Dudley Group of Hospitals NHS Trust

Dudley, United Kingdom

Dudley Group of Hospitals NHS Trust

Dudley, United Kingdom
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Saratzis A.,Dudley Group of Hospitals NHS Trust | Saratzis A.,Aristotle University of Thessaloniki | Saratzis A.,NHS England | Sarafidis P.,Aristotle University of Thessaloniki | And 2 more authors.
Journal of Vascular Surgery | Year: 2014

Objective: The impact of any intervention on renal function is a crucial determinant of outcome. Open (OR) and endovascular (EVAR) abdominal aortic aneurysm (AAA) repair can affect renal function during the short and longer term. This study aimed to directly compare the effect of those different types of aneurysm repair during a period of 2 years. Methods: This was a nested case-control study including patients undergoing either OR or EVAR of an infrarenal AAA. Three groups were included: OR, EVAR with suprarenal endograft fixation, and EVAR with infrarenal fixation. These were matched for age (within 2 years), sex, AAA size (within 1 cm), hypertension, smoking, and proximal neck diameter (within 5 mm). The primary end point was change in estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration formula at baseline, 6 months, 12 months, and 2 years. Results: A total of 225 patients were included [(45 ORs matched vs 90 suprarenal and 90 infrarenal fixation EVARs; 35 women (16%); age, 71 ± 8 years; AAA size, 6.4 ± 1 cm]. Groups did not differ significantly in terms of diabetes, hypercholesterolemia, or baseline eGFR (P =.89). On average, those undergoing OR lost a mean 5.39 mL/min/1.73 m2 (P =.48) within 1 year and 5.49 units (P =.42) after 2 years. The suprarenal fixation patients lost 5.58 units (P =.002) after 1 year and 6.57 units (P =.001) after 2 years. Finally, the infrarenal fixation patients lost 0.53 unit (P =.74) after 1 year and 2.24 units (P =.22) after 2 years. Conclusions: OR and suprarenal fixation EVAR are associated with significant declines in renal function during 2 years, in contrast to infrarenal EVAR fixation. The patterns of eGFR decline in OR and suprarenal fixation EVAR are not similar, suggesting different causal mechanisms. Copyright © 2014 by the Society for Vascular Surgery.

Summers G.D.,Royal Derby Hospital | Metsios G.S.,University of Wolverhampton | Stavropoulos-Kalinoglou A.,University of Birmingham | Kitas G.D.,Dudley Group of Hospitals NHS Trust
Nature Reviews Rheumatology | Year: 2010

Both cachexia and cardiovascular disease are strongly associated with rheumatoid arthritis (RA) and linked to the chronic inflammatory process. Typically, rheumatoid cachexia occurs in individuals with normal or increased BMI (reduced muscle mass and increased fat mass). Classic cachexia (reduced muscle mass and reduced fat mass) is rare in RA but is associated with high inflammatory activity and aggressive joint destruction in patients with a poor cardiovascular prognosis. Conversely, obesity is linked to hypertension and dyslipidemia but, paradoxically, lower RA disease activity and less cardiovascular disease-related mortality. Rheumatoid cachexia might represent the 'worst of both worlds' with respect to cardiovascular outcome, but until diagnostic criteria for this condition are agreed upon, its effect on cardiovascular disease risk remains controversial. © 2010 Macmillan Publishers Limited.

Toms T.E.,Dudley Group of Hospitals NHS Trust | Panoulas V.F.,Dudley Group of Hospitals NHS Trust | Kitas G.D.,Dudley Group of Hospitals NHS Trust | Kitas G.D.,University of Manchester
Open Cardiovascular Medicine Journal | Year: 2011

Autoimmunity forms the basis of many rheumatological diseases, and may contribute not only to the classical clinical manifestations but also to the complications. Many of the autoimmune rheumatological diseases, including rheumatoid arthritis and systemic lupus erythematosus are associated with an excess cardiovascular morbidity and mortality. Much of this excess cardiovascular risk can be attributed to atherosclerotic disease. Atherosclerosis is a complex pathological process, with dyslipidaemia and inflammation fundamental to all stages of plaque evolution. The heightened inflammatory state seen in conjunction with many rheumatological diseases may accelerate plaque formation, both through direct effects on the arterial wall and indirectly through inflammation-mediated alterations in the lipid profile. Alongside these factors, antibodies produced as part of the autoimmune nature of these conditions may lead to alterations in the lipid profile and promote atherosclerosis. In this review, we discuss the association between several of the rheumatological autoimmune diseases and dyslipidaemia, and the potential cardiovascular impact this may confer. © Toms et al.

