Systematic review of endovascular intervention and surgery for common femoral artery atherosclerotic disease.

BACKGROUND: Endovascular intervention has emerged as a potential alternative to open surgery in treating common femoral artery (CFA) atherosclerotic disease. The aim of this systematic review was to assess the safety and efficacy of both techniques. METHODS: Thirteen electronic databases from 1980 to 3 January 2018 were searched. Study quality was assessed using the National Institute for Health and Care Excellence Interventional Procedure Programme quality assessment tool. Safety and efficacy outcome measures were analysed. RESULTS: Thirty-one studies reporting 813 endovascular procedures and 3835 endarterectomies were included. Only two small RCTs have been reported. The methodological quality of available studies was generally low and follow-up short. Safety endpoint assessment revealed a similar risk of wound haematoma for endovascular intervention and endarterectomy (5·5 (95 per cent c.i. 0·2 to 17·2) versus 3·9 (1·7 to 6·9) per cent respectively), a lower risk of wound infection with endovascular procedures (0 versus 5·9 (3·4 to 9·0) per cent) and a lower risk of wound lymph leakage (0 versus 5·7 (3·3 to 8·6) per cent). Efficacy endpoint assessment at 1 year identified that endovascular intervention had a lower primary patency rate than endarterectomy (78·8 (73·3 to 83·8) versus 96·0 (92·2 to 98·6) per cent respectively), a higher revascularization rate (16·0 (6·1 to 29·4) versus 5·8 (1·0 to 14·2) per cent) and a similar amputation rate (2·7 (1·2 to 4·8) versus 1·9 (0·7 to 3·8) per cent). CONCLUSION: Endovascular intervention of CFA disease appears to reduce the risk of wound complications but is associated with a lower patency rate and increased rates of subsequent revascularization procedures. Standardization of the endovascular technique and quantification of the proportions of patients suitable for either technique are required.

Circulating biomarkers of angiogenesis as indicators of left ventricular systolic dysfunction amongst patients with coronary artery disease.

BACKGROUND: Patients with coronary artery disease (CAD) and left ventricular systolic dysfunction (LVSD) are often asymptomatic. Angiogenesis is implicated in the physiology of vascular repair and cardiac remodelling, and is one of many pathophysiological processes implicated in heart failure. We hypothesized that plasma indices associated with angiogenesis [angiogenin, vascular endothelial growth factor (VEGF), and angiopoietin (Ang)-1 and Ang-2] would be abnormal in CAD patients with LVSD, being correlated with EF and wall motion abnormalities (wall motion score) independently of underlying CAD (coronary atheroma score). We also evaluated the specificity of angiogenic 'biomarkers' in their detection of LVSD [ejection fraction (EF) <40%] amongst CAD patients. METHODS: Using a cross sectional approach, we measured angiogenin, VEGF, Ang-1 and Ang-2 by ELISA in 194 CAD patients (aged 34-81 years) undergoing elective coronary angiography. RESULTS: Levels of angiogenin were inversely related with EF (r = -0.17, P = 0.02) and positively with coronary atheroma scores (r = 0.15, P = 0.04, but not independently of EF). Other angiogenic markers were unrelated to objective measures of LVSD but VEGF (P = 0.008) and Ang-2 (P = 0.015) were lower amongst those patients with heart failure. Angiogenin levels were related to wall motion scores (r = 0.16, P = 0.024). CONCLUSION: Heart failure has a modest impact on biomarkers of angiogenesis, in patients with CAD. Further research is warranted into the diagnostic and prognostic utility of biomarkers of angiogenesis, in this common cardiac condition.

Effects of coronary artery disease and percutaneous intervention on the cardiac metabolism of nonesterified fatty acids and insulin: Implications of diabetes mellitus.

