CALM may be a feasible intervention to benefit patients with advanced cancer. The results are encouraging, despite attrition and small effect sizes, and support further study.

Findings from a qualitative study suggest that the CALM intervention provides substantial benefits for patients with advanced cancer prior to the end of life. Findings informed the development of a randomized controlled trial to evaluate the effectiveness of this intervention.

We examined the role of CD4+ T cell IL-21 production in viral control of HIV infection. HIV-infected individuals had greater circulating IL-21–producing CD4+ T cells in blood compared with uninfected volunteers. HIV-specific IL-21–producing CD4+ T cells were detected in blood during untreated acute and chronic HIV infection, and elevated frequencies of these cells correlated with relative viral control. These cells had an effector memory or end effector phenotype and expressed CXCR5. HIV-specific CD8+ T cells exhibited high levels of IL-21R, indicating sensitivity to IL-21. Low or aviremic long-term nonprogressors, however, showed absent or low HIV-specific IL-21 CD4+ T cells, but more easily detectable HIV-specific IL-2–producing CD4+ T cells, suggesting changing requirements for particular γ-chain cytokines depending on Ag abundance. Thus, IL-21–producing CD4+ T cells are induced in viremic HIV infection and likely contribute to viral control by affecting CD8+ T cell maintenance.

The findings suggest that death anxiety in patients with advanced cancer is common and determined by the interaction of individual factors, family circumstances and physical suffering. Multidimensional interventions that take into account these and other factors may be most likely to be effective to alleviate this death-related distress.

These findings support the view that a synergistic relationship exists between depression and a broad array of physical symptoms in patients with advanced cancer.

The ESAS-CS and ESAS-r-CS NRS versions are valid and reliable for measuring symptoms in this population of outpatients with advanced cancer. Although the ESAS-r-CS was preferred, patients favored the 24-hour time window of the ESAS-CS, which also may best characterize fluctuating symptoms.

How to cite TSpace itemsAlways cite the published version, so the author(s) will receive recognition through services that track citation counts, e.g. Scopus. If you need to cite the page number of the author manuscript from TSpace because you cannot access the published version, then cite the TSpace version in addition to the published version using the permanent URI (handle) found on the record page.This article was made openly accessible by U of T Faculty. Please tell us how this access benefits you. Your story matters. 1 Full citation and link to published version:Krause S, Rydall A, Hales S, Rodin G, Lo C. Abstract ContextThe experience of death anxiety in patients with advanced cancer has been understudied partly due to the lack of a tailored measure for this population. The Death and Dying Distress Scale (DADDS) was constructed to address this gap. Although an initial version of this instrument has shown promising psychometric properties, validation of the finalized version is needed. ObjectivesThis study aims to validate the recent 15-item DADDS by examining its factor structure and construct validity. MethodsSixty participants with advanced or metastatic cancer were recruited from the Princess Margaret Cancer Centre, Toronto, Canada, into a pilot trial of a psychological intervention. This paper analyzes the baseline measures on death anxiety, depressive symptoms (PHQ-9, SCID), generalized anxiety (GAD-7), and preparation for end of life (QUAL-EC). Exploratory factor analysis was conducted. Construct validity was assessed by correlations between measures. ResultsFactor analysis revealed a dominant single factor explaining over 75% of the shared variation between items. Factor loadings were high, ranging from 0.57 to 0.86. Item communalities were evenly ranged from 0.33 to 0.75 and with the 15:1 variable to factor ratio, suggest the viability of parameter estimates despite the small sample size. Cronbach's alpha was 0.95. Death anxiety was associated with less preparation for end of life, r = -0.68, p < 0.0001, and more generalized anxiety, r = 0.63, p < 0.0001, and depressive symptom severity, r = 0.50, p < 0.0001. Individuals with major depression had greater death anxiety than the non-depressed, mean difference = 17, CI .95 = (1.5, 33), as did individuals with minor depression, mean difference = 25, CI .95 = (10, 41). ConclusionThe DADDS is a valid measure of death anxiety in patients with advanced cancer. It may provide useful information in the assessment and treatment of distress in patients near the end of life.4

T cell Ig mucin domain-containing molecule 3 (Tim-3) is a glycoprotein found on the surface of a subset of CD8+ and Th1 CD4+ T cells. Elevated expression of Tim-3 on virus-specific T cells during chronic viral infections, such as HIV-1, hepatitis B virus, and hepatitis C virus, positively correlates with viral load. Tim-3+ cytotoxic T cells are dysfunctional and are unable to secrete effector cytokines, such as IFN-γ and TNF-α. In this study, we examined potential inducers of Tim-3 on primary human T cells. Direct HIV-1 infection of CD4+ T cells, or LPS, found to be elevated in HIV-1 infection, did not induce Tim-3 on T cells. Tim-3 was induced by the common γ-chain (γc) cytokines IL-2, IL-7, IL-15, and IL-21 but not IL-4, in an Ag-independent manner and was upregulated on primary T cells in response to TCR/CD28 costimulation, as well as γc cytokine stimulation with successive divisions. γc cytokine-induced Tim-3 was found on naive, effector, and memory subsets of T cells. Tim-3+ primary T cells were more prone to apoptosis, particularly upon treatment with galectin-9, a Tim-3 ligand, after cytokine withdrawal. The upregulation of Tim-3 could be blocked by the addition of a PI3K inhibitor, LY 294002. Thus, Tim-3 can be induced via TCR/CD28 costimulation and/or γc cytokines, likely through the PI3K pathway.