Pediatric liver transplantation in Australia and New Zealand: The case for a collaborative anesthetic database.

BACKGROUND: Liver transplantation is conducted with strict oversight of organizational structure and clinical practice. However, specific regulations pertaining to the delivery of anesthetic services are lacking and consideration of departmental structure and mechanisms for quality control must occur at a local level. Busy centers collect and process sufficient data to guide this process but those with low case loads may not generate enough data for useful analysis. In Australia and New Zealand, pediatric liver transplants are performed at only four locations. As these operations are not equally distributed geographically or temporally there are periods of low activity at some centers. As anesthesia affects patient outcome, quality assurance activities are important in this setting. AIMS: Provide a global overview of the structure and function of liver transplantation networks. Identify issues related to provision of pediatric anesthetic services with specific reference to Australasia. Examine anesthetic data from a single pediatric center to illustrate benefits and limitations of such activity. METHODS: Pediatric liver transplant centers from Australia and New Zealand were surveyed to determine the organizational and logistical issues related to a liver transplant service. An audit of 15 years of liver transplants from a single center was conducted for benchmarking purposes and to identify changes in anesthetic practice over time. RESULTS: Pediatric liver transplants performed in Queensland from January 2005 to December 2019 were reviewed. Changes in transfusion practice reflected international trends. Morbidity and mortality were comparable to international data. Important complications such as hepatic artery and portal vein thrombosis were uncommon and did not generate enough data for further analysis. CONCLUSIONS: Combining the anesthetic liver transplant data from all sites in a single registry would expand data collection and generate broadly applicable findings. We propose the establishment of an Australasian pediatric anesthetic liver transplant database.

Intercellular Ca2+ wave propagation involving positive feedback between CRAC channels and cysteinyl leukotrienes.

Mast cells are key components of the immune system, where they help orchestrate the inflammatory response. Aberrant mast cell activation is linked to a variety of allergic diseases, including asthma, eczema, rhinitis, and nasal polyposis, which in combination affect up to 20% of the population in industrialized countries. On activation, mast cells release a variety of signals that target the bronchi and vasculature and recruit other immune cells to the inflammatory site. Prominent among such signals are the cysteinyl leukotrienes, a family of potent proinflammatory lipid mediators comprising leukotriene C(4) (LTC(4)), LTD(4), and LTE(4). LTC(4), the parent compound, is secreted from mast cells following Ca(2+) influx through store-operated calcium release-activated calcium (CRAC) channels. Here, we show that activated mast cells release a paracrine signal that evokes Ca(2+) signals in spatially separate resting mast cells. The paracrine signal was identified as a cysteinyl leukotriene because 1) RNAi knockdown or pharmacological block of the 5-lipoxygenase enzyme prevented activated mast cells from stimulating resting cells. 2) Block of cysteinyl leukotriene type I receptors on resting mast cells with the clinically prescribed receptor antagonist montelukast prevented their activation by active mast cells. 3) RNAi knockdown of cysteinyl leukotriene type I receptors on resting cells prevented them from responding to the paracrine signal derived from activated mast cells. 4) Purified LTC(4) evoked Ca(2+) signals in mast cells that were identical to those triggered by the paracrine signal. Low levels of stimulus intensity released sufficient levels of leukotriene to activate resting cells. Leukotriene secretion still occurred tens of minutes after stimulation, suggesting a role as a long-lasting trigger in mast cell activation. Stimulation of the cysteinyl leukotriene receptor activated CRAC channels and evoked prominent store-operated Ca(2+) entry. This resulted in further cysteinyl leukotriene production, triggering a positive feedback cascade. Acutely isolated mast cells from patients with allergic rhinitis exhibited store-operated Ca(2+) influx through CRAC channels and responded to cysteinyl leukotrienes. Histological analysis of samples taken from patients revealed clustering of mast cells, often located within 20 microm of each other, a distance sufficient for paracrine signaling by leukotrienes to operate effectively. We conclude that a positive-feedback cascade involving CRAC channels and cysteinyl leukotrienes constitute a novel mechanism for sustaining mast cell activation.