Postoperative virtual reality for recovery after bariatric surgery: study protocol for a randomised clinical trial.

Background: Enhanced Recovery After Surgery (ERAS) protocols for bariatric surgery improve clinical outcomes. However, the impact of ERAS protocols on patient satisfaction is unknown. Virtual reality has been implemented as an effective adjunct to standard analgesic regimens. This study seeks to find out if immersive virtual reality in the immediate postoperative period could improve the subjective quality of recovery and further reduce opioid requirements for bariatric surgery patients compared with ERAS care alone. Methods: This is a single-centre, randomised clinical trial of patients recovering from laparoscopic bariatric surgery. Once in the post-anaesthesia care unit (PACU), participants will receive either an immersive virtual reality plus ERAS protocol or ERAS protocol alone. The primary outcome will be the Quality of Recovery-15 (QoR-15) score at PACU discharge. Secondary outcomes include PACU opioid requirements, length of PACU stay, PACU pain scores, QoR-15 score on postoperative day 1, hospital length of stay, opioid requirements, and opioid-related adverse effects until hospital discharge. Conclusions: Positive findings from this study could introduce virtual reality as a non-pharmacological adjunct during PACU care that improves subjective recovery for patients undergoing bariatric surgery. Clinical trial registration: NCT04754165.

Rigosertib Induces Mitotic Arrest and Apoptosis in RAS-Mutated Rhabdomyosarcoma and Neuroblastoma.

Relapsed pediatric rhabdomyosarcomas (RMS) and neuroblastomas (NBs) have a poor prognosis despite multimodality therapy. In addition, the current standard of care for these cancers includes vinca alkaloids that have severe toxicity profiles, further underscoring the need for novel therapies for these malignancies. Here, we show that the small-molecule rigosertib inhibits the growth of RMS and NB cell lines by arresting cells in mitosis, which leads to cell death. Our data indicate that rigosertib, like the vinca alkaloids, exerts its effects mainly by interfering with mitotic spindle assembly. Although rigosertib has the ability to inhibit oncogenic RAS signaling, we provide evidence that rigosertib does not induce cell death through inhibition of the RAS pathway in RAS-mutated RMS and NB cells. However, the combination of rigosertib and the MEK inhibitor trametinib, which has efficacy in RAS-mutated tumors, synergistically inhibits the growth of an RMS cell line, suggesting a new avenue for combination therapy. Importantly, rigosertib treatment delays tumor growth and prolongs survival in a xenograft model of RMS. In conclusion, rigosertib, through its impact on the mitotic spindle, represents a potential therapeutic for RMS.

CASZ1 induces skeletal muscle and rhabdomyosarcoma differentiation through a feed-forward loop with MYOD and MYOG.

Embryonal rhabdomyosarcoma (ERMS) is a childhood cancer that expresses myogenic master regulatory factor MYOD but fails to differentiate. Here, we show that the zinc finger transcription factor CASZ1 up-regulates MYOD signature genes and induces skeletal muscle differentiation in normal myoblasts and ERMS. The oncogenic activation of the RAS-MEK pathway suppresses CASZ1 expression in ERMS. ChIP-seq, ATAC-seq and RNA-seq experiments reveal that CASZ1 directly up-regulates skeletal muscle genes and represses non-muscle genes through affecting regional epigenetic modifications, chromatin accessibility and super-enhancer establishment. Next generation sequencing of primary RMS tumors identified a single nucleotide variant in the CASZ1 coding region that potentially contributes to ERMS tumorigenesis. Taken together, loss of CASZ1 activity, due to RAS-MEK signaling or genetic alteration, impairs ERMS differentiation, contributing to RMS tumorigenesis.