Symptomatic Carotid Atheroma Inflammation Lumen-stenosis score compared with Oxford and Essen risk scores to predict recurrent stroke in symptomatic carotid stenosis.

BACKGROUND: The Oxford Carotid Stenosis tool (OCST) and Essen Stroke Risk Score (ESRS) are validated to predict recurrent stroke in patients with and without carotid stenosis. The Symptomatic Carotid Atheroma Inflammation Lumen stenosis (SCAIL) score combines stenosis and plaque inflammation on fluorodeoxyglucose positron-emission tomography (18FDG-PET). We compared SCAIL with OCST and ESRS to predict ipsilateral stroke recurrence in symptomatic carotid stenosis. PATIENTS AND METHODS: We pooled three prospective cohort studies of patients with recent (<30 days) non-severe ischaemic stroke/TIA and internal carotid artery stenosis (>50%). All patients had carotid 18FDG-PET/CT angiography and late follow-up, with censoring at carotid revascularisation. RESULTS: Of 212 included patients, 16 post-PET ipsilateral recurrent strokes occurred in 343 patient-years follow-up (median 42 days (IQR 13-815)).Baseline SCAIL predicted recurrent stroke (unadjusted hazard ratio [HR] 1.96, CI 1.20-3.22, p = 0.007, adjusted HR 2.37, CI 1.31-4.29, p = 0.004). The HR for OCST was 0.996 (CI 0.987-1.006, p = 0.49) and for ESRS was 1.26 (CI 0.87-1.82, p = 0.23) (all per 1-point score increase). C-statistics were: SCAIL 0.66 (CI 0.51-0.80), OCST 0.52 (CI 0.40-0.64), ESRS 0.61 (CI 0.48-0.74). Compared with ESRS, addition of plaque inflammation (SUVmax) to ESRS improved risk prediction when analysed continuously (HR 1.51, CI 1.05-2.16, p = 0.03) and categorically (ptrend = 0.005 for risk increase across groups; HR 3.31, CI 1.42-7.72, p = 0.006; net reclassification improvement 10%). Findings were unchanged by further addition of carotid stenosis. CONCLUSIONS: SCAIL predicted recurrent stroke, had discrimination better than chance, and improved the prognostic utility of ESRS, suggesting that measuring plaque inflammation may improve risk stratification in carotid stenosis.

The dietary impact of the COVID-19 pandemic.

The COVID-19 pandemic led to significant changes in people's budgets, the opportunity cost of their time, and where they can purchase and consume food. We use novel data on food and non-alcoholic drink purchases from stores, takeaways, restaurants and other outlets to estimate the impact of the pandemic on the diets of a large, representative panel of British households. We find that a substantial and persistent increase in calories consumed at home more than offset reductions in calories eaten out. Households increased total calories relative to pre-pandemic by 280 per adult per day from March to July 2020, and by 150 from July to the end of 2020. Although quantity increased, there was little change in diet quality over the pandemic. All socioeconomic groups increased their calorie intake, with the largest rises for the highest SES households and the smallest for retired ones. We estimate that the changes could increase the proportion of adults who are overweight by at least five percentage points, two years after the pandemic onset.

Bone segmentation in contrast enhanced whole-body computed tomography.

Segmentation of bone regions allows for enhanced diagnostics, disease characterisation and treatment monitoring in CT imaging. In contrast enhanced whole-body scans accurate automatic segmentation is particularly difficult as low dose whole body protocols reduce image quality and make contrast enhanced regions more difficult to separate when relying on differences in pixel intensities. This paper outlines a U-net architecture with novel preprocessing techniques, based on the windowing of training data and the modification of sigmoid activation threshold selection to successfully segment bone-bone marrow regions from low dose contrast enhanced whole-body CT scans. The proposed method achieved mean Dice coefficients of 0.979 ± 0.02, 0.965 ± 0.03, and 0.934 ± 0.06 on two internal datasets and one external test dataset respectively. We have demonstrated that appropriate preprocessing is important for differentiating between bone and contrast dye, and that excellent results can be achieved with limited data.

Braak's Unfinished Hypothesis: A Clinicopathological Case Report of α-Synuclein Peripheral Neuropathy Preceding Parkinsonism by 20 Years.

