The persistent challenges faced by vascular surgery services during the UK coronavirus pandemic: a snapshot qualitative survey.

INTRODUCTION: The coronavirus (COVID-19) pandemic continues to affect the NHS. The Vascular and Endovascular Research Network (VERN) COvid Vascular sERvice (COVER) study has prospectively shown the significant global impact of the COVID-19 pandemic on vascular surgery. The aim of this study is to investigate the way in which this second wave has affected surgeons' ability to treat patients with urgent vascular conditions, using contemporaneous snapshot data from 30 UK vascular centres. METHODS: This is a contemporary (18-28 January 2021) re-run of the Tier 1 COVER survey. This used closed and open questions, related to centres' provision of common vascular services, threshold for treatment, imaging, screening, staff and theatre availability, multidisciplinary team input, clinics, personal protective equipment, vaccination policies and case-backlogs. The survey was disseminated to clinicians via email. A service reduction score was calculated. RESULTS: Forty-two complete responses were received from 30 vascular centres (England, Northern Ireland, Scotland and Wales). Overall, 56.7% of units are performing only urgent procedures. The threshold for abdominal aortic aneurysm (AAA) repair has increased in the majority of UK centres (60%). One in six AAA screening programmes have stopped all screening activity: 30% having a significantly reduced programme and only half running as normal. Waiting lists are increasing for AAA, lower limb revascularisation and venous disease. CONCLUSION: Overall, these data suggest that vascular care in the NHS is facing unprecedented pressures due to COVID-19. Vascular stakeholders will have to urgently address these issues in the coming months. STUDY REGISTRATION NUMBER: ISRCTN 80453162 (registered prospectively).

Multimodal analysis of the effects of dexamethasone on high-altitude cerebral oedema: protocol for a pilot study.

BACKGROUND: Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. METHODS/DESIGN: D4H is a double-blind placebo-controlled randomised trial assessing the effect of dexamethasone on hypoxia-induced cerebral oedema. In total, 20 volunteers were randomised in pairs to receive either 8.25 mg dexamethasone or normal saline placebo intravenously after 8 h of hypoxia with an FiO2 of 12%. Serial MRI images of the brain and spinal cord were obtained at hours 0, 7, 11, 22 and 26 of the study along with serum and urinary markers to correlate with the severity of cerebral oedema and the effect of the intervention. DISCUSSION: MRI has been used to identify changes in cerebral vasculature in the development of AMS and HACE. Dexamethasone is effective at reducing the symptoms of AMS; however, the mechanism of this effect is unknown. If this study demonstrates a clear objective benefit of dexamethasone in this setting, future studies may be able to demonstrate that dexamethasone is an effective therapy for oedema associated with brain and spinal cord ischaemia beyond AMS. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03341676 . Registered on 14 November 2017.

Neutrophil swarming and extracellular trap formation play a significant role in Alum adjuvant activity.

There are over 6 billion vaccine doses administered each year, most containing aluminium-based adjuvants, yet we still do not have a complete understanding of their mechanisms of action. Recent evidence has identified host DNA and downstream sensing as playing a significant role in aluminium adjuvant (aluminium hydroxide) activity. However, the cellular source of this DNA, how it is sensed by the immune system and the consequences of this for vaccination remains unclear. Here we show that the very early injection site reaction is characterised by inflammatory chemokine production and neutrophil recruitment. Intravital imaging demonstrates that the Alum injection site is a focus of neutrophil swarms and extracellular DNA strands. These strands were confirmed as neutrophil extracellular traps due to their sensitivity to DNAse and absence in mice deficient in peptidylarginine deiminase 4. Further studies in PAD4-/- mice confirmed a significant role for neutrophil extracellular trap formation in the adjuvant activity of Alum. By revealing neutrophils recruited to the site of Alum injection as a source of the DNA that is detected by the immune system this study provides the missing link between Alum injection and the activation of DNA sensors that enhance adjuvant activity, elucidating a key mechanism of action for this important vaccine component.

A systematic review of postoperative cognitive decline following open and endovascular aortic aneurysm surgery.

