The relationship between tumour glucose metabolism and host systemic inflammatory responses in patients with cancer: a systematic review

One of the most important and long recognised characteristics of tumour cells is their dysregulated cellular energetics with anaerobic driven glucose uptake. In patients with cancer the prognostic value of the systemic inflammatory response has been well established and the recent combination of PET and CT scanning combines the assessment of tumour physiological activity with detailed anatomical localisation. The aim of this study was to carry out a systematic review of the assessment of the relationship between both the tumour and host inflammatory responses using PETCT. An extensive literature review using targeted subject headings was carried out in the US National Library of Medicine, the Excerpta Medica database and Cochrane Database of Systematic Reviews until the 31st March 2018. On completion of the online search, the title and abstracts of each identified study was examined for relevance. Studies with duplicate datasets, not available in English and that did not have full text availability were excluded. Full texts of relevant articles were obtained and were then examined to identify any further relevant articles. Twelve studies containing 2,588 patients were included in the final analysis. All of the included studies used the FDG tracer in PETCT imaging and had biochemical assessment of the systemic inflammatory response. The majority of studies showed a direct relationship between the tumour and bone marrow glucose uptake and host systemic inflammatory responses as measured by C-Reactive Protein (CRP) ( = 2), albumin ( = 2), White Cell Count (WCC) ( = 3), neutrophils ( = 2) and platelets ( = 2). The majority of the studies ( = 8) also showed a direct relationship between tumour and bone marrow glucose uptake and poor outcomes. This review suggests a direct relationship between the tumour and bone marrow glucose uptake and host systemic inflammation. This may suggest new approaches for more optimal therapeutic targeting and monitoring strategies in patients with cancer

Relation of severe COVID-19 in Scotland to transmission-related factors and risk conditions eligible for shielding support:REACT-SCOT case-control study

Abstract Background Clinically vulnerable individuals have been advised to shield themselves during the COVID-19 epidemic. The objectives of this study were to investigate (1) the rate ratio of severe COVID-19 associated with eligibility for the shielding programme in Scotland across the first and second waves of the epidemic and (2) the relation of severe COVID-19 to transmission-related factors in those in shielding and the general population. Methods In a matched case-control design, all 178,578 diagnosed cases of COVID-19 in Scotland from 1 March 2020 to 18 February 2021 were matched for age, sex and primary care practice to 1,744,283 controls from the general population. This dataset (REACT-SCOT) was linked to the list of 212,702 individuals identified as eligible for shielding. Severe COVID-19 was defined as cases that entered critical care or were fatal. Rate ratios were estimated by conditional logistic regression. Results With those without risk conditions as reference category, the univariate rate ratio for severe COVID-19 was 3.21 (95% CI 3.01 to 3.41) in those with moderate risk conditions and 6.3 (95% CI 5.8 to 6.8) in those eligible for shielding. The highest rate was in solid organ transplant recipients: rate ratio 13.4 (95% CI 9.6 to 18.8). Risk of severe COVID-19 increased with the number of adults but decreased with the number of school-age children in the household. Severe COVID-19 was strongly associated with recent exposure to hospital (defined as 5 to 14 days before presentation date): rate ratio 12.3 (95% CI 11.5 to 13.2) overall. The population attributable risk fraction for recent exposure to hospital peaked at 50% in May 2020 and again at 65% in December 2020. Conclusions The effectiveness of shielding vulnerable individuals was limited by the inability to control transmission in hospital and from other adults in the household. Mitigating the impact of the epidemic requires control of nosocomial transmission

Risk of hospital admission with covid-19 among teachers compared with healthcare workers and other adults of working age in Scotland, March 2020 to July 2021:population based case-control study