BACKGROUND: α-synuclein aggregates in the form of Lewy bodies and Lewy neurites are the pathological hallmark of Parkinson disease (PD) and dementia with Lewy bodies (DLB). Autopsy studies suggest that α-synuclein aggregates appear in localized areas of the central nervous system before spreading in a sequential pattern from the brainstem to the cerebral cortex, known as the Braak hypothesis. Increased prevalence of peripheral neuropathy in PD is recognized, with multiple hypothesized mechanisms including α-synuclein deposition. METHOD: We describe a patient who developed a peripheral sensory neuropathy at age 60, which progressed insidiously over the following decade. RESULTS: During the patient's eighth decade, the patient developed a fluctuant cognitive disturbance with hallucinations before becoming overtly parkinsonian at age 78 years leading to a diagnosis of DLB. At this point, histology slides from a sural nerve biopsy taken at age 72 were re-evaluated and immunohistochemistry demonstrated α-synuclein deposition. CONCLUSION: This case provides important in vivo clinical correlation for the Braak hypothesis, extending its scope beyond idiopathic PD. A growing body of evidence supports the α-synuclein spreading hypothesis that posits the pathologic process begins in the peripheral nerves and spreads trans-synaptically to the CNS in an ascending pattern.

Carotid Plaque Inflammation Imaged by PET and Prediction of Recurrent Stroke at 5 Years.

BACKGROUND AND OBJECTIVES: To determine whether carotid plaque inflammation identified by 18F-fluorodeoxyglucose (18FDG)-PET is associated with late (5-year) recurrent stroke. METHODS: We did an individual-participant data pooled analysis of 3 prospective studies with near-identical study methods. Eligible patients had recent nonsevere (modified Rankin Scale score ≤3) ischemic stroke/TIA and ipsilateral carotid stenosis (50%-99%). Participants underwent carotid 18FDG-PET/CT angiography ≤14 days after recruitment. 18FDG uptake was expressed as maximum standardized uptake value (SUVmax) in the axial single hottest slice of symptomatic plaque. We calculated the previously validated Symptomatic Carotid Atheroma Inflammation Lumen-Stenosis (SCAIL) score, which incorporates a measure of stenosis severity and 18FDG uptake. The primary outcome was 5-year recurrent ipsilateral ischemic stroke after PET imaging. RESULTS: Of 183 eligible patients, 181 patients completed follow-up (98.9%). The median duration of follow-up was 4.9 years (interquartile range 3.3-6.4 years, cumulative follow-up period 901.8 patient-years). After PET imaging, 17 patients had a recurrent ipsilateral ischemic strokes at 5 years (recurrence rate 9.4%, 95% confidence interval [CI] 5.6%-14.6%). Baseline plaque SUVmax independently predicted 5-year ipsilateral recurrent stroke after adjustment for age, sex, carotid revascularization, stenosis severity, NIH Stroke Scale score, and diabetes mellitus (adjusted hazard ratio [HR] 1.98, 95% CI 1.10-3.56, p = 0.02 per 1-g/mL increase in SUVmax). On multivariable Cox regression, SCAIL score predicted 5-year ipsilateral stroke (adjusted HR 2.73 per 1-point increase, 95% CI 1.52-4.90, p = 0.001). DISCUSSION: Plaque inflammation-related 18FDG uptake improved identification of 5-year recurrent ipsilateral ischemic stroke. Addition of plaque inflammation to current selection strategies may target patients most likely to have late and early benefit from carotid revascularization. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in individuals with recent ischemic stroke/TIA and ipsilateral carotid stenosis, carotid plaque inflammation-related 18FDG uptake on PET/CT angiography was associated with 5-year recurrent ipsilateral stroke.

Early evidence for historical overfishing in the Gulf of Mexico.

Fisheries encompass complex interplays between social, economic, and environmental factors, but limitations on historical fisheries data can hamper efforts to identify and contextualize the long-term spatiotemporal patterns that shape them. We integrate 2500 years of stable isotope (δ34S, δ13C, and δ15N) and zooarchaeological evidence from Gulf of Mexico fisheries to assess cultural, demographic, and technological changes affecting sheepshead (Archosargus probatocephalus) populations and fishing practices in Louisiana, USA. Concurrent with human population growth, average sizes of sheepshead caught decreased from the 1720s to 1830s. The size of fish caught after the 1830s increased to pre-1720 levels at the same time that isotopic compositions of fish bone collagen show that fish were being caught from a more diverse range of ecosystems, including distant seagrass beds. Our findings provide the first evidence for large-scale depressions of historical sheepshead populations and the processes driving them, including rapid human population growth and sustained harvesting pressure.

Preparing for a pandemic: spending dynamics and panic buying during the COVID-19 first wave.

