Emergency presentation of colorectal cancer in older adults:A retrospective cohort analysis

INTRODUCTION: Adults aged 70 years and over account for almost 60% of colorectal cancer (CRC) diagnoses in the United Kingdom. Whilst emergency presentation of CRC is known to be associated with poorer outcomes across all ages, older adults are less likely to be treated with curative intent and have poorer overall survival (OS). We aimed to investigate whether presentation, management, or outcome differed in older (≥70 years) versus younger (&lt;70 years) adults in our population.MATERIALS AND METHODS: The electronic records of patients diagnosed with CRC within the period 2016 to 2019 in National Health Service (NHS) Tayside, Scotland were retrospectively analysed. Patients were grouped by age (&lt;70 years and ≥70 years). Demographics were compared by Chi-squared or t-test, and Kaplan-Meier and Cox proportional hazard regression were used for survival analyses.RESULTS: In total, 1245 patients were diagnosed with CRC (median age 71 years, range 20-98). Of these, 215 patients (17.3%) presented emergently and were included in the analysis. Older adults accounted for 65.1% (n = 140) of emergency presentations. Older adults were less likely to present with classical symptoms of CRC (80.0% vs 90.7%, p = 0.04) and more likely to present via the medical assessment unit (46.4% vs 30.7%, p = 0.03). Additionally, older adults were less likely to receive a histological diagnosis of CRC (71.4% vs 97.3%, p &lt; 0.001) or have complete staging investigations performed (78.6% vs 96.0%, p &lt; 0.001). Fewer older adults underwent surgical management (55.0% vs 86.7%, p &lt; 0.001) and fewer were treated with chemotherapy (14.3% vs 69.3%, p &lt; 0.001). Whilst older adults had poorer median OS than those aged &lt;70 years (12.0 vs 34.4 months, p &lt; 0.001), multivariate Cox proportional hazards regression demonstrated that higher stage (stage III hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.7, stage IV HR 16.7, 95% CI 9.7-28.8, incomplete HR 8.2, 95% CI 4.6-14.7) and not receiving chemotherapy (HR 2.6, 95% CI 1.7-4.0) were associated with poorer survival, whereas age and sex were not.DISCUSSION: Emergency presentation of colorectal cancer was more common in older adults. Older adults were more likely to present atypically, less likely to have completed staging, and had lower rates of intervention, which were associated with poorer survival outcome.</p

Emergency presentation of colorectal cancer in older adults:A retrospective cohort analysis

Introduction: Adults aged 70 years and over account for almost 60% of colorectal cancer (CRC) diagnoses in the United Kingdom. Whilst emergency presentation of CRC is known to be associated with poorer outcomes across all ages, older adults are less likely to be treated with curative intent and have poorer overall survival (OS). We aimed to investigate whether presentation, management, or outcome differed in older (≥70 years) versus younger (&lt;70 years) adults in our population.Materials and Methods: The electronic records of patients diagnosed with CRC within the period 2016 to 2019 in National Health Service (NHS) Tayside, Scotland were retrospectively analysed. Patients were grouped by age (&lt;70 years and ≥70 years). Demographics were compared by Chi-squared or t-test, and Kaplan-Meier and Cox proportional hazard regression were used for survival analyses.Results: In total, 1245 patients were diagnosed with CRC (median age 71 years, range 20–98). Of these, 215 patients (17.3%) presented emergently and were included in the analysis. Older adults accounted for 65.1% (n = 140) of emergency presentations. Older adults were less likely to present with classical symptoms of CRC (80.0% vs 90.7%, p = 0.04) and more likely to present via the medical assessment unit (46.4% vs 30.7%, p = 0.03). Additionally, older adults were less likely to receive a histological diagnosis of CRC (71.4% vs 97.3%, p &lt; 0.001) or have complete staging investigations performed (78.6% vs 96.0%, p &lt; 0.001). Fewer older adults underwent surgical management (55.0% vs 86.7%, p &lt; 0.001) and fewer were treated with chemotherapy (14.3% vs 69.3%, p &lt; 0.001). Whilst older adults had poorer median OS than those aged &lt;70 years (12.0 vs 34.4 months, p &lt; 0.001), multivariate Cox proportional hazards regression demonstrated that higher stage (stage III hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6–4.7, stage IV HR 16.7, 95% CI 9.7–28.8, incomplete HR 8.2, 95% CI 4.6–14.7) and not receiving chemotherapy (HR 2.6, 95% CI 1.7–4.0) were associated with poorer survival, whereas age and sex were not.Discussion: Emergency presentation of colorectal cancer was more common in older adults. Older adults were more likely to present atypically, less likely to have completed staging, and had lower rates of intervention, which were associated with poorer survival outcome