BACKGROUND: Nonesterified fatty acids (NEFA) and insulin have been implicated in the pathogenesis of diabetes mellitus (Type 2 diabetes) and coronary artery disease (CAD). We hypothesized that intracardiac levels of insulin and NEFA within the aortic root, coronary sinus and systemic venous levels would be different in patients with coronary atherosclerosis and/or diabetes. We also studied the metabolic cardiac response following percutaneous coronary intervention (PCI). METHODS: A total of 67 subjects (42 males; mean age 60 +/- 11 years) were recruited, of which three groups were identified: Group I - those with no CAD or Type 2 diabetes (n = 17); Group II - those with CAD but no Type 2 diabetes (n = 40); and Group III - patients with Type 2 diabetes and CAD (n = 10). Of the whole cohort, 34 patients (51%) proceeded to PCI. NEFA and insulin levels were analysed using enzymatic colorimetric and a monoclonal immuno-autoanalyser techniques, respectively. Subsequently, fractional extraction (FFE) of both variables was calculated. RESULTS: Nonesterified fatty acids and insulin concentrations were lower in the aortic root versus coronary sinus (both P < 0.05). FFE of NEFA was 2x higher in Group I (P < 0.01) with a sevenfold reduction in insulin FFE in Group III. Following PCI, systemic NEFA levels increased significantly (P < 0.05) with no significant change seen within the coronary sinus (P = NS), whilst a reduction in insulin concentrations at all three sites was observed (all P < 0.01). No significant difference in FFE of NEFA was seen after PCI when comparing Groups II and III. There was a drop in insulin extraction in Group II (nondiabetic subjects, from 12% to -4%, P = 0.04), compared with an increase seen in Group III (Type 2 diabetes patients, from -4% to 3%, P = 0.03). CONCLUSION: There is an intracardiac gradient of NEFA and insulin in Groups I-III. Cardiac NEFA metabolism was higher in those with mild CAD compared with those with obstructive CAD whereas intracardiac insulin extraction was lower in Group III (diabetic) patients. PCI was associated with a systemic rise in NEFA, with a reduction in insulin levels and cardiac utilization, but these effects were blunted in diabetic patients.

Audit of the use of IVC filters in the UK: experience from three centres over 12 years.

AIM: To audit the use of inferior vena cava (IVC) filter insertions at three UK centres over 12 years to assess whether trends in filter use in the UK mirrored those seen elsewhere. MATERIALS AND METHODS: Radiology department databases were interrogated for IVC filter insertions and removals between 1994 and 2006. Reports for these interventions, along with prior and subsequent imaging reports, were analysed. Follow-up data were obtained when available. RESULTS: Five hundred and sixteen filters were placed with a significant year-on-year trend towards increasing use. Fifty-seven percent of filters placed were for absolute indications and 37% for relative indications. The filters were used for prophylaxis in 6% of patients in the absence of proven pulmonary embolism (PE) or deep vein thrombosis (DVT). A retrievable filter was used in 74% of cases with retrieval attempted in 40% of these and no evidence of an increasing rate of retrieval over time. A significant complication related to insertion or retrieval was encountered in 0.4 and 1% of procedures, respectively. Mean 24 h and 30 day mortalities were 1 and 8%, respectively. There was an absence of organized follow-up at all three centres. CONCLUSION: IVC filter use in the UK is increasing. The use of retrievable filters has not resulted in increased filter retrieval. Filter insertion and retrieval is associated with a low risk of significant complication, but lack of systematic follow-up limits conclusions regarding safety and efficacy.

Circulating serum adiponectin levels in patients with coronary artery disease: relationship to atherosclerotic burden and cardiac function.

BACKGROUND: Abnormal adipocyte function is implicated in both the pathophysiology of coronary heart disease (CHD) and cardiac function, where adiponectin provides a putative link. However, the utility of adiponectin as a discriminator of CHD severity is unclear and may be confounded by cardiac function. We hypothesized that plasma adiponectin would relate to indices of coronary artery disease severity (coronary atheroma scores, CAS), ejection fraction (EF) and regional wall motion abnormalities (RWMA) therein. METHOD: We measured adiponectin using a cross-sectional approach, we measured plasma adiponectin enzyme-linked immunosorbent assay in 204 consecutive patients (aged 34-81 years) undergoing elective coronary angiography. RESULTS: Levels of adiponectin decreased in an ordinal fashion across tertiles of increasing CAS (P = 0.047), but were nonsignificantly correlated to absolute values of CAS (P = 0.06). Adiponectin levels were unrelated to left ventricular dysfunction related measures of RWMA or EF. On multivariate analysis, (including factors relating to CHD risk, history and medication) adiponectin levels were independently inversely associated with triglycerides (P = 0.001), CAS tertiles (P = 0.01) and positively with age (P < 0.001). CONCLUSION: Levels of adiponectin decreased with coronary artery disease severity, without impact from systolic dysfunction, but levels may be moderated through established CHD risk factors such as smoking and triglycerides. Further work is warranted as to the clinical prognostic utility of this marker amongst CHD patients.