In times of heightened uncertainty, consumers face incentives to build up precautionary stocks of essential supplies. We study consumer spending dynamics during one such time, the first infection wave of the COVID-19 pandemic, using household scanner data covering fast-moving consumer goods in the United Kingdom. We document large increases in demand for storable products, such as food staples and household supplies, in the days before lockdown. Households in all socio-economic groups exhibit unusually high demand pre-lockdown, but there is a clear gradient, with the largest demand spikes for wealthier households. Although stories of people purchasing extreme amounts received a lot of attention, higher aggregate demand was mainly driven by more households than usual choosing to buy storable products, with only small increases in average quantities bought on a given trip. Temporary limits on the number of units per transaction, introduced following the demand spike, are therefore unlikely to lead to the avoidance of stock-outs.

Incidental cardiac uptake in bone scintigraphy: increased importance and association with cardiac amyloidosis.

Extraosseous radiotracer uptake during bone scintigraphy must be carefully assessed and it offers the potential to detect previously undiagnosed disease processes. A range of neoplastic, metabolic, traumatic, ischaemic and inflammatory disorders can cause soft tissue accumulation of bone avid radiopharmaceuticals. Accordingly, cardiac uptake in bone scintigraphy has a broad differential diagnosis and is commonly attributed to ischaemia/infarction related to coronary artery disease. However, there has been renewed focus on incidental cardiac uptake in recent years in light of significant developments in the diagnosis and management of cardiac amyloidosis.

Solitary late metastasis of primary renal cell carcinoid tumor to the extraocular muscles imaged with indium-111 octreotide.

A 75-year-old male presented with right eye pain and proptosis. His history was significant for renal cell carcinoma treated with left nephrectomy 2 years previously. Computed tomography (CT) imaging demonstrated a 1.6-cm enhancing lesion in the right retrobulbar space. Surgical biopsy revealed a low-grade metastatic carcinoid tumor. At retrospective review, the primary renal lesion from 2 years prior was rediagnosed as consistent with a renal carcinoid tumor. Indium-111 octreotide single photon emission CT/CT imaging demonstrated a solitary metastasis within the right extraocular muscles. The patient subsequently developed additional metastases within the remaining right kidney and lung.

Association Between 18-FDG Positron Emission Tomography and MRI Biomarkers of Plaque Vulnerability in Patients With Symptomatic Carotid Stenosis.

Purpose: Pathologic studies suggest that unstable plaque morphology and inflammation are associated with cerebrovascular events. 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) is a validated technique for non-invasive imaging of inflammation-related plaque metabolism, and MRI can identify morphologic features of plaque instability. The aim of this study was to investigate the association of selected imaging characteristics of plaque vulnerability measured with MRI and PET in patients with symptomatic carotid stenosis. Methods: Patients from the BIOVASC study were selected based on the following inclusion criteria: (1) age ≥ 50 years; (2) recent (<30 days) ischaemic stroke (modified Rankin scale ≤3) or motor/speech/vision TIA; (3) ipsilateral internal carotid artery stenosis (≥5 0% lumen-narrowing); (4) carotid PET/CTA and MRI completed. Semi-automated plaque analysis of MRI images was performed to quantify morphologic features of plaque instability. PET images were co-registered with CTA and inflammation-related metabolism expressed as maximum standardised uptake value (SUVmax). Results: Twenty-five patients met inclusion criteria (72% men, mean age 65 years). MRI-measured plaque volume was greater in men (1,708-1,286 mm3, p = 0.03), patients who qualified with stroke (1,856-1,440 mm3, p = 0.05), and non-statin users (1,325-1,797 mm3, p = 0.03). SUVmax was associated with MRI-measured plaque lipid-rich necrotic core (LRNC) in the corresponding axial slice (r s = 0.64, p < 0.001) and was inversely associated with whole-plaque fibrous cap thickness (r s = -0.4, p = 0.02) and calcium volume (r s = -0.4, p = 0.03). Conclusion: This study demonstrated novel correlations of non-invasive imaging biomarkers of inflammation-related plaque metabolism with morphological MRI markers of plaque instability. If replicated, our findings may support the application of combined MRI and PET to detect vulnerable plaque in future clinical practise and randomised trials.

A comparative analysis: international variation in PET-CT service provision in oncology-an International Cancer Benchmarking Partnership study.

