Head and neck cancer in the UK: what was the stage before COVID-19? UK cancer registries analysis (2011-2018)

Introduction: People who present with more advanced stage head and neck cancer (HNC) are associated with poorer outcomes and survival. The burden and trends of advanced stage HNC are not fully known at the population level. The UK national cancer registries routinely collect data on HNC diagnoses. Aims: To describe trends in stage of diagnosis of HNCs across the UK before the COVID-19 pandemic. Methods: Aggregated HNC incidence data were requested from the national cancer registries of the four UK countries for the ten most recent years of available data by subsite and American Joint Commission on Cancer stage at diagnosis classification. Additionally, data for Scotland were available by age group, sex and area-based socioeconomic deprivation category. Results: Across the UK, rates of advanced stage HNC had increased, with 59% of patients having advanced disease at diagnosis from 2016-2018. England had a lower proportion of advanced disease (58%) than Scotland, Wales or Northern Ireland (65-69%) where stage data were available. The completeness of stage data had improved over recent years (87% by 2018). Conclusion: Prior to the COVID-19 pandemic, diagnoses of HNC at an advanced stage comprised the majority of HNCs in the UK, representing the major challenge for the cancer healthcare system

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Descriptive epidemiology of cancer of unknown primary site in Scotland, 1961–2010

Background: Cancers of unknown primary site (CUP) pose problems for diagnosis, treatment, and accurate prediction of prognosis. However, there are limited published data describing the epidemiology of this disease entity. Our aim was to describe the epidemiology of CUP in Scotland.<p></p> Methods: Anonymised data, covering the period 1961–2010, were extracted from the Scottish Cancer Registry database, based on the following ICD-10 diagnostic codes: C26.0, C26.8, C26.9, C39, and C76–C80. Age-standardised incidence rates were calculated by direct standardisation to the World Standard Population. Estimates of observed survival were calculated by the Kaplan–Meier method.<p></p> Results: Between 1961 and 2010, there were 50,941 registrations of CUP, representing 3.9% of all registrations of invasive cancers. Age-standardised rates increased to a peak in the early to mid-1990s, followed by a steeper decrease in rates. During 2001–2010, age-standardised rates of CUP were higher in the most compared with the least deprived fifth of the population. Observed survival was marginally higher in patients diagnosed during 2001–2010 (median 5.6 weeks) compared with those diagnosed in the previous two decades. During the most recent decade, survival decreased with age at diagnosis, and was higher in patients with squamous cell carcinoma and with lymph node metastases.<p></p> Conclusion: Patterns of CUP in Scotland are largely consistent with those reported from the few other countries that have published data. However, in comparing studies, it is important to note that there is heterogeneity in terms of definition of CUP, as well as calendar period of diagnosis or death. Variation in the definition of CUP between different epidemiological studies suggests that there would be merit in seeking international agreement on guidelines for the registration of CUP as well as a standard grouping of diagnostic codes for analysis.<p></p&gt

Differential DNA methylation in blood as a mediator of the association between cigarette smoking and bladder cancer risk among postmenopausal women

Smoking accounts for approximately 52% of bladder cancer incidence among postmenopausal women, but the underlying mechanism is poorly understood. Our study investigates whether changes in DNA methylation, as measured in blood, mediate the impact of smoking on bladder cancer risk among postmenopausal women. We conducted analyses among 206 cases and 251 controls that were current or never smokers at baseline from a previous case-control study of bladder cancer and genome-wide DNA methylation nested within the Women’s Health Initiative. Separate mediation analyses were conducted for three CpG sites demonstrating robust associations with smoking in prior methylome-wide association studies: cg05575921 (AhRR), cg03636183 (F2RL3), and cg19859270 (GPR15). We estimated causal effects using the regression-based, four-way decomposition approach, which addresses the interaction between smoking and each CpG site. The overall proportion of the excess relative risk mediated by cg05575921 was 92% (p-value = 0.004) and by cg19859270 was 79% (p-value = 0.02). The largest component of the excess relative risk of bladder cancer due to 30 pack-years of smoking history in current smokers was the mediated interaction for both cg05575921 (72%, p = 0.02) and cg19859270 (72%, p-value = 0.04), where the mediated interaction is the effect of smoking on bladder cancer that both acts through differential methylation and depends on smoking history. There was little evidence that smoking was mediated through cg03636183. Our results suggest that differential methylation of cg05575921 and cg19859270 mediate the effects of smoking on bladder cancer, potentially revealing downstream effects of smoking relevant for carcinogenesis

Improving barocaloric properties by tailoring transition hysteresis in Mn3Cu Sn N antiperovskites

The magnetically frustrated manganese nitride antiperovskite family displays significant changes of entropy under changes in hydrostatic pressure near a first-order antiferromagnetic to paramagnetic phase transition that can be useful for the emerging field of solid-state barocaloric cooling. In previous studies, the transition hysteresis has significantly reduced the reversible barocaloric effects (BCE). Here we show that the transition hysteresis can be tailored through quaternary alloying in the Mn _3 Cu $_{1-x}$ Sn $_{x}$ N system. We find the magnitude of hysteresis is minimised when Cu and Sn are equiatomic ( x  = 0.5) reaching values far less than previously found for Mn _3 A N ( $A =$ Pd, Ni, Ga, Zn), whilst retaining entropy changes of the same order of magnitude. These results demonstrate that reversible BCE are achievable for p  < 100 MPa in the Mn _3 ( A , B )N family and suggest routes to modify the transition properties in compounds of the same family

Walking the Talk: Moving Indigenous Studies from the Classroom to the Community

In this session students will showcase their final assignments from the course Anthropology 4050: Canadian Status/Treaty Indian Reserve Communities. Throughout the course we have discussed the complexities of the history of the reserve system in Canada, the nuances of the Treaty process, the rigidity of the Indian Act, the traumas of residential schools and lived implications of forced relocations on Indigenous communities. We have examined how colonial relations are spatialized and how this spacialization translates into lived social relations. This showcase represents our desire to share what we have learned and why it matters with our TRU community in the hopes of nurturing a space of understanding, compassion, and mutually respectful conversation

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P &lt; 5 × 10 ) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10 ). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P &lt; 5 × 10 ), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture. [Abstract copyright: © 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.