Background Previous research has suggested that patients with peripheral artery disease (PAD) are not offered adequate risk factor modification, despite their high cardiovascular risk. The aim of this study was to assess the cardiovascular profiles of patients with PAD and quantify the survival benefits of target‐based risk factor modification. Methods The Vascular and Endovascular Research Network (VERN) prospectively collected cardiovascular profiles of patients with PAD from ten UK vascular centres (April to June 2018) to assess practice against UK and European goal‐directed best medical therapy guidelines. Risk and benefits of risk factor control were estimated using the SMART‐REACH model, a validated cardiovascular prediction tool for patients with PAD. Results Some 440 patients (mean(s.d.) age 70(11) years, 24·8 per cent women) were included in the study. Mean(s.d.) cholesterol (4·3(1·2) mmol/l) and LDL‐cholesterol (2·7(1·1) mmol/l) levels were above recommended targets; 319 patients (72·5 per cent) were hypertensive and 343 (78·0 per cent) were active smokers. Only 11·1 per cent of patients were prescribed high‐dose statin therapy and 39·1 per cent an antithrombotic agent. The median calculated risk of a major cardiovascular event over 10 years was 53 (i.q.r. 44–62) per cent. Controlling all modifiable cardiovascular risk factors based on UK and European guidance targets (LDL‐cholesterol less than 2 mmol/l, systolic BP under 140 mmHg, smoking cessation, antiplatelet therapy) would lead to an absolute risk reduction of the median 10‐year cardiovascular risk by 29 (20–38) per cent with 6·3 (4·0–9·3) cardiovascular disease‐free years gained. Conclusion The medical management of patients with PAD in this secondary care cohort was suboptimal. Controlling modifiable risk factors to guideline‐based targets would confer significant patient benefit.

Background: The accuracy with which surgeons can predict outcomes following surgery has not been explored in a systematic way. The aim of this review was to determine how accurately a surgeon's 'gut feeling' or perception of risk correlates with patient outcomes and available risk scoring systems.Methods: A systematic review was undertaken in accordance with PRISMA guidelines. A narrative synthesis was performed in accordance with the Guidance on the Conduct of Narrative Synthesis In Systematic Reviews. Studies comparing surgeons' preoperative or postoperative assessment of patient outcomes were included. Studies that made comparisons with risk scoring tools were also included. Outcomes evaluated were postoperative mortality, general and operation-specific morbidity and long-term outcomes.Results: Twenty-seven studies comprising 20 898 patients undergoing general, gastrointestinal, cardiothoracic, orthopaedic, vascular, urology, endocrine and neurosurgical operations were included. Surgeons consistently overpredicted mortality rates and were outperformed by existing risk scoring tools in six of seven studies comparing area under receiver operating characteristic (ROC) curves (AUC).Surgeons' prediction of general morbidity was good, and was equivalent to, or better than, pre-existing risk prediction models. Long-term outcomes were poorly predicted by surgeons, with AUC values ranging from 0⋅51 to 0⋅75. Four of five studies found postoperative risk estimates to be more accurate than those made before surgery.Conclusion: Surgeons consistently overestimate mortality risk and are outperformed by pre-existing tools; prediction of longer-term outcomes is also poor. Surgeons should consider the use of risk prediction tools when available to inform clinical decision-making.