Cocco G.,Cardiology Office | Gasparyan A.Y.,Dudley Group of Hospitals NHS Trust
Open Cardiovascular Medicine Journal | Year: 2010

Behçet's disease (BD) is an enigmatic inflammatory disorder, with vasculitis (perivasculitis) underlying pathophysiology of its multisystemic affections. Venous pathology and thrombotic complications are hallmarks of BD. However, it has been increasingly recognized that cardiac involvement and arterial complications (aneurysms, pseudoaneurysms, rupture and thrombosis) are important part of the course of BD. Pericarditis, myocardial (diastolic and/or systolic dysfunction), valvular and coronary (thrombosis, aneurysms, rupture) involvement, intracardiac thrombi (predominantly right-sided) are, probably, the most frequent cardiac manifestations. Treatment of cardiovascular involvement in BD is largely empirical and aimed at suppression of vasculitis. The most challenging seems to be the treatment of arterial aneurysms and thromboses due to the associated risk of bleedings. Cardiologists should always bear in mind potential threats of (a)symptomatic cardiovascular involvement in BD. © Cocco and Gasparyan.

Cocco G.,Cardiology Office | Gasparyan A.Y.,Dudley Group of Hospitals NHS Trust
Open Cardiovascular Medicine Journal | Year: 2010

Wegener's granulomatosis (WG) is one of the most common small-and medium-sized necrotizing vasculitides that mainly affects the upper and lower respiratory tract and the kidneys. Cardiac manifestations in WG are relatively rare, and their role and place among different causes of mortality remain largely unknown. Substantially increased number of reports describing involvement of all structures of the heart, which underlie conduction disturbances, valvular disease, ischemic heart disease and other potentially serious conditions, underscores importance of comprehensive cardiovascular investigations and monitoring of patients with WG. The majority of previous reports and our current observation distinguish coronary vasculitis and thrombosis as a cause of myocardial ischemia and cardiovascular co-morbidities in WG. It seems plausible that inflammatory processes in this disease, like in some other systemic vasculitidies, do not predispose to accelerated atherogenesis. However, characteristic small-and mediumsized vasculitis still can manifest as myocardial ischemia and infarction. We overview diverse cardiac manifestations and present our own rare case of angina in the oligosymptomatic debut of WG. Importantly, in this case, coronarography failed to reveal atherosclerotic disease or thrombotic occlusion. However, magnetic resonance imaging (MRI) with adenosine test revealed subendocardial ischemia. As a result of immunosuppressive therapy with a steroid and cyclophosphamide, myocardial ischemia disappeared. © Cocco and Gasparyan.

Toms T.E.,Dudley Group of Hospitals NHS Trust | Symmons D.P.,University of Manchester | Kitas G.D.,Dudley Group of Hospitals NHS Trust | Kitas G.D.,University of Manchester
Current Vascular Pharmacology | Year: 2010

Rheumatoid arthritis (RA) associates with excess cardiovascular morbidity and mortality, resulting in significantly shortened lifespan. Traditional risk factors (e.g. dyslipidaemia and hypertension) and novel risk factors (e.g. systemic inflammation) contribute to the development of cardiovascular disease (CVD) in RA. In the general population, dyslipidaemia has been found to be central to the development of CVD, playing an important role in all stages of atherosclerotic plaque formation. In RA, lipid metabolism may be altered by systemic inflammation, environmental lifestyle factors, drug therapy and several genetic factors. This may result in changes in overall lipid levels, as well as modifications of lipid/lipoprotein structure and function. In this review, we discuss lipid abnormalities specifically in the context of RA and highlight the potential impact of inflammation, genetic factors, lifestyle, and anti-rheumatic drugs on lipid metabolism. © 2010 Bentham Science Publishers Ltd.

Dimitroulas T.,Dudley Group of Hospitals NHS Trust | Nikas S.N.,Dudley Group of Hospitals NHS Trust | Trontzas P.,Polycliniki Hospital | Kitas G.D.,Dudley Group of Hospitals NHS Trust | Kitas G.D.,University of Manchester
Autoimmunity Reviews | Year: 2013

Chronic inflammation affects bone metabolism leading to disequilibrium in the rates of bone resorption and repair and subsequently to local and generalized bone loss. Osteoporosis represents an important co-morbidity of rheumatoid arthritis (RA) patients, which exhibit increased fracture risk. Osteoclasts play a pivotal role in the development and progression of bone loss, while resident synovial cells such as T cells, monocytes and synovial fibroblasts have been identified as sources of osteoclast differentiation signals in RA. This process is mainly mediated through the receptor activator of nuclear-kappa B ligand (RANKL) signalling system, which is upregulated by numerous proinflammatory cytokines involved in the pathogenesis of RA. Improved knowledge of the association between cells and cytokines of the immune system and their relationship to bone remodeling has revealed several promising targets for the treatment of inflammatory bone loss in RA. In this respect, initiation of biologic therapies targeting inflammatory cytokines and/or lymphocyte activation has modified RA therapy not only by blocking local and systemic inflammatory cascades but also by providing beneficial effects against bone and joint degradation. In this article we briefly present the modern view of the mechanisms that govern inflammatory bone loss, highlighting the role of cytokine-induced molecular pathways, and discuss in detail the effects of different biologic treatment strategies on bone mass in RA patients. © 2013 Elsevier B.V.

