Introduction Only a minority of patients with acute ischaemic stroke receive reperfusion treatment, primarily due to prehospital delay. We aimed to investigate predictors of a primary contact to the emergency medical services, arrival at stroke centre within 3 h of symptom onset and initiation of reperfusion therapy in patients with acute stroke. Patients and methods We conducted a cross-sectional study of consecutive patients with acute ischaemic stroke, intracerebral haemorrhage or transient ischaemic attack. Structured interviews of patients and bystanders were performed and combined with clinical information from the Danish Stroke Registry. Eligible patients were aged ≥18 years and were independent in activities of daily living before the stroke. Results We included 435 patients. Presence of a bystander at symptom onset and knowledge of ≥2 core symptoms of stroke were associated with a primary emergency medical services contact. Higher stroke severity and patients or bystanders perceiving the situation as very serious were associated with a primary emergency medical services contact (ORpatients 2.10; 95% CI 1.12–3.95 and ORbystanders 22.60; 95% CI 4.98–102.67), <3 h from onset to arrival (ORpatients 3.01; 95% CI 1.46–6.21 and ORbystanders 4.44; 95% CI 1.37–14.39) and initiation of reperfusion therapy (ORpatients 3.08; 95% CI 1.23–7.75 and ORbystanders 4.70; 95% CI 1.14–19.5). Conclusion: Having a bystander, knowledge of ≥2 core symptoms and understanding that stroke is a serious event are associated with appropriate help-seeking behaviour, shorter prehospital delay and higher chance of reperfusion therapy in acute stroke patients.
The anti-diabetic biguanide drugs metformin (METF) and phenformin (PHEN) may have anti-cancer effects. Biguanides suppress plasma growth factors, but nonetheless, the view that these mitochondrial inhibitors accumulate in tumor tissue to an extent that leads to severe energetic stress or alleviation of hypoxia-induced radioresistance is gaining ground. Our cell studies confirm that biguanides inhibits cell proliferation by targeting respiration, but only at highly suprapharmacological concentrations due to low drug retention. Biodistribution/PET studies of 11C-labeled metformin (11C-METF) revealed that plasma bioavailability remained well below concentrations with metabolic/anti-proliferative in vitro effects, following a high oral dose. Intraperitoneal administration resulted in higher drug concentrations, which affected metabolism in normal organs with high METF uptake (e.g., kidneys), but tumor drug retention peaked at low levels comparable to plasma levels and hypoxia was unaffected. Prolonged intraperitoneal treatment reduced tumor growth in two tumor models, however, the response did not reflect in vitro drug sensitivity, and tumor metabolism and hypoxia was unaffected. Our results do not support that direct inhibition of tumor cell respiration is responsible for reduced tumor growth, but future studies using 11C-METF-PET are warranted, preferably in neoplasia’s originating from tissue with high drug transport capacity, to investigate the controversial idea of direct targeting.
DCE-MRI and FDG-PET revealed loss of vessel functionality, impaired glucose delivery and reduced metabolic activity prior to cell death. [1-C]lactate-to-[C]bicarbonate ratios increased significantly during treatment, indicating a decline in respiratory activity driven by the onset of hypoxia. HPMRS is promising for early detection of metabolic stress inflicted by VDAs, which cannot easily be inferred based on blood flow measurements.
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