the cylinder base simulate several synovial membrane sizes. The effective treatment range for each radionuclide was also calculated. Quantification of the synovial joint features (synovial thickness and synovial surface) by diagnostic imaging, such as magnetic resonance (MRI) combined with a Monte Carlo simulation, can be used to achieve a treatment planning strategy in RSO with the available radionuclides.

Comparison between semiquantitative and quantitative methods for the assessment of knee synovitis in osteoarthritis using non-enhanced and gadolinium-enhanced MRI.

OBJECTIVE: To compare different semiquantitative and quantitative methods using both non-enhanced and gadolinium-enhanced MRI techniques for the assessment of synovitis in knee osteoarthritis (OA). METHODS: Knees with end-stage clinical OA in patients undergoing total knee replacement surgery were included in this cross-sectional study. MRI was performed on all knees. Standard non-enhanced and gadolinium-enhanced sequences were acquired. Using non-enhanced MRI, we semiquantitatively assessed two features widely used as surrogates for synovitis: effusion-synovitis and Hoffa-synovitis. Using gadolinium-enhanced sequences, we semiquantitatively assessed synovial thickness. We quantitatively evaluated the total synovial volume on the gadolinium-enhanced sequences as well. We assessed the correlations of effusion-synovitis and Hoffa-synovitis with synovial thickness and volume, applying Spearman correlation analysis. The diagnostic performance of both synovitis features on non-enhanced MRI was assessed using synovial thickness on gadolinium-enhanced MRI as the reference. RESULTS: A total of 104 subjects (one knee per subject) were included. Correlations of effusion-synovitis with synovial thickness and volume were r = 0.41 and r = 0.43 (P < .001) r = 0.32 and r = 0.39 (P < .0001). CONCLUSION: Using synovial thickness assessed on gadolinium-enhanced sequences as the reference, effusion-synovitis showed superior correlations and sensitivity. Effusion-synovitis should be preferred over Hoffa-synovitis as a surrogate marker for synovial thickening, in studies of knee OA for which gadolinium-enhanced sequences are not available.

Comprehensive analysis of translational osteochondral repair: Focus on the histological assessment.

Articular cartilage guarantees for an optimal functioning of diarthrodial joints by providing a gliding surface for smooth articulation, weight distribution, and shock absorbing while the subchondral bone plays a crucial role in its biomechanical and nutritive support. Both tissues together form the osteochondral unit. The structural assessment of the osteochondral unit is now considered the key standard procedure for evaluating articular cartilage repair in translational animal models. The aim of this review is to give a detailed overview of the different methods for a comprehensive evaluation of osteochondral repair. The main focus is on the histological assessment as the gold standard, together with immunohistochemistry, and polarized light microscopy. Additionally, standards of macroscopic, non-destructive imaging such as high resolution MRI and micro-CT, biochemical, and molecular biological evaluations are addressed. Potential pitfalls of analysis are outlined. A second focus is to suggest recommendations for osteochondral evaluation.

Ultrasound assessment of response to intra-articular therapy in osteoarthritis of the knee.

