Introduction Regional techniques are a key component of multimodal analgesia and help decrease opioid use perioperatively, but some techniques may not be suitable for all patients, such as those with spina bifida. We hypothesized peripheral regional catheters would reduce postoperative opioid use compared with no regional analgesia without increasing pain scores in pediatric patients with spina bifida undergoing major urological surgery. Methods A retrospective review of a multicenter database established for the study of enhanced recovery after surgery was performed of patients from 2009 to 2021 who underwent bladder augmentation or creation of catheterizable channels. Patients without spina bifida and those receiving epidural analgesia were excluded. Opioids were converted into morphine equivalents and normalized to patient weight. Results 158 patients with pediatric spina bifida from 7 centers were included, including 87 with and 71 without regional catheters. There were no differences in baseline patient factors. Anesthesia setup increased from median 40 min (IQR 34–51) for no regional to 64 min (IQR 40–97) for regional catheters (p<0.01). The regional catheter group had lower median intraoperative opioid usage (0.24 vs 0.80 mg/kg morphine equivalents, p<0.01) as well as lower in-hospital postoperative opioid usage (0.05 vs 0.23 mg/kg/day morphine equivalents, p<0.01). Pain scores were not higher in the regional catheters group. Discussion Continuous regional analgesia following major urological surgery in children with spina bifida was associated with a 70% intraoperative and 78% postoperative reduction in opioids without higher pain scores. This approach should be considered for similar surgical interventions in this population. Trial registration number NCT03245242.

Pediatric regional anesthesia is evolving with new peripheral nerve blocks and techniques aimed at improving perioperative pain management. While caudal blocks have long been standard due to their simplicity and low complication rates, newer fascial plane blocks offer comparable efficacy with enhanced nerve coverage tailored to specific surgeries. Moreover, adjuncts like dexmedetomidine and dexamethasone have shown promise in prolonging block duration and enhancing post-operative pain relief and patient satisfaction. The integration of these advancements into clinical practice has yielded significant benefits, including reduced intraoperative fluid requirements, decreased reliance on opioids postoperatively, earlier initiation of enteral nutrition, lower readmission rates, shorter hospital stays, and decreased overall hospital costs. Our review underscores the technical progress and expanding literature supporting the rapid adoption of these impactful regional anesthesia techniques in pediatric care.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Laurence Booth1, Cameron West2, Robert P. Moore2, Daniel Von Hoff3 and Paul Dent1 1 Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA 2 Genzada Pharmaceuticals, Sterling, KS 67579, USA 3 Physician-in-Chief, Distinguished Professor, Translational Genomics Research Institute (TGEN), Phoenix, AZ 85004, USA Correspondence to: Paul Dent, email: paul.dent@vcuhealth.org Keywords: GZ17-6.02; axitinib; renal cell carcinoma; autophagy; HDAC Received: December 09, 2021 Accepted: January 25, 2022 Published: February 04, 2022 Copyright: © 2022 Booth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT GZ17-6.02 is undergoing clinical evaluation in solid tumors and lymphoma. The present studies were performed to define its biology in renal carcinoma cells and to determine whether it interacted with axitinib to enhance tumor cell killing. GZ17-6.02 interacted in an arithmetically greater than additive fashion with axitinib to kill kidney cancer cells. GZ17-6.02 and axitinib cooperated to inactivate ERBB2, c-MET, c-KIT, c-SRC, the AMPK, STAT3, STAT5 and eIF2α and to activate PERK, ULK1 and ATG13. The drugs interacted to increase the expression of FAS-L and to decrease the levels of MCL1, BCL-XL, and HDACs 1–3. The drugs as single agents inactivated the Hippo pathway. GZ17-6.02 and axitinib interacted to enhance autophagosome formation and autophagic flux. Knock down of Beclin1, ATG5, eIF2α, toxic BH3 domain proteins or CD95/FADD significantly reduced drug combination lethality. GZ17-6.02 and axitinib increased the expression of BAK, BIM, Beclin1 and ATG5, effects blocked by knock down of eIF2α. The drugs increased phosphorylation of ULK1 S757 and ATG13 S318 and decreased the phosphorylation of mTORC1 and mTORC2, effects blocked by knock down of AMPKα. Knock down of Beclin1 or ATG5 prevented the drug combination reducing expression of HDACs 1–3 and from enhancing the expression of MHCA. Knock down of HDACs 1–3 enhanced MHCA expression. We conclude that GZ17-6.02 and axitinib interact to kill requiring ER stress signaling, autophagy and death receptor signaling. Autophagic degradation of HDACs played a key role in enhancing MHCA expression and of a potential improved response to checkpoint inhibitory immunotherapy. <!--x2o[c3ff2785]-->

Compared to the adult literature, there are few enhanced recovery after surgery (ERAS) protocols standardized in the pediatric population. The objective of the current study is to determine if the implementation of an ERAS protocol would improve patient outcomes in the ambulatory pediatric urologic population. A retrospective analysis was performed on pediatric patients who underwent urologic procedures (circumcision, orchiopexy, hypospadias correction, and urethroplasty) in the ambulatory surgical setting affiliated with a tertiary pediatric hospital. Outcomes measured include opioid use, home pain control, time in recovery, need for rescue pain medications, and adverse events between pediatric patients receiving standard of care (n = 30) and pediatric patients receiving the ERAS protocol (n = 29). The application of the ERAS pathway led to significantly increased opioid‐free care (7% vs. 43%, p < 0.01). There was a reduction in the cost of care, a trend toward reduced opioid use, a trend toward reduced PACU stays for ERAS patients, and families of ERAS patients reported a 100% rate of well‐controlled pain at home. These changes occurred without any increased need for rescue pain medications (16% vs. 13%, p = 1) or any change in adverse events (0% vs. 0%, p = 1.0). Postoperative pain measures are improved in pediatric patients receiving the ERAS protocol in an ambulatory surgery setting when compared to patients receiving the standard of care, without an increased risk of adverse events or the need for rescue analgesia. Therefore, this work serves as a proof of concept that ERAS protocols can improve postoperative outcomes in the pediatric ambulatory surgical population.