Medical management of newborn infants often necessitates recurrent painful procedures, which may alter nociceptive pathways during a critical developmental period and adversely effect neuropsychological outcomes. To mitigate the effects of repeated painful stimuli, opioid administration for peri-procedural analgesia and ICU (intensive care unit) sedation is common in the NICU (neonatal intensive care unit). A growing body of basic and animal evidence suggests potential long-term harm associated with neonatal opioid therapy. Morphine increases apoptosis in human microglial cells, and animal studies demonstrate long-term changes in behavior, brain function, and spatial recognition memory following morphine exposure. This comprehensive review examines existing preclinical and clinical evidence on the long-term impacts of neonatal pain and opioid therapy.

Epidural analgesia resulted in substantial improvements in pain control and safety. The data supports the superiority of a multimodal analgesia approach centered on epidural analgesia. A similar protocol should be considered following simple laminectomies or procedures associated with lower-extremity muscle spasm.

Medical records of three male and three female callitrichids of four species (Leontopithecus chrysopygus, Leontopithecus rosalia, Callithrix argentata argentata, Callithrix kuhlii) diagnosed with cholelithiasis were reviewed. Ages of affected animals at the time of diagnosis ranged from 2-14 yr. Definitive antemortem diagnosis of cholelithiasis was made in four of the six cases. Chronic weight loss, lethargy, and weakness were seen in all cases. Chronic intermittent diarrhea was seen in three cases. Icterus and abnormal gait were each present in two of the animals. Hematologic and serum biochemical abnormalities included leukocytosis in five cases, elevated bilirubin (direct and indirect) in four cases, and anemia in four cases. Radiographic evidence of choleliths was observed in three cases. Surgical removal of choleliths was successfully performed on two animals. Full necropsies were performed on all cases, and choleliths were believed to contribute to morbidity in all cases. However, inflammatory bowel disease was determined to be the primary cause of weight loss and mortality in at least three animals. All choleliths analyzed were pigment stones, two being primarily composed of cystine.

ObjectivePediatric liver transplantation presents a number of anesthetic challenges, especially in providing adequate perioperative analgesia. In an effort to reduce opioid consumption and improve functional outcomes following pediatric liver transplantation, we have instituted a novel analgesia protocol centered on the provision of continuous regional analgesia with erector spinae plane (ESP) blockade.CasesWe describe preincisional bilateral ESP catheter placement in two pediatric patients undergoing orthotopic liver transplantation. The first case was a 12-year-old boy with maple syrup urine disease undergoing initial transplantation and the second case was an 8-year-old boy who underwent an 11 hours complex redo liver transplant in the setting of glycogen storage disease type 1A requiring initial liver transplant in 2014. The 8-year-old boy presented to the operating suite with acute Budd-Chiari syndrome with comorbid ascites and a large right pleural effusion. In both cases, ESP blockade resulted in good analgesia, markedly reduced intraoperative and postoperative opioid consumption as compared with institutional data and published rates of consumption and was associated with rapid return of bowel function.ConclusionsThese early experiences suggest a role for continuous ESP blockade to improve analgesia and potentially change the paradigm of treatment in this fragile patient population. The technique should be considered in similar interventions. Further study will be undertaken to validate our observation.

GZ17-6.02 is presently undergoing clinical evaluation in solid tumors and lymphoma. The present studies were performed to define its biology in estrogen receptor positive breast cancer cells and to determine whether it interacted with palbociclib to enhance tumor cell killing. GZ17-6.02 interacted in an additive fashion with palbociclib to kill ER+ breast cancer cells. GZ17-6.02 and palbociclib cooperated to inactivate mTOR and AKT and to activate ULK1 and PERK. The drugs interacted to increase the expression of FAS-L and BAX, and to decrease the levels of MCL1, the estrogen receptor, and HDACs 1-3. Palbociclib activated ERBB3, an effect blocked by GZ17-6.02. GZ17-6.02 and palbociclib interacted to increase the expression of multiple toxic BH3 domain proteins and to reduce MCL1 and BCL-XL expression. Knock down of FAS-L reduced the lethality of [GZ17-6.02 + palbociclib]. GZ17-6.02 and palbociclib interacted to enhance autophagosome formation and autophagic flux. Knock down of Beclin1, ATG5, BAG3, eIF2α, toxic BH3 domain proteins or CD95 significantly reduced drug combination lethality. GZ17-6.02 and palbociclib increased the expression of Beclin1 and ATG5, effects blocked by knock down of eIF2α. The drugs also increased the phosphorylation of the AMPK and ATG13, effects blocked by knock down of ATM. Knock down of ATM or the AMPK, or expression of activated mTOR significantly reduced the abilities of GZ17-6.02 and palbociclib to enhance autophagosome formation and autophagic flux.