A comparative study into the effects of venous and arterial blood on clot microstructure in critically unwell patients. Assessment of the diagnostic potential of a biomarker of haemostasis.

Blood for coagulation analysis can be sampled from the arterial or venous system in intensive care units (ICU). The determination of clot microstructure and strength by fractal analysis (d) gives valuable information in a range of vascular haemostatic disease and sepsis. We aimed to determine if d could be measured equally and comparatively in arterial or venous blood, and 45 critically ill patients in an ICU were recruited.

The Impact of Patient Characteristics and Antiplatelet Regimes on Clot Microstructure in Patients Treated for ST Elevation Myocardial Infarction: Clot Microstructure can Evaluate Therapeutic Efficacy.

Background: Unfavourable clot microstructure is associated with adverse outcomes in ST elevation myocardial infarction (STEMI). We investigated the effect of comorbidities and anti-platelet treatment on clot microstructure in STEMI patients using fractal dimension (d), a novel biomarker of clot microstructure derived from the visco-elastic properties of whole blood.

Methods: Patients with STEMI (n = 187) were recruited sequentially receiving aspirin with Clopidogrel (n = 157) then Ticagrelor (n = 30).

The efficacy of low molecular weight heparin is reduced in COVID-19.

Background: A significant degree of mortality and morbidity in COVID-19 is through thromboembolic complications, only partially mitigated by anticoagulant therapy. Reliable markers of infection severity are not fully established.

Objectives: This study investigated whether visco-elastic biomarkers predict disease severity on presentation to the Emergency Department (ED) and how they measure response to anticoagulationMETHODS:Patients testing positive for COVID-19 at a large University Teaching Hospital ED were recruited at presentation.

High levels of soluble RAGE are associated with a greater risk of mortality in COVID-19 patients treated with dexamethasone.

Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients.

Impaired fibrinolysis in severe Covid-19 infection is detectable in early stages of the disease.

Background: A significant degree of mortality and morbidity in Covid-19 is due to thromboembolic disease. Coagulopathy has been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time.

The effects of apixaban on clot characteristics in atrial fibrillation: A novel pharmacodynamic biomarker.

Atrial fibrillation (AF) is a major risk factor for stroke. We aim to characterize AF patients and the effects of apixaban therapy in terms of clot microstructure using gel point analysis, a novel biomarker. Seventy-eight patients were included in the study, 50 Stroke with AF (AF-S), and 28 AF without stroke (AF).

The effect of diabetic ketoacidosis (DKA) and its treatment on clot microstructure: Are they thrombogenic?

Background: Diabetic ketoacidosis (DKA) is a medical emergency with a high mortality rate and is associated with severe metabolic acidosis and dehydration. DKA patients have an increased risk of arterial and venous thromboembolism, however little is known about this metabolic derangement in the first 24 hours of admission and to assess its effect on coagulation. We therefore utilised a novel functional marker of clot microstructure (fractal dimension - df) to assess these changes within the first 24 hours.

The effect of tyramine infusion and exercise on blood flow, coagulation and clot microstructure in healthy individuals.

Background: The long term benefits of exercise on the cardiovascular status of a patient have been proven, however, their benefit/risk relationship with exercise intensity is unclear. Furthermore, many thromboembolic diseases such as myocardial infarction and ischaemic stroke are associated with profound catecholamine release. In this study we explore the relationship between catecholamine release and hemodynamic changes and their effect on coagulation.

Epidemiology of burns and scalds in children presenting to the emergency department of a regional burns unit: a 7-year retrospective study.

Background: Variation in the incidence and mechanism of thermal injury has been reported in different age groups in children. The aim of this study was to report the incidence, mechanisms, and environmental factors of all burns presentations to the emergency department (ED) of a regional burns centre over a 7-year period.

Methods: A retrospective, chart review study of all burns presentations to the ED of a regional burns centre in South Wales was conducted.

Electrochemical monitoring of transport by a vesicular monoamine transporter expressed in Xenopus oocytes.

Xenopus laevis oocytes were injected with synthetic mRNA coding for a rat VMAT2 mutant (rVMAT2-I483A/L484A) shown previously to be retained on the plasma membrane as a result of a presumed reduction of endocytosis. Binding of the specific VMAT inhibitor [3H]dihydrotetrabenazine indicated that expression did occur at a level of approximately 3 fmol per oocyte. To determine if rVMAT2-I483A/L484A expressed in oocytes was capable of substrate transport, oocytes were placed in buffer at pH 6.

Two decades of orphan product development.

Over the past 20 years, incentives of the Orphan Drug Act (ODA), the largest single source of extramural clinical grants at the US Food and Drug Administration, have had a substantial impact on public health. ODA incentives have contributed to the development of many innovative biotechnology products, and as our understanding of the human genome evolves, it is anticipated that pharmacogenomics will result in the identification of more 'orphan diseases'.