Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial.

PURPOSE: To evaluate the potential of etanercept versus sulfasalazine to reduce active inflammatory lesions on whole-body MRI in active axial spondyloarthritis with a symptom duration of less than 5 years. METHODS: Patients were randomly assigned to etanercept (n=40) or sulfasalazine (n=36) treatment over 48 weeks. All patients showed active inflammatory lesions (bone marrow oedema) on MRI in either the sacroiliac joints or the spine. MRI was performed at weeks 0, 24 and 48 and was scored for active inflammatory lesions in sacroiliac joints and the spine including posterior segments and peripheral enthesitis by two radiologists, blinded for treatment arm and MRI time point. RESULTS: In the etanercept group, the reduction of the sacroiliac joint score from 7.7 at baseline to 2.0 at week 48 was significantly (p=0.02) larger compared with the sulfasalazine group from 5.4 at baseline to 3.5 at week 48. A similar difference in the reduction of inflammation was found in the spine from 2.2 to 1.0 in the etanercept group versus from 1.4 to 1.3 in the sulfasalazine group between baseline and week 48, respectively (p=0.01). The number of enthesitic sites also improved significantly from 26 to 11 in the etanercept group versus 24 to 26 in the sulfasalazine group (p=0.04 for difference). 50% of patients reached clinical remission in the etanercept group versus 19% in the sulfasalazine group at week 48. CONCLUSION: In patients with early axial spondyloarthritis active inflammatory lesions detected by whole-body MRI improved significantly more in etanercept versus sulfasalazine-treated patients. This effect correlated with a good clinical response in the etanercept group.

Relationship between active inflammatory lesions in the spine and sacroiliac joints and new development of chronic lesions on whole-body MRI in early axial spondyloarthritis: results of the ESTHER trial at week 48.

AIM: To investigate the relationship between active inflammatory lesions on whole-body MRI (wb-MRI) and new development of chronic lesions on T1 MRI in patients with early axial spondyloarthritis (SpA) treated either with etanercept (ETA) or sulfasalazine (SSZ). METHODS: Wb-MRIs of 65 patients treated either with ETA (n=35) or SSZ (n=30) over 1 year were scored for active inflammation, fatty lesions, erosions and ankylosis in the 23 vertebral units (VUs) of the spine and in the sacroiliac joints (SI joints). Scoring was performed by two blinded radiologists. RESULTS: If there was no previous inflammation in the bone no new fatty lesions occurred in SI joint quadrants and only a few (0.6%) in spine VUs. There was a significant relationship between disappearance of inflammation and the appearance of fatty lesions: if baseline inflammation resolved fatty lesions occurred in 10.5% of SI joint quadrants and 17.9% of VUs. If inflammation did not resolve over 1 year, fatty lesions occurred less frequently: 2.4% (SI joint quadrants) and 7.2% (VUs). There was a significantly higher increase of the mean fatty lesion score between baseline and week 48 in the ETA (4.0 vs 4.8 for the SI joints and 1.9 vs 2.7 for the spine) compared to the SSZ (3.0 vs 3.2 for the SI joints and 1.1 vs 1.2 for the spine, respectively) group (p=0.001 and p=0.020 for the differences). No significant changes in the erosion or ankylosis score were observed in any of the two groups during this time. CONCLUSIONS: These data indicate that there is a close interaction between inflammation, tumour necrosis factor blockade and the development of fatty lesions in subchondral bone marrow of patients with axial SpA.

Contrast-enhanced ultrasound in monitoring the efficacy of a bradykinin receptor 2 antagonist in painful knee osteoarthritis compared with MRI.

