Usefulness of the presence of peripheral vascular disease in predicting mortality in acute myocardial infarction patients treated with primary angioplasty (from the Primary Angioplasty in Myocardial Infarction Database)

Patients with acute myocardial infarction (AMI) often have multiple co-morbidities that influence outcome. We sought to evaluate the impact of peripheral vascular disease (PVD) on the outcome of patients with AMI treated with primary angioplasty. We evaluated 3,716 patients with AMI who underwent emergency catheterization with planned primary angioplasty in the Primary Angioplasty in Myocardial Infarction trials. Patients with a history of PVD (claudication, stroke, or transient ischemic attack) were compared with patients without PVD. Of the 3,716 patients, 394 (10.6%) had PVD and were older, more often women, and more frequently had a history of diabetes mellitus, hypertension, smoking, congestive heart failure, angina, myocardial infarction, and coronary revascularization. They presented more often with a heart rate >100 beats/min, Killip class >1, lower ejection fraction, and multivessel disease. No difference was found in stent use, final percentage of stenosis, or Thrombolysis In Myocardial Infarction 3 flow. Patients with PVD had a twofold increased in-hospital mortality (5.3% vs 2.6%, p = 0.0021). The difference remained significant at 1 month, 6 months, and 1 year (12.6% vs 6%, p < 0.0001). In multivariate logistic regression analysis, a history of PVD was an independent predictor of in-hospital mortality and death at 1 year (odds ratio 1.64, 95% confidence interval 1.04 to 2.57, p = 0.032). In conclusion, patients with AMI with PVD have increased co-morbidities and higher mortality despite treatment with primary angioplasty. The presence of PVD is an independent predictor of in-hospital mortality and death at 1 year.     

Cardiovascular features of homozygous familial hypercholesterolemia: analysis of 16 patients

Familial hypercholesterolemia (FH) is characterized by an autosomal codominant inheritance, an abnormality in low-density lipoprotein (LDL) receptor function, elevated plasma cholesterol levels and premature atherosclerosis. Sixteen patients with homozygous FH were studied to correlate the extent of their atherosclerotic disease with their lipid levels and receptor function. The age range at initial presentation was 3 to 38 years (mean 12), and at the last examination, 6 to 43 years (mean 20). The mean pretreatment total plasma cholesterol concentration for all patients was 729 +/- 58 mg/dl (+/- standard error of the mean), and the mean LDL cholesterol level was 672 +/- 58 mg/dl (normal 60 to 176). High-density lipoprotein cholesterol was 28 +/- 3 mg/dl (normal 30 to 74). In the 7 patients with FH who had symptoms of myocardial ischemia (Group I), the mean pretreatment LDL cholesterol value (817 +/- 62 mg/dl) was higher than that of the 9 asymptomatic patients (Group II) (560 +/- 74 mg/dl). In Group I, 5 of 7 patients had left or right coronary ostial narrowing and 3 had significant left ventricular outflow obstruction. Most coronary arterial narrowing occurred in the right coronary and left anterior descending arteries and the least amount in the left circumflex coronary artery. A femoral bruit was the physical finding that correlated best with the Group I population; brother:sister pairs revealed a milder clinical course for the female. Seven of the 16 patients have survived into their third decade without symptoms. Comparison of these persons with those in whom angina developed reveals a marked heterogeneity in their clinical course, which appears to be associated with receptor negative/defective status.     

Diabetes translation research: where are we and where do we want to be?

Translation research transforms currently available knowledge into useful measures for everyday clinical and public health practice. We review the progress in diabetes translation research and identify future challenges and opportunities in this field. Several promising interventions to optimize implementation of efficacious diabetes treatments are available. Many of these interventions, singly or in combination, need to be more formally tested in larger randomized or quasi-experimental practical trials using outcomes of special interest to patients (for example, patient satisfaction and quality of life) and policymakers (for example, cost and cost-effectiveness). The long-term outcomes (such as morbidity, mortality, quality of life, and costs) of strategies aimed at improving diabetes care must be assessed. Translation research also needs to incorporate ways of studying complex systems of care. The challenges and opportunities offered by translation research are tremendous.     

Elastic distortion determining conduction in BiFeO3 phase boundaries

It is now well-established that boundaries separating tetragonal-like (T) and rhombohedral-like (R) phases in BiFeO₃ thin films can show enhanced electrical conductivity. However, the origin of this conductivity remains elusive. Here, we study mixed-phase BiFeO₃ thin films, where local populations of T and R can be readily altered using stress and electric fields. We observe that phase boundary electrical conductivity in regions which have undergone stress-writing is significantly greater than in the virgin microstructure. We use high-end electron microscopy techniques to identify key differences between the R–T boundaries present in stress-written and as-grown microstructures, to gain a better understanding of the mechanism responsible for electrical conduction. We find that point defects (and associated mixed valence states) are present in both electrically conducting and non-conducting regions; crucially, in both cases, the spatial distribution of defects is relatively homogeneous: there is no evidence of phase boundary defect aggregation. Atomic resolution imaging reveals that the only significant difference between non-conducting and conducting boundaries is the elastic distortion evident – detailed analysis of localised crystallography shows that the strain accommodation across the R–T boundaries is much more extensive in stress-written than in as-grown microstructures; this has a substantial effect on the straightening of local bonds within regions seen to electrically conduct. This work therefore offers distinct evidence that the elastic distortion is more important than point defect accumulation in determining the phase boundary conduction properties in mixed-phase BiFeO₃.

