Assessment of tissue fibrosis in skin biopsies from patients with systemic sclerosis employing confocal laser scanning microscopy: an objective outcome measure for clinical trials?

OBJECTIVES: To obtain an objective, unbiased assessment of skin fibrosis in patients with SSc for use in clinical trials of SSc disease-modifying therapeutics. METHODS: Skin biopsies from the dorsal forearm of six patients with diffuse SSc and six healthy controls, and skin biopsies from the forearm of one patient with diffuse SSc before and following 1 year treatment with mycophenolate mofetil were analysed by confocal laser scanning microscopy (CLSM) with specific antibodies against collagen types I and III or fibronectin. The integrated density of fluorescence (IDF) was calculated employing National Institutes of Health-ImageJ software in at least four different fields per biopsy spanning the full dermal thickness. RESULTS: The intensities of collagen types I and III and fibronectin IDF were 174, 147 and 139% higher in SSc skin than in normal skin, respectively. All differences were statistically significant. The sum of the IDF values obtained for the three proteins yielded a comprehensive fibrosis score. The average fibrosis score for the six SSc samples was 28.3 x 10(6) compared with 18.6 x 10(6) for the six normal skin samples (P \u3c 0.0001). Comparison of skin biopsies obtained from the same SSc patient before treatment and after 12 months of treatment with mycophenolate mofetil showed a reduction of 39% in total fibrosis score after treatment. CONCLUSIONS: CLSM followed by quantitative image analysis provides an objective and unbiased assessment of skin fibrosis in SSc and could be a useful end-point for clinical trials with disease-modifying agents to monitor the response or progression of the disease

Sonographically Guided Posterior Subtalar Joint Injections via the Sinus Tarsi Approach

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135311/1/jum201534183.pd

Self-directed learning of basic musculoskeletal ultrasound among rheumatologists in the United States

Objective Because musculoskeletal ultrasound (MSUS) is highly user dependent, we aimed to establish whether non-mentored learning of MSUS is sufficient to achieve the same level of diagnostic accuracy and scanning reliability as has been achieved by rheumatologists recognized as international experts in MSUS. Methods A group of 8 rheumatologists with more experience in MSUS and 8 rheumatologists with less experience in MSUS participated in an MSUS exercise to assess patients with musculoskeletal abnormalities commonly seen in a rheumatology practice. Patients' established diagnoses were obtained from chart review (gout, osteoarthritis, rotator cuff syndrome, rheumatoid arthritis, and seronegative arthritis). Two examining groups were formed, each composed of 4 less experienced and 4 more experienced examiners. Each group scanned 1 predefined body region (hand, wrist, elbow, shoulder, knee, or ankle) in each of 8 patients, blinded to medical history and physical examination. Structural abnormalities were noted with dichotomous answers, and an open-ended answer was used for the final diagnosis. Results Less experienced and more experienced examiners achieved the same diagnostic accuracy (US-established diagnosis versus chart review diagnosis). The interrater reliability for tissue pathology was slightly higher for more experienced versus less experienced examiners (Κ = 0.43 versus Κ = 0.34; P = 0.001). Conclusion Non-mentored training in MSUS can lead to the achievement of diagnostic accuracy in MSUS comparable to that achieved by highly experienced international experts. Reliability may increase slightly with additional experience. Further study is needed to determine the minimal training requirement to achieve proficiency in MSUS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65036/1/20063_ftp.pd

A Vascular obstacle in ultrasound-Guided hip joint injection

Background: We evaluated the risk of lateral circumflex femoral artery (LCFA) injury during ultrasound-guided intra-articular hip injections. Methods: This study was divided into three parts. (1) Four ultrasound-guided hip injections were performed on human cadavers. With needles in place, tissues were dissected to expose the LCFA. (2) Ultrasound-trained rheumatologists marked a planned needle trajectory from skin to hip joint on live human ultrasound images during an Observed Structured Clinical Examination (OSCE). Doppler was subsequently activated to locate the LCFA, and the distance between trajectory and arterial signal was recorded. (3) Rheumatologists certified in musculoskeletal ultrasound were surveyed about joint injection vascular complications. Results:(1) In one of the four cadaveric dissections, the needle made direct contact with the LCFA. (2) Of 27 OSCE participants, only two activated Doppler before marking simulated hip injection trajectories. Trajectories passed through LCFA Doppler signal in six (22%) cases. Mean minimal distance from trajectory to arterial signal was 4 mm (range, 0–11 mm). (3) Of 62 survey respondents, 24% stated that they did not use Doppler routinely. While none reported bleeding injuries with their patients, 16% knew of a hip injection-related vascular complication performed by another provider. Conclusion: There is a risk of LCFA injury during ultrasound-guided hip joint injection. Routine use of Doppler should be considered in standard hip injection protocols

Consensus-based semi-quantitative ultrasound scoring system for gout lesions: Results of an OMERACT Delphi process and web-reliability exercise

International audienceObjective: This study aimed to develop (1) a new ultrasound definition for aggregates and (2) a semi-quantitative ultrasound scoring system (0–3) for tophus, double contour and aggregates. Furthermore, the intra- and inter-reader reliabilities of both the re-defined aggregates and the semi-quantitative scoring system were assessed using static image exercises. Methods: Thirty-seven rheumatologists were invited. A Delphi process was used for re-defining aggregates and for selecting a semi-quantitative scoring system with >75% agreement obligate for reaching consensus. Subsequently, a web-based exercise on static ultrasound images was conducted in order to assess the reliability of both the re-defined aggregates and the semi-quantitative scoring system. Results: Twenty rheumatologists contributed to all rounds of the Delphi and image exercises. A consensual re-definition of aggregates was obtained after three Delphi rounds but needed an overarching principle for scoring aggregates in patients. A consensus-based semi-quantitative ultrasound scoring system for gout lesions was developed after two Delphi rounds. The re-definition of aggregates showed good intra- and inter-reader reliability (κ-values 0.71 and 0.61). The reliabilities of the scoring system were good for all lesions with slightly higher intra-reader (κ-values 0.74–0.80) than inter-reader reliabilities (κ-values 0.61–0.67). Conclusion: A re-definition of aggregates was obtained with a good reliability when assessing static images. The first consensus-based semi-quantitative ultrasound scoring system for gout-specific lesions was developed with good inter- and intra-reader reliability for all lesions when tested in static images. The next step is to assess the reliabilities when scoring lesions in patients