Closed traumatic brain injury model in sheep mimicking high-velocity, closed head trauma in humans.

To date, there are only a few, non-evidence based, cerebroprotective therapeutic strategies for treatment and, accordingly, for prevention of secondary brain injuries following severe closed head trauma. In order to develop new therapy strategies, existing realistic animal models need to be advanced. The objective is to bridge standardized small animal models and actual patient medical care, since the results of experimental small animal studies often cannot be transferred to brain-injured humans. For improved standardization of high-velocity trauma, new trauma devices for initiating closed traumatic brain injury in sheep were developed. The following new devices were tested: 1. An anatomically shaped rubber bolt with an integrated oscillation absorber for prevention of skull fractures; 2. Stationary mounting of the bolt to guarantee stable experimental conditions; 3. Varying degrees of trauma severity, i. e., mild and severe closed traumatic brain injury, using different cartridges; and 4. Trauma analysis via high-speed video recording. Peritraumatic measurements of intracranial pressure, brain tissue pH, brain tissue oxygen, and carbon dioxide pressure, as well as neurotransmitter concentrations were performed. Cerebral injuries were documented with magnetic resonance imaging and compared to neuropathological results. Due to the new trauma devices, skull fractures were prevented. The high-speed video recording documented a realistic trauma mechanism for a car accident. Enhancement of extracellular glutamate, aspartate, and gamma amino butyric acid concentrations began 60 min after the trauma. Magnetic resonance imaging and neuropathological results showed characteristic injury patterns of mild, and severe, closed traumatic brain injury. The severe, closed traumatic brain injury group showed diffuse axonal injuries, traumatic subarachnoid hemorrhage, and hemorrhagic contusions with inconsistent distribution among the animals. The model presented here achieves a gain in standardization of severe, closed traumatic brain injury by increasing approximation to reality. The still existent heterogeneity of brain pathology mimics brain changes observed in patients after high-energy trauma. This model seems to close the gap between experimental small animal models and clinical studies. However, further investigations are needed to evaluate if this model can be used for testing new therapeutic strategies for these patients.

Safety and tolerability of ferric carboxymaltose (FCM) for treatment of iron deficiency in patients with chronic kidney disease and in kidney transplant recipients.

BACKGROUND: Iron deficiency is common in patients with chronic kidney disease and in kidney transplant recipients. PATIENTS AND METHODS: We analyzed the safety and tolerability of the new intravenous iron preparation ferric carboxymaltose (FCM) in these two patient groups. Adverse events after administration of the drug were assessed by using a questionnaire. Vital signs and laboratory data were collected before and after the application of FCM. A total of 46 FCM doses were applied to 44 patients (17 with chronic kidney disease and 27 kidney transplant recipients) either as single injection of 100 or 200 mg (n = 42) or as short infusion with up to 500 mg (n = 4). RESULTS: Mild and transient adverse events (metallic taste, headache, dizziness) occurred in six patients. The estimated glomerular filtration rate remained unchanged by the FCM administration. CONCLUSION: We conclude that safety and tolerability of FCM were excellent. Compared with other intravenous iron preparations the considerably shorter administration time of FCM allows to save time and to reduce costs.