Objective: To determine the risk of hospital admission with covid-19 and severe covid-19 among teachers and their household members, overall and compared with healthcare workers and adults of working age in the general population. Design: Population based nested case-control study. Setting: Scotland, March 2020 to July 2021, during defined periods of school closures and full openings in response to covid-19. Participants: All cases of covid-19 in adults aged 21 to 65 (n=132 420) and a random sample of controls matched on age, sex, and general practice (n=1 306 566). Adults were identified as actively teaching in a Scottish school by the General Teaching Council for Scotland, and their household members were identified through the unique property reference number. The comparator groups were adults identified as healthcare workers in Scotland, their household members, and the remaining general population of working age. Main outcome measures: The primary outcome was hospital admission with covid-19, defined as having a positive test result for SARS-CoV-2 during hospital admission, being admitted to hospital within 28 days of a positive test result, or receiving a diagnosis of covid-19 on discharge from hospital. Severe covid-19 was defined as being admitted to intensive care or dying within 28 days of a positive test result or assigned covid-19 as a cause of death. Results: Most teachers were young (mean age 42), were women (80%), and had no comorbidities (84%). The risk (cumulative incidence) of hospital admission with covid-19 was <1% for all adults of working age in the general population. Over the study period, in conditional logistic regression models adjusted for age, sex, general practice, race/ethnicity, deprivation, number of comorbidities, and number of adults in the household, teachers showed a lower risk of hospital admission with covid-19 (rate ratio 0.77, 95% confidence interval 0.64 to 0.92) and of severe covid-19 (0.56, 0.33 to 0.97) than the general population. In the first period when schools in Scotland reopened, in autumn 2020, the rate ratio for hospital admission in teachers was 1.20 (0.89 to 1.61) and for severe covid-19 was 0.45 (0.13 to 1.55). The corresponding findings for household members of teachers were 0.91 (0.67 to 1.23) and 0.73 (0.37 to 1.44), and for patient facing healthcare workers were 2.08 (1.73 to 2.50) and 2.26 (1.43 to 3.59). Similar risks were seen for teachers in the second period, when schools reopened in summer 2021. These values were higher than those seen in spring/summer 2020, when schools were mostly closed. Conclusion: Compared with adults of working age who are otherwise similar, teachers and their household members were not found to be at increased risk of hospital admission with covid-19 and were found to be at lower risk of severe covid-19. These findings should reassure those who are engaged in face-to-face teaching

Vision-threatening retinal abnormalities in chronic kidney disease stages 3 to 5

SUMMARY: BACKGROUND AND OBJECTIVES: Retinal abnormalities are common in inherited and acquired renal disease. This study determined the prevalence of retinal abnormalities in chronic kidney disease (CKD) stages 3 to 5. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One hundred fifty patients with CKD stages 3 to 5 and 150 age- and gender-matched hospital patients with CKD stages 1 to 2 underwent bilateral retinal photography. These images were reviewed for incidental abnormalities, microvascular (Wong and Mitchell classification) and diabetic retinopathy (Airlie House criteria), and macular degeneration (Seddon classification). RESULTS: Three (2%) patients with CKD stages 3 to 5 had retinal features characteristic of inherited renal disease (atrophy in Myopathy, Encephalopathy, Lactic Acidosis, Stroke-like episodes [MELAS] syndrome; and 2 with drusen in dense deposit disease). Fifty-nine (39%) patients had moderate-severe microvascular retinopathy (hemorrhages, exudates, etc.) compared with 19 (13%) with CKD stages 1 to 2. Forty-one (28%) had moderate-severe diabetic retinopathy (microaneurysms, exudates, etc.) compared with 16 (11%) with CKD stages 1 to 2. Ten (7%) had severe macular degeneration (geographic atrophy, hemorrhage, exudates, membranes) compared with one (1%) with CKD stages 1 to 2. Renal failure was an independent risk factor for microvascular retinopathy, diabetic retinopathy, and macular degeneration. Eleven (7.3%) patients with renal failure and one (0.7%) with CKD stages 1 to 2 had previously unrecognized vision-threatening retinal abnormalities that required immediate ophthalmologic attention. CONCLUSIONS: Retinal abnormalities are common in CKD stages 3 to 5, and are more severe and more likely to threaten vision than in hospital patients with CKD stages 1 to 2

A participatory model for co-creating accessible rehabilitation technology for stroke survivors

