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Predicting when a patient with advanced cancer is dying is a challenge and currently no prognostic test is available. We hypothesised that a dying process from cancer is associated with metabolic changes and specifically with changes in volatile organic compounds (VOCs). We analysed urine from patients with lung cancer in the last weeks of life by headspace gas chromatography mass spectrometry. Urine was acidified or alkalinised before analysis. VOC changes in the last weeks of life were identified using univariate, multivariate and linear regression analysis; 12 VOCs increased (11 from the acid dataset, 2 from the alkali dataset) and 25 VOCs decreased (23 from the acid dataset and 3 from the alkali dataset). A Cox Lasso prediction model using 8 VOCs predicted dying with an AUC of 0.77, 0.78 and 0.85 at 30, 20 and 10 days and stratified patients into a low (median 10 days), medium (median 50 days) or high risk of survival. Our data supports the hypothesis there are specific metabolic changes associated with the dying. The VOCs identified are potential biomarkers of dying in lung cancer and could be used as a tool to provide additional prognostic information to inform expert clinician judgement and subsequent decision making.

Inflammatory Bowel Disease (IBD) is an incurable, chronic, gastrointestinal condition that can constrain young people’s social relationships. Few studies have specifically explored friendships of people with IBD. This qualitative, participatory study used interviews, photographs, and friendship maps to explore friendships and friendship networks of young people with IBD. A Young Person’s Advisory Group was actively engaged throughout the study. Thirty-one young people participated (n=16 male, n=15 female; n=24 Crohn’s, n=7 colitis; mean age at study was 18.7 years; range 14-25 years). Findings present a meta-theme ‘The importance and meaning of friendships’ and three interwoven sub-themes of ‘Sustaining friendships’, ‘Forming new friendships’, and ‘Letting go of friendships’. Friendship was important to the young people with IBD, providing support, but associated with challenges such as disclosure. Such challenges could be mitigated by clearer conversations with clinicians about friendships and more extensive conversations about friendships and long-term conditions in education settings.

Purpose. Adolescents and young adults (AYA) with Inflammatory Bowel Disease (IBD) report higher depressive symptoms and anxiety compared to healthy controls, with disease severity and abdominal pain being important factors. In the current study, building on what young people had told us in our previous work, we examined whether embarrassment of the condition, social self-efficacy, and friendship quality mediated the relationship between abdominal pain and disease severity, and mental health/well-being. We also included loneliness as a component of well-being. Methods. Data on depression, anxiety, loneliness, friendship quality, social self-efficacy, and disease embarrassment were collected from 130 AYA ages 14-25 years; data on disease severity and abdominal pain were taken from their medical records. Structural Equation Modeling (SEM) was used to test the relationships between the variables. Results. Using SEM, we established that higher IBD disease activity negatively impacted how AYA felt about their friendships and how embarrassed they were about their condition; embarrassment then influenced reports of mental health, including loneliness. Abdominal pain, disease onset, and social self-efficacy directly predicted internalising problems. Conclusion. In this sample of 14-25 years old patients with IBD, specifics about the disease (severity and pain) predicted poorer mental health, suggesting discussion of mental health should be part of the clinical dialogue between patient and consultant. In addition, embarrassment about their condition increased depression, anxiety, and loneliness, mediating the relationship between disease severity and well-being. Thus, it is important to consider how perceived stigma affects those with chronic illness, and those issues should be explored in clinic.

Inflammatory Bowel Disease (IBD) describes a group of conditions that includes Crohn’s disease and ulcerative colitis. Unlike some chronic conditions, to a greater or lesser extent, IBD is hidden from or invisible to others which enables concealment of the condition, especially when stigma is associated with the condition. Concealment or nondisclosure allows a means of identity management. Disclosure of a chronic condition is not a single event, and it is dependent on many factors. There is little literature that specifically addresses stigma and/or disclosure in relation to children and young people with IBD. An in-depth qualitative study was undertaken, framed by Interpretive Description and using interviews, friendship maps, and photographs within a participatory framework. Public and patient involvement and engagement (PPIE) was undertaken throughout (inception to dissemination) the study. Young people aged 14-25 years with IBD who had participated in the survey phase of the larger study self-selected to participate in interviews that focused broadly on friendship and feelings of social connectedness. Data were analysed using an iterative, interpretive approach. Preliminary themes were developed and these were explored further, and then tentative theoretical connections about friendship were developed. One superordinate theme focused on disclosure. Thirty-one young people (16 males, 15 females, mean age 18.7 years; 24 Crohn’s, 7 colitis) participated in the interviews (of these, five created friendship maps and six utilised photographs). Three discrete, but interlinked, themes were generated, revealing young people’s experiences of disclosure: to tell or not to tell; controlling the flow: the who, when, what, and how of telling; and reactions and responses to telling: anticipated and actual. Decisions about telling friends about having IBD are challenging for many young people. Having control over disclosure is not always possible, and the potential consequences

The heterogeneous nature of inflammatory bowel disease (IBD) presents challenges, particularly when choosing therapy. Activation of the NF-κB transcription factor is a highly regulated, dynamic event in IBD pathogenesis. Using a lentivirus approach, NF-κB-regulated luciferase was expressed in patient macrophages, isolated from frozen peripheral blood mononuclear cell samples. Following activation, samples could be segregated into three clusters based on the NF-κB-regulated luciferase response. The ulcerative colitis (UC) samples appeared only in the hypo-responsive Cluster 1, and in Cluster 2. Conversely, Crohn's disease (CD) patients appeared in all Clusters with their percentage being higher in the hyper-responsive Cluster 3. A positive correlation was seen between NF-κB-induced luciferase activity and the concentrations of cytokines released into medium from stimulated macrophages, but not with serum or biopsy cytokine levels. Confocal imaging of lentivirally-expressed p65 activation revealed that a higher proportion of macrophages from CD patients responded to endotoxin lipid A compared to controls. In contrast, cells from UC patients exhibited a shorter duration of NF-κB p65 subunit nuclear localization compared to healthy controls, and CD donors. Analysis of macrophage cytokine responses and patient metadata revealed a strong correlation between CD patients who smoked and hyper-activation of p65. These in vitro dynamic assays of NF-κB activation in blood-derived macrophages have the potential to segregate IBD patients into groups with different phenotypes and may therefore help determine response to therapy.

Oral budesonide is a second-generation steroid that allows local, selective treatment of the gastrointestinal tract and the liver, minimizing systemic exposure. The results of randomized trials comparing budesonide versus placebo or active comparators have led to expert recommendations that budesonide be used to treat mild or moderate active ileocecal Crohn's disease, microscopic colitis (including both collagenous and lymphocytic colitis), ulcerative colitis, and non-cirrhotic autoimmune hepatitis. The mechanism of budesonide action obviates the need for dose tapering due to safety reasons after induction therapy. Where low-dose budesonide is used to maintain remission, usually in microscopic colitis, it does not appear to have adverse safety implications other than slight reductions in cortisol levels on rare occasions. As a gut-selective and liver-selective corticosteroid, budesonide offers an appealing alternative to conventional systemic glucocorticoids in diseases of these organs.