Effectiveness of ustekinumab in patients with psoriatic arthritis in a real-world, multicenter study.

OBJECTIVE: To assess the effectiveness and survival of ustekinumab (UST) among patients with psoriatic arthritis (PsA) treated under routine clinical care. METHODS: Multicenter study. Epidemiological and clinical data was collected through electronic medical records of all patients with PsA who started UST in 15 hospitals of Spain. RESULTS: Two hundred and one patients were included, 130 (64.7%) with 45 mg and 71 (35.3%) with 90 mg. One hundred and thirty one patients (65.2%) had previously received another biological therapy. The median baseline DAS 28 ESR was 3.99, and Psoriasis Area and Severity Index (PASI) was 3. Overall, there was a significant decrease in DAS66/68 CRP, swollen joint count (SJC), tender joint count (TJC), and PASI in the first month of treatment, with earlier improvement in skin (PASI) than joints outcomes. Survival was numerically lower in patients with UST 45 mg (58.1%) than 90 mg (76.1%), although significant differences were not found (p = 0.147). When comparing naïve and < 1 TNF blocker versus > 2 TNF blocker-experienced patients, a significantly earlier response was seen in the former group regarding SJC (p = 0.029) at 1 month. Fifty-one patients (25.3%) stopped UST due to joint inefficacy and 4 patients due to adverse events (1.9%). Drug survival was significantly better in patients with fewer lines of previous biological agents (p = 0.003 for < 1 TNF blocker versus > 2 TNF blocker users). CONCLUSIONS: UST was effective in PsA patients in a routine clinical care setting. Patients with UST 90 mg and fewer lines of previous biologics achieved better and faster responses. Key Points • Largest cohort of patients with PsA in treatment with UST with specific rheumatological indication. • First cohort of patients with PsA comparing effectiveness of UST according to 45/90 mg dose.

Three-dimensional volumetric ultrasonography. Does it improve reliabililty of musculoskeletal ultrasound?

OBJECTIVE: To compare the interobserver reliability of three-dimensional (3D) volumetric ultrasonography (US) and 2D real-time US in detecting inflammatory and destructive changes in rheumatoid arthritis (RA) wrist and hand. METHODS: Two RA patients were selected by a rheumatologist who performed independently a grey-scale and power Doppler (PD) volumetric acquisition at three anatomic sites in their more symptomatic wrist/hand using two identical scanners equipped with 3D volumetric probe. Twelve rheumatologists expert in MSUS were randomly assigned to a US scanner and a patient. In the first part of the study, each group of experts blindly, independently, and consecutively performed a 2D real-time grey-scale and PD US investigation of inflammatory changes and/or bone erosions at the three anatomic sites. In the second part of the study, each group of investigators blindly evaluated the same pathologic changes in the 6 volumes from the patient not scanned by them. RESULTS: The kappa values were higher for 3D volumetric US than for 2D US in the detection of synovitis/tenosyno-vitis (0.41 vs. 0.37) and PD signal (0.82 vs 0.45) and in the PD signal grading (0.81 vs. 0.55). CONCLUSION: 3D volumetric US may improve the interobserver reliability in RA multicentre studies.

Ultrasound validity in the measurement of knee cartilage thickness.

OBJECTIVE: To assess the multiexaminer reproducibility and the accuracy comparing with cadaver anatomic specimens of ultrasound (US) measurement of femoral articular cartilage (FAC) thickness. METHODS: In 8 flexed cadaver knees, FAC thickness was blindly, independently and consecutively measured twice by 10 rheumatologists at the lateral condyle (LC), medial condyle (MC) and intercondylar notch (IN) with US. After the US measurements, the knees were dissected. Articular cartilage integrity was evaluated macroscopically in the femoral condyles. FAC thickness was blindly measured in the specimens using a stereoscopic magnifying loupe and a digitised image software. Interexaminer and intraexaminer reliability of US FAC thickness measurement and agreement between US and anatomic measurements were assessed by estimating the intraclass correlation coefficient (ICC). RESULTS: Interexaminer ICCs were higher than 0.90 for MC (p<0.001) and IN (p<0.001) and higher than 0.75 for LC (p<0.01). Mean intraexaminer ICCs were 0.832 for MC (p<0.001), 0.696 for LC (p<0.001) and, 0.701 for IN (p<0.001). Agreement between US and anatomic FAC thickness measurements was good for MC (ICC 0.719; p = 0.020) and poor for LC (p = 0.285) and IN (p = 0.332). Bland-Altman analysis showed that the difference between US and anatomic values was considerably high in the one knee with severely damaged FAC. After eliminating this knee from the analysis, ICCs were 0.883 (p<0.001) for MC, 0.795 (p = 0.016) for LC and 0.732 for IN (p = 0.071). CONCLUSION: US demonstrated a good reproducibility in FAC thickness measurement by multiple examiners. In addition, US FAC thickness measurement was accurate in normal to moderately damaged cartilage.

