Background: In addition to causing the loss of voluntary sensory and motor function, spinal cord injury (SCI) often creates a state of central neuropathic pain. Rats given SCI display increases in the activated form of transcription factors ERK 1/2 MAPK and CREB in the spinal cord, which correspond to allodynia in a model of neuropathic pain. This study was conducted to determine if low dose ketamine had an effect on the activation of ERK 1/2 and CREB in the development of neuropathic pain.Methods: This study was conducted to evaluate ERK 1/2 and CREB protein in a sham operated (control) group, neuropathic pain and normal saline (NP ＋ NS) group and neuropathic pain and ketamine (NP ＋ Keta) group. To accomplish this, male Sprague-Dawley rats were anesthetized and then subjected to L5-L6 spinal nerve ligation (SNL, neuropathic rats). The total amounts of ERK 1/2 and CREB protein were then assessed by western blot analysis. In addition, changes in the amounts of ERK 1/2 and CREB mRNA were evaluated by RT-PCR.Results: There was a significant increase in the amount of ERK 1/2 and CREB in the NP ＋ NS group when compared with the sham group. However, the amount of ERK 1/2 and CREB protein induced due to SNL were significantly reduced by continuous infusion with ketamine in the NP ＋ Keta group. Conclusions:The results of this study revealed a positive linkage between NMDA receptors and the ERK-CREB signaling pathway. Therefore, NMDA receptors could be the target of future therapeutic approaches. Additionally, the results of the present study provide additional evidence that low dose ketamine effectively prevents and treats central neuropathic pain following SNL.

Cholangiocarcinoma (CCA) represents approximately 3% of gastrointestinal malignancies worldwide and constitutes around 10–15% of all primary liver cancers, being only second to hepatocellular carcinoma. Mortality from CCA has been on the rise in recent decades, and in the United States alone there has been a 36% increase in CCA from 1999 to 2014, with over 7000 CCA mortalities since 2013. Targeted therapies, which have been gaining interest due to their greater specificity toward cancer cells, have only recently started gaining FDA approval for the treatment of CCA. In this manuscript, we will go through the timeline of current FDA-approved targeted therapies as well as those that have gained FDA breakthrough therapy designation.

Mutation of the BRAF proto-oncogene is found in approximately 10% of colorectal cancers (CRC), with much of the mutation conferred by a V600E mutation. Unlike other CRC subtypes, BRAF-mutant CRC have had relatively limited response to conventional therapies and overall poor survival. We present the case of a 75-year-old man with severe nonischemic cardiomyopathy on a LifeVest who was found to have a transverse colonic mass with widespread hepatic metastatic disease and was subsequently found to have BRAFV600E-mutant CRC (MSI High/dMMR). After a failed therapy with FOLFOX and pembrolizumab, the patient was started on a regimen of vemurafenib, irinotecan, and cetuximab (VIC) based on the SWOG 1406 trial which had shown improved progression-free survival and response rate for the treatment of BRAFV600E-mutant metastatic CRC. After 40 cycles of VIC, the patient attained complete response and is in remission off chemotherapy with significant improvement. This case highlights the effectiveness of the triple-regimen of vemurafenib, irinotecan, and cetuximab as a treatment option for BRAFV600E-mutant CRC, which is a treatment regimen based on the SWOG 1406 trial, and also demonstrates the synergistic role of BRAFV600E inhibitors and EGFR inhibitors in the treatment of BRAFV600E-mutant CRC.