Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): A multicenter randomized controlled trial.

BACKGROUND: Therapeutic hypothermia may need prolonged duration for the patients with severe traumatic brain injury (sTBI). METHODS: The Long-Term Hypothermia trial was a prospective, multicenter, randomized, controlled clinical trial to examine the safety and efficacy in adults with sTBI. Eligible patients were 18-65, Glasgow Coma Scale score at 4 to 8, and initial intracranial pressure (ICP) ≥ 25 mm Hg, randomly assigned to the long-term mild hypothermia group (34-35 °C for 5 days) or normothermia group at 37 °C. The primary outcome was the Glasgow outcome scale (GOS) at 6 months. Secondary outcomes included ICP control, complications and laboratory findings, the length of ICU and hospital stay, and GOS at 6 months in patients with initial ICP ≥ 30 mm Hg. This trial is registered with ClinicalTrials.gov, NCT01886222. FINDINGS: 302 patients were enrolled from June 25, 2013, to December 31, 2018, with 6 months follow-up in 14 hospitals, 156 in hypothermia group and 146 in normothermia group. There was no difference in favorable outcome (OR 1·55, 95%CI 0·91-2·64; P = 0·105) and in mortality (P = 0·111) between groups. In patients with an initial ICP ≥ 30 mm Hg, hypothermic treatment significantly increased favorable outcome over normothermia group (60·82%, 42·71%, respectively; OR 1·861, 95%CI 1·031-3·361; P = 0·039). Long-term mild hypothermia did not increase the incidences of complications. INTERPRETATION: Long-term mild hypothermia did not improve the neurological outcomes. However, it may be a potential option in sTBI patients with initial ICP ≥ 30 mm Hg. FUNDING: : Shanghai municipal government and Shanghai Jiao Tong University/School of Medicine.

Mitochondrial Fusion and Fission in Neuronal Death Induced by Cerebral Ischemia-Reperfusion and Its Clinical Application: A Mini-Review.

Mitochondria are highly dynamic organelles which are joined by mitochondrial fusion and divided by mitochondrial fission. The balance of mitochondrial fusion and fission plays a critical role in maintaining the normal function of neurons, of which the processes are both mediated by several proteins activated by external stimulation. Cerebral ischemia-reperfusion (I/R) injury can disrupt the balance of mitochondrial fusion and fission through regulating the expression and post-translation modification of fusion- and fission-related proteins, thereby destroying homeostasis of the intracellular environment and causing neuronal death. Furthermore, human intervention in fusion- and fission-related proteins can influence the function of neurons and change the outcomes of cerebral I/R injury. In recent years, researchers have found that mitochondrial dysfunction was one of the main factors involved in I/R, and mitochondria is an attractive target in I/R neuroprotection. Therefore, mitochondrial-targeted therapy of the nervous system for I/R gradually started from basic study to clinical application. In the present review, we highlight recent progress in mitochondria fusion and fission in neuronal death induced by cerebral I/R to help understanding the regulatory factors and signaling networks of aberrant mitochondrial fusion and fission contributing to neuronal death during I/R, as well as the potential neuroprotective therapeutics targeting mitochondrial dynamics, which may help clinical treatment and development of relevant dugs.

[Pterional keyhole approach in surgical treatment of ruptured anterior circulation intracranial aneurysm: a report of 313 cases].

OBJECTIVE: To review the surgical modality with pterional keyhole approach in treatment of anterior circulation aneurysm. METHODS: Three hundred and thirteen patients with ruptured anterior circulation intracranial aneurysm treated surgically with pterional keyhole approach between January 2009 and June 2014 in Department of Neurosurgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, were included in the analysis. Complete occlusion rate of aneurysms and incidence of major complications including delayed cerebral ischemia and chronic hydrocephalus were documented. Surgical outcomes at 6-month follow up were assessed by modified Rankin Scale. RESULTS: Totally 348 aneurysms were treated with pterional keyhole approach, 326 aneurysms were completely clipped, 16 aneurysms were partly clipped, and 6 aneurysms were wrapped with gauze material. Among 313 patients, 15 patients (4.79%) suffered from delayed cerebral ischemia, and 10 patients (3.19%) suffered from hydrocephalus. At the 6-month follow up, the rate of good outcome was 66.77% (209/313). CONCLUSIONS: The pterional keyhole approach can be used to clip most of anterior circulation aneurysms, and it seems to have advantages over the traditional approaches with lower incidence of complications and similar outcomes.