Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells.

Thoracic aortic disease (TAD) is often silent until a life-threatening complication occurs. However, genetic information can inform both identification and treatment at an early stage. Indeed, a diagnosis is important for personalised surveillance and intervention plans, as well as cascade screening of family members. Currently, only 20% of heritable TAD patients have a causative mutation identified and, consequently, further advances in genetic coverage are required to define the remaining molecular landscape. The rapid expansion of next generation sequencing technologies is providing a huge resource of genetic data, but a critical issue remains in functionally validating these findings. Induced pluripotent stem cells (iPSCs) are patient-derived, reprogrammed cell lines which allow mechanistic insights, complex modelling of genetic disease and a platform to study aortic genetic variants. This review will address the need for iPSCs as a frontline diagnostic tool to evaluate variants identified by genomic discovery studies and explore their evolving role in biological insight through to drug discovery.

Understanding the current acute aortic syndrome (AAS) pathways-The Collaborative Acute Aortic Syndrome Project (CAASP) protocol.

BACKGROUND: Acute aortic syndrome (AAS) is an emergency associated with high peri-hospital mortality rates. Variable clinical presentation makes timely diagnosis challenging and such delays in diagnosis directly impact patient outcomes. AIMS AND OBJECTIVES: The aims of the Collaborative Acute Aortic Syndrome Project (CAASP) are to characterise and evaluate the current AAS pathways of a cohort of hospitals in the UK, USA and New Zealand to determine if patient outcomes are influenced by the AAS pathway (time to hospital admission, diagnosis and management plan) and demographic, social, geographic and patient-specific factors (clinical presentation and comorbidities). The objectives are to describe different AAS pathways and time duration between hospital admission to diagnosis and management plan instigation, and to compare patient outcomes between pathways. METHODS: The study is a multicentre, retrospective service evaluation project of adult patients diagnosed on imaging with AAS. It will be coordinated by the UK National Interventional Radiology Trainee Research (UNITE) network and Vascular and Endovascular Research Network (VERN) in conjunction with The Aortic Dissection Charitable Trust (TADCT). All AAS cases diagnosed on imaging between 1st January 2018 to 1st June 2021 will be included and followed-up for 6 months. Eligibility criteria include aortic dissection (AD) Type A, Type B, non A/B, penetrating aortic ulcer, and intramural haematoma. Exclusion criteria are non-AAS pathology, acute on chronic AAS, and age<18. This project will evaluate patient demographics, timing of presentation, patient symptoms, risk factors for AD, physical examination findings, timing to imaging and treatment, hospital stay, and mortality. Univariate and multivariate analysis will be used to identify predictors associated with prolonged time to diagnosis or treatment and mortality at 30 days.

A State-of-the-Art Review of Intra-Operative Imaging Modalities Used to Quality Assure Endovascular Aneurysm Repair.

Endovascular aortic aneurysm repair (EVAR) is the preferred method for elective abdominal aortic aneurysm (AAA) repair. However, the success of this technique depends greatly on the technologies available. Intra-operative imaging is essential but can come with limitations. More complex interventions lead to longer operating times, fluoroscopy times, and greater contrast doses. A number of intra-operative imaging modalities to quality assure the success of EVAR have been developed. A systematic literature search was performed with separate searches conducted for each imaging modality in the study: computed tomography (CT), digital subtraction angiography (DSA), fusion, ultrasound, intra-operative positioning system (IOPS), and non-contrast imaging. CT was effective at detecting complications but commonly resulted in increased radiation and contrast dose. The effectiveness of DSA can be increased, and radiation exposure reduced, through the use of adjunctive technologies. We found that 2D-3D fusion was non-inferior to 3D-3D and led to reduced radiation and contrast dose. Non-contrast imaging occasionally led to higher doses of radiation. Ultrasound was particularly effective in the detection of type II endoleaks with reduced radiation and contrast use but was often operator dependent. Unfortunately, no papers made it past full text screening for IOPS. All of the imaging techniques discussed have advantages and disadvantages, and clinical context is relevant to guide imaging choice. Fusion and ultrasound in particular show promise for the future.