Emergency presentation of colorectal cancer in older adults:A retrospective cohort analysis

INTRODUCTION: Adults aged 70 years and over account for almost 60% of colorectal cancer (CRC) diagnoses in the United Kingdom. Whilst emergency presentation of CRC is known to be associated with poorer outcomes across all ages, older adults are less likely to be treated with curative intent and have poorer overall survival (OS). We aimed to investigate whether presentation, management, or outcome differed in older (≥70 years) versus younger (&lt;70 years) adults in our population.MATERIALS AND METHODS: The electronic records of patients diagnosed with CRC within the period 2016 to 2019 in National Health Service (NHS) Tayside, Scotland were retrospectively analysed. Patients were grouped by age (&lt;70 years and ≥70 years). Demographics were compared by Chi-squared or t-test, and Kaplan-Meier and Cox proportional hazard regression were used for survival analyses.RESULTS: In total, 1245 patients were diagnosed with CRC (median age 71 years, range 20-98). Of these, 215 patients (17.3%) presented emergently and were included in the analysis. Older adults accounted for 65.1% (n = 140) of emergency presentations. Older adults were less likely to present with classical symptoms of CRC (80.0% vs 90.7%, p = 0.04) and more likely to present via the medical assessment unit (46.4% vs 30.7%, p = 0.03). Additionally, older adults were less likely to receive a histological diagnosis of CRC (71.4% vs 97.3%, p &lt; 0.001) or have complete staging investigations performed (78.6% vs 96.0%, p &lt; 0.001). Fewer older adults underwent surgical management (55.0% vs 86.7%, p &lt; 0.001) and fewer were treated with chemotherapy (14.3% vs 69.3%, p &lt; 0.001). Whilst older adults had poorer median OS than those aged &lt;70 years (12.0 vs 34.4 months, p &lt; 0.001), multivariate Cox proportional hazards regression demonstrated that higher stage (stage III hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.7, stage IV HR 16.7, 95% CI 9.7-28.8, incomplete HR 8.2, 95% CI 4.6-14.7) and not receiving chemotherapy (HR 2.6, 95% CI 1.7-4.0) were associated with poorer survival, whereas age and sex were not.DISCUSSION: Emergency presentation of colorectal cancer was more common in older adults. Older adults were more likely to present atypically, less likely to have completed staging, and had lower rates of intervention, which were associated with poorer survival outcome.</p

Emergency presentation of colorectal cancer in older adults:A retrospective cohort analysis

Introduction: Adults aged 70 years and over account for almost 60% of colorectal cancer (CRC) diagnoses in the United Kingdom. Whilst emergency presentation of CRC is known to be associated with poorer outcomes across all ages, older adults are less likely to be treated with curative intent and have poorer overall survival (OS). We aimed to investigate whether presentation, management, or outcome differed in older (≥70 years) versus younger (&lt;70 years) adults in our population.Materials and Methods: The electronic records of patients diagnosed with CRC within the period 2016 to 2019 in National Health Service (NHS) Tayside, Scotland were retrospectively analysed. Patients were grouped by age (&lt;70 years and ≥70 years). Demographics were compared by Chi-squared or t-test, and Kaplan-Meier and Cox proportional hazard regression were used for survival analyses.Results: In total, 1245 patients were diagnosed with CRC (median age 71 years, range 20–98). Of these, 215 patients (17.3%) presented emergently and were included in the analysis. Older adults accounted for 65.1% (n = 140) of emergency presentations. Older adults were less likely to present with classical symptoms of CRC (80.0% vs 90.7%, p = 0.04) and more likely to present via the medical assessment unit (46.4% vs 30.7%, p = 0.03). Additionally, older adults were less likely to receive a histological diagnosis of CRC (71.4% vs 97.3%, p &lt; 0.001) or have complete staging investigations performed (78.6% vs 96.0%, p &lt; 0.001). Fewer older adults underwent surgical management (55.0% vs 86.7%, p &lt; 0.001) and fewer were treated with chemotherapy (14.3% vs 69.3%, p &lt; 0.001). Whilst older adults had poorer median OS than those aged &lt;70 years (12.0 vs 34.4 months, p &lt; 0.001), multivariate Cox proportional hazards regression demonstrated that higher stage (stage III hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6–4.7, stage IV HR 16.7, 95% CI 9.7–28.8, incomplete HR 8.2, 95% CI 4.6–14.7) and not receiving chemotherapy (HR 2.6, 95% CI 1.7–4.0) were associated with poorer survival, whereas age and sex were not.Discussion: Emergency presentation of colorectal cancer was more common in older adults. Older adults were more likely to present atypically, less likely to have completed staging, and had lower rates of intervention, which were associated with poorer survival outcome