OBJECTIVE: Assessment of the synovium in patients with knee OA is of great potential value for clinical trials. Ultrasonography could provide this but few data exist on its ability to assess synovial response to therapies. The aim of this study was to examine whether US can detect synovial response to IA corticosteroid (IACS) therapy and to explore associations between synovial characteristics and symptoms. METHODS: A total of 35 people with ACR radiographic knee OA were included, including those who required an injection of 80 mg of IA methylprednisolone. All participants completed a visual analogue scale for pain and underwent US of the knee at baseline, 1 and 4 weeks. Minimum clinically important improvement (MCII) in pain was ≥20 mm. RESULTS: One week of data were available for 33 patients (19 received IACS and 14 others). Synovial thickness (ST) decreased in 16 IACS patients and 2 others [mean between-group difference 4.7 mm (95% CI 1.1, 8.2), P = 0.012]. Absolute reduction was not associated with absolute reduction in pain (r = 0.20, P = 0.289), but decreased ST was substantively associated with reduction in pain greater than or equal to the MCII (52.9% vs 23.1%, P = 0.098, φ = 0.30). The power Doppler score decreased in 13 IACS patients and 3 others {median change in IACS patients -1.0 [interquartile range (IQR) -5.0-0.0], others 0.0 [-0.3-1.3], P = 0.004}. Absolute changes in pain and power Doppler score were weakly associated (ρ = 0.36, P = 0.049) and a decreased power Doppler score was associated with reduction in pain greater than or equal to the MCII (64.3% vs 18.8%, P = 0.011, φ = 0.46). CONCLUSION: Ultrasonography can detect short-term synovial response in knee OA. In particular, power Doppler score may be both responsive to and associated with pain, warranting further investigation.

An MRI assessment of chronic synovial-based inflammation in gout and its correlation with serum urate levels.

It is unclear when the synovial-based inflammatory process of gout begins. The aim of this study was to determine the percentage of patients with inter-critical gout who have chronic synovial-based inflammation as evidenced by synovial pannus on a contrast-enhanced magnetic resonance imaging (MRI) of their most involved joint and determine if the presence and/or severity correlates with their serum urate levels. All patients received a 3 T MRI of their index joint, serum urate level, CRP, and creatinine. The primary endpoint was to determine the prevalence of synovial pannus and the correlation of serum urate levels with the presence and/or severity of the synovial pannus on that same joint. MRI erosions, tophi, swelling, effusion, and osteitis were also documented. Seventy-two of 74 subjects (90% men) completed the protocol. Fifty-three of 72 (74%) index joints were the first metatarsophalangeal joint. Thirty-nine (54.2%) of the patients were on urate-lowering therapy; 15 (20.8%) and 7 (9.7%) were taking colchicine or a NSAID daily, respectively. Of the 72 subjects, 63 (87.5%) had synovial pannus on their MRI with good inter-reader agreement between the two radiologists. The mean serum urate level was 7.93 mg/dL. There was no correlation with the presence (p = 0.33) or severity (p = 0.34) of synovial pannus and serum urate levels. There was also no correlation with the presence or severity of synovial pannus and the secondary endpoints. The majority of patients with inter-critical gout have evidence of chronic synovial-based inflammation. However, the presence and severity of this inflammation do not appear to correlate with serum urate levels.

MR imaging assessment of arthritis of the knee.

The magnetic resonance (MR) imaging presentations of arthritis of the knee are important for radiologists to recognize because these disorders are often clinically unsuspected. When they are known or clinically suspected, knowledge of imaging features allows for the confirmation and characterization of the extent of disease. This article reviews the fundamental MR imaging manifestations of rheumatologic disorders of the knee and their presentation in specific arthropathies.

Ultrasound composite scores for the assessment of inflammatory and structural pathologies in Psoriatic Arthritis (PsASon-Score).

