The role of heart rate variability in predicting delirium: A systematic review and meta-analysis.

Brain and heart interact through multiple ways. Heart rate variability, a non-invasive measurement is studied extensively as a predicting model for various health conditions including subarachnoid hemorrhage, cancer, and diabetes. There is limited evidence to predict delirium, an acute fluctuating disorder of brain dysfunction, as it poses a significant challenge in the intensive care unit (ICU) and post-operative setting. In this systematic review of 9 articles, heart rate variability indices were used to investigate the occurrence of post-operative and ICU delirium. This systematic review and meta-analysis reveal evidence of a strong predilection between postoperative and intensive care unit delirium and alterations in the heart rate variability, measured by mean differences for standard deviation of NN-intervals. Other heart rate variability indices [root mean squares of successive differences, low-frequency (LF), high-frequency (HF), and LF:HF ratio] showed lack of or very weak association. A non-invasive tool of brain and heart interaction may refine diagnostic predictions for acute brain dysfunctions like delirium in such population and would be an important step in delirium research.

Role of midazolam on cancer progression/survival - An updated systematic review.

Background and Aims: Cancer is a leading cause of mortality worldwide. Despite advancements in cancer management, cancer progression remains a challenge, requiring the development of novel therapies. Midazolam is a commonly used adjunct to anaesthesia care for various surgeries, including cancer. Recently, there has been a growing interest in exploring the potential role of midazolam as an anticancer agent; however, the exact mechanism of this linkage is yet to be investigated thoroughly. Methods: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, this systematic review presented aggregated evidence (till November 2022) of the effects of midazolam on cancer progression and survival. All primary research article types where midazolam was administered in vivo or in vitro on subjects with cancers were included. No restrictions were applied on routes of administration or the type of cancer under investigation. Narrative synthesis depicted qualitative findings, whereas frequencies and percentages presented numerical data. Results: Of 1720 citations, 19 studies were included in this review. All articles were preclinical studies conducted either in vitro (58%, 11/19) or both in vivo and in vitro (42%, 8/19). The most studied cancer was lung carcinoma (21%, 4/19). There are two main findings in this review. First, midazolam delays cancer progression (89%, 17/19). Second, midazolam reduces cancer cell survival (63%, 12/19). The two major mechanisms of these properties can be explained via inducing apoptosis (63%, 12/19) and inhibiting cancer cell proliferation (53%, 10/19). In addition, midazolam demonstrated antimetastatic properties via inhibition of cancer invasion (21%, 4/19), migration (26%, 5/19), or epithelial-mesenchymal transition (5%, 1/19). These anticancer properties of midazolam were demonstrated through different pathways when midazolam was used alone or in combination with traditional cancer chemotherapeutic agents. Conclusion: This systematic review highlights that midazolam has the potential to impede cancer progression and decrease cancer cell survival. Extrapolation of these results into human cancer necessitates further investigation.