The localized crystallography of conducting and non-conducting phase boundaries in mixed-phase BiFeO₃ is directly compared using scanning transmission electron microscopy techniques.

The complexity of electrical conductivity in domain walls in BiFeO₃ (and in ferroics in general) is as multifaceted as ever. Various influences such as point defect accumulation, octahedral rotations, magnetic interactions and electrostatic discontinuities are thought to be possible mechanisms at play,^1–8 either alone or in combination. The research area of domain wall conductivity is currently flourishing and the view that domain walls offer exciting prospects in terms of engineering systems in which the domain walls act as distinct identities to the domains which they separate is now widely accepted. We believe that it is pertinent timing to address a lack of experimental investigations providing meaningful direct comparison of the localised crystallography and defect structure responsible for observed enhanced electrical conductivity. This study is stimulated by the interesting discoveries of conductive phase boundaries, specifically, in mixed-phase BiFeO₃.^9,10 By tuning the local populations of the tetragonal-like (T) and rhombohedral-like (R) phases in BiFeO₃ thin films via electric and stress fields, we demonstrate that electrical conductivity along phase boundaries is significantly greater after stress-writing. We probe the key crystallographic differences between the R–T boundaries created via stress, compared to those already present in the as-grown microstructures, to disentangle the mechanism determining electrical conduction in mixed-phase BiFeO₃.The growth of BiFeO₃ on substrates enforcing a large in-plane compressive strain drives the formation of monoclinic phases that are approximately rhombohedral (R) and tetragonal (T). Similar to materials such as PbZr_0.53Ti_0.47O₃ that straddle a morphotropic phase boundary, highly strained BiFeO₃ can readily undergo phase transitions between the R and T phases (and vice versa). The high-strain T phase exhibits a tetragonal-like symmetry (almost P4mm) with a c/a ratio of ∼1.2; the Fe displacement towards one of the apical oxygens along [001]_pc results in fivefold oxygen coordinated Fe, and an enhanced polarisation roughly 1.5 times that of the bulk single crystal.^7,11 The R phase, on the other hand, resembles the rhombohedral bulk phase (almost R3c), where the Fe is octahedrally coordinated, with a ferroelectric distortion along the pseudocubic [111]_pc axis, and antiferrodistortive rotations of the FeO₆ octahedra around [111]_pc occur. The crystal structure and misfit strain associated with the native (as-grown) R and T phases is reported elsewhere, both theoretically^12–15 and experimentally,^6,7,16–21 making it well-known that the ferroelectric and the antiferrodistortive degrees of freedom in mixed-phase BiFeO₃ set it apart from other typical perovskites. Notably, despite the ample evidence provided on phase reversal and characterisation of the as-grown phases, most of the literature (especially regarding electric field cycling of the mixed-phase state) has been primarily concerned with X-ray diffraction (XRD) i.e. global measurements that will not necessarily pick up on the more subtle, atomic-scale aspects of structure local to the phase boundaries. The importance of the study described herein resides in the uniqueness of creating microstructures such that both the as-grown and stress-induced R–T phase boundaries can be included within one single cross-sectional transmission electron microscopy (TEM) lamella; this gives the best possible scenario to allow meaningful direct comparison of the localised crystallography and defect structure responsible for the observed enhanced electrical conductivity found at stress-induced phase boundaries.     

Dissections of regional lymph nodes for treatment of skin cancer: predicting annual caseloads that will optimise outcomes

IntroductionDissection of regional lymph nodes (RLNs) can lead to significant morbidity and a high prevalence of complications. Published guidance states that these procedures should be carried out by surgeons who are members of a specialist skin multidisciplinary team who carry out a combined minimum of 15 axillary/groin dissections per year. However, there is little evidence to guide this minimum figure of procedures. We report on the burden of service provision and prevalence of complications across the South West of England and Wales.MethodsA 12-month review of dissections of RLNs for skin cancer was undertaken covering five Plastic Surgery Units with a collective catchment of 8.4 million people. Detailed data were collected on patient demographics, pathology, timing of surgery, and prevalence of complications.ResultsA total of 163 dissections were carried out. Forty-three per cent of patients experienced one or more complication. In that 12-month period, an average of 8 axillary/groin dissections was carried out per surgeon. A funnel plot demonstrated that the prevalence of complications for individual surgeons was within the limit of the plot but, in many cases, this was based only on a relatively small number of procedures per consultant. If surgeons carried out 10 procedures per year, the upper and lower limits on the plot were 73% and 11%, respectively.ConclusionsFunnel plots can provide a useful guide as to whether the prevalence of complications for procedures for individual surgeons lies within acceptable limits. Based on these results, 10 procedures per consultant per year should be sufficient to enable meaningful assessment of the prevalence of complications.