Background: Globally, one in three people live with health conditions that could be improved with rehabilitation. Ideally this is provided by trained professionals delivering evidence based levels of dose, intensity and content, for optimal recovery. The inability of healthcare providers to deliver this, creates an opportunity for technological innovation. Design processes that lack close consideration of users’ needs and healthcare budgets, however, mean that many rehabilitation technologies are neither useful, nor used. Objective: To develop a model for designing accessible rehabilitation technology using a co-creation approach that is informed by users who have completed, or are completing, an eight-week technology based rehabilitation programme. Methods: To address this problem our multi-disciplinary research group established a co-creation centre for rehabilitation technology that places the user at the centre of the innovation process. The core of this model is an eight-week holistic rehabilitation programme delivered exclusively through commercial and prototype technology so that users are able to provide truly informed feedback on technologies under development, as well as creating an observatory to better understand how patients interact with rehabilitation technologies. The process is supported by focus groups for product development and a translation group advising on broader issues of adoption. As the leading cause of global adult disability, the target population for the centre has been stroke, however the principles can be applied to any clinical population. Results: Our model has been active for more than two years with 80/86 individuals completing the programme. Five new devices have emerged from the process with further ideas logged for future development. In addition, it has led to accessibility modifications to existing technology, including modifications to hand grips and the structure of rehabilitation games. Critically it has also produced a set of co-created protocols for technology enriched rehabilitation that has allowed us to replicate the model on an acute stroke ward. Conclusions: Sub-optimal rehabilitation limits recovery from health conditions. Technology offers support to increase access to intensive and enriched rehabilitation, but needs to be designed to suit users and not just their impairment. Our co-creation model, built around participation in an intensive, technology-based programme, has produced new accessible technology and demonstrated the feasibility of our overall approach to providing the rehabilitation that people need, for as long as needed

Increasing density leads to generalization in both coarse-grained habitat selection and fine-grained resource selection in a large mammal

Summary 1. Density is a fundamental driver of many ecological processes including habitat selection. Theory on density-dependent habitat selection predicts that animals should be distributed relative to profitability of habitat, resulting in reduced specialization in selection (i.e. generalization) as density increases and competition intensifies. 2. Despite mounting empirical support for density-dependent habitat selection using isodars to describe coarse-grained (interhabitat) animal movements, we know little of how density affects fine-grained resource selection of animals within habitats [e.g. using resource selection functions (RSFs)]. 3. Using isodars and RSFs, we tested whether density simultaneously modified habitat selection and within-habitat resource selection in a rapidly growing population of feral horses (Equus ferus caballus Linnaeus; Sable Island, Nova Scotia, Canada; 42% increase in population size from 2008 to 2012). 4. Among three heterogeneous habitat zones on Sable Island describing population clusters distributed along a west-east resource gradient (west-central-east), isodars revealed that horses used available habitat in a density-dependent manner. Intercepts and slopes of isodars demonstrated a pattern of habitat selection that first favoured the west, which generalized to include central and east habitats with increasing population size consistent with our understanding of habitat quality on Sable Island. 5. Resource selection functions revealed that horses selected for vegetation associations similarly at two scales of extent (total island and within-habitat zone). When densities were locally low, horses were able to select for sites of the most productive forage (grasslands) relative to those of poorer quality. However, as local carrying capacity was approached, selection for the best of available forage types weakened while selection for lower-quality vegetation increased (and eventually exceeded that of grasslands). 6. Isodars can effectively describe coarse-grained habitat selection in large mammals. Our study also shows that the main predictions of density-dependent habitat selection are highly relevant to our interpretation of RSFs in space and time. At low but not necessarily high population size, density will be a leading indicator of habitat quality. Fitness maximization from specialist vs. generalist strategies of habitat and resource selection may well be apparent at multiple spatial extents and grains of resolution

The relationship between 18F-FDG-PETCT-derived tumour metabolic activity, nutritional risk, body composition, systemic inflammation and survival in patients with lung cancer

The aim of this study was to examine the relationship between PET-CT derived tumour glucose uptake as measured by maximum standard glucose uptake (SUVmax) and total lesion glycolysis (TLG), nutritional risk as measured by the malnutrition universal screening tool (MUST), CT derived body composition as measured by skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD), the systemic inflammatory response as measured by the modified Glasgow prognostic score (mGPS) and the neutrophil to lymphocyte ratio (NLR) and survival in patients with lung cancer, treated with radiotherapy. In a retrospective cohort study, 119 patients were included in final analyses. The majority of patients were over 65 (86%), female (52%), had a performance status (ECOG-PS) of 0 or 1 (57%), were at nutritional risk (57%), were overweight (53%), had visceral obesity (62%), had a normal SMI (51%), had a low SMD (62%) and were systemically inflammed (mGPS 1/2, 51%). An elevated TLG was associated with sex (p < 0.05), TNM stage (p < 0.001), MUST (p < 0.01) and mGPS (p < 0.01). An elevated mGPS was associated with age (p < 0.05), NLR (p < 0.01), MUST (p < 0.01), and TLG (p < 0.01). On univariate survival analysis, TNM stage (p < 0.01), mGPS (p < 0.05), NLR (p < 0.01), MUST (p ≤ 0.001), Low SMD (p < 0.05), SUVmax (p ≤ 0.001) and TLG (p < 0.001) were associated with overall survival. On multivariate survival analysis MUST (HR: 1.49 95%CI 1.12–01.98 p < 0.01) and TLG (HR: 2.02 95%CI 1.34–3.04 p = 0.001) remained independently associated with survival. In conclusion, elevated tumour metabolic activity was associated with more advanced stage, greater nutritional risk, the systemic inflammatory response and poorer survival but not body composition analysis in patients with lung cancer. These results suggest that detrimental body composition is not directly determined by tumour metabolic activity but rather an ongoing systemic inflammatory response