OBJECTIVE: To explore differences in position emission tomography-computed tomography (PET-CT) service provision internationally to further understand the impact variation may have upon cancer services. To identify areas of further exploration for researchers and policymakers to optimize PET-CT services and improve the quality of cancer services. DESIGN: Comparative analysis using data based on pre-defined PET-CT service metrics from PET-CT stakeholders across seven countries. This was further informed via document analysis of clinical indication guidance and expert consensus through round-table discussions of relevant PET-CT stakeholders. Descriptive comparative analyses were produced on use, capacity and indication guidance for PET-CT services between jurisdictions. SETTING: PET-CT services across 21 jurisdictions in seven countries (Australia, Denmark, Canada, Ireland, New Zealand, Norway and the UK). PARTICIPANTS: None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULTS: PET-CT service provision has grown over the period 2006-2017, but scale of increase in capacity and demand is variable. Clinical indication guidance varied across countries, particularly for small-cell lung cancer staging and the specific acknowledgement of gastric cancer within oesophagogastric cancers. There is limited and inconsistent data capture, coding, accessibility and availability of PET-CT activity across countries studied. CONCLUSIONS: Variation in PET-CT scanner quantity, acquisition over time and guidance upon use exists internationally. There is a lack of routinely captured and accessible PET-CT data across the International Cancer Benchmarking Partnership countries due to inconsistent data definitions, data linkage issues, uncertain coverage of data and lack of specific coding. This is a barrier in improving the quality of PET-CT services globally. There needs to be greater, richer data capture of diagnostic and staging tools to facilitate learning of best practice and optimize cancer services.

High-Frequency Changes in Shopping Behaviours, Promotions and the Measurement of Inflation: Evidence from the Great Lockdown.

We use real-time scanner data in Great Britain during the COVID-19 pandemic to investigate the drivers of the inflationary spike at the beginning of lockdown and to quantify the impact of high-frequency changes in shopping behaviours and promotions on inflation measurement. Although changes in product-level expenditure shares were unusually high during lockdown, we find that the induced bias in price indices that do not account for expenditure switching is not larger than in prior years. We also document substantial consumer switching towards online shopping and across retailers, but show this was not a key driver of the inflationary spike. In contrast, a reduction in price and quantity promotions was key to driving higher inflation, and lower use of promotions by low-income consumers explains why they experienced moderately lower inflation. Overall, changes in shopping behaviours played only a minor role in driving higher inflation during lockdown; higher prices were the main cause, in particular through a reduced frequency of promotions.

The potential health impact of restricting less-healthy food and beverage advertising on UK television between 05.30 and 21.00 hours: A modelling study.

BACKGROUND: Restrictions on the advertising of less-healthy foods and beverages is seen as one measure to tackle childhood obesity and is under active consideration by the UK government. Whilst evidence increasingly links this advertising to excess calorie intake, understanding of the potential impact of advertising restrictions on population health is limited. METHODS AND FINDINGS: We used a proportional multi-state life table model to estimate the health impact of prohibiting the advertising of food and beverages high in fat, sugar, and salt (HFSS) from 05.30 hours to 21.00 hours (5:30 AM to 9:00 PM) on television in the UK. We used the following data to parameterise the model: children's exposure to HFSS advertising from AC Nielsen and Broadcasters' Audience Research Board (2015); effect of less-healthy food advertising on acute caloric intake in children from a published meta-analysis; population numbers and all-cause mortality rates from the Human Mortality Database for the UK (2015); body mass index distribution from the Health Survey for England (2016); disability weights for estimating disability-adjusted life years (DALYs) from the Global Burden of Disease Study; and healthcare costs from NHS England programme budgeting data. The main outcome measures were change in the percentage of the children (aged 5-17 years) with obesity defined using the International Obesity Task Force cut-points, and change in health status (DALYs). Monte Carlo analyses was used to estimate 95% uncertainty intervals (UIs). We estimate that if all HFSS advertising between 05.30 hours and 21.00 hours was withdrawn, UK children (n = 13,729,000), would see on average 1.5 fewer HFSS adverts per day and decrease caloric intake by 9.1 kcal (95% UI 0.5-17.7 kcal), which would reduce the number of children (aged 5-17 years) with obesity by 4.6% (95% UI 1.4%-9.5%) and with overweight (including obesity) by 3.6% (95% UI 1.1%-7.4%) This is equivalent to 40,000 (95% UI 12,000-81,000) fewer UK children with obesity, and 120,000 (95% UI 34,000-240,000) fewer with overweight. For children alive in 2015 (n = 13,729,000), this would avert 240,000 (95% UI 65,000-530,000) DALYs across their lifetime (i.e., followed from 2015 through to death), and result in a health-related net monetary benefit of £7.4 billion (95% UI £2.0 billion-£16 billion) to society. Under a scenario where all HFSS advertising is displaced to after 21.00 hours, rather than withdrawn, we estimate that the benefits would be reduced by around two-thirds. This is a modelling study and subject to uncertainty; we cannot fully and accurately account for all of the factors that would affect the impact of this policy if implemented. Whilst randomised trials show that children exposed to less-healthy food advertising consume more calories, there is uncertainty about the nature of the dose-response relationship between HFSS advertising and calorie intake. CONCLUSIONS: Our results show that HFSS television advertising restrictions between 05.30 hours and 21.00 hours in the UK could make a meaningful contribution to reducing childhood obesity. We estimate that the impact on childhood obesity of this policy may be reduced by around two-thirds if adverts are displaced to after 21.00 hours rather than being withdrawn.