Secular trends in the cardiovascular risk profile and mortality of stroke admissions in an inner city, multiethnic population in the United Kingdom (1997-2005).

Our objective was to study ethnic differences in the cardiovascular risk profile and mortality of stroke admissions to an inner city teaching hospital serving a multiethnic population in Birmingham, UK, over a 9-year period (1997-2005). Hospital case notes and registry data of 3083 patients admitted with a first onset stroke were reviewed. Secular trends in the prevalence of risk factors (hypertension, diabetes, hyperlipidaemia, atrial fibrillation and myocardial infarction), hospital admission rates and 30-day mortality among Afro-Caribbean, European Caucasian and South Asian ethnic groups were analysed. Between 1997 and 2005, there were 3083 first onset strokes, of whom 47.6% (1595) were men, 9.3% Afro-Caribbean, 57.8% European Caucasian and 15.1% South Asian. There was a significant trend towards a reduction in non-haemorrhagic stroke admissions over the study period (P<0.001), with no ethnic variation (P=0.07). Increases in hypertension and hyperlipidaemia were observed (P<0.001), whereas myocardial infarction showed a decline (P<0.001). Compared to other ethnic groups, South Asian patients were younger on admission (P<0.001), had more hyperlipidaemia (P<0.05) and poorer survival at 30 days (P=002). We conclude that cardiovascular risk profiles among patients admitted with non-haemorrhagic stroke have changed over the last decade. In particular, hyperlipidaemia has increased, especially among South Asians. The reduced decline in stroke admissions and 30-day survival of stroke in South Asians in recent years warrants further investigation and highlights the importance of a targeted health-care approach in the migrant ethnic minorities.

Assessment of apparent internal carotid occlusion on ultrasound: prospective comparison of contrast-enhanced ultrasound, magnetic resonance angiography and digital subtraction angiography.

OBJECTIVES: Modern conventional ultrasound is sensitive to slow flow, but may misclassify some tight stenoses as occlusion. Symptomatic patients with tight proximal internal carotid artery stenoses may benefit from carotid endarterectomy but those with occlusion or long-segment disease do not. DESIGN: A prospective study of the diagnostic accuracy of contrast-enhanced ultrasound (CE-US), 2D time-of-flight magnetic resonance angiography (2D-TOF MRA) and contrast-enhanced magnetic resonance angiography (CE-MRA) against a reference standard of digital subtraction angiography (DSA) in patients with apparent carotid occlusion on conventional ultrasound. MATERIALS AND METHODS: Thirty-one patients with apparent carotid occlusion on conventional ultrasound and with recent ispilateral hemispheric transient ischaemeic attacks (TIAs) were studied. The primary endpoint was confirmation of occlusion with a secondary endpoint of identification of a surgically correctible lesion. RESULTS: The sensitivity and specificity of CE-US, 2D-TOF MRA and CE-MRA for patency were 1 & 1, 0.33 & 1 and 0.6 & 1 respectively and for the detection of a surgically correctible lesion were 1 & 0.96, 0.67 & 1 and 1 and 0.96 respectively. CE-US was difficult to interpret, precluding confident diagnosis in 5 cases. CONCLUSIONS: 2D-TOF MRA had poor sensitivity for patency and cannot be recommended as a second-line investigation to assess vessels apparently occluded on conventional ultrasound. Confident diagnosis on CE-US and CE-MRA accurately identified occlusion. If occlusion is confirmed by either of these modalities, no further imaging is required. The relative advantages of CE-US or CE-MRA in this situation are uncertain.

Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin.