INTRODUCTION: This study was performed to develop ultrasound composite scores for the assessment of inflammatory and structural lesions in Psoriatic Arthritis (PsA). METHODS: We performed a prospective study on 83 PsA patients undergoing two study visits scheduled 6 months apart. B-mode and Power Doppler (PD) findings were semi-quantitatively scored at 68 joints (evaluating synovia, perisynovial tissue, tendons and bone) and 14 entheses. We constructed bilateral and unilateral (focusing the dominant site) ultrasound composite scores selecting relevant sites by a hierarchical approach. We tested convergent construct validity, reliability and feasibility of inflammatory and structural elements of the scores as well as sensitivity to change for inflammatory items. RESULTS: The bilateral score (termed PsASon22) included 22 joints (6 metacarpophalangeal joints (MCPs), 4 proximal interphalangeal joints (PIPs) of hands (H-PIPs), 2 metatarsophalangeal joints (MTPs), 4 distal interphalangeal joints (DIPs) of hands (H-DIPs), 2 DIPs of feet (F-DIPs), 4 large joints) and 4 entheses (bilateral assessment of lateral epicondyle and distal patellar tendon). The unilateral score (PsASon13) compromised 13 joints (2 MCPs, 3 H-PIPs, 1 PIP of feet (F-PIP), 2 MTPs, 1 H-DIP and 2 F-DIPs and 2 large joints) and 2 entheses (unilateral lateral epicondyle and distal patellar tendon). Both composite scores revealed a moderate to high sensitivity (bilateral composite score 43% to 100%, unilateral 36% to 100%) to detect inflammatory and structural lesions compared to the 68-joint/14-entheses score. The inflammatory and structural components of the composite scores correlated weakly with clinical markers of disease activity (corrcoeffs 0 to 0.40) and the health assessment questionnaire (HAQ, corrcoeffs 0 to 0.39), respectively. Patients with active disease achieving remission at follow-up yielded greater reductions of ultrasound inflammatory scores than those with stable clinical activity (Cohen's d effect size ranging from 0 to 0.79). Inter-rater reliability of bi- and unilateral composite scores was moderate to good with ICCs ranging from 0.42 to 0.96 and from 0.36 to 0.71, respectively for inflammatory and structural sub-scores. The PsASon22 and PsASon13 required 16 to 26 and 9 to 13 minutes, respectively to be completed. CONCLUSION: Both new PsA ultrasound composite scores (PsASon22 and PsASon13) revealed sufficient convergent construct validity, sensitivity to change, reliability and feasibility.

Arthroscopic assessment of stifle synovitis in dogs with cranial cruciate ligament rupture.

Cranial cruciate ligament rupture (CR) is a degenerative condition in dogs that typically has a non-contact mechanism. Subsequent contralateral rupture often develops in dogs with unilateral CR. Synovitis severity is an important factor that promotes ligament degradation. Consequently, we wished to evaluate the utility of arthroscopy for assessment of stifle synovitis in dogs with CR. Herein, we report results of a prospective study of 27 dogs with unilateral CR and bilateral radiographic osteoarthritis. Arthroscopic images and synovial biopsies from the lateral and medial joint pouches were obtained bilaterally and graded for synovial hypertrophy, vascularity, and synovitis. Synovial tartrate-resistant acid phosphatase-positive (TRAP+) macrophages, CD3(+) T lymphocytes, Factor VIII+ blood vessels, and synovial intima thickness were quantified histologically and related to arthroscopic observations. Risk of subsequent contralateral CR was examined using survival analysis. We found that arthroscopic scores were increased in the index stifle, compared with the contralateral stifle (p<0.05). Numbers of CD3+ T lymphocytes (SR = 0.50, p<0.05) and TRAP+ cells in joint pouches (SR = 0.59, p<0.01) were correlated between joint pairs. Arthroscopic grading of vascularity and synovitis was correlated with number density of Factor VIII+ vessels (SR>0.34, p<0.05). Arthroscopic grading of villus hypertrophy correlated with numbers of CD3(+) T lymphocytes (SR = 0.34, p<0.05). Synovial intima thickness was correlated with arthroscopic hypertrophy, vascularity, and synovitis (SR>0.31, p<0.05). Strong intra-observer and moderate inter-observer agreement for arthroscopic scoring was found. Dog age and arthroscopic vascularity significantly influenced risk of contralateral CR over time. We conclude that arthroscopic grading of synovitis is a precise tool that correlates with histologic synovitis. Arthroscopy is useful for assessment of stifle synovitis in client-owned dogs, and could be used in longitudinal clinical trials to monitor synovial responses to disease-modifying therapy.

Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome.

