Survivors of out-of-hospital cardiac arrest (OHCA) experience between 30% and 50% cognitive deficits several years post-discharge. Especially spatial memory is affected due to ischemia-induced... Show moreSurvivors of out-of-hospital cardiac arrest (OHCA) experience between 30% and 50% cognitive deficits several years post-discharge. Especially spatial memory is affected due to ischemia-induced neuronal damage in the hippocampus. Aim of this study was to investigate the potential neuroprotective effect of 2-iminobiotin (2-IB), a biotin analogue, on memory and learning in a four-vessel occlusion model of global ischemia using the Water Maze test. Sprague-Dawley rats were randomly assigned to either sham operation (n = 6), vehicle treatment (n = 20), 1.1 (n = 15), 3.3 (n = 14), 10 (n = 14), or 30 mg/kg/dose 2-IB treatment (n = 15). Treatment was subcutaneously (s.c.) administered immediately upon reperfusion, at 12h, and at 24h after reperfusion. Memory function on day 32 was significantly preserved in all doses of 2-IB rats compared to vehicle, as was the learning curve in the 1.1, 3.3 and 30 mg/kg dose group. Adult rats treated s.c. with 3 gifts of 2-IB every 12 h in a dose range of 1.1-30 mg/kg/dose directly upon reperfusion showed significant improved memory and learning after four vessel occlusion compared to vehicle-treated rats. Since 2-IB has already shown to be safe in a phase 1 clinical trial in adult human volunteers, it is a suitable candidate for translation to a human phase 2 study after OHCA. Show less
Verbeek, F.H.O.; Ham, W.H.W.; Verbeek, A.L.M.; Ginkel, J.D.M.; Os-Medendorp, H. van; Westers, P.; Leenen, L.P.H. 2022
BACKGROUND: Falls in people 65 years and older evaluated in the emergency department are increasing. Of all unintentional injury-related deaths among older people, 55% are due to falls. The impact... Show moreBACKGROUND: Falls in people 65 years and older evaluated in the emergency department are increasing. Of all unintentional injury-related deaths among older people, 55% are due to falls. The impact of falls, especially concerning Dutch older people with the highest proportion of living independently worldwide, is unclear. OBJECTIVE: To identify the influence of age, gender, health conditions, and type of fall on the severity of injury, hospital length of stay, mortality, and discharge destination. METHODS: A total number of 6,084 patients from a comprehensive regional trauma care system, 65 years and older and hospitalized after a fall, were included. Groups were compared for patient-related factors and multivariable logistic regression analysis to explore the consequences. RESULTS: Mean age was 82 years (SD = 8.3), and 70% were female. Most falls (66.4%) were due to "slipping and tripping" or "falls on the same level," 57.4% had Injury Severity Scores between 9 and 12, and 43.3% were discharged home. Higher age and type of fall increased the likelihood of severe injuries. Men experienced shorter hospital stays than women and were less frequently discharged home. Mortality was higher in males (10.8%) than in females (6.7%) and increased with the American Society of Anesthesiologists scores for preexisting health conditions. CONCLUSION: Advanced age, gender, type of fall, and prior health status play a significant role in the severity of injuries, length of hospital stay, 30-day mortality, and higher discharge destination to care homes in older people hospitalized after a fall. Show less