Real-time price indices: Inflation spike and falling product variety during the Great Lockdown.

We characterize inflation dynamics during the Great Lockdown using scanner data covering millions of transactions for fast-moving consumer goods in the United Kingdom. We show that there was a significant and widespread spike in inflation. First, aggregate month-to-month inflation was 2.4% in the first month of lockdown, a rate over 10 times higher than in preceding months. Over half of this increase stems from reduced frequency of promotions. Consumers' purchasing power was further eroded by a reduction in product variety. Second, 96% of households have experienced inflation in 2020, while in prior years around half of households experienced deflation. Third, there was inflation in most product categories, including those that experienced output falls. Only 13% of product categories experienced deflation, compared with over half in previous years. While market-based measures of inflation expectations point to disinflation or deflation, these findings indicate a risk of stagflation should not be ruled out. We hope our approach can serve as a template to facilitate rapid diagnosis of inflation risks during economic crises, leveraging scanner data and appropriate price indices in real-time.

Could COVID-19 Infect the Consumer Prices Index?

The spread of COVID-19 has led to sweeping changes in the way households work, spend their time and shop, resulting in different shopping patterns and rapid price changes in some goods. How will changes such as these be reflected in headline inflation measures such as the Consumer Prices Index (CPI)? This paper discusses problems in interpreting the CPI as a measure of how the cost of living is changing during the lockdown.

Cohort profile: BIOVASC-late, a prospective multicentred study of imaging and blood biomarkers of carotid plaque inflammation and risk of late vascular recurrence after non-severe stroke in Ireland.

PURPOSE: Inflammation is important in stroke. Anti-inflammatory therapy reduces vascular events in coronary patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) identifies plaque inflammation-related metabolism. However, long-term prospective cohort studies investigating the association between carotid plaque inflammation, identified on 18F-FDG PET and the risk of recurrent vascular events, have not yet been undertaken in patients with stroke. PARTICIPANTS: The Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) study and Dublin Carotid Atherosclerosis Study (DUCASS) are two prospective multicentred observational cohort studies, employing near-identical methodologies, which recruited 285 patients between 2008 and 2016 with non-severe stroke/transient ischaemic attack and ipsilateral carotid stenosis (50%-99%). Patients underwent coregistered carotid 18F-FDG PET/CT angiography and phlebotomy for measurement of inflammatory cytokines. Plaque 18F-FDG-uptake is expressed as maximum standardised uptake value (SUVmax) and tissue-to-background ratio. The BIOVASC-Late study is a follow-up study (median 7 years) of patients recruited to the DUCASS/BIOVASC cohorts. FINDINGS TO DATE: We have reported that 18F-FDG-uptake in atherosclerotic plaques of patients with symptomatic carotid stenosis predicts early recurrent stroke, independent of luminal narrowing. The incorporation of 18F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. However, the relationship between 18F-FDG-uptake and late vascular events has not been investigated to date. FUTURE PLANS: The primary aim of BIOVASC-Late is to investigate the association between SUVmax in symptomatic 'culprit' carotid plaque (as a marker of systemic inflammatory atherosclerosis) and the composite outcome of any late major vascular event (recurrent ischaemic stroke, coronary event or vascular death). Secondary aims are to investigate associations between: (1) SUVmax in symptomatic plaque, and individual vascular endpoints (2) SUVmax in asymptomatic contralateral carotid plaque and SUVmax in ipsilateral symptomatic plaque (3) SUVmax in asymptomatic carotid plaque and major vascular events (4) inflammatory cytokines and vascular events.

What's on the Menu? Policies to Reduce Young People's Sugar Consumption.

Young people in the UK consume far above the maximum recommended levels of added sugar. It is likely that neither they nor their parents fully take account of the future health, social and economic costs of this high sugar consumption. This provides a rationale for policy intervention. The majority of young people's added sugar consumption occurs in the home, where purchases are typically made by parents. This means that understanding the purchase decisions of adults is important for policy design, even if the policies aim to reduce the consumption of young people. We discuss the merits of popular policies, including taxes, advertising restrictions and restrictions on the availability of specific foods, and we identify promising avenues for future research.