Carotid Ultrasound for Stroke Prediction

Introduction: The aims of this thesis were to identify if carotid endarterectomy was cost-effective and affordable in the United Kingdom and secondly to explore the potential of contrast enhanced ultrasound and plaque texture analysis for risk stratification in asymptomatic patients with carotid atherosclerosis. Methods: A cost-utility analysis based on results from the Asymptomatic Carotid Surgery Trial was performed using a Markov transition state model. Three cross-sectional studies of symptomatic and asymptomatic individuals with 50-99% carotid stenosis were performed for late phase and dynamic phase contrast enhanced ultrasound, followed by plaque texture analysis. Results: There was a high probability of surgical endarterectomy lying under the £20-30, 000 per quality adjusted life year National Institute for Health and Clinical Excellence acceptability threshold in the United Kingdom. In men under 75 years of age, the cost per quality adjusted life year gained was lower and in women there was improved effectiveness with reduced long-term costs. Late phase contrast enhanced ultrasound imaging of carotid atherosclerosis suffered from a tissue suppression artefact which limited its ability to image microbubble retention. Quantification of plaque perfusion using low mechanical index imaging demonstrated a pseudoenhancement phenomenon from non-linear propagation, which artificially increased far wall intensity, again limiting its use for quantification of plaque perfusion. Semi-quantitative grading of plaque perfusion revealed no significant difference in generalised plaque perfusion between symptomatic and asymptomatic individuals, however detection of ulceration using dynamic contrast enhanced ultrasound showed a trend towards an association with symptomatic status. Type II plaque showed a significant independent association with symptomatic status. Conclusion: Carotid endarterectomy is likely to be cost-effective in those under 75 years of age, particularly women. However, without further selection, the upfront costs and high number needed to treat with endarterectomy limit its potential as a large scale strategy. Improvements in non-linear pulse sequencing are required before quantitative contrast enhanced ultrasound can reliably be used for functional imaging of carotid atherosclerosis. Qualitative assessment of plaque perfusion is unlikely to gain widespread use due to its high subjectivity. However assessment of plaque type and to a lesser extent imaging of ulceration using contrast enhanced ultrasound are promising and reproducible imaging biomarkers for further study. Validation of these markers with histology and then prospective study of individuals with these plaque phenotypes is proposed. In the future individuals with a recent transient ischaemic attack and moderate (50-69%) stenosis may prove to be an ideal group for risk stratification

Risk of intracerebral aneurysm rupture during carotid revascularization

ObjectiveRobust guidelines exist for the treatment of carotid stenosis and intracranial aneurysms independently, however, the management of tandem carotid stenosis and intracranial aneurysms remains uncertain. Although the prevalence of tandem pathologies is small (1.9%-3.2%), treating carotid stenosis can alter intracranial hemodynamics potentially predisposing to aneurysm rupture. In this review, our aim was to assess the safety of intervention in this cohort, by analyzing outcomes from the published literature.MethodsThe preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to conduct the review. Articles from 1947 to 2012 were searched using EMBASE Classic and EMBASE (November, 1947 -March, 2012) and Ovid MEDLINE(R) In-Process and other NonIndexed Citations and Ovid MEDLINE(R) on Ovid SP, http://ClinicalTrials.gov, http://controlled-trials.com and the Cochrane review database using a predefined search strategy.ResultsOne hundred forty-one patients from 27 articles were included. Interventions ranged from single (n = 104, 74%), staged (n = 26, 18%) to simultaneous procedures (n = 11, 8%). The largest cohort of patients was treated by carotid endarterectomy alone (n = 92, 66%). The majority of patients presented with a symptomatic carotid stenosis and an asymptomatic ipsilateral intracranial aneurysm (n = 70, 50%). Five subarachnoid hemorrhages occurred (4% [5/140], three within 30 days of the procedure and two thereafter) of which two were fatal. All five occurred in patients who underwent carotid endarterectomy as a single procedure (5%). Two of the five patients presented with ruptured posterior communicating artery aneurysms.ConclusionsPublished reports of perioperative aneurysm rupture are rare in individuals with tandem carotid stenosis and intracranial aneurysms. This is the first analysis of all published cases. However, it is limited by the small number of studies and the possible underreporting due to publication bias and underdiagnosis where angiography was not performed. Although we report a low incidence of subarachnoid hemorrhage, analysis of registry data with a larger cohort is warranted to confirm these findings

Multiple arterial emboli secondary to left ventricular thrombus in a 35-year-old obese male

The very unusual case of a 35-year-old obese male patient with a left ventricular (LV) thrombus secondary to a silent myocardial infarction and resultant shower emboli to multiple arterial sites is described. His presentation with acute limb ischemia led to arterial imaging and the identification of the underlying cardiac pathology in addition to splenic and bilateral renal infarcts. He was also found to suffer from previously undiagnosed hypertension. He underwent femoral embolectomy and multiple arterial revascularization attempts but required bilateral above knee amputations and a prolonged intensive care unit stay. This rare and extreme example of a LV thrombus in a young male emphasizes the potential sequellae of the condition. Furthermore, with the increasing incidence of obesity this case demonstrates the importance of considering undiagnosed cardiovascular risk factors when assessing obese patients

