Experience of musculoskeletal ultrasound scanning improves physicians' physical examination skills in assessment of synovitis.

OBJECTIVE: Musculoskeletal ultrasound (US) is more sensitive than physical examination in detecting synovitis and helps physicians to understand its pathophysiology. In this study, we aimed to determine if the experience in musculoskeletal US scanning is independently associated with improved physical examination skills to detect synovitis. METHOD: Seventy patients with rheumatoid arthritis and twenty-three physicians were enrolled. Patients were first assessed by multiple physicians with a range of clinical/sonographic experience for the swelling of the wrist, metacarpophalangeal and proximal interphalangeal (PIP) joints and next underwent US assessment performed by another physician experienced in musculoskeletal US. We then calculated the positive/negative predictive values (PPV/NPV) of joint swelling to identify US-detected synovial hypertrophy. Finally, the factors independently associated with the accuracy of clinical assessment were identified by using multivariate analyses. RESULTS: One thousand five hundred forty joints were assessed 6116 times in total for swelling. Overall, PPV and NPV of joint swelling were 51.7% and 88.3%, respectively. Multivariate analyses identified wrist joint, tenderness, male and greater patients' age as the factors significantly associated with higher PPV. In addition, there was a trend that longer experience in rheumatology clinical practice was associated with higher PPV (p = 0.058). On the other hand, longer experience in musculoskeletal US, PIP joint and positive rheumatoid factor were identified as the significant factors for higher NPV, while wrist joint, tenderness, presence of osteophyte and obesity as those for lower NPV. CONCLUSION: Our data suggest that the experience in musculoskeletal US improves physical examination skills particularly to avoid overestimation.Key Points• Physicians with longer US experience are less likely to overestimate synovitis by physical examination.• Musculoskeletal US is a useful tool for rheumatologists to improve their physical examination skill.• Presence of osteophytes, joint tenderness and obesity influence the accuracy of physical examination of joints.

Combined Assessment of Stress Myocardial Perfusion Cardiovascular Magnetic Resonance and Flow Measurement in the Coronary Sinus Improves Prediction of Functionally Significant Coronary Stenosis Determined by Fractional Flow Reserve in Multivessel Disease.

BACKGROUND: Recent studies using stress-rest perfusion cardiovascular magnetic resonance (CMR) demonstrated a close correlation between myocardial ischemia and reduced fractional flow reserve (FFR). However, its diagnostic concordance may be reduced in patients with multivessel disease. We sought to evaluate the concordance of adenosine stress-rest perfusion CMR for predicting reduced FFR, and to determine the additive value of measuring global coronary flow reserve (CFR) in the coronary sinus in multivessel disease. METHODS AND RESULTS: Ninety-six patients with angiographic luminal narrowing >50% underwent comprehensive CMR study and FFR measurements in 139 coronary vessels. FFR <0.80 was considered hemodynamically significant. Global CFR was quantified as the ratio of stress-rest coronary sinus flow measured by phase-contrast cine CMR. In 25 patients with single-vessel disease, visual assessment of perfusion CMR yielded high diagnostic concordance for predicting flow-limiting stenosis, with the area under receiver operating characteristic curve of 0.93 on a per-patient basis. However, in 71 patients with multivessel disease, perfusion CMR underestimated flow-limiting stenosis, resulting in the reduced area under receiver operating characteristic curve of 0.74. When CFR of <2.0 measured in the coronary sinus was considered as global myocardial ischemia, combined assessment provided correct reclassifications in 7 patients with false-negative myocardial ischemia, and improved the diagnostic concordance to 92% sensitivity and 73% specificity with the area under receiver operating characteristic curve of 0.88 (95% confidence interval, 0.80%-0.97%, P=0.002). CONCLUSIONS: Visual analysis of stress-rest perfusion CMR has limited concordance with FFR in patients with multivessel disease. Multiparametric CMR integrating stress-rest perfusion CMR and flow measurement in the coronary sinus is useful for detecting reduced FFR in multivessel disease.

[Perspective of ultrasound-guided strategy to reduce/discontinue biologics].

Biologics has revolutionized the treatment strategy of rheumatoid arthritis(RA) and improved the clinical outcome. On the other hand, the medication cost of biologics has become a substantial socioeconomic burden. Researchers are now discussing the strategies to optimize the use of biologics, which include the dose reduction/discontinuation of biologics. A pilot study suggests that musculoskeletal ultrasound determines 'deep remission' and predicts relapse after discontinuation of biologics more accurately than does clinical assessment. The perspective of ultrasound-guided strategy to reduce/discontinue biologics is discussed.

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.

Prediction of relapse after discontinuation of biologic agents by ultrasonographic assessment in patients with rheumatoid arthritis in clinical remission: high predictive values of total gray-scale and power Doppler scores that represent residual synovial inflammation before discontinuation.

