Review of Burn Resuscitation: Is Plasmalyte® a Comparable Alternative to Ringer's Lactate?

Ringer's lactate has been the most widely used fluid for burn resuscitation for decades. Plasmalyte® (PL), a newer balanced crystalloid, is gaining popularity for use in the critically ill, including patients with burns. This popularity is partly due to the fact that PL theoretically offers a favorable metabolic profile, but may also be attributed to its relatively lower cost. Patients who are critically ill with large burns receive enormous volumes of fluids, especially during the resuscitation period. The choice of balanced crystalloid solution used is likely to have an impact on the metabolic status of patients and their overall outcomes. The choice of fluid for burn resuscitation has been one of the most researched topics in burn care and various types of fluids have been superseded based on research findings. This narrative review examines the evidence guiding fluid management in burns and explores the data supporting the use of balanced crystalloid solutions, in particular PL for burn resuscitation. Our literature search revealed only one study that focused on a direct comparison between PL and standard Ringer's Lactate for burn resuscitation. Based on the limited literature on the use of PL in burns, it is difficult to draw meaningful conclusions. Further research, into the suitability of PL for use in burns, is needed before formulary changes are instituted widely.

Primary Colorectal Cells Culture as a Translational Research Model.

Preclinical studies are an essential stage for any pharmacological agent hoping to make its way into clinical trials. An ideal preclinical model that can accurately predict clinical response does not exist and the best that the scientific community have at the moment is to select the most relevant study model pertaining to the disease of interest from those available, which includes: cell lines, animal models, and even in-silico methodology. Currently, there is a huge gap between preclinical and clinical trial results, indicating that there is much room for improvement in developing a better model to bridge the translational gap.

Re-examining HSPC1 inhibitors.

HSPC1 is a critical protein in cancer development and progression, including colorectal cancer (CRC). However, clinical trial data reporting the effectiveness of HSPC1 inhibitors on several cancer types has not been as successful as predicted. Furthermore, some N-terminal inhibitors appear to be much more successful than others despite similar underlying mechanisms. This study involved the application of three N-terminal HSPC1 inhibitors, 17-DMAG, NVP-AUY922 and NVP-HSP990 on CRC cells. The effects on client protein levels over time were examined. HSPC1 inhibitors were also applied in combination with chemotherapeutic agents commonly used in CRC treatment (5-fluorouracil, oxaliplatin and irinotecan). As HSPA1A and HSPB1 have anti-apoptotic activity, gene-silencing techniques were employed to investigate the significance of these proteins in HSPC1 inhibitor and chemotherapeutic agent resistance. When comparing the action of the three HSPC1 inhibitors, there are distinct differences in the time course of important client protein degradation events. The differences between HSPC1 inhibitors were also reflected in combination treatment-17-DMAG was more effective compared with NVP-AUY922 in potentiating the cytotoxic effects of 5-fluorouracil, oxaliplatin and irinotecan. This study concludes that there are distinct differences between N-terminal HSPC1 inhibitors, despite their common mode of action. Although treatment with each of the inhibitors results in significant induction of the anti-apoptotic proteins HSPA1A and HSPB1, sensitivity to HSPC1 inhibitors is not improved by gene silencing of HSPA1A or HSPB1. HSPC1 inhibitors potentiate the cytotoxic effects of chemotherapeutic agents in CRC, and this approach is readily available to enter clinical trials. From a translational point of view, there may be great variability in sensitivity to the inhibitors between individual patients.