Multi-organ abnormalities assessed by a single MRI scan in individuals with blood cancer.

BACKGROUND: During the COVID-19 pandemic individuals with all blood cancers were classified as clinically vulnerable and at high risk of complications and death. Our study sought to determine if individuals with specific blood cancers were at a heightened risk of longer term organ impairment, secondary to SARS-CoV-2 infection. METHODS: We set up a prospective observational study, utilising quantitative multi-parametric MRI to determine organ health over time in patients with specific blood cancers who had recovered from COVID-19. RESULTS: Multi-organ abnormality was more prevalent in blood cancer patients than in healthy controls (42 % vs 6 % p < 0.001) but comparable to the long COVID controls (42 % vs 33 %, p > 0.05). At 6 month follow up scans, organ abnormalities persisted in most individuals with blood cancer (71 % ≥1 organ and 52 % multi-organ). CONCLUSION: A multi-organ MRI platform offers the capacity to accurately evaluate organ health dynamically in blood cancers and detect asymptomatic organ impairment. The application of multi-organ MRI could aid early detection and longitudinal monitoring of organ impairment, potentially guiding more personalised treatment strategies and improving clinical outcomes in many rare diseases.

Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing.

Influenza A virus (IAV) infection is a global public health burden causing up to 650,000 deaths per year. Yearly vaccination programmes and anti-viral drugs currently have limited benefits; therefore, research into IAV is fundamental. Leukocyte trafficking is a crucial process which orchestrates the immune response to infection to protect the host. It involves several homing molecules and receptors on both blood vessels and leukocytes. A key mediator of this process is the transmembrane glycoprotein L-selectin, which binds to vascular addressins on blood vessel endothelial cells. L-selectin classically mediates homing of naïve and central memory lymphocytes to lymph nodes via high endothelial venules (HEVs). Recent studies have found that L-selectin is essential for homing of activated CD8+ T cells to influenza-infected lungs and reduction in virus load. A disintegrin and metalloproteinase 17 (ADAM17) is the primary regulator of cell surface levels of L-selectin. Understanding the mechanisms that regulate these two proteins are central to comprehending recruitment of T cells to sites of IAV infection. This review summarises the immune response to IAV infection in humans and mice and discusses the roles of L-selectin and ADAM17 in T lymphocyte homing during IAV infection.

The role and uses of antibodies in COVID-19 infections: a living review.

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity.

L-Selectin Enhanced T Cells Improve the Efficacy of Cancer Immunotherapy.

The homing molecule, L-selectin (CD62L), is commonly used as a T cell activation marker, since expression is downregulated following engagement of the T cell receptor. Studies in mice have shown that CD62L+ central memory T cells are better at controlling tumor growth than CD62L- effector memory T cells, while L-selectin knockout T cells are poor at controlling tumor growth. Here, we test the hypothesis that T cells expressing genetically modified forms of L-selectin that are maintained following T cell activation (L-selectin enhanced T cells) are better at controlling tumor growth than wild type T cells. Using mouse models of adoptive cell therapy, we show that L-selectin enhancement improves the efficacy of CD8+ T cells in controlling solid and disseminated tumor growth. L-selectin knockout T cells had no effect. Checkpoint blockade inhibitors synergized with wild type and L-selectin enhanced T cells but had no effect in the absence of T cell transfers. Reduced tumor growth by L-selectin enhanced T cells correlated with increased frequency of CD8+ tumor infiltrating T cells 21 days after commencing therapy. Longitudinal tracking of Zirconium-89 (89Zr) labeled T cells using PET-CT showed that transferred T cells localize to tumors within 1 h and accumulate over the following 7 days. L-selectin did not promote T cell homing to tumors within 18 h of transfer, however the early activation marker CD69 was upregulated on L-selectin positive but not L-selectin knockout T cells. L-selectin positive and L-selectin knockout T cells homed equally well to tumor-draining lymph nodes and spleens. CD69 expression was upregulated on both L-selectin positive and L-selectin knockout T cells but was significantly higher on L-selectin expressing T cells, particularly in the spleen. Clonal expansion of isolated L-selectin enhanced T cells was slower, and L-selectin was linked to expression of proliferation marker Ki67. Together these findings demonstrate that maintaining L-selectin expression on tumor-specific T cells offers an advantage in mouse models of cancer immunotherapy. The beneficial role of L-selectin is unrelated to its' well-known role in T cell homing and, instead, linked to activation of therapeutic T cells inside tumors. These findings suggest that L-selectin may benefit clinical applications in T cell selection for cancer therapy and for modifying CAR-T cells to broaden their clinical scope.

Preventing Suicide and Self-Harm.

BACKGROUND: Telephone helplines are considered to play an important role in preventing suicide and self-harm among callers in distress. However, inconsistency in the methods of evaluating such services has limited the firm conclusions that can be drawn. AIMS: To evaluate the efficacy of a UK-based helpline from a service user and helpline worker perspective. METHOD: Callers were asked about their mental state at the beginning and end of the call with a short questionnaire. Helpline workers were surveyed about their experiences of using the questionnaire as part of routine service provision. RESULTS: The helpline was successful at reducing suicidal and self-harming ideation. The short questionnaire method was also successfully integrated into routine practice. CONCLUSION: Evaluating the efficacy of helplines can be successfully achieved using the short questionnaire method.

Does a novel method of delivering the safe surgical checklist improve compliance? A closed loop audit.

BACKGROUND: In February 2010, the UK National Patient Safety Agency set a mandate that the World Health Organisation's Surgical Safety Checklist (SSC) should be completed for every surgical patient within the NHS in a bid to improve surgical safety. However since its introduction, there have been issues with checklist compliance, staff engagement and surgical serious incidents continue. AIMS: This study seeks to explore if an unavoidable pre-recorded audio delivery of the SSC improves compliance and staff engagement with the checklist. METHODS: The performance of the time-out and sign-out sections of the SSC were observed in three phases: standard practice, audio prompt and full audio delivery. Two researchers visited operating theatres throughout a three-week period. The outcome measures were occurrence of time-out/sign-out, completion of checklist, and presence, and engagement of staff during checklist administration. Staff feedback on the process was also sought. RESULTS: Observation of time-out and sign-out was undertaken for 92 procedures. Time-out and sign-out were performed for 100% of the procedures when using full audio delivery of the SSC, an improvement on findings during the standard practice phase (time out- 97.4%, sign out- 86.8%). The compliance with completion of checklist items also improved with audio delivery of the SSC. However, the presence of all key staff and active participation of team members with the checklist was unaffected by the mode of delivery. Team members' self-reported engagement did not significantly vary across the different practices. CONCLUSION: The intervention seems to improve rate of checklist completion, particularly signout. It also brought more consistency on the questions read out during checklist administration. It doesn't necessarily ensure all key staff are present neither does it significantly improve staff engagement in the process.