What Italian PICU Healthcare Providers Think About Donation After Cardiocirculatory Determination of Death: A National Survey.

BACKGROUND: Italy presently does not have a pediatric organ donation program after cardiocirculatory determination of death (pDCDD). Before implementing a pDCDD program, many centers globally have conducted studies on the attitudes of pediatric intensive care unit (PICU) staff. This research aims to minimize potential adverse reactions and evaluate the acceptance of the novel donation practice. METHODS: We conducted an electronic and anonymous survey on attitudes toward pDCDD among healthcare professionals (HCPs) working at eight Italian PICUs. The survey had three parts: (I) questions about general demographic data; (II) 18 statements about personal wishes to donate, experience of discussing donation, and knowledge about donation; (III) attitudinal statements regarding two pediatric Maastricht III scenarios of organ donation. RESULTS: The response rate was 54.4%, and the majority of respondents were nurses. Of those who responded, 45.3% worked in the Center, 40.8% in the North, and 12.8% in the South of Italy. In total, 93.9% supported pediatric organ and tissue donation, 90.3% supported donation after neurological determination of death (DNDD), 78.2% supported pDCDD, and 69.7% felt comfortable about the idea of participating in pDCDD on Type III patients, with a higher percentage of supportive responses in the Center (77.2%) than in the North (65.1%) and South (54.5%) of Italy (p-value < 0.004). Concerning scenarios, 79.3% of participants believed that organ retrieval took place in a patient who was already deceased. Overall, 27.3% considered their knowledge about DCDD to be adequate. CONCLUSIONS: Our study provides insight into the attitudes and knowledge of PICU staff members regarding pDCDD in Italy. Despite a general lack of knowledge on the subject, respondents showed positive attitudes toward pDCDD and a strong consensus that the Italian legislation protocol for determining death based on cardiocirculatory criteria respects the "dead donor rule." There were several distinctions among the northern, central, and southern regions of Italy, and in our view, these disparities can be attributed to the varying practices of commemorating the deceased. In order to assess how practice and training influence the attitude of PICU staff members, it would be interesting to repeat the survey after the implementation of a program.

Mobile Extracorporeal Membrane Oxygenation Teams for Organ Donation After Circulatory Death.

The shortage of available organ donors is a significant problem worldwide, and various efforts have been carried out to avoid the loss of potential organ donors. Among them, organ donation from cardiocirculatory deceased donors (DCD), in which withdrawal of life-sustaining therapies is ongoing (Maastricht type III donors), is one emerging strategy. Thanks to the latest advances in transplantation and organ preservation, such as normothermic regional perfusion (NRP), ex vivo perfusion techniques, and good organization and communication among prehospital care providers, emergency departments, intensive care units, and transplantation units, DCD is rapidly increasing; it's estimated that it will increase the number of donations of lungs and splanchnic organs by more than 40%. Although Maastricht type II DCD requires a 24/7 available experienced extra corporeal membrane oxygenation (ECMO) team in the institution, Maastricht DCD type III could be organized in secondary care and spoke hospitals without in loco ECMO facilities for NRP. This article analyses a potential mobile team organization based on the hub-and-spoke model, which already exists and functions in Italy, by estimating the dimension of the controlled DCD phenomenon in Italy, coordination requirements, costs, personnel training, and education, and reporting a single center experience in Milan, Italy.

Redundant and antagonistic functions of galectin-1, -3, and -8 in the elicitation of T cell responses.

Galectins, a family of mammalian lectins, have emerged as key regulators of the immune response. We previously demonstrated that galectin (Gal)-8, from the tandem-repeat subgroup, exerts two well-defined effects on mouse naive peripheral CD4 T cells: Ag-specific costimulation and Ag-independent proliferation. These stimulatory signals on naive T cells have not been described for any other Gal. Therefore, we investigated whether Gal-1 and Gal-3, two prominent members of the Gal family, share the stimulatory effects exerted by Gal-8 on naive T cells. We found that Gal-1 costimulated Ag-specific T cell responses similarly to Gal-8, as evaluated in the DO11.10 TCR(OVA)-transgenic mouse model, by acting simultaneously on APCs and target CD4 T cells. In contrast, Gal-3 failed to costimulate Ag-specific T cell responses; moreover, it antagonized both Gal-1 and Gal-8 signals. We observed that both Gal-1 and Gal-3 were unable to induce Ag-independent proliferation; however, when two Gal-1 molecules were covalently fused, the resulting chimeric protein efficiently promoted proliferation. This finding indicates that Gal-1 might eventually induce proliferation and, moreover, stresses the requirement of a tandem-repeat structure. Remarkably, a single dose of recombinant Gal-1 or Gal-8 administered together with a suboptimal Ag dose to DO11.10 mice strengthened weak responses in vivo. Taken together, these findings argue for the participation of Gals in the initiation of the immune response and allow the postulation of these lectins as enhancers of borderline Ag responses, thus representing potential adjuvants for vaccine formulations.

Pharmacokinetics of orally administered melatonin in critically ill patients.

Critically ill patients exhibit reduced melatonin secretion, both in nocturnal peaks and basal daytime levels. Oral melatonin supplementation may be useful for known sedative and antioxidant properties. Its early enteral absorption and daily pharmacokinetics were determined in two cohorts of six high-risk patients in this prospective trial. During their third and fourth Intensive Care Unit (ICU) day, they underwent two different sets of repeated blood samples to detect serum melatonin levels through radio-immuno-assay. Cohort 1: samples taken at 20:00, 20:45, 21:30, 24:00, 03:00, 06:00, 14:00, 20:00 to describe the daily pharmacokinetics. Cohort 2: 20:00, 20:05, 20:10, 20:20, 20:30, 20:45 to study the early absorption. On ICU day 3, endogenous levels were measured, while the absorption of exogenous melatonin was determined on ICU day 4 after administration, at 20:00, of 3 mg melatonin. All basal levels were below the expected values. Following enteral administration, pharmacological levels were already reached in 5 min, with a serum peak after 16 min (half-absorption time: 3 min 17 s). The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half-elimination time of 1 hr 34 min. Serum melatonin levels decreased significantly after midnight; pharmacological levels were maintained up to 10 hr following administration. No excessive sleepiness was reported in this patient group. Critically ill patients exhibited reduced melatonin secretion, as reported in the literature. Despite the critical illness, the oral bioavailability was satisfactory: serum levels after oral administration showed basically unchanged intestinal absorption, while disappearance rate was slower than reported elsewhere in healthy volunteers.