Ketorolac after free tissue transfer: a comparative effectiveness study.

OBJECTIVE: We sought to compare postoperative pain and complications in patients undergoing free tissue transfer for reconstruction of head and neck defects with and without ketorolac. METHODS: In this retrospective cohort study, we identified patients who underwent head and neck free tissue transfer procedures at the University of Iowa between July 2010 and December 2012. A subset of patients received ketorolac as an anti-platelet agent. Main outcome measures include postoperative analgesic use, pain scores, and bleeding complications. RESULTS: We identified 138 free tissue transfers, with 42 procedures in the ketorolac cohort. In the first 7 postoperative days, patients in the ketorolac and non-ketorolac cohorts received equivalent narcotic doses (morphine equivalents, 48.9 mg/day vs 46.6 mg/day, P = .72). The ketorolac group reported higher mean pain scores (3.1 vs 2.4, P = .004). Ketorolac use was not associated with need for transfusion (P = .86) or number of days with neck drains (P = .79). CONCLUSION: Ketorolac did not demonstrate a significant analgesic effect in this group of patients in terms of pain scores and opioid requirements. However, there also was no evidence to suggest a higher likelihood of bleeding complications. Ketorolac may be safely used as an anti-platelet agent, with narcotic requirements unchanged.

WNT5A mutations in patients with autosomal dominant Robinow syndrome.

Robinow syndrome is a skeletal dysplasia with both autosomal dominant and autosomal recessive inheritance patterns. It is characterized by short stature, limb shortening, genital hypoplasia, and craniofacial abnormalities. The etiology of dominant Robinow syndrome is unknown; however, the phenotypically more severe autosomal recessive form of Robinow syndrome has been associated with mutations in the orphan tyrosine kinase receptor, ROR2, which has recently been identified as a putative WNT5A receptor. Here, we show that two different missense mutations in WNT5A, which result in amino acid substitutions of highly conserved cysteines, are associated with autosomal dominant Robinow syndrome. One mutation has been found in all living affected members of the original family described by Meinhard Robinow and another in a second unrelated patient. These missense mutations result in decreased WNT5A activity in functional assays of zebrafish and Xenopus development. This work suggests that a WNT5A/ROR2 signal transduction pathway is important in human craniofacial and skeletal development and that proper formation and growth of these structures is sensitive to variations in WNT5A function.

Wnt5a is required for cardiac outflow tract septation in mice.

Lack of septation of the cardiac outflow tract (OFT) results in persistent truncus arteriosus (PTA), a form of congenital heart disease. The outflow myocardium expands through addition of cells originating from the pharyngeal mesoderm referred to as secondary/anterior heart field, whereas cardiac neural crest (CNC) cell-derived mesenchyme condenses to form an aortopulmonary septum. We show for the first time that a mutation in Wnt5a in mice leads to PTA. We provide evidence that Wnt5a is expressed in the pharyngeal mesoderm adjacent to CNC cells in both mouse and chicken embryos and in the myocardial cell layer of the conotruncus at the time when CNC cells begin to form the aortopulmonary septum in mice. Although expression domains of secondary heart field markers are not altered in Wnt5a mutant embryos, the expression of CNC cell marker PlexinA2 is significantly reduced. Stimulation of CNC cells with Wnt5a protein elicits Ca2+ transients, suggesting that CNC cells are capable of responding to Wnt5a. We propose a novel model in which Wnt5a produced in the OFT by cells originating from the pharyngeal mesoderm signals to adjacent CNC cells during formation of the aortopulmonary septum through a noncanonical pathway via localized intracellular increases in Ca2+.