Reliability of ultrasonography in detecting shoulder disease in patients with rheumatoid arthritis.

OBJECTIVE: To assess the intra and interobserver reproducibility of musculoskeletal ultrasonography (US) among rheumatologists in detecting destructive and inflammatory shoulder abnormalities in patients with rheumatoid arthritis (RA) and to determine the overall agreement between US and MRI. METHODS: A total of 14 observers examined 5 patients in 2 rounds independently and blindly of each other. US results were compared with MRI. Overall agreement of all findings, of positive findings on MRI, as well as intra and interobserver reliabilities, were calculated. RESULTS: Overall agreement between US and MRI was seen in 79% with regard to humeral head erosions (HHE), in 64% with regard to posterior recess synovitis (PRS), in 31% with regard to axillary recess synovitis (ARS), in 64% with regard to bursitis, in 50% with regard to biceps tenosynovitis (BT), and in 84% for complete cuff tear (CCT). Intraobserver and interobserver kappa was 0.69 and 0.43 for HHE, 0.29 and 0.49 for PRS, 0.57 and 1.00 for ARS, -0.17 and 0.51 for bursitis, 0.17 and 0.46 for BT and 0.52 and 0.6 for CCT, respectively. The intraobserver and interobserver kappa for power Doppler (PD) was 0.90 and 0.70 for glenohumeral signals and 0.60 and 0.51 for bursal signals, respectively. CONCLUSIONS: US is a reliable imaging technique for most shoulder pathology in RA especially with regard to PD. Standardisation of scanning technique and definitions of particular lesions may further enhance the reliability of US investigation of the shoulder.

Ultrasound in the study and monitoring of osteoarthritis.

This review addresses the use of ultrasound (US) as an imaging technique for the evaluation and monitoring of the osteoarthritic joint. US complements both the clinical examination and radiological imaging by allowing the rheumatologist to recognize not only the bony profile but also to visualize the soft tissues. Systematic US scanning following established guidelines can demonstrate even minimal abnormalities of articular cartilage, bony cortex and synovial tissue. US is also extremely sensitive in the detection of soft tissue changes in the involved joints including the proliferation of the synovium and changes in the amount of fluid present within the joint. Monitoring the amount of fluid in the hip and knee joint with osteoarthritis may be a potentially useful finding in the selection of patients for clinical investigation and for assessing their response to therapeutic interventions.

Recommendations for the content and conduct of European League Against Rheumatism (EULAR) musculoskeletal ultrasound courses.

OBJECTIVE: To develop education guidelines for the conduct of future European League Against Rheumatism (EULAR) musculoskeletal ultrasound (MSUS) courses. METHODS: We undertook a consensus-based, iterative process using two consecutive questionnaires sent to 29 senior ultrasonographer rheumatologists who comprised the faculty of the 14th EULAR ultrasound course (June 2007). The first questionnaire encompassed the following issues: type of MSUS educational model; course timing; course curriculum; course duration; number of participants per teacher in practical sessions; time spent on hands-on sessions; and the requirements and/or restrictions for attendance at the courses. The second questionnaire consisted of questions related to areas where consensus had not been achieved in the first questionnaire, and to the topics and pathologies to be assigned to different educational levels. RESULTS: The response rate was 82.7% from the first questionnaire and 87.5% from the second questionnaire. The respondents were from 11 European countries. The group consensus on guidelines and curriculum was for a three-level education model (basic, intermediate and advanced) with timing and location related to the annual EULAR Congresses. The topics and pathologies to be included in each course were agreed. The course duration will be 20 h. There will be a maximum of six participants per teacher and 50-60% of total time will be spent on practical sessions. There was also agreement on prerequisite experience before attending the intermediate and advanced courses. CONCLUSION: We have developed European agreed guidelines for the content and conduct of EULAR ultrasound courses, which may also be recommended to national and local MSUS training programmes.

