Echocardiographic Screening for Rheumatic Heart Disease: A Brief History and Implications for the Future.

Transthoracic echocardiography is the gold standard for early detection of rheumatic heart disease (RHD) in asymptomatic children living in high-risk regions. Advances in technology allowing miniaturisation and increased portability of echocardiography devices have improved the accessibility of this vital diagnostic tool in RHD-endemic locations. Automation of image optimisation techniques and simplified RHD screening protocols permit use by non-experts after a brief period of training. While these changes are welcome advances in the battle to manage RHD, it is important that the sensitivity and specificity of RHD detection be maintained by all echocardiography users on any device to ensure accurate and timely diagnosis of RHD to facilitate initiation of appropriate therapy. This review of the evolution of echocardiography and its use in the detection of rheumatic valve disease may serve as a reminder of the key strengths and potential pitfalls of this increasingly relied-upon diagnostic test.

Extracellular matrix metalloproteinase inducer shows active perivascular cuffs in multiple sclerosis.

Inflammatory perivascular cuffs are comprised of leucocytes that accumulate in the perivascular space around post-capillary venules before their infiltration into the parenchyma of the central nervous system. Inflammatory perivascular cuffs are commonly found in the central nervous system of patients with multiple sclerosis and in the animal model experimental autoimmune encephalomyelitis. Leucocytes that accumulate in the perivascular space secrete matrix metalloproteinases that aid their transmigration into the neural parenchyma. We described previously that the upstream inducer of matrix metalloproteinase expression, extracellular matrix metalloproteinase inducer (CD147), was elevated in experimental autoimmune encephalomyelitis, and that its inhibition reduced leucocyte entry into the central nervous system. Here we investigated whether the expression of extracellular matrix metalloproteinase inducer varies with the temporal evolution of lesions in murine experimental autoimmune encephalomyelitis, whether it was uniformly upregulated across multiple sclerosis specimens, and whether it was a feature of inflammatory perivascular cuffs in multiple sclerosis lesions. In experimental autoimmune encephalomyelitis, elevation of extracellular matrix metalloproteinase inducer was correlated with the appearance and persistence of clinical signs of disease. In both murine and human samples, extracellular matrix metalloproteinase inducer was detected on endothelium in healthy and disease states but was dramatically increased in and around inflammatory perivascular cuffs on leucocytes, associated with matrix metalloproteinase expression, and on resident cells including microglia. Leucocyte populations that express extracellular matrix metalloproteinase inducer in multiple sclerosis lesions included CD4+ and CD8+ T lymphocytes, B lymphocytes and monocyte/macrophages. The extra-endothelial expression of extracellular matrix metalloproteinase inducer was a marker of the activity of lesions in multiple sclerosis, being present on leucocyte-containing perivascular cuffs but not in inactive lesions. By using a function-blocking antibody, we implicate extracellular matrix metalloproteinase inducer in the adhesion of leucocytes to endothelial cells and determined that its activity was more crucial on leucocytes than on endothelium in leucocyte-endothelial cell engagement in vitro. Extracellular matrix metalloproteinase inducer activity regulated the level of alpha 4 integrin on leucocytes through a mechanism associated with nuclear factor κB signalling. Blocking extracellular matrix metalloproteinase inducer attenuated the transmigration of monocytes and B lymphocytes across a model of the blood-brain barrier in culture. In summary, we describe the prominence of extracellular matrix metalloproteinase inducer in central nervous system inflammatory perivascular cuffs, emphasize its dual role in matrix metalloproteinase induction and leucocyte adhesion, and highlight the elevation of extracellular matrix metalloproteinase inducer as an orchestrator of the infiltration of leucocytes into the central nervous system parenchyma.

Severe bicycling injury risk factors in children and adolescents: a case-control study.

BACKGROUND: Bicycling is the most common cause of sports and recreation injury in children and adolescents; yet, there is limited evidence on the factors associated with severe bicycling injuries in youth. METHODS: Case-control study of injured bicyclists less than 18 years old seen in seven emergency departments (EDs) from May 2008 to October 2010. Cases were bicyclists hospitalized after their ED visit (severe injury). Controls were bicyclists seen and discharged from the ED (non-severe injury). Personal, environmental, and crash characteristics were collected by interview. Injury data were collected from medical charts. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression were used to estimate the odds of hospitalization associated with risk factors. Multiple imputation techniques were employed to address missing data. RESULTS: There were 1470 participants including 119 cases. Those ages 13-17 had the highest proportion (23%) of severe injuries resulting from motor vehicle [MV] collision. In models including age, sex and MV collision, being male (OR: 2.02; 95% CI: 1.21-3.38), not wearing a helmet (OR: 2.18; 95% CI: 1.43-3.31) and MV collision (OR: 3.91; 95% CI: 2.26-6.78) were significant risk factors for severe injury. Riding on a paved surface (OR: 0.63; 95% CI: 0.41-0.97) and utilitarian (school, work) bicycling (OR: 0.44; 95% CI: 0.2-0.94) decreased injury risk. Results were similar, apart from utilitarian bicycling (OR: 0.49; 95% CI: 0.22-1.06), after imputation for missing data. CONCLUSION: Bicycle-MV collisions increase severe injury risk in youth, and adolescents are often injured in these events. This suggests separating bicyclists from MVs or traffic calming strategies could improve safety.