OBJECTIVES Postoperative cognitive decline (POCD) is a well-recognised neurological phenomenon following major surgery. Most commonly seen in elderly patients, it has direct links to increased long-term morbidity and reduced quality of life. Its incidence following open and endovascular abdominal and thoracic aneurysm surgery is unclear. The purpose of this systematic review is to collate available evidence for POCD following abdominal and thoracic aortic surgery, and to identify continuing controversies directing future research. METHODS A MEDLINE search was conducted following the recommendations of the PRISMA guidelines. Terms searched for included but were not limited to: aortic surgery, delirium, postoperative cognitive decline/dysfunction thoracic aortic surgery, abdominal aortic surgery. Reference lists were searched for additional studies. RESULTS Five observational studies were identified from the literature search. Variation in study methods, cognitive test batteries and thresholds set by the study coordinators did not allow for pooled results. In those studies that did find evidence of decline, risk was linked to age over 65 years, presence of postoperative delirium and decreased years in education. CONCLUSIONS Evidence thus far suggests that POCD can affect patients following major aortic, non-cardiothoracic as well as cardiothoracic surgery. Future research should focus on using a validated repeatable battery of cognitive tests and a single defined threshold for POCD to allow pooled analysis and more robust conclusions. Larger, adequately powered studies are required to re-evaluate the effect of aortic aneurysm surgery on postoperative cognitive function.

Symptomatic Renal Artery Stenosis and Infra-renal AAA.

OBJECTIVES: To identify evidence to guide the vascular surgeon as to the relevance of renal artery stenting in a patient with symptomatic renal artery stenosis undergoing elective endovascular aortic aneurysm repair (EVAR). METHODS: A comprehensive literature search of MEDLINE was performed without time limits. The following terms were used in the first instance: renal artery stenting and renal artery stenosis, and any other analogous terms identified during the search. Selection criteria were set to randomised control trials. RESULTS: Despite several large, randomised controlled trials investigating renal artery stenting against medical treatment alone in symptomatic renal artery stenosis, there has been no significant benefit identified in terms of improvement in renal function, control of blood pressure, or need for dialysis. The stented populations were also more likely to suffer from complications caused by the procedure such as bleeding, cholesterol embolisation and flash pulmonary oedema. CONCLUSION: There is no evidence for the use of renal artery stenting over optimal medical management in the treatment of patients with symptomatic atherosclerotic renal artery stenosis, irrelevant of the degree of stenosis. In the setting of EVAR, prevention of deterioration of renal function should be with involvement of the renal physicians, adequate hydration, and use of minimal contrast agent. Repair should be undertaken in centres with access to 24-hour haemofiltration services.

Embolisation of type 2 endoleaks after endovascular aneurysm repair.

Endovascular treatment has become the preferred method of repair of abdominal and thoracic aortic aneurysms, and comes with a unique complication in the form of endoleaks (type I-IV). Type II endoleaks are the focus of this review. They are the most common form of endoleak detected in CT surveillance following endovascular repair. They are observed in 9% to 30% of patients after abdominal endovascular repair (EVR), and 1.4% following thoracic endovascular aortic repair (TEVR). They are classified as primary or secondary, depending on when they are identified following EVR. Typically, retrograde filling of the aneurysm sac is caused by single or multiple, patent feeding vessels. Despite its relative frequency, there is a lack of consensus on the threshold at which treatment should be considered. The aims of treatment are to halt sac expansion or to prevent rupture. A majority of patients may be managed conservatively. In those that are treated, the most common form of management is single vessel embolization. As we will discuss here, there are several ways of performing this procedure, based on the site of endoleak, and causative vessel. Possible reasons for poor success rates will also be discussed. A general consensus on how to best manage these patients is yet to be reached. The aim of this review is to give an overview of type II endoleaks, their natural history and vessels most commonly involved, as well as different approaches to embolisation.

Effects of Streptococcus mutans on dendritic cell activation and function.