Psychological impact of working in paediatric intensive care. A UK-wide prevalence study

OBJECTIVE: To determine the prevalence of work-related psychological distress in staff working in UK paediatric intensive care units (PICU). DESIGN: Online (Qualtrics) staff questionnaire, conducted April to May 2018. SETTING: Staff working in 29 PICUs and 10 PICU transport services were invited to participate. PARTICIPANTS: 1656 staff completed the survey: 1194 nurses, 270 physicians and 192 others. 234 (14%) respondents were male. Median age was 35 (IQR 28-44). MAIN OUTCOME MEASURES: The Moral Distress Scale-Revised (MDS-R) was used to look at moral distress, the abbreviated Maslach Burnout Inventory to examine the depersonalisation and emotional exhaustion domains of burnout, and the Trauma Screening Questionnaire (TSQ) to assess risk of post-traumatic stress disorder (PTSD). RESULTS: 435/1194 (36%) nurses, 48/270 (18%) physicians and 19/192 (10%) other staff scored above the study threshold for moral distress (≥90 on MDS-R) (χ2 test, p<0.00001). 594/1194 (50%) nurses, 99/270 (37%) physicians and 86/192 (45%) other staff had high burnout scores (χ2 test, p=0.0004). 366/1194 (31%) nurses, 42/270 (16%) physicians and 21/192 (11%) other staff scored at risk for PTSD (χ2 test, p<0.00001). Junior nurses were at highest risk of moral distress and PTSD, and junior doctors of burnout. Larger unit size was associated with higher MDS-R, burnout and TSQ scores. CONCLUSIONS: These results suggest that UK PICU staff are experiencing work-related distress. Further studies are needed to understand causation and to develop strategies for prevention and treatment

Improved PCR based methods for detecting C9orf72 hexanucleotide repeat expansions

Due to the GC-rich, repetitive nature of C9orf72 hexanucleotide repeat expansions, PCR based detection methods are challenging. Several limitations of PCR have been reported and overcoming these could help to define the pathogenic range. There is also a need to develop improved repeat-primed PCR assays which allow detection even in the presence of genomic variation around the repeat region. We have optimised PCR conditions for the C9orf72 hexanucleotide repeat expansion, using betaine as a co-solvent and specific cycling conditions, including slow ramping and a high denaturation temperature. We have developed a flanking assay, and repeat-primed PCR assays for both 3′ and 5′ ends of the repeat expansion, which when used together provide a robust strategy for detecting the presence or absence of expansions greater than ∼100 repeats, even in the presence of genomic variability at the 3′ end of the repeat. Using our assays, we have detected repeat expansions in 47/442 Scottish ALS patients. Furthermore, we recommend the combined use of these assays in a clinical diagnostic setting

Does the Southern Green Anaconda, <i>Eunectes murinus</i>, seek areas of high prey concentration in southeastern Peru?

Although behavior of E. murinus was broadly described over a century ago, observations of predation by E. murinus are rare. Some evidence suggests that it may target sites when hunting. We report details of six livestock depredation events at a single locality near Puerto Maldonado, Peru. Additionally, we compare positions of three radio-tagged snakes with known locations of mineral licks in their home ranges and describe the relationship of a single radio-tagged individual with game trails. Our observations of predation at mineral licks, and the association of radio-tagged individuals with them, suggest that E. murinus may specifically target mineral licks due to high prey concentration. We believe this is the first report of a reptile actively seeking prey at mineral licks. Our observations indicate that E. murinus actively seeks areas with higher prey concentration