OBJECTIVES: To evaluate contrast-enhanced ultrasound (CE-US) as a monitoring tool to assess hypervascularisation of synovial processes in knee osteoarthritis (OA) treated with intra-articular injections of the bradykinin-receptor 2 antagonist icatibant compared to contrast-enhanced magnetic resonance imaging (CE-MRI). PATIENTS AND METHODS: In a randomised, double-blind, placebo-controlled trial, 41 patients with painful knee OA underwent US (12.5 MHz for B-mode and 3-8 MHz for CE-US), and 36 of the patients underwent additional MRI (0.2T) at baseline and after 3 injections of the study drug (after a mean of 22.2 days). A total of 15 patients received placebo (group A), 12 patients 500 microg icatibant (group B) and 14 patients 2000 microg icatibant (group C). Pain and the synovial process (B-mode, power Doppler US (PD-US), CE-US, CE-MRI) were assessed at both time points. RESULTS: At baseline, the placebo group showed more activity in terms of effusion in the superior and lateral recess in ultrasound as well as in PD-US in the lateral recess. Pain improved significantly in all subgroups. Effect sizes were 0.43 (pain at rest) and 0.52 (pain during activity) in group B vs 0.48 and 1.11 in group C. There was no change of US and MRI parameters. We found moderate to good correlation (r) and kappa values (kappa) for effusion in the superior recess (r = 0.591, k = 0.453), effusion in the lateral recess (r = 0.304, k = 0.440) and contrast enhancement (r = 0.601, k = 0.242) between US and MRI. CONCLUSIONS: Our results show that CE-US and CE-MRI have good agreement in assessing inflammatory changes in knee OA. For the 41 patients with OA, an analgesic effect of icatibant could clearly be shown, especially for pain during activity in the high dose icatibant group. However, we could not find an anti-inflammatory effect of icatibant by CE-US compared to CE-MRI.

Knee osteoarthritis. Efficacy of a new method of contrast-enhanced musculoskeletal ultrasonography in detection of synovitis in patients with knee osteoarthritis in comparison with magnetic resonance imaging.

OBJECTIVE: To develop a new method of digital synovial vascularisation quantification by using contrast-enhanced musculoskeletal ultrasonography (MUS) in detecting synovitis in patients with knee osteoarthritis (OA) compared with healthy subjects and MRI. METHODS: Evaluation of 41 patients with painful knee OA and 6 healthy subjects. The severity of knee pain was evaluated. All patients and all 6 healthy subjects underwent contrast medium-enhanced (CE)-MUS with SonoVue, and 36 patients additionally underwent CEMRI with Magnevist. Joint effusion, synovial thickening and pain were assessed and compared with B-mode and Power Doppler sonography (PDS) as well as contrast medium enhancement. RESULTS: Pain evaluated by the visual analogue scale(VAS) hardly correlated with other markers of disease activity measured by ultrasound (US) in B-mode or MRI. US of the superior recess revealed an effusion or synovial thickening in 58%. PDS findings were positive in 63%, and CE-MUS in the superior knee recess was positive in 95%. MRI showed effusion in the superior recess in 61% and showed positive findings in 82% when using contrast medium. The kappa value was 0.48 between US and MRI with regard to the effusion in the superior recess, and 0.53 between PD signal in the superior recess and effusion in the superior recess by US. Using MRI as the reference standard, there was a sensitivity of 72% for assessing effusion in the superior recess and 81% for assessing effusion in the lateral recess. CONCLUSION: Assessment of disease activity (synovitis) in knee OA by VAS is not sufficient. US PDS was more sensitive than B-mode, and CE-MUS was more sensitive than PDS and CE-MRI in detecting synovitis in patients with painful knee OA. Also, CE-MRI was more sensitive in detecting inflammatory changes in the superior recess than without contrast medium. Using CE-MUS and performing time/intensity analysis has shown to be a good model for evaluation of an inflammatory process in the setting of knee OA in the superior recess.

[Ankylosing spondylitis--current state of imaging including scoring methods]. / Ankylosierende Spondylitis. Aktueller Stand der bildgebenden Verfahren einschliesslich Scoring-Methoden.

Conventional radiography and magnetic resonance imaging (MRI) are currently the most widely used imaging methods for the initial diagnostic evaluation and follow-up of patients with ankylosing spondylitis (AS). Scintigraphy, computed tomography (CT), and positron emission tomography (PET) only play minor roles, although some are being further developed. AS is characterized by inflammatory changes to the sacroiliac joints (SIJs) and spine, as well as asymmetrical arthritis of the peripheral joints and joints near the trunk. The diagnosis of AS is based on clinical parameters and the presence of chronic inflammatory changes to the SIJs on conventional radiographs. Typical radiographic changes also involve the spine. MRI depicts not only chronic changes, but also active inflammatory lesions, which are important for the diagnosis of early disease and precursors of AS. The scoring system of choice for quantifying spinal changes depicted by conventional radiography is the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). MRI allows the quantitative evaluation of changes involving the SIJs and the spine. Various MRI scoring systems have been proposed to quantify these changes, but they require further validation. This review article presents the imaging modalities used in AS patients, typical findings, and relevant methods of analysis. The most recent developments are discussed.