Acute appendicitis management during the COVID-19 pandemic: A prospective cohort study from a large UK centre.

BACKGROUND: During the Covid-19 pandemic, non-operative management for acute appendicitis (AA) was implemented in the UK. The aim of this study was to determine the efficacy and outcomes of conservative versus surgical management of AA during the pandemic. MATERIALS & METHODS: We conducted an observational study in a tertiary referral centre. Data was collected from all patients (≥16 years) with a diagnosis of AA between November 1, 2019 to March 10, 2020 (pre-COVID period) and March 10, 2020 to July 5, 2020 (COVID period). RESULTS: A total of 116 patients in the pre-COVID period were included versus 91 in the COVID period. 43.1% (n = 50) of patients pre-COVID were classified as ASA 2 compared to 26.4% (n = 24) during the COVID period (p-value = 0.042). 72.5% (n = 66) of the patients during the COVID period scored as high risk using the Alvarado score compared to 24.1% (n = 28) in the pre-COVID period (p-value<0.001). We observed a significant increase in radiological evaluation, 69.8% versus 87.5% of patients had a CT in the pre-COVID and COVID periods respectively (p-value = 0.008). 94.9% of patients were managed operatively in the pre-COVID period compared to 60.4% in the COVID period (p-value<0.001). We observed more open appendicectomies (37.3% versus 0.9%; p-value<0.001) during the COVID period compared to the pre-COVID period. More abscess formation and free fluid were found intraoperatively in the COVID period (p-value = 0.021 and 0.023 respectively). Re-attendance rate due to appendicitis-related issues was significantly higher in the COVID period (p = 0.027). CONCLUSION: Radiological diagnosis of AA was more frequent during the COVID period. More conservative management for AA was employed during the COVID-19 pandemic, and for those managed operatively an open approach was preferred. Intra-operative findings were suggestive of delayed presentation during the COVID period without this affecting the length of hospital stay.

Ligation Alone Versus Immediate Revascularization for Femoral Artery Pseudoaneurysms Secondary to Intravascular Drug Use: A Systematic Review and Meta-Analysis.

BACKGROUND: Femoral artery pseudoaneurysms (FA-PSAs) remain a common vascular aneurysmal pathology associated with intravascular drug use (IVDU). To date no internationally agreed consensus regarding optimal surgical management of FA-PSAs exists. The aim of this systematic review and meta-analysis was to determine the optimal surgical treatment of FA-PSAs associated with IVDU. METHODS: A systematic search was undertaken following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines identifying original studies reporting outcomes of ligation-debridement and/or excision-revascularization of FA-PSAs secondary to IVDU. Outcomes of interest were 30-day mortality, incidence of amputation at 12 months, chronic limb threatening ischemia (CLTI) at any follow-up appointment, reintervention, and bleeding. RESULTS: A total of 39 cohort studies describing 1,217 FA-PSA operative outcomes met inclusion criteria, 993 (81.6%) treated by ligation-debridement and 224 (18.4%) by excision-revascularization. The incidence of 30-day mortality was 0.8% (n = 8) and 1.3% (n = 3) in the ligation-debridement and excision-revascularization groups, respectively, with only one study reporting mortality in both groups. This meta-analysis found no difference in amputation (8.89% vs. 8.03%, odds ratio (OR) 0.74 95% confidence interval (CI) 0.35-1.56, P = 0.42, 11 studies) or CLTI (21.5% vs. 12.4%, OR 1.24 95% CI 0.35-4.38, P = 0.74, 9 studies) after ligation and debridement compared with excision and revascularization. There was a higher incidence of reintervention (24.7% vs. 10.6%, OR 0.31 [95% CI 0.16, 0.62], P = 0.0009, 13 studies) and rebleeding (7.1% vs. 1.6%, OR 0.61 [95% CI 0.16, 2.38], P = 0.48, 5 studies) after excision and revascularization compared with ligation alone. CONCLUSIONS: For treatments of IVDU-related FA-PSAs, this study suggests no significant difference in association of mortality, incidence of amputation, or CLTI with ligation-debridement or excision-revascularization, but a significantly higher reintervention rate and greater rebleeding rate for revascularized patients.

