Research news in brief

Repeat liver transplantation in children is justified

REPEAT liver transplantation in children is justified on both medical and ethical grounds, according to potentially practice-changing research published online by the MJA. According to current guidelines, repeat liver transplantation is not routinely considered because of poorer recipient survival and the shortage of donor organs, but research led by Sir Charles Gairdner Hospital in Perth and the University of Western Australia has found that “survival for children following retransplantation is excellent”. The authors, led by Dr Angus Jeffrey from Sir Charles Gairdner, analysed data from the Australia and New Zealand Liver Transplant Registry for all liver retransplantations in children (under 18 years of age) in the two countries, between 1986 and 2017, in all four paediatric and six adult liver transplantation centres. During the study period, 142 liver retransplantations were undertaken in children (59 during 1986–2000, 83 during 2001–2017). Survival analysis indicated that survival was significantly greater during 2001–2017 than 1986–2000. During 2001–2017, graft survival one year after retransplantation was 84%, at 5 years 75%, at 10 years 70%, and at 15 years 54%; patient survival was 89% at one year, 87% at 5 years, 87% at 10 years, and 71% at 15 years. Median time between transplantations was 0.2 years during 1986–2000, 1.8 years during 2001–2017. The proportion of graft failures that involved split grafts was larger during 2001–2017 (35 of 83, 42%) than 1986–2000 (10 of 59, 17%). Graft type, cause of graft failure, and number of transplants did not influence survival following retransplantation. “We found that 15-year patient and graft survival for children following liver retransplantation during 2001–2017 were excellent,” Jeffrey and colleagues wrote. “Further, outcomes for patients in Australia and New Zealand receiving split liver grafts are similar to those for children receiving other graft types. Finally, graft and patient survival for the few children requiring multiple retransplantations were similar to those undergoing retransplantation only once. Our findings challenge views of the relative priority of children requiring first or subsequent liver transplants,” they concluded. “The routine use of split liver grafts in Australia and New Zealand has increased the supply of donor grafts for candidate recipients and reduced waiting list mortality. Accordingly, split liver grafts should be used for both first and subsequent transplantations in children, and organ allocation should be based solely on need, not on the number of grafts the child has previously received.”

New Australian melanoma management guidelines: the patient perspective

The involvement of patient advocates should ensure that new Australian melanoma management guidelines are rigorously patient-focused, according to the authors of a Perspective published online by the MJA. “In addition to clinicians and researchers, two patient advocates (consumer representatives), representing patients with melanoma from around Australia through their affiliations with patient advocacy and support networks, were invited to join the working party,” the authors wrote. “These patient advocates had personal experience of melanoma diagnosis and treatment and extensive prior involvement in melanoma advocacy. This meant that they were able to make important contributions based on their experience as well as providing feedback from the patient networks they represented.” While different stakeholders will use guidelines in different ways, they are intended to be useful to both clinicians and patients: to GPs, particularly those who work in skin cancer clinics; to dermatologists, who see many patients when they first present with a primary melanoma but who rarely manage patients with metastatic melanoma; to surgeons who treat patients with both primary and metastatic melanoma; to medical and radiation oncologists who are involved in the care of patients with metastatic disease; and importantly, to patients by providing a reliable source of information. “The ongoing involvement of patient advocates in the process of developing and updating the Australian melanoma guidelines should ensure that they are useful and relevant to patients and that the health care outcomes most valued by them are considered, resulting in guidelines that are rigorously patient-focused, as they should be,” the authors concluded.

No evidence of excess deaths in New Zealand and Australia due to pandemic

England, Wales and Spain experienced the highest numbers of excess deaths as a result of the COVID-19 pandemic from mid-February to May 2020, suggests a modelling study of 19 European countries and Australia and New Zealand, published in Nature Medicine. The results indicate that around 206 000 additional deaths occurred across these countries than were expected had the pandemic not occurred. The current COVID-19 pandemic has caused over 1 million deaths directly from SARS-CoV-2 infections globally. However, the indirect effects of the pandemic and responses to it through social, economic, environmental and health care pathways can also be substantial. Understanding the total impact of the pandemic on mortality is important for assessing its full impact on public health and policy responses. Majid Ezzati and colleagues used weekly data on deaths from 2010 to mid-February 2020, from 21 countries, to create a model that could predict how many deaths would have occurred by May 2020 had there not been a COVID-19 pandemic. They compared this figure with the actual reported deaths in the countries studied to calculate the excess deaths that resulted from the pandemic whether it was of COVID-19 or other causes. The authors estimate that an additional 206 000 deaths had occurred as a result of the pandemic in these 21 countries, with the highest figures for all-cause mortality per 100 000 people in Spain, England, Wales, Italy, Scotland and Belgium. The authors found that the numbers of excess deaths for men and women were similar, with 105 800 deaths in men and 100 000 deaths in women. They indicated that England, Wales and Spain experienced the largest increase in mortality, with nearly 100 excess deaths per 100 000 people, which was an increase of 37% for England and Wales and 38% for Spain, relative to levels without a pandemic. The authors conclude that the differences in mortality among the 21 countries reflect the variability in characteristics of the populations, policy responses to the pandemic, the preparedness of public health systems, and extent of community-based and facility-based care systems. They argue that in addition to suppressing transmission, building integrated care pathways to allow appropriate triage and care for those with long term health conditions will be important for minimising deaths resulting both directly and indirectly from the ongoing pandemic. To achieve this, countries may need to reallocate and expand health care resources, particularly in settings where there has been underinvestment in health and social care systems, they suggest. New Zealand and Australia had “no detectable excess deaths,” compared with a high mortality rate in England, Wales and Spain. In New Zealand, the authors found a small decline in the number of deaths among men below the age of 65 years, which they say may be due to fewer injuries.

Fats fighting back against bacteria

Droplets of fat inside cells are helping the body’s own defence system fight back against infection, University of Queensland (UQ) researchers have discovered. The international collaboration between UQ Institute for Molecular Bioscience researchers Professor Robert Parton and Professor Matt Sweet and the University of Barcelona’s Professor Albert Pol found that these fat droplets are both a food source and weapon against bacterial invaders. “It was previously thought that bacteria were merely using the lipid droplets to feed on, but we have discovered these fatty droplets are involved in the battle between the pathogens and our cells,” Professor Parton said. “Fat is part of the cell’s arsenal — cells manufacture toxic proteins, package them into the lipid droplets, then fire them at the intruders. This is a new way that cells are protecting themselves, using fats as a covert weapon, and giving us new insights into ways of fighting infection.” With antibiotic-resistant superbugs on the rise, researchers are determined to find alternative ways to fight infection. One possibility is ramping up the body’s natural defences. “We showed that upon infection of white blood cells called macrophages, lipid droplets move to the part of the macrophage where the bacteria are present,” Professor Sweet said. The bacterial infection also changed the way that white blood cells used energy. “Lipid droplets can be used as a fuel source for mitochondria when there aren’t enough other nutrients,” Professor Sweet said. “During an infection, lipid droplets move away from the mitochondria and attack the bacteria instead, altering the metabolism of the cell.” Cell biologist Professor Parton was inspired to continue this research after the phenomenon was seen in fruit flies. “Most people thought the lipid droplets were ‘blobs of fat’, only useful for energy storage but now we are seeing that they act as metabolic switches in the cell, defend against infection and much more — there are now entire scientific conferences of researchers working on them,” he said. “Our next step is to find out how the lipid droplets target the bacteria. By understanding the body’s natural defences, we can develop new therapies that don’t rely on antibiotics to fight drug-resistant infections.” The research is published in Science.