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

γδ T Cells Are Reduced and Rendered Unresponsive by Hyperglycemia and Chronic TNFα in Mouse Models of Obesity and Metabolic Disease

Epithelial cells provide an initial line of defense against damage and pathogens in barrier tissues such as the skin; however this balance is disrupted in obesity and metabolic disease. Skin γδ T cells recognize epithelial damage, and release cytokines and growth factors that facilitate wound repair. We report here that hyperglycemia results in impaired skin γδ T cell proliferation due to altered STAT5 signaling, ultimately resulting in half the number of γδ T cells populating the epidermis. Skin γδ T cells that overcome this hyperglycemic state are unresponsive to epithelial cell damage due to chronic inflammatory mediators, including TNFα. Cytokine and growth factor production at the site of tissue damage was partially restored by administering neutralizing TNFα antibodies in vivo. Thus, metabolic disease negatively impacts homeostasis and functionality of skin γδ T cells, rendering host defense mechanisms vulnerable to injury and infection

Mouse anti-RANKL antibody delays oral wound healing and increases TRAP-positive mononuclear cells in bone marrow

Objectives: Denosumab, a human monoclonal antibody (mAb) that neutralizes receptor activator for nuclear factor κB ligand (RANKL), is associated with osteonecrosis of the jaw. However, the effect of denosumab on oral wounds is unclear. The aim was to determine the effect of anti-RANKL mAb on oral wounds and bone marrow. Materials and methods: The direct effect of the mAb on fibroblasts, macrophages, and osteoclasts were assessed in vitro. In vivo, mouse anti-RANKL mAb was administered to mice for 9 weeks prior to palatal bone denudation surgery. Mice were euthanized 3 weeks post-surgery, and wound healing was histomorphometrically analyzed. Long bones were assessed using micro-computed tomography, quantitative real-time polymerase chain reaction, and flow cytometry. Results: The mAb had no effect on macrophages and fibroblasts but significantly suppressed osteoclast proliferation in vitro. The mAb treatment significantly increased bone mass by suppressing osteoclasts in vivo. The expression of pro-osteoclastic genes was promoted in the bone marrow of the mAb-administered animals. Consistently, the mAb significantly induced the development of tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells (MNCs) but not osteoclasts in bone marrow. The mAb treatment had no effect on gross healing of the palatal wounds. However, significant inflammation was retained in the connective tissue facing the once denuded bone surface. Conclusions: Repair of the damaged palate was delayed, and significant inflammation was sustained in the connective tissue by anti-RANKL mAb treatment. Clinical relevance: Denosumab impairs osteoclastic bone repair. Care should be exercised to minimize osseous trauma when invasive procedures are performed on patients taking denosumab

Relationship between visual field progression and baseline refraction in primary open-angle glaucoma

Tomoko Naito,1 Keiji Yoshikawa,2 Shiro Mizoue,3 Mami Nanno,4 Tairo Kimura,5 Hirotaka Suzumura,6 Yuzo Umeda,7 Fumio Shiraga1 1Department of Ophthalmology, Okayama University Graduate School of Medicine, Okayama, Japan; 2Yoshikawa Eye Clinic, Tokyo, Japan; 3Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan; 4Kagurazaka Minamino Eye Clinic, 5Ueno Eye Clinic, 6Suzumura Eye Clinic, Tokyo, Japan; 7Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan Purpose: To analyze the relationship between visual field (VF) progression and baseline refraction in Japanese patients with primary open-angle glaucoma (POAG) including normal-tension glaucoma.Patients and methods: In this retrospective study, the subjects were patients with POAG who had undergone VF tests at least ten times with a Humphrey Field Analyzer (Swedish interactive thresholding algorithm standard, Central 30-2 program). VF progression was defined as a significantly negative value of mean deviation (MD) slope at the final VF test. Multivariate logistic regression models were applied to detect an association between MD slope deterioration and baseline refraction.Results: A total of 156 eyes of 156 patients were included in this analysis. Significant deterioration of MD slope was observed in 70 eyes of 70 patients (44.9%), whereas no significant deterioration was evident in 86 eyes of 86 patients (55.1%). The eyes with VF progression had significantly higher baseline refraction compared to those without apparent VF progression (-1.9±3.8 diopter [D] vs -3.5±3.4 D, P=0.0048) (mean ± standard deviation). When subject eyes were classified into four groups by the level of baseline refraction applying spherical equivalent (SE): no myopia (SE > -1D), mild myopia (-1D ≥ SE > -3D), moderate myopia (-3D ≥ SE > -6D), and severe myopia (-6D ≥ SE), the Cochran–Armitage trend analysis showed a decreasing trend in the proportion of MD slope deterioration with increasing severity of myopia (P=0.0002). The multivariate analysis revealed that baseline refraction (P=0.0108, odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03–1.25) and intraocular pressure reduction rate (P=0.0150, OR: 0.97, 95% CI: 0.94–0.99) had a significant association with MD slope deterioration.Conclusion: In the current analysis of Japanese patients with POAG, baseline refraction was a factor significantly associated with MD slope deterioration as well as intraocular pressure reduction rate. When baseline refraction was classified into four groups, MD slope in myopia groups was less deteriorated as compared to those in the emmetropic/hyperopic group.Keywords: primary open-angle glaucoma, normal-tension glaucoma, myopia, refraction, visual field progression, MD slope, intraocular pressure reduction rat