INTRODUCTION: Arthritis is the most frequent manifestation of Blau syndrome, an autoinflammatory disorder caused by the genetic mutation of NOD2. However, detailed information on arthritis in Blau syndrome on which the therapeutic strategy should be based on is lacking. This multi-center study aimed to accurately characterize the articular manifestation of Blau syndrome and also to demonstrate the utility of musculoskeletal ultrasound in Blau syndrome. METHODS: Patients who had been diagnosed with Blau syndrome by genetic analysis of NOD2 were recruited. A total of 102 synovial sites in 40 joints were assessed semiquantitatively by ultrasound for gray-scale synovitis and synovial power Doppler (PD) signal. RESULTS: In total, 10 patients whose age ranged from 10 months to 37 years enrolled in this study. Although only 4 joints (0.8%) were tender on physical examination, 81 joints (16.9%) were clinically swollen. Moreover, 240 (50.0%), and 124 (25.8%) joints showed gray-scale (GS) synovitis and synovial PD signal on ultrasound, respectively. Importantly, GS synovitis was present in 168 out of 399 non-swollen joints, in which 61 also exhibited synovial PD signal. Among 40 joint regions, the ankle, the wrist, and the proximal interphalangeal joints were the most frequently and severely affected joints. Comparisons between different synovial tissues demonstrated a significantly higher proportion of the joints with tenosynovitis as compared with that with intra-articular synovitis (41.5% versus 27.9%, P < 0.0001). In respect of age and treatment, synovial PD signals were minimal in the youngest patient and in the oldest two patients, and were relatively mild in patients receiving treatment with methotrexate plus TNF antagonists. In two patients who underwent the second ultrasound examination, total PD scores markedly decreased after initiating the treatment with a tumor necrosis factor (TNF) antagonist. CONCLUSIONS: The detailed information on synovial inflammation obtained by ultrasound confirms the dissociation between pain and inflammation and the frequently involved joint regions and synovial tissue in the arthritis of Blau syndrome. Our data also demonstrate that ultrasonography can be a potent tool in monitoring the activity of synovial inflammation and in investigating the pathophysiology of arthritis in this rare but archetypical autoinflammatory condition.

Ultrasound assessment of synovial pathologic features in rheumatoid arthritis using comprehensive multiplane images of the second metacarpophalangeal joint: identification of the components that are reliable and influential on the global assessment of the whole joint.

OBJECTIVE: The aim of this pilot study was to provide groundwork that could be utilized to optimize the global ultrasound (US) assessment of the whole joint for synovial pathologic features in patients with rheumatoid arthritis (RA). METHODS: US images of the second metacarpophalangeal joint in 8 predefined imaging planes, comprising regions that comprehensively capture the synovial pathologic features of the whole joint, were obtained from 30 patients with RA. Twelve experienced sonographers evaluated these images at the level of both the individual image and the whole joint, using a visual analog scale (VAS) to assess pathologic severity. Interrater reproducibility of the VAS scores was evaluated with intraclass correlation coefficients (ICCs), and factors that independently influenced the global assessment of the whole joint were identified using multiple linear regression analysis. RESULTS: A total of 14,276 VAS scores were analyzed. Interrater reproducibility of any eligible VAS assessment of synovial pathologic features was good (ICC 0.65). US assessment of synovial pathologic features in joints with mild inflammation was less reproducible than that in joints with severe inflammation. Although the most severely affected region in a joint did not always represent the average pathologic severity among the 8 regions, global assessment of the whole joint strongly correlated with assessment of the most severely affected region (P < 0.001). Importantly, the standard, midline imaging plane was not the most influential plane on the global assessment of the whole joint. Assessment of synovial fluid accumulation was not reproducible (ICCs 0.20-0.42) and did not substantially influence the global assessment of synovial inflammation (ß = 0.06). CONCLUSION: The results of this study provide a unique data set that could be utilized to optimize the global US assessment of synovial pathologic features of the whole joint in patients with RA.

Comparing non-enhanced and enhanced sequences in the assessment of effusion and synovitis in knee OA: associations with clinical, macroscopic and microscopic features.