BACKGROUND: Type 1 diabetes mellitus (DM) is an autoimmune disorder with disturbed glucose/insulin metabolism, which has no medical treatment other than life-long insulin therapy, despite which 30% of subjects develop organ failure. Herein we have reported the use of human adipose-tissue-derived, insulin-making mesenchymal stem cells (h-AD-MSC) transfused with unfractionated cultured bone marrow (CBM) in 5 insulinopenic DM patients. PATIENTS AND METHODS: Five (M:F, 2:3) insulinopenic DM patients of 0.6 to 10 years' duration, ages 14 to 28 years under treatment insulin (Human with 14-70 U/d) showed postprandial blood sugars between 156 to 470 mg%, glycosylated hemoglobin 6.8% to 9.9% and c-peptide levels of 0.02 to 0.2 ng/mL. They underwent intraportal administration of xenogeneic-free h-AD-MSC (mean dose = 1.5 mL; cell counts, 2.1 x 10(3)/muL). The CD45-/90+/73(+) cells (29.8/16.8%) showed c-peptide levels of 3.08 ng/mL, insulin level of 1578 micro IU/mL. The aliquot was supplemented with CBM (mean dose 94 mL with cell counts: 18.7 x 10(3)/microL) containing CD45-/34+ elements of 0.93%. The Institutional Review Board approved the study protocol and consent forms. RESULTS: All patients were successfully infused CBM plus h-AD-MSC without any untoward effects and showed 30% to 50% decreased insulin requirements with 4- to 26-fold increased serum c-peptide levels, with a mean follow-up of 2.9 months. CONCLUSION: This report describes safe and effective treatment of insulinopenic diabetics using insulin-producing h-AD-MSC plus CBM without xenogeneic materials.

Coronary subclavian steal syndrome-is there a need for routine assessment for subclavian artery stenosis following coronary bypass surgery?

Subclavian artery stenosis (SAS) resulting in coronary subclavian steal syndrome (CSSS) is a common but under recognized pathology following coronary artery bypass surgery (CABG). Patients with SAS may be asymptomatic due to the sub-clinical diversion of blood flow from the myocardium and retrograde blood flow during catheter angiography in the left internal mammary artery (LIMA) may be the first suggestion of CSSS. The management of SAS, causing CSSS, may rarely require acute assessment and intervention. However, full anatomical assessment of the stenosis morphology may be limited on fluoroscopy. Correction of SAS may be essential to achieve effective reperfusion therapy.

Successful generation of donor specific hematopoietic stem cell lines from co-cultured bone marrow with human embryonic stem cell line: a new methodology.

We report the generation of 30 healthy human embryonic stem cell (h-ESC) lines from 33 voluntary oocyte donors using a donor somatic cell nuclear transfer (SCNT) technique on 190 oocytes. Our aim was to coculture them with their own bone marrow (BM) to generate hematopoietic progenitor cells for therapeutic purposes. Pluripotency and undifferentiated stage were confirmed using molecular cell surface markers. Normal karyotype of these cell lines was confirmed. Here we demonstrate that SCNT-h-ESCs differentiate to hematopoietic precursors when cocultured with unmodified, nonirradiated donor BM. We did not use any xenogeneic material for this hematopoietic differentiation. Hematopoietic precursors derived from them expressed cell surface antigens CD45/34. When further cultured with hematopoietic growth factors these hematopoietic precursors formed characteristic myeloid, erythroid, and megakaryocyte lineages. Phenotypic CD34+ cells derived from NT-h-ESCs were functionally similar to their counterparts in primary hematopoietic tissues like BM, umbilical cord, and blood. More terminally differentiated hematopoietic cells derived from h-ESCs under these culture conditions also expressed normal surface antigens like glycophorin A on erythroid cells, CD15 on myeloid cells, and CD41 on megakaryocytes. We report generation of hematopoietic progenitor cells from h-ESC lines by a SCNT technique, with differentiation into further lineages with structural and functional similarities to their adult counterparts in vivo. This novel alternative source of CD34+ stem cells from h-ESC lines generated without any xenogeneic material might be used to create transplantation tolerance, to implement regenerative medicine, and to treat autoimmune disorders.

Angiogenin: a review of the pathophysiology and potential clinical applications.

