Protocol for an observational study to assess the impact of pharmacogenetics on outcomes in vascular surgery (PROSPER).

Introduction: Patients with chronic limb-threatening ischaemia (CLTI) are often prescribed clopidogrel in order to reduce their risk of major adverse limb and cardiovascular events. Clopidogrel is metabolised by the CYP2C19 enzyme and genetic variations in are common. These variants can influence an individual's ability to metabolise clopidogrel to its active metabolite.

A review of clopidogrel resistance in lower extremity arterial disease.

Objective: Lower extremity arterial disease (LEAD) is a prevalent condition that produces a significant burden on health care systems. Patients with LEAD have an increased risk of major adverse cardiovascular events as well as major adverse limb events. Despite significant variation in guidance on antiplatelet therapy for LEAD worldwide, many governing bodies recommend clopidogrel as the preferred single anti-platelet agent.

Development and Validation of a Rapid Point-of-Care CYP2C19 Genotyping Platform.

Pharmacogenetic-guided prescribing can lead to more accurate medicine selection and dosing, improving patient outcomes and leading to better use of health care budgets. Loss-of-function variants in CYP2C19 influence an individual's ability to metabolize clopidogrel, increasing the risk of secondary vascular events following ischemic stroke and percutaneous coronary intervention. In acute clinical contexts, centralized laboratory-based testing is too slow to inform timely clinical decision-making.

Outcomes of Endovascular Aneurysm Repair using the Ovation Stent Graft System in Adverse Anatomy.

Objective: The aim was the evaluation of mid-term efficacy and safety outcome measures for the Ovation (Endologix, Santa Rosa, CA, USA) stent graft system in the management of infrarenal abdominal aortic aneurysms (iAAA) with adverse anatomy.

Methods: A retrospective observational study of all patients undergoing elective iAAA repair was carried out from 2012 to 2017 using Ovation Prime or iX stent grafts with a minimum of 3 months follow-up at a single UK vascular centre. Post-operative surveillance involved computed tomography scans at 3 months and 1 year, with duplex ultrasound yearly thereafter.

Chemokines in Wound Healing and as Potential Therapeutic Targets for Reducing Cutaneous Scarring.

Cutaneous scarring is an almost inevitable end point of adult human wound healing. It is associated with significant morbidity, both physical and psychological. Pathological scarring, including hypertrophic and keloid scars, can be particularly debilitating.

Noninvasive device readouts validated by immunohistochemical analysis enable objective quantitative assessment of acute wound healing in human skin.

Objective evaluation of cutaneous wounds through use of noninvasive devices has important implications for diagnosis, monitoring treatment efficacy, progression and may lead to development of improved theranostic treatment strategies. However, there is a lack of validation in the use of certain devices in wound repair, where objective measurements taken by noninvasive devices have been corroborated by immunohistochemical analysis. Thus, data from three acute wound-healing studies in healthy volunteers using three noninvasive objective devices were further evaluated by immunohistochemistry.

Skin substitute-assisted repair shows reduced dermal fibrosis in acute human wounds validated simultaneously by histology and optical coherence tomography.

Skin substitutes are heterogeneous biomaterials designed to accelerate wound healing through provision of replacement extracellular matrix. Despite growing evidence for their use in chronic wounds, the role of skin substitutes in acute wound management and their influence on fibrogenesis remains unclear. Skin substitute characteristics including biocompatibility, porosity, and elasticity strongly influence cellular behavior during wound healing.

Acute cutaneous wounds treated with human decellularised dermis show enhanced angiogenesis during healing.

Background: The influence of skin substitutes upon angiogenesis during wound healing is unclear.

Objectives: To compare the angiogenic response in acute cutaneous human wounds treated with autogenic, allogenic and xenogenic skin substitutes to those left to heal by secondary intention.

Methods: On day 0, four 5mm full-thickness punch biopsies were harvested from fifty healthy volunteers (sites 1-4).

Single-stage application of a novel decellularized dermis for treatment-resistant lower limb ulcers: positive outcomes assessed by SIAscopy, laser perfusion, and 3D imaging, with sequential timed histological analysis.

We present results of an original clinical study investigating efficacy of a decellularized dermal skin substitute (DCD) as part of a one-stage therapeutic strategy for recalcitrant leg ulcers. Twenty patients with treatment-resistant ulcers underwent hydrosurgical debridement, after which DCD was applied and covered with negative pressure dressings for 1 week. Participants were reviewed on seven occasions over 6 months.

Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing.

Cutaneous wound healing ultimately functions to facilitate barrier restoration following injury-induced loss of skin integrity. It is an evolutionarily conserved, multi-cellular, multi-molecular process involving co-ordinated inter-play between complex signalling networks. Cellular proliferation is recognised as the third stage of this sequence.

The role of skin substitutes in the management of chronic cutaneous wounds.

Chronic wounds, including diabetic and venous ulcers, represent disruption of normal healing processes resulting in a pathological state of nonhealing cutaneous inflammation. They place an increasingly significant economic burden on healthcare providers as their prevalence is rising in keeping with an aging population. Current treatment modalities are slow acting and resource intensive.