A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis.

Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral blood. Although AML can occur at any age, the incidence peaks at age 65. The pathobiology of AML also varies with age with associated differences in incidence, as well as the frequency of cytogenetic change and somatic mutations. In addition, 5-year survival rates in paediatrics are 60-75% but fall to 5-15% in older AML patients. This systematic review aimed to determine whether the altered genes in AML affect the same molecular pathways, indifferent of patient age, and, therefore, whether patients could benefit from the repurposing drugs or the use of the same immunotherapeutic strategies across age boundaries to prevent relapse. Using a PICO framework and PRISMA-P checklist, relevant publications were identified using five literature databases and assessed against an inclusion criteria, leaving 36 articles, and 71 targets for therapy, for further analysis. QUADAS-2 was used to determine the risk of bias and perform a quality control step. We then priority-ranked the list of cancer antigens based on predefined and pre-weighted objective criteria as part of an analytical hierarchy process used for dealing with complex decisions. This organized the antigens according to their potential to act as targets for the immunotherapy of AML, a treatment that offers an opportunity to remove residual leukaemia cells at first remission and improve survival rates. It was found that 80% of the top 20 antigens identified in paediatric AML were also within the 20 highest scoring immunotherapy targets in adult AML. To analyse the relationships between the targets and their link to different molecular pathways, PANTHER and STRING analyses were performed on the 20 highest scoring immunotherapy targets for both adult and paediatric AML. There were many similarities in the PANTHER and STRING results, including the most prominent pathways being angiogenesis and inflammation mediated by chemokine and cytokine signalling pathways. The coincidence of targets suggests that the repurposing of immunotherapy drugs across age boundaries could benefit AML patients, especially when used in combination with conventional therapies. However, due to cost implications, we would recommend that efforts are focused on ways to target the highest scoring antigens, such as WT1, NRAS, IDH1 and TP53, although in the future other candidates may prove successful.

The mental health and well-being benefits of exercise during the COVID-19 pandemic: a cross-sectional study of medical students and newly qualified doctors in the UK.

BACKGROUND: University students have been uniquely affected by the COVID-19 pandemic. However, there is currently little data upon the measures that medical students and newly qualified doctors have taken to help their mental well-being and mood during the COVID-19 pandemic. AIM: We aimed to identify the activities respondents found beneficial for their well-being and mental health and recorded a mood score from survey respondents. METHODS: A nationwide study was completed to investigate the mental health impact of the COVID-19 pandemic upon medical students and newly qualified doctors (interim foundation year one). We received 2075 respondents from across the UK. RESULTS: Physical activity was found to be the most common activity used by the survey respondents to help with their mental well-being (80.1%) (medical students, 83.7%; interim foundation doctors, 72.3%). Participants who stated that exercise helped their well-being had a mean score (SD) of 52.3 (20.7) which was significantly higher (P = 0.048) than those who reported that they did not exercise (49.8 (21.1)). Respondents who stated they had used exercise to help with their mental well-being had (on average) a higher mood score than those who did not. This was seen in both the medical student and interim foundation doctor subgroups. DISCUSSION: Exercise can help to benefit the well-being of medical students and interim foundation doctors. It is hoped that higher education providers and employers recognise the importance of promoting physical activity for the well-being of their students and staff, respectively.