LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Identify the clinical features of oxaliplatin-induced neuropathy.2. Discuss the current approaches for managing chemotherapy-induced neuropathy.3. Explain the rationale for using glutamine in preventing oxaliplatin-induced neuropathy.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME
ABSTRACTOxaliplatin is effective in the treatment of metastatic colorectal cancer (MCRC) patients; however, severe neurotoxicity develops frequently. To assess the efficacy of oral glutamine for preventing neuropathy induced by oxaliplatin, a pilot study was performed. A total of 86 patients with MCRC treated at Taipei Veterans General Hospital were enrolled. Oxaliplatin (85 mg/m 2 , days 1 and 15) plus weekly bolus 5-fluorouracil (5-FU; 500 mg/m 2 ) and folinic acid (FA; 20 mg/m 2 ) on days 1, 8, and 15 were given every 28 days as firstline treatment. Patients were randomized to receive (glutamine group; n ؍ 42) or not receive (control group; n ؍ 44) glutamine (15 g twice a day for seven consecutive days every 2 weeks starting on the day of oxaliplatin infusion). Efficacy of chemotherapy, neurological toxicity, and electrophysiological alterations were assessed. A lower percentage of grade 1-2 peripheral neuropathy was observed in the glutamine group (16.7% versus 38.6%) after two cycles of treatment, and a significantly lower incidence of grade 3-4 neuropathy was noted in the glutamine group after four cycles (4.8% versus 18.2%) and six cycles (11.9% versus 31.8%). By adding glutamine, interference with activities of daily living was lower (16.7% versus 40.9%), and need for oxaliplatin dose reduction was lower (7.1% versus 27.3%). There were no significant between-group differences in response to chemotherapy (52.4% versus 47.8%), electrophysiological abnormalities, grade 3-4 non-neurological toxicities (26.2% versus 22.8%), or survival. These data indi- Disclosure of potential conflicts of interest is found at the end of this article.
A two-terminal analog synaptic device that precisely emulates biological synaptic features is expected to be a critical component for future hardware-based neuromorphic computing. Typical synaptic devices based on filamentary resistive switching face severe limitations on the implementation of concurrent inhibitory and excitatory synapses with low conductance and state fluctuation. For overcoming these limitations, we propose a Ta/TaOx/TiO2/Ti device with superior analog synaptic features. A physical simulation based on the homogeneous (nonfilamentary) barrier modulation induced by oxygen ion migration accurately reproduces various DC and AC evolutions of synaptic states, including the spike-timing-dependent plasticity and paired-pulse facilitation. Furthermore, a physics-based compact model for facilitating circuit-level design is proposed on the basis of the general definition of memristor devices. This comprehensive experimental and theoretical study of the promising electronic synapse can facilitate realizing large-scale neuromorphic systems.
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