Thyroid Hemiagenesis: Narrative Review and Clinical Implications

Thyroid Hemiagenesis (THA) is an uncommon, congenital anomaly defined by the absence of one thyroid lobe with or without the isthmus. Reports suggest it may be found more often in regions endemic for hypothyroidism. Genetic abnormalities are thought to have a role based on findings in monozygotic twins. Most cases are sporadic, however familiar clusters have also been documented. It is found more frequently in females. A majority of patients report no symptoms and THA is found incidentally during investigations or intraoperatively. THA is usually associated with normal thyroid function, but it can present with thyroid hypofunction. Since a majority of patients are asymptomatic, there are no specific recommendations for management. Ultrasound imaging and thyroid scintigraphy using technetium or iodine are useful in diagnosis. Its clinical importance occurs when the remnant thyroid lobe requires excision leading to the lifelong requirement for thyroxine supplementation. Published English literature (Medline, PubMed, and Embase databases) was searched. Medical subject headings (MeSH) terms used were “thyroid hemiagenesis,” “one thyroid lobe,” and “thyroid aplasia”. Case reports, case series, and original articles were selected to provide a framework for this review. Articles reviewed were published in the past 20 years. The association of THA with thyroid cancer was explored. In this group, the F:M ratio was 3.25:1. Left THA constituted 53% of cases, right THA in 29.4%, and isthmus absence in 17.6% of cases. Also, the authors investigated the link between THA and hyperparathyroidism, both left and right THA are seen in an equal number of cases in the hyperparathyroidism subgroup. In patients with THA and Grave’s disease, left THA was seen in a majority of cases (86.7%), while an equal number of left and right THA was observed in patients with Hashimoto’s thyroiditis. In addition, congenital abnormalities associated with THA were observed, the left THA was seen in 60% and right THA in 40% of cases of this subgroup. The summative review provided a detailed insight into the epidemiology, aetiopathogenesis, genetics, symptomatology, diagnosis, and treatment for THA by combining findings and results from almost a hundred research papers from around the world. THA remains a poorly understood, often incidentally detected, abnormality in euthyroid patients undergoing investigations and treatment for other thyroid disorders

Compression hosiery to avoid post-thrombotic syndrome (CHAPS) protocol for a randomised controlled trial (ISRCTN73041168)

Introduction: Up to 50% of patients develop post-thrombotic syndrome (PTS) after an above knee deep vein thrombosis (DVT). The aim of the study was to determine the effect of graduated compression stockings in preventing PTS after DVT. Methods and analysis: Pragmatic, UK multicentre randomised trial in adults with first above knee DVT. The standard of care arm is anticoagulation. The intervention arm will receive anticoagulation plus stockings (European class II, 23–32 mm Hg compression) worn for a median of 18 months. The primary endpoint is PTS using the Villalta score. Analysis of this will be through a time to event approach and cumulative incidence at median 6, 12 and 18 months. An ongoing process evaluation will examine factors contributing to adherence to stockings to understand if and how the behavioural interventions were effective. Ethics and dissemination: UK research ethics committee approval (reference 19/LO/1585). Dissemination though the charity Thrombosis UK, the Imperial College London website, peer-reviewed publications and international conferences. Trial registration number: ISRCTN registration number 73041168

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

QoL and PROMS Following Percutaneous and Surgical Intervention for Renal Artery Disease

Isolated renal artery intervention is performed in adults mainly for atherosclerosis and fibromuscular dysplasia. Indications for treatment include acute ischaemic nephropathy, transplant renal artery stenosis and multi-drug resistant severe hypertension, particularly in the setting of a solitary functioning kidney.There is limited data on QoL and PROMS after renal artery intervention. Outcomes for these may be better for those who have fibromuscular dysplasia as the driving pathology and who undergo successful endovascular treatment, particularly if dialysis would otherwise have been imminent, and if side effects from antihypertensive agents are severe

Fulminant Wegener's granulomatosis presenting as epistaxis

The case of a 63‐year‐old woman who presented to the emergency department with epistaxis and haemodynamic instability is reported. Subsequent investigation showed renal failure and multiple pulmonary nodules. A positive proteinase 3 antineutrophil cytoplasmic antibody test supported the diagnosis of fulminant Wegener's granulomatosis, requiring urgent dialysis, plasma exchange and immunosuppression. This is the first report in the emergency literature of Wegener's granulomatosis presenting as acute epistaxis. Emergency physicians should consider Wegener's granulomatosis in patients with atypical epistaxis. In patients presenting with clinically severe, active disease early proteinase 3 antineutrophil cytoplasmic antibody testing is recommended