1Elevated Heat Shock Protein 27 levels predict relative freedom from cardiovascular events. In 2 ApoE -/mice HSP27 over-expression or twice daily subcutaneous injections reduce blood and 3 plaque cholesterol levels, inflammation and atherogenesis. While natural antibodies to HSP27 4 are present in human blood their role is unknown. Here, we show that blood levels of both 5 HSP27 and anti-HSP27 IgG antibodies are elevated in healthy controls compared to patients with 6 cardiovascular disease. ApoE -/mice vaccinated with recombinant HSP25 (murine ortholog) 7 develop elevated anti-HSP25 IgG antibodies and reduced levels of cholesterol, inflammation and 8 atherosclerosis. The effects on cholesterol metabolism were divergent: increased hepatic LDLR 9 expression and reduced plasma PCSK9 levels. In vitro, a polyclonal anti-HSP27 IgG antibody 10 combined with rHSP27 to upregulate hepatocyte LDLR expression via an NF-kB-dependent 11 pathway that is independent of SREBP2 expression and intracellular cholesterol levels. HSP27 12 immunotherapy represents a novel means of lowering not only cholesterol but also PCSK9. 13Small heat shock proteins, such as Heat Shock Protein 27 (HSP27), are intracellular chaperones 1 that promote the proper reassembly of misfolded proteins and act as mediators of extracellular 2 cellular signaling 1 . HSP27 effectively preserves cellular homeostasis under various conditions of 3 degenerative or inflammatory stress -including those common to the pathogenesis of 4 atherosclerosis 2 . There is overwhelming genetic, epidemiological and clinical evidence that 5 irrefutably establishes low density lipoprotein cholesterol (LDL-C) as causal for atherosclerosis 3, 6 4 . Experiments from our group 5 and four others using proteomic discovery approaches 6,7,8,9 show 7 that serum HSP27 levels decline as human atherosclerosis develops, with its tissue abundance 8 inversely corelated with the degree of coronary artery plaque burden. In atherosclerosis-prone 9 Apolipoprotein E null (ApoE -/-) mice augmentation of extracellular HSP27 levels via constitutive 10 over-expression, transplantation of bone marrow from mice that over-express HSP27, twice-11 daily subcutaneous administration of recombinant HSP27 (rHSP27; 100 µg) or estrogenic 12 therapy post-ovariectomy (that augment HSP27 blood levels) reduce both plasma and plaque 13 cholesterol content, resulting in the formation of more stable plaques that are less inflamed 10, 11, 14 12, 13 . Clinically, elevated HSP27 blood levels are associated with a lower 5-year risk of 15 myocardial infarction, stroke or cardiovascular death 11 . Interestingly, natural antibodies to 16 HSP27 (AAbs) are detectable in the blood, yet their biological significance is unclear 14, 15 . 18In this study we sought to address three questions. First, what is the correlation between blood 19 HSP27 and AAb abundance in human cardiovascular disease (CVD) patients compared to 20 healthy control subjects (CON)? Second, does augmenting levels of antibodies to HSP25 (the 21 murine ortholog of ...

WHAT THIS PAPER ADDSThis review supports closed incision negative pressure wound therapy (ciNPWT) as an effective intervention for preventing both superficial and deep surgical site infections (SSIs) in groin incisions following arterial intervention. Available evidence suggests local antibiotics do not reduce overall SSI rates, but may reduce superficial SSIs, however data are heterogenous and lacking. Subcuticular sutures, as opposed to other methods of closure, appear to reduce SSIs. The cost effectiveness of ciNPWT, and efficacy of local antibiotics (for both superficial and deep SSI) in vascular groin wounds, are research questions that should be addressed with future randomised trials.Objective: Groin incision surgical site infections (SSIs) following arterial surgery are common and are a source of considerable morbidity. This review evaluates interventions and adjuncts delivered immediately before, during, or after skin closure, to prevent SSIs in patients undergoing arterial interventions involving a groin incision.Data sources: MEDLINE, EMBASE, and CENTRAL databases were searched. Review methods: This review was undertaken according to established international reporting guidelines and was registered prospectively with the International prospective register of systematic reviews (CRD42020185170). The MEDLINE, EMBASE, and CENTRAL databases were searched using pre-defined search terms without date restriction. Randomised controlled trials (RCTs) and observational studies recruiting patients with non-infected groin incisions for arterial exposure were included; SSI rates and other outcomes were captured. Interventions reported in two or more studies were subjected to meta-analysis. Results:The search identified 1 532 articles. Seventeen RCTs and seven observational studies, reporting on 3 747 patients undergoing 4 130 groin incisions were included. A total of seven interventions and nine outcomes were reported upon. Prophylactic closed incision negative pressure wound therapy (ciNPWT) reduced groin SSIs compared with standard dressings (odds ratio [OR] 0.34, 95% CI 0.23 e 0.51; p < .001, GRADE strength of evidence: moderate). Local antibiotics did not reduce groin SSIs (OR 0.60 95% CI 0.30 e 1.21 p ¼ .15, GRADE strength: low). Subcuticular sutures (vs. transdermal sutures or clips) reduced groin SSI rates (OR 0.33, 95% CI 0.17 e 0.65, p ¼ .001, GRADE strength: low). Wound drains, platelet rich plasma, fibrin glue, and silver alginate dressings did not show any significant effect on SSI rates. Conclusion:There is evidence that ciNPWT and subcuticular sutures reduce groin SSI in patients undergoing arterial vascular interventions involving a groin incision. Local antibiotics did not reduce groin wound SSI, although the strength of this evidence is lower. No other interventions demonstrated a significant effect.