Successful ageing in an area of deprivation: Part 1—A qualitative exploration of the role of life experiences in good health in old age

Objectives: To determine the life histories and current circumstances of healthy and unhealthy older people who share an ecology marked by relative deprivation and generally poor health. Study design: In-depth interview study with a qualitative analysis. Methods: Matched pairs of healthy and unhealthy ‘agers’ were interviewed face-to-face. Healthy ageing was assessed in terms of hospital morbidity and self-reported health. Study participants consisted of 22 pairs (44 individuals), aged 72–89 years, matched for sex, age and deprivation category, and currently resident in the West of Scotland. All study participants were survivors of the Paisley/Renfrew (MIDSPAN) survey, a longitudinal study commenced in 1972 with continuous recording of morbidity and mortality since. Detailed life histories were obtained which focused on family, residence, employment, leisure and health. This information was supplemented by more focused data on ‘critical incidents’, financial situation and position in social hierarchies. Results: Data provided rich insights into life histories and current circumstances but no differences were found between healthy and unhealthy agers. Conclusions: It is important to understand what differentiates individuals who have lived in circumstances characterized by relative deprivation and poor health, yet have aged healthily. This study collected rich and detailed qualitative data. Yet, no important differences were detected between healthy and unhealthy agers. This is an important negative result as it suggests that the phenomenon of healthy ageing and the factors that promote healthy ageing over a lifetime are so complex that they will require even more detailed studies to disentangle

The dynamics of cardiolipin synthesis post-mitochondrial fusion

AbstractAlteration in mitochondrial fusion may regulate mitochondrial metabolism. Since the phospholipid cardiolipin (CL) is required for function of the mitochondrial respiratory chain, we examined the dynamics of CL synthesis in growing Hela cells immediately after and 12h post-fusion. Cells were transiently transfected with Mfn-2, to promote fusion, or Mfn-2 expressing an inactive GTPase for 24h and de novo CL biosynthesis was examined immediately after or 12h post-fusion. Western blot analysis confirmed elevated Mfn-2 expression and electron microscopic analysis revealed that Hela cell mitochondrial structure was normal immediately after and 12h post-fusion. Cells expressing Mfn-2 exhibited reduced CL de novo biosynthesis from [1,3-3H]glycerol immediately after fusion and this was due to a decrease in phosphatidylglycerol phosphate synthase (PGPS) activity and its mRNA expression. In contrast, 12h post-mitochondrial fusion cells expressing Mfn-2 exhibited increased CL de novo biosynthesis from [1,3-3H]glycerol and this was due to an increase in PGPS activity and its mRNA expression. Cells expressing Mfn-2 with an inactive GTPase activity did not exhibit alterations in CL de novo biosynthesis immediately after or 12h post-fusion. The Mfn-2 mediated alterations in CL de novo biosynthesis were not accompanied by alterations in CL or monolysoCL mass. [1-14C]Oleate incorporation into CL was elevated at 12h post-fusion indicating increased CL resynthesis. The reason for the increased CL resynthesis was an increased mRNA expression of tafazzin, a mitochondrial CL resynthesis enzyme. Ceramide-induced expression of PGPS in Hela cells or in CHO cells did not alter expression of Mfn-2 indicating that Mfn-2 expression is independent of altered CL synthesis mediated by elevated PGPS. In addition, Mfn-2 expression was not altered in Hela cells expressing phospholipid scramblase-3 or a disrupted scramblase indicating that proper CL localization within mitochondria is not essential for Mfn-2 expression. The results suggest that immediately post-mitochondrial fusion CL de novo biosynthesis is “slowed down” and then 12h post-fusion it is “upregulated”. The implications of this are discussed

Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease : UK collaborative randomised trial