Bayley R.,University College Birmingham | Kite K.A.,University College Birmingham | McGettrick H.M.,University College Birmingham | Smith J.P.,Dudley Group of Hospitals NHS Trust | And 3 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Objectives: A genetic variant of the leukocyte phosphatase PTPN22 (R620W) is strongly associated with autoimmune diseases including rheumatoid arthritis (RA). Functional studies on the variant have focussed on lymphocytes, but it is most highly expressed in neutrophils. We have investigated the effects of the variant on neutrophil function in health and in patients with RA. Methods: Healthy individuals and patients with RA were genotyped for PTPN22 (R620W) and neutrophils isolated from peripheral blood. Neutrophil adhesion and migration across inflamed endothelium were measured. Calcium (Ca2+) release and reactive oxygen species (ROS) production in response to fMLP stimulation were also assessed. Results: Expression of R620W enhanced neutrophil migration through cytokine activated endothelium (non-R620W=24%, R620W=45% migrating cells, p<0.001). Following fMLP stimulation, neutrophils that were heterozygous and homozygous for R620W released significantly more Ca2+ when compared to non-R620W neutrophils, in healthy individuals and patients with RA. fMLP stimulation, after TNF-α priming, provoked more ROS from neutrophils heterozygous for R620W in patients with RA (non-R620W vs R620W=̃1.75-fold increase) and healthy individuals (non-R620W vs R620W=fourfold increase) and this increase was statistically significant in healthy individuals (p<0.001) but not in patients with RA (p<0.25). Conclusions: Expression of PTPN22 (R620W) enhanced neutrophil effector functions in health and RA, with migration, Ca2+ release and production of ROS increased. Neutrophils are found in large numbers in the RA joint, and this hyperactivity of R620W cells may directly contribute to the joint damage, as well as to the initiation and perpetuation of the chronic immune-mediated inflammatory processes driving the disease. © 2014 BMJ Publishing Group Ltd & European League Against Rheumatism.

Sandoo A.,Dudley Group of Hospitals NHS Trust
Rheumatology (Oxford, England) | Year: 2011

RA associates with significantly increased morbidity and mortality from cardiovascular disease (CVD). This may be due to complex interactions between traditional CVD risk factors, systemic rheumatoid inflammation and the vasculature. We reviewed the current literature to answer: (i) whether there is sufficient evidence that patients with RA have altered vascular function and morphology compared with normal controls; (ii) whether there is sufficient evidence to determine if such changes relate predominantly to systemic inflammation; and (iii) whether any changes of vascular function and morphology in RA can be modified with therapy. The MEDLINE database was searched to identify publications from 1974 to 1 November 2010 pertaining to vascular function and morphology in RA. The total number of articles included in the present review was 93. This included 57 cross-sectional studies, 27 longitudinal studies without randomization and 9 longitudinal studies with randomization. Vascular function and morphology was impaired in RA relative to healthy controls. The majority of studies reported no associations between systemic inflammation and vascular function. Treatment with anti-inflammatory medication resulted in both transient and long-term improvements in the vasculature, but only a few studies reported associations between change in inflammation and change in vascular function and morphology. The link between systemic inflammation and vascular function and morphology is not wholly supported by the available literature. Long-term studies examining specific predictors (including CVD risk factors) on the vasculature in RA are needed.

Sandoo A.,Dudley Group of Hospitals NHS Trust | Kitas G.D.,Dudley Group of Hospitals NHS Trust | Carmichael A.R.,Dudley Group of Hospitals NHS Trust
Anticancer Research | Year: 2014

Background: Breast cancer is the most common cancer in females in the UK and has greater severity in patients who overexpress human epidermal growth receptor 2 (HER2) proteins in the breast tissue. Trastuzumab is a humanised monoclonal antibody and is targeted towards blocking the HER2 pathway and effectively reduces the recurrence of breast cancer and associated mortality. However, trastuzumab is also associated with an increased risk of cardiotoxicity which likely results from inhibition of the HER2 pathway. Under normal conditions HER2 pathways help maintain the integrity of the myocardial contractile elements, as well as the coronary vasculature, but trastuzumab inhibits these survival pathways and increases the risk for congestive heart failure (CHF). In the present review, we summarise the pathways that are implicated in the development of CHF in patients receiving trastuzumab. We also highlight the role of trastuzumab-mediated endothelial dysfunction and CHF.

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