RESUMO
The brain avidly consumes glucose to fuel neurophysiology. Cancers of the brain, such as glioblastoma (GBM), lose aspects of normal biology and gain the ability to proliferate and invade healthy tissue. How brain cancers rewire glucose utilization to fuel these processes is poorly understood. Here we perform infusions of 13 C-labeled glucose into patients and mice with brain cancer to define the metabolic fates of glucose-derived carbon in tumor and cortex. By combining these measurements with quantitative metabolic flux analysis, we find that human cortex funnels glucose-derived carbons towards physiologic processes including TCA cycle oxidation and neurotransmitter synthesis. In contrast, brain cancers downregulate these physiologic processes, scavenge alternative carbon sources from the environment, and instead use glucose-derived carbons to produce molecules needed for proliferation and invasion. Targeting this metabolic rewiring in mice through dietary modulation selectively alters GBM metabolism and slows tumor growth. Significance: This study is the first to directly measure biosynthetic flux in both glioma and cortical tissue in human brain cancer patients. Brain tumors rewire glucose carbon utilization away from oxidation and neurotransmitter production towards biosynthesis to fuel growth. Blocking these metabolic adaptations with dietary interventions slows brain cancer growth with minimal effects on cortical metabolism.
RESUMO
The posterior cranial fossa with its complex anatomy houses key pathways regulating consciousness, autonomic functions, motor and sensory pathways, and cerebellar centers regulating balance and gait. The most common posterior fossa pathologies for which neurosurgical intervention may be necessary include cerebellopontine angle tumors, aneurysms, and metastatic lesions. The posterior cranial fossa can be accessed from variations of the supine, lateral, park-bench, prone, and sitting positions. Notable complications from positioning include venous air embolism, paradoxic air embolism, tension pneumocephalus, nerve injuries, quadriplegia, and macroglossia. An interdisciplinary approach with careful planning, discussion, and clinical management contributes to improved outcomes and reduced complications.
Assuntos
Anestésicos , Procedimentos Neurocirúrgicos , Fossa Craniana Posterior , HumanosRESUMO
BACKGROUND: Deep brain stimulation (DBS) is a U.S. Food and Drug Administration-approved therapy for medically refractory Parkinson's disease, essential tremor, and other neurological conditions. The procedure requires prolonged immobility and can result in significant patient discomfort, potentially limiting patient selection. In addition, surgical requirements necessitate avoidance of medications that may alter or suppress the patient's arousal or baseline tremor during macrostimulation testing. OBSERVATIONS: In this study, the authors describe the use of continuous spinal anesthesia with local anesthetic to manage a patient with severe back pain who was intolerant of semisupine position during stereotactic computed tomography and stage 1 of DBS placement. LESSONS: Continuous spinal anesthesia is an effective strategy to manage patients with severe back pain undergoing DBS surgery for upper extremity motor symptoms.
RESUMO
Recent studies have investigated local oscillations, long-range connectivity, and global network patterns to identify neural changes associated with anesthetic-induced unconsciousness. These studies typically employ anesthetic protocols that either just cross the threshold of unconsciousness, or induce deep unconsciousness for a brief period of time-neither of which models general anesthesia for major surgery. To study neural patterns of unconsciousness and recovery in a clinically-relevant context, we used a realistic anesthetic regimen to induce and maintain unconsciousness in eight healthy participants for 3 h. High-density electroencephalogram (EEG) was acquired throughout and for another 3 h after emergence. Seven epochs of 5-min eyes-closed resting states were extracted from the data at baseline as well as 30, 60, 90, 120, 150, and 180-min post-emergence. Additionally, 5-min epochs were extracted during induction, unconsciousness, and immediately prior to recovery of consciousness, for a total of 10 analysis epochs. The EEG data in each epoch were analyzed using source-localized spectral analysis, phase-lag index, and graph theoretical techniques. Posterior alpha power was significantly depressed during unconsciousness, and gradually approached baseline levels over the 3 h recovery period. Phase-lag index did not distinguish between states of consciousness or stages of recovery. Network efficiency was significantly depressed and network clustering coefficient was significantly increased during unconsciousness; these graph theoretical measures returned to baseline during the 3 h recovery period. Posterior alpha power may be a potential biomarker for normal recovery of functional brain networks after general anesthesia.
RESUMO
STUDY OBJECTIVE: Steep Trendelenburg position is frequently used during gynecologic minimally invasive surgery (MIS). However, little attention has been given to the potential impact of this nonphysiologic positioning on patients, specifically intraocular pressure (IOP). The purpose of our study was to evaluate IOP changes during laparoscopic or robotic hysterectomy conducted in the steep Trendelenburg position. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: John Sealy Hospital at the University of Texas Medical Branch, Galveston, TX. PATIENTS: Female patients with no history of ocular pathology who underwent elective robotic or laparoscopic hysterectomy. INTERVENTIONS: The anesthesia protocol was standardized for all study patients. IOP and mean arterial pressure (MAP) were obtained before anesthesia, after general anesthesia and intubation were achieved, after 1 hour of steep Trendelenburg positioning, after 2 hours of steep Trendelenburg positioning, and after the patient was returned to the supine position. Ocular perfusion pressure (OPP) was calculated using the following equation: OPP = MAP - IOP. MAIN RESULTS: A total of 10 patients were included in this prospective study. A significant increase in IOP from baseline was observed after 1 hour and 2 hours of steep Trendelenburg positioning (p = .005 and .002, respectively). There was a statistically significant trend of increasing the IOP from baseline to the second hour of steep Trendelenburg positioning (p < .001). The IOP remained significantly elevated once the patient was returned to the supine position when compared with the baseline IOP (p = .006). OPP significantly decreased from baseline after 2 hours of steep Trendelenburg positioning (p = .03). CONCLUSIONS: IOP increases significantly when patients are placed in the steep Trendelenburg position. Although further studies are needed to better characterize this process, given the aging population of our MIS patients in whom risk for glaucoma is significant, preoperative ocular health assessment should be considered in certain cases.