Highly integrated workflows for exploring cardiovascular conditions: Exemplars of precision medicine in Alzheimer's disease and aortic dissection.

For precision medicine to be implemented through the lens of in silico technology, it is imperative that biophysical research workflows offer insight into treatments that are specific to a particular illness and to a particular subject. The boundaries of precision medicine can be extended using multiscale, biophysics-centred workflows that consider the fundamental underpinnings of the constituents of cells and tissues and their dynamic environments. Utilising numerical techniques that can capture the broad spectrum of biological flows within complex, deformable and permeable organs and tissues is of paramount importance when considering the core prerequisites of any state-of-the-art precision medicine pipeline. In this work, a succinct breakdown of two precision medicine pipelines developed within two Virtual Physiological Human (VPH) projects are given. The first workflow is targeted on the trajectory of Alzheimer's Disease, and caters for novel hypothesis testing through a multicompartmental poroelastic model which is integrated with a high throughput imaging workflow and subject-specific blood flow variability model. The second workflow gives rise to the patient specific exploration of Aortic Dissections via a multi-scale and compliant model, harnessing imaging, computational fluid-dynamics (CFD) and dynamic boundary conditions. Results relating to the first workflow include some core outputs of the multiporoelastic modelling framework, and the representation of peri-arterial swelling and peri-venous drainage solution fields. The latter solution fields were statistically analysed for a cohort of thirty-five subjects (stratified with respect to disease status, gender and activity level). The second workflow allowed for a better understanding of complex aortic dissection cases utilising both a rigid-wall model informed by minimal and clinically common datasets as well as a moving-wall model informed by rich datasets.

Different types of thoracic endografts.

The emerging role of stent-graft strategies for the management of thoracic aortic diseases has attracted growing acceptance, especially in considering the sobering results of open repair in thoracic high-risk settings (e.g., acute dissection, trauma, rupture). Aortic endograft technology for thoracic diseases has rapidly improved after the early use of first generation devices, and the new models show very promising early and mid-term success rates. To date there is no evidence of the superiority of any single device model over the others. Indeed, each device has some peculiarities that makes it more useful in specific settings. Current limitations in thoracic stent-grafts will hopefully be addressed with new designs of highly-individualized low-profile devices in order to extend the applicability of stent-graft technology in the thoracic aorta. Despite progress in configuration and flexibility and the greater availability of different devices compared to a decade ago, shortcomings of specific endovascular grafts including collapse, migration, or dislodgment have not been fully resolved. Nowadays the selection of patients on the basis of favourable anatomy and pathology is the key for the success of the procedure. Not all patients have lesions amenable to stent-graft repair (contraindications for endovascular treatment of thoracic aorta are still not marginal and mainly defined by anatomical constraints) and thoracic endografting is technically challenging, requiring dedicated facilities and experienced specialists. This paper discusses the different configurations and models of stent-graft for thoracic aortic disease as well as the still existing shortcomings.

Carotid endarterectomy; local or general anaesthesia?

OBJECTIVES: to review the evidence for theoretical and clinical benefits of local or general anaesthesia for carotid endarterectomy. METHODS: literature review. RESULTS: animal studies suggest cerebral protection by a variety of general anaesthetic agents but clinical evidence is lacking. There is some clinical evidence that normal cerebral protective reflexes are preserved with local anaesthesia. Shunt insertion is the most widely used method of providing cerebral protection with awake testing the most reliable monitoring technique for the identification of ischaemia. There are therefore theoretical arguments for a reduced risk of perioperative stroke when local anaesthesia is used and this is supported by a meta-analysis of non-randomised studies. Intraoperative blood pressure is always higher with local anaesthesia but the incidence of postoperative haemodynamic instability seems to be independent of anaesthetic technique. There is little evidence that myocardial ischaemia is more common with either anaesthetic technique but meta-analysis of non-randomised again suggests fewer cardiac complications with local anaesthesia. Cranial nerve injury and haematoma formation may be less common with local anaesthesia but the evidence is weak. There is no evidence that surgery is more difficult with local anaesthesia or that it is poorly tolerated by the patients. CONCLUSIONS: there are theoretical arguments and clinical evidence that the outcome from carotid endarterectomy may be better when local anaesthesia is used with no significant disadvantages. An appropriately designed randomised trial is required to confirm this.

Carotid artery dissection. Correlation of different diagnostic techniques.

Dissection of the carotid artery is a rare entity, but a frequent cause of cerebrovascular accidents in young adults and can result in severe neurologic consequences that are often irreversible. Carotid dissection can be secondary to trauma, brisk rotation of hyperextension of the neck, as a complication in certain diseases. It may lead to distal embolization, complete occlusion of the vessel, extensive or limited stenosis, aneurysmal form which has the appearance of a berry aneurysm or resolution of the process with complete patency of the dissected vessel. The authors find color-Doppler sonography to be an invaluable tool in the evaluation of such a process, since it is non invasive, readily available, relatively inexpensive and can yield detailed information about the lumen of the vessel, blood flow, mural and intramural structures. Furthermore, in comparison to MRA, color-Doppler sonography is particularly suitable for the early detection of thrombus. Ultrasonographic investigation has some methodologic limitations: occlusion cannot always be demonstrated directly because of its high cervical location and detection of aneurysms localized in the retrostyloid++ space is usually not possible. The combination of ultrasonographic findings and MRA is the method of choice for follow-up on evaluation of carotid dissection and helps make the decision as to whether one should proceed to angiography in this young age group.