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ObjectiveTo characterize muscle fiber necrosis in immune-mediated necrotizing myopathies (IMNM) with anti–signal recognition particle (SRP) or anti–3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) antibodies and to explore its underlying molecular immune mechanisms.MethodsMuscle biopsies from patients with IMNM were analyzed and compared to biopsies from control patients with myositis. In addition to immunostaining and reverse transcription PCR on muscle samples, in vitro immunostaining on primary muscle cells was performed.ResultsCreatine kinase levels and muscle regeneration correlated with the proportion of necrotic fibers (r = 0.6, p < 0.001). CD68+iNOS+ macrophages and a Th-1 immune environment were chiefly involved in ongoing myophagocytosis of necrotic fibers. T-cell densities correlated with necrosis but no signs of cytotoxicity were detected. Activation of the classical pathway of the complement cascade, accompanied by deposition of sarcolemmal immunoglobulins, featured involvement of humoral immunity. Presence of SRP and HMGCR proteins on altered myofibers was reproduced on myotubes exposed to purified patient-derived autoantibodies. Finally, a correlation between sarcolemmal complement deposits and fiber necrosis was observed (r = 0.4 and p = 0.004). Based on these observations, we propose to update the pathologic criteria of IMNM.ConclusionThese data further corroborate the pathogenic role of anti-SRP and anti-HMGCR autoantibodies in IMNM, highlighting humoral mechanisms as key players in immunity and myofiber necrosis.

Background and Purpose— Pre- and intrahospital time delays are major concerns in acute stroke care. Telemedicine-equipped ambulances may improve time management and identify patients with stroke eligible for thrombolysis by an early prehospital stroke diagnosis. The aims of this study were (1) to develop a telestroke ambulance prototype; (2) to test the reliability of stroke severity assessment; and (3) to evaluate its feasibility in the prehospital emergency setting. Methods— Mobil, real-time audio–video streaming telemedicine devices were implemented into advanced life support ambulances. Feasibility of telestroke ambulances and reliability of the National Institutes of Health Stroke Scale assessment were tested using current wireless cellular communication technology (third generation) in a prehospital stroke scenario. Two stroke actors were trained in simulation of differing right and left middle cerebral artery stroke syndromes. National Institutes of Health Stroke Scale assessment was performed by a hospital-based stroke physician by telemedicine, by an emergency physician guided by telemedicine, and “a posteriori” on the basis of video documentation. Results— In 18 of 30 scenarios, National Institutes of Health Stroke Scale assessment could not be performed due to absence or loss of audio–video signal. In the remaining 12 completed scenarios, interrater agreement of National Institutes of Health Stroke Scale examination between ambulance and hospital and ambulance and “a posteriori” video evaluation was moderate to good with weighted κ values of 0.69 (95% CI, 0.51–0.87) and 0.79 (95% CI, 0.59–0.98), respectively. Conclusion— Prehospital telestroke examination was not at an acceptable level for clinical use, at least on the basis of the used technology. Further technical development is needed before telestroke is applicable for prehospital stroke management during patient transport.