OBJECTIVE: This prospective study aimed to determine whether the comprehensive ultrasonographic assessment of synovial inflammation predicts relapse after discontinuation of treatment with a biologic agent in patients with rheumatoid arthritis (RA) in clinical remission. METHODS: RA patients in clinical remission (Disease Activity Score in 28 joints [DAS28] <2.6) receiving treatment with a biologic agent who agreed to discontinue the treatment were recruited. Patients underwent a comprehensive ultrasound scan on 134 synovial sites in 40 joints and were prospectively followed up for 6 months. Physicians who evaluated the patients during the study period were blinded to the baseline ultrasound findings. RESULTS: Forty-two patients receiving either a tumor necrosis factor antagonist or tocilizumab were enrolled. Using the optimal cutoff values determined by receiver operating characteristic curve analysis, relapse rates were significantly higher in patients whose total ultrasound scores at discontinuation were high than in those whose total ultrasound scores were low (P < 0.001 for both total gray-scale and power Doppler scores), whereas the difference between high and low DAS28 was not statistically significant (P = 0.158 by log rank test). Positive and negative predictive values were 80.0% and 73.3% for the total gray-scale score and 88.9% and 74.2% for the total power Doppler score, respectively. CONCLUSION: In RA patients in clinical remission receiving treatment with a biologic agent, residual synovial inflammation determined by comprehensive ultrasound assessment predicted relapse within a short term after discontinuation of the treatment. Our data provide a rationale and groundwork to conduct a large-scale study for establishment of ultrasound-based strategies to optimize the period of treatment with a biologic agent.

Detection of diminished response to cold pressor test in smokers: assessment using phase-contrast cine magnetic resonance imaging of the coronary sinus.

PURPOSE: The purposes of this study were to evaluate the reproducibility for measuring the cold pressor test (CPT)-induced myocardial blood flow (MBF) alteration using phase-contrast (PC) cine MRI, and to determine if this approach could detect altered MBF response to CPT in smokers. MATERIALS AND METHODS: After obtaining informed consent, ten healthy male non-smokers (mean age: 28±5 years) and ten age-matched male smokers (smoking duration ≥5 years, mean age: 28±3 years) were examined in this institutional review board approved study. Breath-hold PC cine MR images of the coronary sinus were obtained with a 3T MR imager with 32 channel coils at rest and during a CPT performed after immersing one foot in ice water. MBF was calculated as coronary sinus flow divided by the left ventricular (LV) mass which was given as a total LV myocardial volume measured on cine MRI multiplied by the specific gravity (1.05 g/mL). RESULTS: In non-smokers, MBF was 0.86±0.25 mL/min/g at rest, with a significant increase to 1.20±0.36 mL/min/g seen during CPT (percentage change of MBF (∆MBF (%)); 39.2%±14.4%, p<0.001). Inter-study reproducibility for ∆MBF (%) measurements by different MR technologist was good, as indicated by the intraclass correlation coefficient of 0.93 and reproducibility coefficient of 10.5%. There was no significant difference between smokers and non-smokers for resting MBF (0.85±0.32 mL/min/g, p=0.91). However, ∆MBF (%) in smokers was significantly reduced (-4.0±32.2% vs. 39.2±14.4%, p=0.011). CONCLUSION: PC cine MRI can be used to reproducibly quantify MBF response to CPT and to detect impaired flow response in smokers. This MR approach may be useful for monitoring the sequential change of coronary blood flow in various potentially pathologic conditions and for investigating its relationship with cardiovascular risk.

Age-adjusted mortality and its association to variations in urban conditions in Shanghai.

The objective of this study was to explore the association between health and urbanization in a megacity, Shanghai, by calculating the age-adjusted mortality ratio by ward-unit of Shanghai and by examining relationships between mortalities and urban indicators. Crude mortality rates and age-adjusted mortality ratios by ward-unit were calculated. Demographic, residential environment, healthcare, and socioeconomic indicators were formulated for each of the ward-units between 1995 and 1998. Correlation and Poisson regression analyses were performed to examine the association between urban indicators and mortalities. The crude mortality rate by ward-unit in 1997 varied from 6.3 to 9.4 deaths per 1000 population. The age-adjusted mortality ratio in 1997 by ward-units as reference to the average mortality of urban China varied from 57.8 to 113.3 within Shanghai. Age-adjusted mortalities were inversely related with indicators of a larger floor space of dwellings per population, a larger proportion of parks, gardens, and green areas to total land area; a greater number of health professionals per population; and a greater number of employees in retail business per population. Spacious living showed independent association to a higher standard of community health in Shanghai (P < 0.05). Consequences of health policy and the developments of urban infrastructural resources from the viewpoint of the Healthy Cities concept were discussed.