Intravenous fluid therapy: an audit and discussion of improvements required for prescribers and administrators.

BACKGROUND: Foundation doctors and nurses are the clinicians most closely involved in fluid assessment, intravenous (IV) fluid prescription and administration. However, both groups report challenges regarding IV fluids. At a large NHS trust in England, adherence to the National Institute for Health and Care Excellence (NICE) guideline CG174, regarding IV fluids, was largely unknown. AIMS: To assess the baseline adherence, within the hospitals, to CG174 and identify areas for improvement. METHODS: A set of 12 audit standards were developed and used to collect data across 29 clinical areas between September 2022 and May 2023, with 255 patients receiving IV fluids at any time during their inpatient stay included. FINDINGS: For two standards target adherence of 95% was achieved, with an adherence less than 50% in most. Areas of particularly poor adherence included assessing and meeting fluid and electrolyte requirements, patient reassessment and developing IV fluid management plans. CONCLUSION: Trust baseline adherence to NICE CG174 requires improvement, particularly regarding patient assessment and reassessment, and meeting electrolyte requirements.

Ruthenium drug BOLD-100 regulates BRAFMT colorectal cancer cell apoptosis through AhR/ROS/ATR signaling axis modulation.

Patients with class I V600EBRAF-mutant (MT) colorectal cancer (CRC) have a poor prognosis and their response to combined anti-BRAF/EGFR inhibition remains limited. There is clearly an unmet need in further understanding the biology of V600EBRAFMT CRC. We have used differential gene expression of BRAFWT and MT CRC cells to identify pathways underpinning BRAFMT CRC. We tested a panel of molecularly/genetically subtyped CRC cells for their sensitivity to the Unfolded Protein Response (UPR) activator BOLD-100. To identify novel combination strategies for BOLD-100, we performed RNA sequencing and high-throughput drug screening. Pathway enrichment analysis identified that the UPR and DNA repair pathways were significantly enriched in BRAFMT CRC. We found that oncogenic BRAF plays a crucial role in mediating response to BOLD-100. Using a systems biology approach, we identified V600EBRAFMT-dependent activation of the replication stress response kinase ATR as a key mediator of resistance to BOLD-100. Further analysis identified acute increases in BRAFMT-dependent-reactive oxygen species (ROS) levels following treatment with BOLD-100 that was demonstrated to promote ATR/CHK1 activation and apoptosis. Furthermore, activation of ROS/ATR/CHK1 following BOLD-100 was found to be mediated through the AHR transcription factor and CYP1A1. Importantly, pharmacological blockade of this resistance pathway with ATR inhibitors synergistically increased BOLD-100-induced apoptosis and growth inhibition in BRAFMT models. These results unveil possible novel therapeutic opportunity for BRAFMT CRC. Implications: BOLD-100 induces BRAFMT-dependent replication stress, and targeted strategies against replication stress (eg. by using ATR inhibitors) in combination with BOLD-100 may serve as a potential novel therapeutic strategy for clinically aggressive BRAFMT CRC.

Electronic alerts in acute kidney injury: why does evidence of benefit remain elusive?

PURPOSE OF REVIEW: Acute kidney injury (AKI) is a common syndrome characterized by a sudden reduction in kidney function. It is strongly associated with high mortality and longer, more expensive hospital stays. As AKI often presents silently, a lack of recognition can prevent recommended standards of care. Over the last decade or more, electronic alerts (eAlerts) for AKI have been studied and implemented to address this. This review will summarize the major randomized trials in this area. RECENT FINDINGS: A number of randomized trials now exist that study the effectiveness of AKI eAlerts in isolation or as part of more complex interventions. Varying results arise from differences in study design, healthcare system in which the eAlert is introduced, nature of alert, supporting interventions, implementation plan, stated aim (prevention or treatment of established AKI) and choice of outcome measures. SUMMARY: Current randomized trial evidence does not show any benefit of eAlerts on mortality. However, variously reported reductions in AKI incidence, AKI progression and AKI duration support a conclusion that strategies incorporating eAlerts can meaningfully benefit delivery of AKI care. Future work should consider how best eAlerts can be utilised, targeted and implemented.