IntroductionSurgical site infections (SSIs) following groin incision for arterial exposure are commonplace and a significant cause of morbidity and mortality following major arterial surgery. Published incidence varies considerably. The primary aim of GIVE will be to compare individual units’ practice with established guidelines from The National Institute for Health and Care Excellence (NICE). Secondary aims will be to describe the contemporary rate of SSI in patients undergoing groin incision for arterial exposure, to identify risk factors for groin wound infection, to examine the value of published tools in the prediction of SSI, to identify areas of equipoise which could be examined in future efficacy/effectiveness trials and to compare UK SSI rates with international centres.Methods and analysisThis international, multicentre, prospective observational study will be delivered via the Vascular and Endovascular Research Network (VERN). Participating centres will identify all patients undergoing clean emergency or elective groin incision(s) for arterial intervention during a consecutive 3-month period. Follow up data will be captured at 90 days after surgery. SSIs will be defined according to the Centres for Disease Control and Prevention (CDC) criteria. Data will be gathered centrally using an anonymised electronic data collection tool or secure email transfer.Ethics and disseminationThis study will be registered as a clinical audit at all participating UK centres; research ethics approval is not required. National leads will oversee the appropriate registration and approvals in countries outside the UK as required. Site specific reports of SSI rates will be provided to each participating centre. Study results will be disseminated locally at each site, publicised on social media and submitted for peer-reviewed publication.

Objective: Elevated HSP27 (heat shock protein 27) levels predict relative freedom from cardiovascular events. Over-expression or twice daily subcutaneous injections of human HSP27 in ApoE −/− mice reduces blood and plaque cholesterol levels, as well as inflammation and atherosclerotic plaque burden. Antibodies to HSP27 are present in human blood, and the purpose of the current studies is to explore their role. Approach and Results: Blood levels of both HSP27 and anti-HSP27 IgG antibodies are elevated in healthy controls compared with patients with cardiovascular disease. ApoE −/− mice fed a high-fat diet and vaccinated with recombinant HSP25 (rHSP25, murine ortholog) show increased levels of anti-HSP25 IgG antibodies and reductions in plasma cholesterol and atherogenesis. Moreover, rHSP25 vaccination markedly lowered serum amyloid A levels as well as hepatic macrophage abundance and inflammatory cytokine expression. The effects of the HPS25 vaccination on cholesterol metabolism are divergent: increased hepatic LDLR (low-density lipoprotein receptor) mRNA and protein expression and reduced plasma PCSK9 (proprotein convertase subtilisin/kexin type 9) levels—despite no effect on PCSK9 expression. In vitro, the HSP27 immune complex upregulates hepatocyte LDLR mRNA and protein expression independent of intracellular cholesterol levels and increases LDLR promoter activity. The increase in LDLR expression by the HSP27 immune complex is dependent upon activation of the NF-κB (nuclear factor κ light chain enhancer of activated B cells) pathway. Hepatocyte PCSK9 protein levels are reduced after HSP27 immune complex treatment in vitro despite only minor transient effects on gene expression. Conclusions: HSP27 immunotherapy represents a novel means of lowering cholesterol and PCSK9 levels, primarily due to augmentation of LDLR expression and is associated with marked reductions in inflammation.

, epidemiologic information on sepsis is limited. Whilst about 30% of all ICU patients in the UK have severe sepsis, there are no data published on the incidence of sepsis on the general wards in Wales, or indeed in the rest of the UK. 1 It has been suggested that delivering six simple interventions, the 'Sepsis 6' bundle, within 1 hour of recognition of sepsis may improve outcome on the general ward setting. 2 3

Surgical site infections (SSIs) of groin wounds are a common and potentially preventable cause of morbidity, mortality, and healthcare costs in vascular surgery. Our aim was to define the contemporaneous rate of groin SSIs, determine clinical sequelae, and identify risk factors for SSI. An international multicentre prospective observational cohort study of consecutive patients undergoing groin incision for femoral vessel access in vascular surgery was undertaken over 3 months, follow-up was 90 days. The primary outcome was the incidence of groin wound SSI. 1337 groin incisions (1039 patients) from 37 centres were included. 115 groin incisions (8.6%) developed SSI, of which 62 (4.6%) were superficial. Patients who developed an SSI had a significantly longer length of hospital stay (6 versus 5 days, P = .005), a significantly higher rate of post-operative acute kidney injury (19.6% versus 11.7%, P = .018), with no significant difference in 90-day mortality. Female sex, Body mass index≥30 kg/m 2 , ischaemic heart disease, aqueous betadine skin preparation, bypass/patch use (vein, xenograft, or prosthetic), and increased operative time were independent predictors of SSI. Groin infections, which are clinically apparent to the treating vascular unit, are frequent and their development carries significant clinical sequelae. Risk factors include modifiable and non-modifiable variables.