Interobserver reliability in musculoskeletal ultrasonography: results from a "Teach the Teachers" rheumatologist course.

OBJECTIVE: To assess the interobserver reliability of the main periarticular and intra-articular ultrasonographic pathologies and to establish the principal disagreements on scanning technique and diagnostic criteria between a group of experts in musculoskeletal ultrasonography. METHODS: The shoulder, wrist/hand, ankle/foot, or knee of 24 patients with rheumatic diseases were evaluated by 23 musculoskeletal ultrasound experts from different European countries randomly assigned to six groups. The participants did not reach consensus on scanning method or diagnostic criteria before the investigation. They were unaware of the patients' clinical and imaging data. The experts from each group undertook a blinded ultrasound examination of the four anatomical regions. The ultrasound investigation included the presence/absence of joint effusion/synovitis, bony cortex abnormalities, tenosynovitis, tendon lesions, bursitis, and power Doppler signal. Afterwards they compared the ultrasound findings and re-examined the patients together while discussing their results. RESULTS: Overall agreements were 91% for joint effusion/synovitis and tendon lesions, 87% for cortical abnormalities, 84% for tenosynovitis, 83.5% for bursitis, and 83% for power Doppler signal; kappa values were good for the wrist/hand and knee (0.61 and 0.60) and fair for the shoulder and ankle/foot (0.50 and 0.54). The principal differences in scanning method and diagnostic criteria between experts were related to dynamic examination, definition of tendon lesions, and pathological v physiological fluid within joints, tendon sheaths, and bursae. CONCLUSIONS: Musculoskeletal ultrasound has a moderate to good interobserver reliability. Further consensus on standardisation of scanning technique and diagnostic criteria is necessary to improve musculoskeletal ultrasonography reproducibility.

[Low-dose dobutamine echocardiographic assessment of reversible contractile dysfunction (myocardial stunning) after myocardial infarction]. / Evaluation par l'échocardiographie dobutamine à faible dose de la dysfonction contractile réversible (sidération myocardique) après infarctus du myocarde.

Low dose (5 to 10 micrograms/min) dobutamine echocardiography was used to predict the presence of reversible contractile dysfunction (myocardial stunning) after myocardial infarction successfully revascularised in the acute phase of primary angioplasty. The investigation was undertaken in 40 patients, 4 +/- 1 days after inaugural myocardial infarction. The left ventricle was divided into 16 segments. Viable myocardium was diagnosed when the initial regional wall motion score decreased by at least 2. Resting echocardiography was performed at 2 months to evaluate the effective recovery of regional wall motion (myocardial viability). The presence of contractile reserve was documented by dobutamine echocardiography in 18 patients (45%). The sensitivity, specificity and positive and negative predictive values of dobutamine echocardiography for the diagnosis of myocardial viability were 82, 83, 78 and 86% respectively. The negative predictive value was high in all dysnergic segments (86%). The positive predictive value of the investigation was however higher in hypokinetic than in akinetic segments (73 vs 21%; p < 0.05). The recovery of regional wall motion during follow-up was statistically related to higher initial left ventricular ejection fraction (p < 0.04), the presence of angiographically documented collateral circulation before revascularisation (p = 0.007), the contractile response to dobutamine (p = 0.0001) and was observed more frequently in hypokinetic than in akinetic segments (p < 0.05). These results show that low-dose dobutamine echocardiography is a sensitive and specific investigation for predicting irreversible myocardial damage after successful primary angioplasty in acute myocardial infarction. However, even in the absence of residual coronary stenosis, the presence of viable myocardium is only identified specifically in hypokinetic segments.