Progressive Device Failure at Long Term Follow Up of the Nellix EndoVascular Aneurysm Sealing (EVAS) System.

OBJECTIVE: High rates of midterm failure of the Nellix EndoVascular Aneurysm Sealing (EVAS) System resulted in device withdrawal from the UK market. The study aim was to report long term Nellix EVAS outcomes and management of a failing device. METHODS: A retrospective review of EVAS procedures at a tertiary unit was performed. Device failure was defined as a triad of stent migration, stent separation, and secondary sac expansion, or any intervention for type 1 endoleak, device rupture, or explant. RESULTS: 161 (male n = 140, female n = 21) patients with a median follow up of 6.0 (IQR 5.0-6.6) years were included. Freedom from all cause mortality estimate at six years was 41.5%. There were 70 (43.5%) device failures with a freedom from device failure estimate at six years of 32.3%. Failure was the result of sac expansion (n = 41), caudal stent migration (n = 36), stent separation (n = 26), and secondary AAA rupture (n = 15). A substantial number of type 1 endoleaks was present (1a n = 33, 1b n = 11), but the type 2 endoleak rate was low at 3.7%. Some 36 (22.4%) patients required re-intervention. Twenty-one patients underwent explant with no 30 day deaths. Six patients underwent Nellix-in-Nellix application (NINA) with one early death from bowel ischaemia and one patient who died later from non-aneurysm related cause. Two NINA patients have ongoing sac expansion and two have had thrombosis of a Nellix limb or visceral stent. Proximal embolisation was only successful in one of six cases. CONCLUSION: The long term failure rate of Nellix EVAS is high. All patients with a device must be informed and be enrolled in enhanced surveillance. EVAS explant is an acceptable technique with favourable outcomes. Management by open explant, if the patient is fit, should be considered early and offered to those with device failure.

Evaluating quality in clinical care.

Defining and maintaining quality is essential to surgical practice. It is only through structured approaches to assessing outcomes that we can ensure that optimal care is delivered. This article will define quality in healthcare and discuss assessment models with reference to pertinent surgical literature. National initiatives are discussed with a critical appraisal of their role and effectiveness. We discuss the aim of quality improvement initiatives and comment on reporting of outcomes. The difficult question of how to maintain quality during a crisis, such as an infectious disease pandemic, is addressed.

Erectile Dysfunction in Peripheral Vascular Disease: Endovascular Revascularization as a Potential Therapeutic Target.

INTRODUCTION: Erectile dysfunction (ED) affects more than 150 million men worldwide, with deleterious effects on quality of life. ED is known to be associated with ischemic heart disease but the impact of ED in patients with peripheral arterial disease (PAD) is unknown. We assessed the prevalence and severity of ED in patients with PVD. METHODS: Following ethical approval, sequential male patients diagnosed with PAD over a 1-year period following diagnosis of intermittent claudication. The patient demographics and comorbidities were recorded, with the International Index of Erectile Function (IIEF-5) questionnaire used to grade severity of ED. Computed tomographic angiography and severity of stenosis in the proximal vessels and internal pudendal arteries were correlated using a modified Bollinger Matrix scoring system. RESULTS: 60 patients were recruited, most (77.2%) reported erectile dysfunction (52.5% severe, 22.5% moderate). Patients with severe ED were more likely to have 2 or more comorbidities (P = .009). 86.7% with severe ED had bilateral internal pudendal artery stenosis with a mean modified Bollinger score of 17.6. 35.5% of moderate ED patients had bilateral internal pudendal stenosis with a mean Bollinger score of 11.75. There was significant difference in overall scores between moderate and severe erectile dysfunction (p< 0.05), thus indicating a potential link between ED severity and extent of vessel stenosis. CONCLUSION: There is a substantial burden of clinically significant ED among patients with PAD. This study suggests ED should be discussed with all PAD patients and ED may precede a PAD diagnosis. There is scope for endovascular revascularization as a treatment option for ED secondary to arterial insufficiency.