ABSTRACT Objective To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease (GORD). Design Multicentre, pragmatic randomised trial (with parallel preference groups). Setting 21 hospitals in the United Kingdom. Participants 357 randomised participants (178 surgical,179 medical) and 453 preference participants (261, 192); mean age 46; 66% men. All participants had documented evidence of GORD and symptoms for >12 months. Intervention The type of laparoscopic fundoplication used was left to the discretion of the surgeon. Those allocated to medical treatment had their treatment reviewed and adjusted as necessary by a local gastroenterologist, and subsequent clinical management was at the discretion of the clinician responsible for care. Main outcome measures The disease specific REFLUX quality of life score (primary outcome), SF-36, EQ-5D, and medication use, measured at time points equivalent to three and 12 months after surgery, and surgical complications. Main results Randomised participants had received drugs for GORD for median of 32 months before trial entry. Baseline REFLUX scores were 63.6 (SD 24.1) and 66.8 (SD 24.5) in the surgical and medical randomised groups, respectively. Of those randomised to surgery, 111 (62%) actually had total or partial fundoplication. Surgical complications were uncommon with a conversion rate of 0.6% and no mortality. By 12 months, 38% (59/154) randomised to surgery (14% (14/104) among those who had fundoplication) were taking reflux medication versus 90% (147/164) randomised medical management. The REFLUX score favoured the randomised surgical group (14.0, 95% confidence interval 9.6 to 18.4; P<0.001). Differences of a third to half of 1 SD in other health status measures also favoured the randomised surgical group. Baseline scores in the preference for surgery group were the worst; by 12 months these were better than in the preference for medical treatment group. Conclusion At least up to 12 months after surgery, laparoscopic fundoplication significantly increased measures of health status in patients with GORD. Trial registration ISRCTN15517081This study was funded by the NIHR Health Technology Assessment Programme (as part of project no. 97/10/99) and the full project report is published in Health Technology Assessment 2008;12:1/181. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewe

HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia.

BACKGROUND: Hypoxia plays a key role in ischaemic and neovascular disorders of the retina. Cellular responses to oxygen are mediated by hypoxia-inducible transcription factors (HIFs) that are stabilised in hypoxia and induce the expression of a diverse range of genes. The purpose of this study was to define the cellular specificities of HIF-1alpha and HIF-2alpha in retinal ischaemia, and to determine their correlation with the pattern of retinal hypoxia and the expression profiles of induced molecular mediators. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the tissue distribution of retinal hypoxia during oxygen-induced retinopathy (OIR) in mice using the bio-reductive drug pimonidazole. We measured the levels of HIF-1alpha and HIF-2alpha proteins by Western blotting and determined their cellular distribution by immunohistochemistry during the development of OIR. We measured the temporal expression profiles of two downstream mediators, vascular endothelial growth factor (VEGF) and erythropoietin (Epo) by ELISA. Pimonidazole labelling was evident specifically in the inner retina. Labelling peaked at 2 hours after the onset of hypoxia and gradually declined thereafter. Marked binding to Müller glia was evident during the early hypoxic stages of OIR. Both HIF-1alpha and HIF-2alpha protein levels were significantly increased during retinal hypoxia but were evident in distinct cellular distributions; HIF-1alpha stabilisation was evident in neuronal cells throughout the inner retinal layers whereas HIF-2alpha was restricted to Müller glia and astrocytes. Hypoxia and HIF-alpha stabilisation in the retina were closely followed by upregulated expression of the downstream mediators VEGF and EPO. CONCLUSIONS/SIGNIFICANCE: Both HIF-1alpha and HIF-2alpha are activated in close correlation with retinal hypoxia but have contrasting cell specificities, consistent with differential roles in retinal ischaemia. Our findings suggest that HIF-2alpha activation plays a key role in regulating the response of Müller glia to hypoxia

Strong Continuum-continuum Couplings In The Direct Ionization Of Ar And He Atoms By 6-MeV/u U38+ And Th38+ Projectiles

Doubly differential cross sections have been measured as a function of the electron energy and observation angle for electron emission following collisions of 6-MeV/u U38+ and Th38+ on He and Ar. The electron-emission data show an enhancement at forward angles and a decrease at backward angles with respect to scaled-cross-section results based on the Born approximation. Comparison with classical-trajectory Monte Carlo calculations suggests that the deviation from the Born approximation can be explained by continuum-continuum couplings. By comparing with previously published data, we found that the forward enhancement as well as the backward decrease follow a q/vp (q,vp are the projectile charge and velocity) scaling. © 1989 The American Physical Society