Evaluation of circulating type I procollagen propeptides in patients with Paget's disease of bone.

We evaluated circulating aminoterminal and carboxyterminal propeptides of type I procollagen and total alkaline phosphatase levels in eighty consecutive patients affected by Paget's disease of bone. We compared the biochemical data with the extent of bone disease calculated on the basis of the bone scintigraphic indices. Serum aminoterminal propeptide of type I procollagen levels were high in 77% of patients, serum carboxyterminal propeptide of type I procollagen levels in 22% and serum total alkaline phosphatase levels in 76%. We found significant correlations between the three markers studied. The three biochemical markers correlated significantly with the bone scintigraphic activity indices, but the highest correlation coefficient was between the aminoterminal propeptide and total alkaline phosphatase. We conclude that there is a discrepancy between serum levels of the propeptides studied in relation to Paget's disease of bone. The sensitivity of the carboxyterminal propeptide of type I procollagen in this disease is low. In contrast the aminoterminal propeptide may be as sensitive a marker for the evaluation of this disorder as total alkaline phosphatase, and in addition may be more specific.

Myocardial viability assessed by dobutamine echocardiography in acute myocardial infarction after successful primary coronary angioplasty.

Dobutamine echocardiography (5 and 10 microg/kg/ min) was performed in 40 patients 4 +/- 1 days after acute myocardial infarction reperfused by primary coronary angioplasty. The left ventricle was divided into 11 segments. Reversible myocardial dysfunction was indicated by a decrease in at least 2 grades in the total segmental score. Follow-up echocardiography was performed 2 months later. Contractile reserve was documented in 18 patients with dobutamine echocardiography (45%). Sensitivity, specificity, positive, and negative predictive value of dobutamine echocardiography in predicting improvement in contractile function at follow-up were 82%, 83%, 78%, and 86%, respectively. Negative predictive value was high in all dyssynergic segments (86%). Positive predictive value was higher in hypokinetic than in akinetic segments (73% vs 21%; p <0.05). Recovery of wall motion at follow-up was statistically associated with higher left ventricular ejection fraction (p <0.04), collateral blood flow before reperfusion (p = 0.007), and dobutamine responsiveness (p = 0.0001), and was more frequently observed in hypokinetic than in akinetic segments (p <0.05). Thus, low-dose dobutamine echocardiography accurately predicts the extent of irreversibly damaged myocardium early after successful direct coronary angioplasty in acute myocardial infarction.

Tertiary hyperparathyroidism after long-term phosphate supplementation in adult-onset hypophosphataemic osteomalacia.

We report the development of tertiary hyperparathyrodism in a patient with a sporadic form of adult-onset hypophosphataemic osteomalacia who had been treated with vitamin D or calcitriol and large doses of phosphate. This observation suggests that even with concomitant vitamin D or calcitriol therapy, long-term oral phosphate supplementation may lead to the development of hypercalcaemic hyperparathyrodism. Caution is recommended when relatively large doses of phosphate are used to treat hypophosphataemic osteomalacia of diverse causes.

[Lipomatous hypertrophy of the interatrial septum. Apropos of 3 cases and review of the literature]. / Hypertrophie lipomateuse du septum interauriculaire. A propos de 3 cas et revue de la littérature.

Lipomatous hypertrophy of the interatrial septum is characterised by an accumulation of fatty tissue in the interatrial septum. The authors report three cases, one presenting with sinus tachycardia and the other two being chance findings. Echocardiography associated with cardiac computerised tomography or magnetic resonance imaging usually confirms the diagnosis. In half the cases, supraventricular arrhythmias and suggestive P wave abnormalities are observed on the electrocardiogram. The diagnostic value of transoesophageal echocardiography is emphasised; it demonstrates the massive forms which may obstruct flow from the superior vena cava into the right atrium. The authors observe a discrepancy between the prevalence of this condition in autopsy series (about 1%) and the small number of cases described at echocardiography, suggesting that the diagnosis is probably missed.