Association of Stair Use With Risk of Major Chronic Diseases.

INTRODUCTION: Physical inactivity is associated with a higher risk of chronic diseases. Regular stair use can contribute to increasing physical activity in the population. This study aimed to investigate the association between flights of stairs used daily at home and all-cause mortality and cause-specific incidence and mortality. METHODS: Of the 502,628 UK Biobank participants recruited between 2007 and 2010, 442,027 (mean age, 56±8 years) had available data and were included in the analyses conducted in 2023. Participants were categorized on the basis of flights of stairs climbed daily (1-5, 6-10, 11-15, >15). The disease-specific outcomes were cardiovascular disease, respiratory disease, cancer, type 2 diabetes, and all-cause dementia. Cox proportional hazard models, adjusted for sociodemographic, lifestyle, and health-related confounding factors, were used to analyze the associations between stair use frequency and health outcomes. RESULTS: Participants were followed up for a median of 10.9 years. Climbing stairs >15 times per day was associated with a lower risk of 8 of the 9 outcomes analyzed than not using stairs. The magnitude of association ranged from 3% (95% CI=0.94, 0.99) lower risk for all-cause cancer to 51% (95% CI=0.39, 0.60) lower risk of chronic obstructive pulmonary disease. Findings were similar for mortality outcomes, with the hazard ratios ranging from 0.82 (95% CI=0.77, 0.87) for all-cause cancer to 0.46 (95% CI=0.23, 0.92) for chronic obstructive pulmonary disease mortality. CONCLUSIONS: Stair use was associated with a lower risk of all-cause mortality and cause-specific incidence and mortality independent of confounding factors, including adiposity and multimorbidity.

Heightened metabolic responses in NK cells from patients with neuroblastoma suggests increased potential for immunotherapy.

High risk neuroblastoma is responsible for 15% of deaths in pediatric cancer patients. The introduction of anti-GD2 immunotherapy has significantly improved outcomes but there is still only approximately a 50% 5 year event-free-survival for these children and improvements in treatments are urgently required. Anti-GD2 immunotherapy uses the patients' own immune system to kill cancer cells. In particular, Natural Killer (NK) cells kill antibody coated tumor cells by a process called antibody dependent cellular cytotoxicity (ADCC). However, our previous work has highlighted metabolic exhaustion of NK cells in circulating blood of adult cancer patients, identifying this as a potential therapeutic target. In this study, we investigated circulating NK cells in patients newly diagnosed with neuroblastoma. We found evidence of activation of NK cells in vivo by the cancer itself. While some evidence of NK cell dysfunction was observed in terms of IFNγ production, most results indicated that the NK cell compartment remained relatively intact. In fact, some aspects of metabolic and functional activities were actually increased in patients compared to controls. Glycolytic responses, which we show are crucial for ADCC, were actually enhanced in patients and CD16, the NK cell receptor that mediates ADCC, was also expressed at high levels in some patients. Overall, the data suggest that patient NK cells could be harvested at diagnosis for subsequent beneficial autologous use during immunotherapy. Enhancing glycolytic capacity of cell therapies could also be a strategic goal of future cell therapies for patients with neuroblastoma and indeed other cancers.