OBJECTIVE: The purpose of this study was to evaluate synovial membrane (SM) inflammation and joint effusion scores by semiquantitative magnetic resonance imaging (MRI) assessment with and without enhanced sequences. Gold standards used for comparison were microscopic examination of SM biopsies for SM inflammation and joint volume measurement (JVM) after arthrocentesis for effusion. METHODS: Patients (n = 30) fulfilling ACR criteria for knee osteoarthritis (OA) and requiring joint lavage, were evaluated with MRI: (1) SM inflammation was assessed by Whole-Organ Magnetic Resonance Imaging Score (WORMS) on T2 weighted sequences (T2w) a composite score assessing together synovitis and effusion, and the MRI-synovitis score (based on synovitis thickening in five regions of interest) on a T1-weighted fat sat sequence after contrast agent injection (T1wCE). (2) Joint effusion was evaluated by MRI-effusion score (T1wCE) and the WORMS (T2w). JVM was measured after arthrocentesis, and microscopic SM inflammation was determined in SM samples (n = 86). Correlations between MRI scores and clinical, biologic and histologic parameters were studied. RESULTS: Both scores for effusion were well correlated [r = 0.82 (0.65-0.91); P < 0.001] and presented excellent intraclass correlation coefficient (ICC) for intra- and inter-observer reproducibility. MRI scores for effusion were well correlated with JVM (r = 0.60 for WORMS and r = 0.59 for MRI-effusion score). Synovitis scores were highly reproducible but moderately correlated (r = 0.63; P < 0.001). Only MRI-synovitis total score (T1wCE) was correlated with SM microscopic inflammation (r = 0.46; P = 0.01) and most strongly infiltration (r = 0.45; P < 0.005). CONCLUSIONS: T2w sequences are adequate in assessing effusion volume in compare to joint volume by arthrocentesis but only T1wCE sequences are able to detect synovitis according to the reference of synovial biopsy.

Ultrasound imaging for the rheumatologist XXXIII. Sonographic assessment of the foot in early arthritis patients.

OBJECTIVES: To investigate the ability of ultrasonography (US) to detect synovitis in metatarsophalangeal joints (MTP) in patients with suspicion of early arthritis, and to discriminate between diagnoses. METHODS: Patients referred to early arthritis clinics for differential diagnosis were enrolled, and clinical and laboratory measures were recorded. Ultrasonography of MTPs was performed searching for synovial hypertrophy (SH), joint effusion (JE) and power Doppler (PD), graded from 0 to 3 on a semi-quantitative scale. Patients were classified according to definite classification criteria, or as undifferentiated arthritis or non-inflammatory pathology. US findings were compared across different diagnoses and diagnostic accuracy was calculated taking clinical diagnosis as reference. RESULTS: Out of 427 patients (71% rheumatoid arthritis (RA), 20% undifferentiated arthritis (UA), 15% spondyloarthritides (SpA), 13% non-inflammatory), 307 (71.9%) showed SH, 120 (25.5%) JE, 77 (18.0%) PD. RA patients had median JE, SH and PD scores significantly higher than non-inflammatory and other diseases. Patient with UA and SpA had higher scores of SH and JE compared to non-inflammatory, no significant differences were present among different diagnosis. In RA, SH and JE were more frequently detected in the second MTP, and PD in the fifth. Crystal-related arthritis showed a tendency towards a more frequent involvement of the first MTP. The diagnostic accuracy of single US measures was moderate, but the detection of a PD of 2 or more provided a high specificity for the diagnosis of RA. CONCLUSIONS: US can be used as additional information in patients evaluated in an early arthritis setting. High scores of JE, SH and PD, together with the pattern of involvement are suggestive of RA.

Power Doppler sonography, a non-invasive method of assessment of the synovial inflammation in patients with early rheumatoid arthritis.

