The Effect of Porcine Orexin a on C-Peptide Plasma Concentrations in Pigs

The hypothalamus and the neuropeptides that are produced and act within its neuronal circuits constitute an area of extensive laboratory research. In 1998, the neuropeptide, Orexin A, was discovered and isolated from the hypothalamus of the rat. An i.c.v. injection of Orexin A into the lateral ventricle of the rat's brain causes an increase in the consumption of food, and, apart from appetite, it also seems to be regulating many other normal functions of the organism, whose regulatory and metabolic mechanisms remain unknown to date. The neuropeptide is produced by a small cluster located in and round the lateral hypothalamic area. It has been known for decades that this area is involved in the regulation of feeding and energy homeostasis in mammals. The intravenous, subcutaneous, or i.c.v. injection of Orexin A causes changes in insulin and glucagon concentrations. The same effect is also seen under in vitro experimental conditions. In this study, we investigated the potential effects of i.c.v. administration of porcine Orexin A on c-peptide concentrations in the peripheral blood of pigs, and tested whether these changes are associated with the potential effect of the neuropeptide on the function of the pancreas

Evaluation of outcomes among patients with traumatic intracranial hypertension treated with decompressive craniectomy vs standard medical care at 24 month

Importance Trials often assess primary outcomes of traumatic brain injury at 6 months. Longer-term data are needed to assess outcomes for patients receiving surgical vs medical treatment for traumatic intracranial hypertension. Objective To evaluate 24-month outcomes for patients with traumatic intracranial hypertension treated with decompressive craniectomy or standard medical care. Design, Setting, and Participants Prespecified secondary analysis of the Randomized Evaluation of Surgery With Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp) randomized clinical trial data was performed for patients with traumatic intracranial hypertension (>25 mm Hg) from 52 centers in 20 countries. Enrollment occurred between January 2004 and March 2014. Data were analyzed between 2018 and 2021. Eligibility criteria were age 10 to 65 years, traumatic brain injury (confirmed via computed tomography), intracranial pressure monitoring, and sustained and refractory elevated intracranial pressure for 1 to 12 hours despite pressure-controlling measures. Exclusion criteria were bilateral fixed and dilated pupils, bleeding diathesis, or unsurvivable injury. Interventions Patients were randomly assigned 1:1 to receive a decompressive craniectomy with standard care (surgical group) or to ongoing medical treatment with the option to add barbiturate infusion (medical group). Main Outcomes and Measures The primary outcome was measured with the 8-point Extended Glasgow Outcome Scale (1 indicates death and 8 denotes upper good recovery), and the 6- to 24-month outcome trajectory was examined. Results This study enrolled 408 patients: 206 in the surgical group and 202 in the medical group. The mean (SD) age was 32.3 (13.2) and 34.8 (13.7) years, respectively, and the study population was predominantly male (165 [81.7%] and 156 [80.0%], respectively). At 24 months, patients in the surgical group had reduced mortality (61 [33.5%] vs 94 [54.0%]; absolute difference, −20.5 [95% CI, −30.8 to −10.2]) and higher rates of vegetative state (absolute difference, 4.3 [95% CI, 0.0 to 8.6]), lower or upper moderate disability (4.7 [−0.9 to 10.3] vs 2.8 [−4.2 to 9.8]), and lower or upper severe disability (2.2 [−5.4 to 9.8] vs 6.5 [1.8 to 11.2]; χ27 = 24.20, P = .001). For every 100 individuals treated surgically, 21 additional patients survived at 24 months; 4 were in a vegetative state, 2 had lower and 7 had upper severe disability, and 5 had lower and 3 had upper moderate disability, respectively. Rates of lower and upper good recovery were similar for the surgical and medical groups (20 [11.0%] vs 19 [10.9%]), and significant differences in net improvement (≥1 grade) were observed between 6 and 24 months (55 [30.0%] vs 25 [14.0%]; χ22 = 13.27, P = .001). Conclusions and Relevance At 24 months, patients with surgically treated posttraumatic refractory intracranial hypertension had a sustained reduction in mortality and higher rates of vegetative state, severe disability, and moderate disability. Patients in the surgical group were more likely to improve over time vs patients in the medical group