Use of Paclitaxel-Coated Balloon Catheter Dilation to Reduce In-Stent Restenosis in Transjugular Intrahepatic Portosystemic Shunt (TIPS).

PURPOSE: Paclitaxel-coated balloons (PCB) inhibit neointimal proliferation in arteries. The purpose of this retrospective analysis was to investigate the effect of PCB in in-stent restenosis after transjugular intrahepatic portosystemic shunt (TIPS) in patients with cirrhotic liver disease. MATERIALS AND METHODS: Six patients (mean age: 65 ±â€Š10 years) with recurrent in-stent restenoses in TIPS (5 bare stents, 1 covered stent) underwent a single percutaneous transluminal angioplasty (PTA) with PCB (3 µg paclitaxel/mm(2)). Post-interventional outcome and patency were compared with those of prior plain optimal balloon angioplasty (POBA) in the same patients. During a two-year follow-up period, all patients underwent angiographic examinations at 6-month intervals. In-stent minimal lumen diameter (MLD) and late lumen loss (LLL) were assessed. Paclitaxel residues on balloon and sheath surfaces as well as venous plasma concentrations (0 - 24 hours) were analyzed. RESULTS: PCB decreased the need for clinically driven repeat PTA (POBA: 53 % of angiographic examinations; paclitaxel PTA: 19 %; P = 0.014). LLL/diameter stenosis was higher after POBA (2.4 ±â€Š1.5 mm/28 ±â€Š18 %) than after PCB (0.5 ±â€Š0.8 mm/7 ±â€Š11 %, P = 0.029). Residual paclitaxel on balloons was 28 ±â€Š9 % of dose and 0.2 ±â€Š0.1 % on sheath surfaces. Paclitaxel plasma concentrations were below detectable levels throughout the first 24 hours after the interventions in all patients. The procedure was well tolerated and no clinical side effects attributable to paclitaxel were observed. CONCLUSION: In patients with recurrent in-stent stenoses, a single PTA with PCB resulted in a prolonged secondary patency due to pseudointimahyperplasia without a systemic effect of paclitaxel. KEY POINTS: •Intimahyperplasia is a common reason for long-time TIPS dysfunction. •First-in-man local paclitaxel application in TIPS patients with recurrent in-stent stenoses. •PTA with PCB resulted in a prolonged secondary patency compared to POBA. •No systemic effects of Paclitaxel were detected.

Genotypic testing in clinically defined HHT: would Osler approve or turn in his grave?

Modern diagnostic possibilities pose a number of challenges. When is a precise genetic diagnosis justifiable in today's climate of cost-cutting? We would like to pose that question to Sir William Osler. Sir William was a keen observer, a master 'translator' of science into clinical medicine. Would he have required or supported genetic testing? We treated a patient whose case reminded us of Sir William's belief that clinical exactness was the ultimate aim, regardless of cost.

Low-field MRI for assessing synovitis in patients with rheumatoid arthritis. Impact of Gd-DTPA dose on synovitis scoring.

OBJECTIVE: To investigate the impact of a double dose compared to a single dose of contrast material in low-field magnetic resonance imaging (MRI) on semi-quantitative scoring of synovitis in patients with rheumatoid arthritis (RA). METHODS: This prospective study included 38 RA patients (23 women and 15 men, mean age 51 years). All patients underwent low-field MRI of the hand before administration of contrast medium, after intravenous injection of 0.1 mmol/kg gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), and after another dose of 0.1 mmol/kg Gd-DTPA. Two readers (A and B) blinded to dosage independently scored the single dose and double dose image sets for synovitis according to outcome measures in rheumatology (OMERACT) recommendations. Contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were also calculated for each set. RESULTS: 149 metacarpophalangeal (MCP) joints were evaluated. There was good inter-reader agreement for each of the two sets (intra-class correlation coefficient of 0.75 for the single dose set and 0.83 for the double dose). Median CNR and SNR values were 5.4 and 15.9, respectively, for the single dose set and 8.5 and 16.6, respectively, for the double dose set (p<0.0001). Single dose set mean synovitis scores were 1.7 and 1.6 for readers A and B, respectively. Double dose set scores were 1.9 and 2.0, respectively. Thus, higher synovitis scores were recorded for the double dose sets than the single dose sets (p<0.005). CONCLUSION: In low-field MRI, when evaluating RA, the dose of the contrast material influences synovitis scoring. Therefore, dosage of contrast material should be taken into consideration when using extremity dedicated low-field MRI.