A guide to senolytic intervention in neurodegenerative disease.

Cellular senescence is a potential tumor-suppressive mechanism that generally results in an irreversible cell cycle arrest. Senescent cells accumulate with age and actively secrete soluble factors, collectively termed the 'senescence-associated secretory phenotype' (SASP), which has both beneficial and detrimental effects. Although the contribution of senescent cells to age-related pathologies has been well-established outside the brain, emerging evidence indicates that brain cells also undergo cellular senescence and contribute to neuronal loss in the context of age-related neurodegenerative diseases. Contribution of senescent cells in the pathogenesis of neurological disorders has led to the possibility of eliminating senescence cells via pharmacological compounds called senolytics. Recently several senolytics have been demonstrated to elicit improved cognitive performance and healthspan in mouse models of neurodegeneration. However, their translation for use in the clinic still holds several potential challenges. This review summarizes available senolytics, their purported mode of action, and possible off-target effects. We also discuss possible alternative strategies that may help minimize potential side-effects associated with the senolytics approach.

Programmed Intermittent Bolus Regimen for Erector Spinae Plane Blocks in Children: A Retrospective Review of a Single-Institution Experience.

With few published reports on erector spinae plane block use in children, limited guidance on perioperative local anesthetic dosing exists. We present a series of 22 patients who received erector spinae plane catheters with programmed intermittent bolus for various surgeries. Median loading dose of 0.4 mL/kg (interquartile range [IQR], 0.1 mL/kg) ropivacaine 0.5%, intraoperative bolus of 0.3 mL/kg/h (IQR, 0.1 mL/kg) ropivacaine 0.2%, and a postoperative programmed intermittent bolus regimen of maximum 0.6 mg/kg/h resulted in highest pain scores on postoperative day 1 with a median score of 1.7 of 10 (IQR, 1.8) and highest morphine equivalents consumed on postoperative day 2 with a median score of 0.16 mg/kg up to 120 hours after surgery.

A Postoperative Care Bundle Reduces Surgical Site Infections in Pediatric Patients Undergoing Cardiac Surgeries.

BACKGROUND: Pediatric patients undergoing cardiac surgeries are at an increased surgical site infection (SSI) risk, given prolonged cardiopulmonary bypasses and delayed sternal closures. At one institution, the majority of cardiac patients developed SSIs during prolonged recoveries in the cardiovascular intensive care unit (CVICU). Although guidelines have been published to reduce SSIs in the perioperative period, there have been few guidelines to reduce the risk during prolonged hospital recoveries. The aim of this project was to study a postoperative SSI reduction care bundle, with a goal of reducing cardiac SSIs by 50%, from 3.4 to 1.7 per 100 procedures. METHODS: This project was conducted at a quaternary, pediatric academic center with a 20-bed CVICU. Historical control data were recorded from January 2013 through May 2015 and intervention/sustainment data from June 2015 through March 2017. A multidisciplinary SSI reduction team developed five key drivers that led to implementation of 11 postoperative SSI reduction care elements. Statistical process control charts were used to measure process compliance, and Pearson's chi-square test was used to determine differences in SSI rates. RESULTS: Prior to implementation, there were 27 SSIs in 799 pediatric cardiac surgeries (3.4 SSIs per 100 surgeries). After the intervention, SSIs significantly decreased to 5 in 570 procedures (0.9 SSIs per 100 surgeries; p = 0.0045). CONCLUSION: This project describes five key drivers and 11 elements that were dedicated to reducing the risk of SSI during prolonged CVICU recoveries from pediatric cardiac surgery, with demonstrated sustainability.