Hidehisa Nishi

Improving treatment times for patients with in-hospital stroke using a standardized protocol

BACKGROUND Previous reports have shown significant delays in treatment of in-hospital stroke (IHS). We developed and implemented our IHS alert protocol in April 2014. We aimed to determine the influence of implementation of our IHS alert protocol. METHODS Our implementation processes comprise the following four main steps: IHS protocol development, workshops for hospital staff to learn about the protocol, preparation of standardized IHS treatment kits, and obtaining feedback in a monthly hospital staff conference. We retrospectively compared protocol metrics and clinical outcomes of patients with IHS treated with intravenous thrombolysis and/or endovascular therapy between before (January 2008-March 2014) and after implementation (April 2014-December 2016). RESULTS Fifty-five patients were included (pre, 25; post, 30). After the implementation, significant reductions occurred in the median time from stroke recognition to evaluation by a neurologist (30 vs. 13.5min, p<0.01) and to first neuroimaging (50 vs. 26.5min, p<0.01) and in the median time from first neuroimaging to intravenous thrombolysis (45 vs. 16min, p=0.02). The median time from first neuroimaging to endovascular therapy had a tendency to decrease (75 vs. 53min, p=0.08). There were no differences in the favorable outcomes (modified Rankin scale score of 0-2) at discharge or the incidence of symptomatic intracranial hemorrhage between the two periods. CONCLUSION Our IHS alert protocol implementation saved time in treating patients with IHS without compromising safety.

Activatable fluorescence imaging of macrophages in atherosclerotic plaques using iron oxide nanoparticles conjugated with indocyanine green

BACKGROUND AND AIMS Macrophages are key factors in the formation of unstable atherosclerotic plaques, which may be identified through macrophage imaging. We tested whether activatable fluorescence probes of iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG) (IONP-ICG), consisting of biocompatible reagents, can visualize macrophages present in atherosclerotic plaques. METHODS IONP-based probes conjugated with different numbers of ICG molecules were synthesized. Six-week-old spontaneously hyperlipidemic (SHL) mice were fed either a Western or normal diet for 14 weeks, and were intravenously injected with IONP-ICG (55.8 mg Fe/kg). Aortas were harvested 48 h later, and aortas containing atherosclerotic plaques were imaged. RESULTS Phantom imaging studies using IONP-ICG solution demonstrated that the addition of surfactants to IONP-ICG solutions yielded fluorescence activation. Incubation of macrophages with IONP-ICG led to internalization of IONP-ICG and near infrared fluorescence (NIRF) activation. In NIRF imaging studies, intense fluorescence signals were clearly visible primarily at the margins of atherosclerotic plaques, and relatively weak signals were evident inside the plaques, demonstrating the feasibility of detection of NIRF signals at atherosclerotic plaques. In the quantitative evaluation of NIRF, administration of a probe conjugated with more ICG molecules led to a significant increase in the NIRF signal, indicating that probes with greater numbers of ICG molecules are effective for sensitive NIRF detection. SHL mice given a low-cholesterol normal diet showed a significantly lower NIRF signal compared with mice given the Western diet. Histologically, NIRF signals in atherosclerotic plaques strongly correlated with the location of macrophages, suggesting the possibility of NIRF macrophage imaging using IONP-ICG. CONCLUSIONS Localization of macrophages in atherosclerotic plaques may be achieved using the activatable NIRF probe, IONP-ICG.