Nerve stimulation guided bilateral pudendal nerve block versus landmark-based caudal block for hypospadias repair in young children: a prospective, randomized, pragmatic trial.

INTRODUCTION: Caudal block is frequently performed to provide analgesia for hypospadias repair. Literature suggests that pudendal block provides prolonged postoperative analgesia as compared with caudal block in children between 2 and 5 years. We compared the efficacy of pudendal and caudal blocks in children less than 2 years. METHODS: 60 children scheduled for hypospadias repair received standard general anesthesia along with either pudendal or caudal block (groups of 30 each). Variables collected were demographic data, block time, operating room time, intraoperative pain medication need, pain assessment score and medication need in the recovery room and pain assessment at home. RESULT: Groups were demographically similar. No differences were observed in the following recorded times (minutes): block procedure (caudal: 9.5±4.0, pudendal: 10.6±4.1, p=0.30), anesthesia (caudal: 17.3±5.3, pudendal: 17.7±4.3, p=0.75), total OR (caudal: 171±35, pudendal: 172±41; p=0.95) and postanesthesia care unit (PACU) stay (caudal: 88±37, pudendal: 86±42; p=0.80). Additionally, no differences were observed in rescue pain medication need in the operating room (caudal: 0, pudendal: 2 (p=0.49), in PACU (caudal: 4, pudendal: 4, p=0.99), pain assessed at home, time to pain level 2 (caudal: 13.93±8.9, pudendal: 15.17±8.7), average pain scores (p=0.67) and total pain free epochs (pain level of zero) (p=0.80) in the first 24 hours. DISCUSSION: In children less than 2 years, both blocks provide comparable intraoperative and postoperative pain relief in the first 24 hours after hypospadias surgery. TRIAL REGISTRATION NUMBER: NCT03145415.

Epithelial cells in fetal intestine produce chemerin to recruit macrophages.

Macrophages are first seen in the fetal intestine at 11-12 wk and rapidly increase in number during the 12- to 22-wk period of gestation. The development of macrophage populations in the fetal intestine precedes the appearance of lymphocytes and neutrophils and does not require the presence of dietary or microbial antigens. In this study, we investigated the role of chemerin, a recently discovered, relatively selective chemoattractant for macrophages, in the recruitment of macrophage precursors to the fetal intestine. Chemerin mRNA/protein expression was measured in jejunoileal tissue from 10- to 24-wk human fetuses, neonates operated for intestinal obstruction, and adults undergoing bariatric surgery. The expression of chemerin in intestinal epithelial cells (IECs) was confirmed by using cultured primary IECs and IEC-like cell lines in vitro. The regulatory mechanisms involved in chemerin expression were investigated by in silico and immunolocalization techniques. IECs in the fetal, but not mature, intestine express chemerin. Chemerin expression peaked in the fetal intestine at 20-24 wk and then decreased to original low levels by full term. During the 10- to 24-wk period, chemerin accounted for most of the macrophage chemotactic activity of cultured fetal IECs. The maturational changes in chemerin expression correlated with the expression of retinoic acid receptor-beta in the intestine. Chemerin is an important mediator of epithelial-macrophage cross talk in the fetal/premature, but not in the mature, intestine. Understanding the regulation of the gut macrophage pool is an important step in development of novel strategies to boost mucosal immunity in premature infants and other patient populations at risk of microbial translocation.

Developmental changes in circulating IL-8/CXCL8 isoforms in neonates.

Interleukin-8 (IL-8/CXCL8) is widely expressed in fetal tissues although inflammatory changes are not seen. Circulating IL-8 is comprised of an endothelial-derived [ala-IL-8](77) isoform and another, more potent [ser-IL-8](72) secreted by most other cells; [ala-IL-8](77) can be converted into [ser-IL-8](72) by proteolytic removal of an N-terminal pentapeptide from [ala-IL-8](77). In this study, we show [ala-IL-8](77) is the predominant circulating isoform of IL-8 in premature neonates but not in term neonates/adults, who have [ser-IL-8](72) as the major isoform. This isoform switch from the less potent [ala-IL-8](77) to [ser-IL-8](72) correlates with a maturational increase in the neutrophil chemotactic potency of plasma IL-8. The emergence of [ser-IL-8](72) as the major isoform is likely due to increased plasma [ala-IL-8](77)-convertase activity and/or changes in the cellular sources of IL-8. Developmental changes in IL-8 isoforms may serve to minimize its inflammatory effects in the fetus and also provide a mechanism to restore its full activity after birth.

Low intensity shear stress increases endothelial ELR+ CXC chemokine production via a focal adhesion kinase-p38{beta} MAPK-NF-{kappa}B pathway.

CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR(+) CXC chemokines) play an important role in leukocyte trafficking into the tissues. For reasons that are not well elucidated, circulating leukocytes are recruited into the tissues mainly in small vessels such as capillaries and venules. Because ELR(+) CXC chemokines are important mediators of endothelial-leukocyte interaction, we compared chemokine expression by microvascular and aortic endothelium to investigate whether differences in chemokine expression by various endothelial types could, at least partially, explain the microvascular localization of endothelial-leukocyte interaction. Both in vitro and in vivo models indicate that ELR(+) CXC chemokine expression is higher in microvascular endothelium than in aortic endothelial cells. These differences can be explained on the basis of the preferential activation of endothelial chemokine production by low intensity shear stress. Low shear activated endothelial ELR(+) CXC chemokine production via cell surface heparan sulfates, beta(3)-integrins, focal adhesion kinase, the mitogen-activated protein kinase p38beta, mitogen- and stress-associated protein kinase-1, and the transcription factor.