Despite existing preventive and therapeutic measures, caries remains a ubiquitous infectious disease. Vaccine studies suggest that an adaptive immune response, culminating in effective antibody production, may reduce an individual's susceptibility to caries. However, the efficacy of the immune response elicited by mutans streptococci in the oral cavity remains controversial. A greater understanding of the early stages of the adaptive immune response to cariogenic bacteria may potentially assist therapeutic targeting and design. We therefore sought to characterize dendritic cell (DC) activation and antigen presentation following Streptococcus mutans exposure. We found that S. mutans up-regulated DC expression of co-stimulatory molecules and MHCII in vitro and that DCs effectively processed and presented exogenously administered antigen. These DCs effectively initiated T-cell proliferation, but this was abrogated by live bacteria. The in vitro DC activation effects were not mirrored in vivo, where DCs in draining lymph nodes did not mature following oral exposure to S. mutans. Analysis of these data provides a model for studying antigen uptake from the oral cavity and evidence that, in vitro, S. mutans activates dendritic cells, a critical event for initiating adaptive immunity.

Arthritis in space and time--to boldly go!

Despite the profound impact of biologics on the treatment of rheumatoid arthritis (RA), long lasting disease remission remains elusive. We propose that this is a consequence of failing to target the right molecular pathway in the most relevant patient group at the appropriate time and place in disease progression. A limitation to testing this approach is the availability of disease models representing the discrete steps in autoimmune pathogenesis. A particular example is the paucity of models to dissect the conditions permissive for the breach of self-tolerance, which would subsequently allow identification and testing of therapeutics for re-establishment of self-tolerance. We conclude that a detailed understanding of the location and timing of events leading to the systemic breach of self-tolerance and subsequent progression to tissue specific pathology are required if rational application of existing drugs and identification of novel targets is to be achieved. This will take the personalised medicine revolution into the realms of contextualised medicine, whereby the right drug is targeted to the right tissue, in the right patient, at the right time.

Photorefractive keratectomy for residual myopia after radial keratotomy. PRK After RK Study Group.

PURPOSE: To evaluate the visual outcomes in patients having photorefractive keratectomy (PRK) to correct residual myopia after radial keratotomy (RK). SETTING: Nine refractive surgery centers in the United States and one in South Korea. METHODS: This retrospective analysis comprised 38 eyes of 32 patients treated with PRK after RK and followed for 12 months. Analysis was based on pre-RK and pre-PRK refraction as well as response to RK (pre-RK minus pre-PRK refractions). RESULTS: Mean pre-RK and pre-PRK refractions were -8.11 diopters (D) +/- 2.92 (SD) and -4.28 +/- 2.08 D, respectively. One month after PRK, mean refraction was +0.42 +/- 1.56 D and regressed to -0.95 +/- 1.24 D at 12 months. At 12 months, 65% of eyes had an uncorrected visual acuity of 20/40 or worse, and 11.1% lost 2 or more lines of best corrected acuity. Of eyes with an original erro of -6.00 or less, 81.8% were within +/- 1.00 D of intended correction at 12 months and of those with an original error of -9.12 to -20.00 D 50.0% (P = .004). All eyes with residual (pre-PRK) errors of -3.00 D or less and 42.9% with a residual error of -6.12 to -9.00 D were within +/- 1.00 D of intended correction (P = .07). There were no statistically significant differences in the response to PRK between eyes that had an RK response of 0 to 3.00, 3.12 to 6.00, or 6.12 to 12.00 D. CONCLUSION: Patients with lower original and residual myopia achieved better visual outcomes after PRK than those with higher myopia. The amount of myopic correction achieved using RK was not predictive of the amount of myopic correction using PRK.

Suicide by overdoses of medicines among the aged.

The current literature on suicide by medicinal overdose among the elderly population of the United States and Britain is discussed. The older white male is a high risk in this regard. Physical and mental illnesses contribute to the problem of suicide among the aged, and some of the drugs prescribed for treatment (e.g., barbiturates and psychotherapeutic agents) are often accessible to the older person for misuse in suicide. The responsibilities of the prescribing physician and the practices of the dispensing pharmacist are considered in relation to the exposure of the elderly patient to potentially lethal drugs. Prediction of suicidal attitudes in the elderly is complicated by the fact that any attempt at suicide usually is serious and rarely preceded by gestures. Depression, based on social factors, is common among older people. Some of them face problems of declining income and prestige, as well as a loss of physical and mental powers. A change in the attitude of society towards the elderly may help to alleviate the depressive state which so often contributes to the suicidal potential.