Priority of the basic and instrumental activities of daily living in older patients with cancer prescribed rehabilitation: a cross-sectional survey.

BACKGROUND: There is no information on whether vulnerable older patients with cancer consider basic activities of daily living (BADL) and instrumental activities of daily living (IADL) important outcomes. Our survey aimed to investigate the priority of BADL and IADL in outcomes among vulnerable older patients with cancer. METHODS: This was a single-center survey in a Japanese cancer center. Eligible patients were ≥ 65 years of age and were prescribed in-hospital rehabilitation while under cancer treatment. Using original self-administered ranking questionnaires, patients were asked to rank outcomes and subdomain of BADL and IADL. High-priority domains were defined as the highest, second-highest, and third-highest priority domains in individuals. RESULTS: A total of 169 patients were analyzed. The mean age was 74.0 years (standard deviation, 5.1 years) and the number of males was 107 (63%). The order of ranking of high-priority outcomes was BADL and IADL (n = 155), cognitive function (n = 91), mental function (n = 82), nutrition (n = 61), social function (n = 51), comorbidity (n = 39), and life span (n = 28). The top three high-priority independence subdomains of BADL and IADL were toilet use (n = 140), feeding (n = 134), and mobility (n = 69) among the BADL and shopping (n = 93), food preparation (n = 88), and ability to handle finances (n = 85) among the IADL. CONCLUSIONS: BADL and IADL can be considered the most important health outcomes in clinical trials and in practice among older patients with cancer and physical vulnerabilities.

Interferon-ß promotes the survival and function of induced regulatory T cells.

Type I interferons (IFNs) are pleiotropic cytokines and impact various immune cells, including regulatory T cells (Treg cells). The effect of type-I IFNs on the development and function of Treg cells is quite controversial. Here we induced Treg cells (iTreg cells) from naïve CD4+ T cells in vitro in the presence or absence of IFN-ß to elucidate its direct effect on the induction of iTreg cells. We found that IFN-ß suppressed the proliferation of iTreg cells but enhanced their expression of anti-apoptotic genes Bcl-2 and Mcl-1 during the development of iTreg cells. We also found that IFN-ß promoted suppression of conventional T cell proliferation by iTreg cells. These results suggest that IFN-ß promotes the survival and immunomodulatory function of iTreg cells.

The efficacy of specialised rehabilitation using the Op-reha Guide for cancer patients in palliative care units: protocol of a multicentre, randomised controlled trial (JORTC-RHB02).

BACKGROUND: Although rehabilitation is recommended for terminal cancer patients, the specific components and methods of such programs are poorly documented. No studies to date have examined the effectiveness of rehabilitation for terminal cancer patients. This study aims to evaluate the efficacy of a new intervention for rehabilitation therapists, using the Op-reha Guide (Guide to Optimal and Patient-Centred Rehabilitation Practice for Patients in Palliative Care Units [PCUs]) in rehabilitation practice. This guide consists of recommended actions and attitudes for rehabilitation therapists and aims to optimise therapists' actions according to the patient's needs and condition. It shares goals with terminal cancer patients to maintain their activities of daily living (ADL). METHODS: This study uses a multicentre, prospective, randomised controlled trial (RCT) design with two parallel groups in PCUs where specialised rehabilitation will be routinely performed for terminal cancer patients by rehabilitation therapists. Participants will be randomised (1:1) to intervention (the Op-reha Guide) and control groups (usual rehabilitation). We will then conduct an observational study in PCUs that do not perform specialised rehabilitation for terminal cancer patients; this will be considered the usual care group, and the efficacy of usual rehabilitation will be quantitatively evaluated. Inclusion criteria are hospitalisation in PCU, European Cooperative Oncology Group Performance Status of 2 or 3, and clinical estimation of life expectancy of 3 weeks or more. Patients with severe symptom burden will be excluded. We hypothesise that the Op-reha Guide will be more effective in maintaining the ADL of terminal cancer patients hospitalised in PCUs than usual rehabilitation. The primary endpoint is defined as the change in (total) modified Barthel Index from baseline to Day 22. Quality of life will be a secondary endpoint. In total, 135 patients will be recruited from 16 Japanese sites between July 2019 and December 2021. DISCUSSION: This will be the first trial to evaluate the efficacy of specialised rehabilitation for terminal cancer patients hospitalised in PCUs, and will contribute to the evidence on the efficacy of implementing rehabilitation for terminal cancer patients. TRIAL REGISTRATION: UMIN-CTR, UMIN000037298 R000042525 (date of registration 7 July 2019).

Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a.

Although tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated in tumor microenvironments remains unclear. Here, we found that mice deficient in the inhibitory immunoreceptor CD300a on their dendritic cells (DCs) have increased numbers of Treg cells in tumors and greater tumor growth compared with wild-type mice after transplantation of B16 melanoma. Pharmacological impairment of extracellular vesicle (EV) release decreased Treg cell numbers in CD300a-deficient mice. Coculture of DCs with tumor-derived EV (TEV) induced the internalization of CD300a and the incorporation of EVs into endosomes, in which CD300a inhibited TEV-mediated TLR3-TRIF signaling for activation of the IFN-ß-Treg cells axis. We also show that higher expression of CD300A was associated with decreased tumor-infiltrating Treg cells and longer survival time in patients with melanoma. Our findings reveal the role of TEV and CD300a on DCs in Treg cell activation in the tumor microenvironment.

Common elements of service delivery models that optimise quality of life and health service use among older people with advanced progressive conditions: a tertiary systematic review.

INTRODUCTION: Health and social care services worldwide need to support ageing populations to live well with advanced progressive conditions while adapting to functional decline and finitude. We aimed to identify and map common elements of effective geriatric and palliative care services and consider their scalability and generalisability to high, middle and low-income countries. METHODS: Tertiary systematic review (Cochrane Database of Systematic Reviews, CINAHL, Embase, January 2000-October 2019) of studies in geriatric or palliative care that demonstrated improved quality of life and/or health service use outcomes among older people with advanced progressive conditions. Using frameworks for health system analysis, service elements were identified. We used a staged, iterative process to develop a 'common components' logic model and consulted experts in geriatric or palliative care from high, middle and low-income countries on its scalability. RESULTS: 78 studies (59 geriatric and 19 palliative) spanning all WHO regions were included. Data were available from 17 739 participants. Nearly half the studies recruited patients with heart failure (n=36) and one-third recruited patients with mixed diagnoses (n=26). Common service elements (≥80% of studies) included collaborative working, ongoing assessment, active patient participation, patient/family education and patient self-management. Effective services incorporated patient engagement, patient goal-driven care and the centrality of patient needs. Stakeholders (n=20) emphasised that wider implementation of such services would require access to skilled, multidisciplinary teams with sufficient resource to meet patients' needs. Identified barriers to scalability included the political and societal will to invest in and prioritise palliative and geriatric care for older people, alongside geographical and socioeconomic factors. CONCLUSION: Our logic model combines elements of effective services to achieve optimal quality of life and health service use among older people with advanced progressive conditions. The model transcends current best practice in geriatric and palliative care and applies across the care continuum, from prevention of functional decline to end-of-life care. PROSPERO REGISTRATION NUMBER: CRD42020150252.