OBJECTIVE: To detect synovitis is important in both the diagnosis and outcome assessment of early rheumatoid arthritis. This study was meant to assess the validity and reproducibility of ultrasonography (US) as a mean of detection for the knee synovitis, by comparing US findings with clinical examination and histopathological findings in synovial membrane. METHODS: The study group included 65 patients with early rheumatoid arthritis - below 12 months from the debut, naive for DMARDs, in whom demographic data - gender, age, disease duration, the number of tender and swollen joints, HAQ score (Health Assessment Questionnaire) and serum samples for CRP, RF, anti-CCP2 antibodies (ELISA, QUANTA LiteTM, CCP IgG, INOVA Diagnostics Inc, USA), VEGF (ELISA, VEGF2, DRG International, IRC, USA) determination were recorded. Disease Activity Score for 28 joints (DAS28) was calculated. PDS signal was scored from 0 to 3 according to the overall expression of PDS findings at the knees. A sample of synovial tissue was obtained in 35 patients during the arthroscopy, and the vascularisation of the synovial tissue was evaluated by immunohistochemistry and was analyzed qualitatively by a pathologist who was unaware of the PDS findings. Written, informed consent was obtained from each patient before entering the study. They all had active synovitis of the knee, ultrasonographically confirmed, with the identification of the target biopsy sites. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy of Craiova. RESULTS: Angiogenesis was evaluated and quantified by immunohistochemical evaluation of synovial VEGF, one of the most specific endothelial growing factors, that proved to correlate significantly with the serum levels of VEGF, DAS28 as well as with the power Doppler sonography (PDS) score. CONCLUSIONS: The statistical analysis of the data showed that PDS could be used as non-invasive marker with predictive value regarding synovial inflammation and disease progression in early forms of the disease as well as a useful method in the assessment of the therapeutic response.

Pathologic findings in synovial tissue of the musculoskeletal system: role of MRI in therapeutic clinic assessment.

OBJECTIVES: The clinical diagnosis of synovial lesions is difficult and radiographic findings may establish a confident diagnosis only in some cases. MR imaging has become the technique of choice in evaluating these lesions, because a presumptive diagnosis can be made in most cases. The purpose of this study was to evaluate the joint synovial disease through intravenous contrast MRI examination and the following histological validation. MATERIALS AND METHODS: Forty-eight patients were considered, twenty-seven women and twenty-one men, with pain relief or collectively determined by a known joint synovial disease, who underwent MRI at our institution between 2000 and the second half of 2010. All patients underwent magnetic resonance imaging using a low field magnet (0.2 Tesla) or high field magnet (1,5Tesla). RESULTS: Only nine patients were diagnosed with an inflammatory arthropathy, in the remaining cases non-inflammatory arthropathy of which the most frequent form was pigmented villonodular synovitis (PVNS) was diagnosed. CONCLUSIONS: MRI is able to provide an accurate representation of all the pathological changes involved in the joint space following acute or chronic inflammation and to define the characteristic features useful in differential diagnosis.

[Histopathological evaluation of the meniscus]. / Histopathologische Begutachtung des Meniskus.

Menisci fulfill many functions within the complex biomechanics of the knee joint. In the case of meniscus lesions, sparing arthroscopic resection and surgical refixation are the treatments of choice. In terms of diagnosis, this means in general that histopathologic diagnostics are carried out on detached meniscus fragments of between 5 mm and 2 cm in size. A good knowledge of physiologically possible cellular and fibrous histological meniscus damage, as opposed to nonphysiological change regarded as normal with respect to age, is essential for diagnostic meniscus evaluation. The clinician expects clear statements from the pathologist regarding the severity of previous or secondary degenerative meniscus damage, the age and type of traumatic tears, and an appraisal of the relationship between trauma and meniscus damage from an insurance point of view. Close cooperation between the clinician and the pathologist allows for a fast and unambiguous correlation of anamnesis, the clinical picture, and morphological reporting such that problematic insurance cases can be clarified quickly.