Angiogenin is a member of the ribonuclease (RNase) superfamily: enzymes of innate substrate specificity, but divergent functional capacities. Angiogenin is a normal constituent of the circulation and contained in a vasculature that rarely undergoes proliferation, but in some physiological and pathological conditions its levels increase in blood, promoting neovascularization. Hence, angiogenesis is a common pathophysiological attribute of angiogenin. In malignant disease, the most studied pathological state in regard to angionenin, abnormally high levels are seen, which may be of prognostic significance. Angiogenin has also been studied in other non-malignant pathological states. The aim of this review article is to provide an overview of the biochemistry and physiology of angiogenin, specifically in relation to the human pathological states where angiogenin has been implicated and finally, its potential clinical applications.

Impact of migration on coronary heart disease risk factors: comparison of Gujaratis in Britain and their contemporaries in villages of origin in India.

The causes of the excess coronary heart disease (CHD) risk in South Asian migrants from the Indian subcontinent remain unclear. Comparisons of CHD risk factors amongst South Asian migrants living in Britain with those of the general UK population provide only a partial explanation. We compared Gujaratis in Britain with similar, non-migrant Gujaratis in India, to test the hypothesis that differences in CHD risk factors associated with migration would be more informative. Randomly sampled Gujaratis aged 25-79 years living in Sandwell (n = 242) were compared with age-, gender- and caste-matched contemporaries remaining in their villages of origin in Navsari, India (n = 295). Lifestyle indices, food intake and physical activity, were assessed with standardised questionnaires and energy expenditure and metabolic parameters measured. British Gujaratis had higher, mean body mass indices by 6 (4.5-7.4) kg/m(2) mean (95% CI), and greater dietary energy intake, fat intake, blood pressure, fasting serum cholesterol, apolipoprotein B, triglycerides, non-esterified fatty acid (NEFA) and C-reative protein concentrations than Gujaratis in India. Dietary folate and serum folate and Vitamin B(12) were lower and plasma homocysteine was higher in India. Smoking was less prevalent and high-density lipoprotein cholesterol tended to be higher in Britain. Diabetes prevalence was high in both populations and impaired fasting or 2 h post-glucose challenge plasma glucose was even more prevalent in Gujarat. In India, however, where insulin secretion and NEFA were lower diabetes and impaired glucose tolerance were less frequently accompanied by excess metabolic CVD risk factors. In conclusion, exposure to increased fat intake and obesity related to migration is likely to explain the disproportionate combination of established and emerging CHD risk factors prevalent in Gujaratis in Britain. Strategies to improve nutrition and to identify and treat cardiovascular risk factors such as dyslipidaemia and hypertension are urgently required.

Improved detection of recurrent bladder cancer using the Bard BTA stat Test.

OBJECTIVES: To evaluate the BTA stat Test in the detection of recurrent bladder cancer. METHODS: Sensitivity and specificity were determined using frozen voided urine samples from patients with recurrent bladder cancer, volunteers, patients with nonurologic conditions, and patients with a history of bladder cancer but free of disease. Results of cytology and the original BTA Test were compared with the sensitivity of the BTA stat Test in a large subgroup of the patients with cancer. RESULTS: The BTA stat Test detected 147 (67%) of 220 recurrent cancers. For those urine samples with previous cytologic and BTA Test results available, cytology had a sensitivity of 23%, the BTA Test 44%, and the BTA stat Test 58% for detection of recurrent cancer (P < 0.001, stat versus cytology). The specificity of the BTA stat Test was 72% for benign genitourinary disease and 95% in healthy volunteers. CONCLUSIONS: The BTA stat Test has high sensitivity and is significantly superior to voided urine cytologic analysis in the detection of recurrent bladder cancer.

Enhancement of lymphocytic SCE frequencies in patients with ovarian cancer.

Sister chromatid exchange (SCE) frequencies were studied in normal and mutagen-treated lymphocyte cultures from patients with ovarian carcinoma and controls. The mean SCE value per cell in normal cultures from the patients was 7.84 which was significantly higher than 6.41 SCEs per cell observed in the controls (p less than 0.01). Similar SCE values obtained for mutagen (mitomycin C, MMC) treated cultures were somewhat lower for patients as compared to the controls, however, the difference was not significant. Cellular kinetics, expressed as average generation time (AGT), was suppressed in lymphocyte cultures from ovarian carcinoma patients as compared to the controls (p much less than 0.05). It was concluded that although baseline SCE rates in lymphocytes of patients with ovarian carcinoma were higher as compared to the controls, they have very limited application as a marker malignancy.