International Cross-Sectional Survey of Bullying, Undermining, and Harassment in the Vascular Workplace.

OBJECTIVE: Bullying, undermining behaviour, and harassment (BUH) may exist in healthcare settings, impacting on patient care. The aim of this international study was to evaluate the characteristics of BUH experienced by physicians treating vascular diseases at various career stages. METHODS: This was an anonymous international structured non-validated cross-sectional survey distributed via relevant professional societies in collaboration with the Research Collaborative in Peripheral Artery Disease. The survey was disseminated through societies' newsletters, emails, and social media. Data were collected online, allowing free text entries alongside structured multiple choice questions based on previous surveys. Demographics, geographical information, and data relating to stage and training environment were collected. RESULTS: Of 587 respondents from 28 countries, 86% were working in vascular surgery, mostly at a university hospital (56%); 81% were aged between 31 and 60 years, 57% were working as a consultant, and 23% as a resident. Respondents were mostly white (83%), male (63%), heterosexual (94%), and without disability (96%). Overall, 253 (43%) reported experiencing BUH personally, 75% had witnessed BUH toward colleagues, and 51% witnessed these in the last 12 months. Female sex and non-white ethnicity were associated with BUH (53% vs. 38% and 57% vs. 40% respectively; p < .001 in both cases). While working as a consultant, 171 (50%) reported experiencing BUH, more often among females, non-heterosexuals, those who were not working in their country of birth, and non-white people. Specialty and hospital type were not associated with BUH. CONCLUSION: BUH remains a major problem in the vascular workplace. Female sex, non-heterosexuality, and non-white ethnicity are associated with BUH at various career stages.

Metformin protects against vascular calcification through the selective degradation of Runx2 by the p62 autophagy receptor.

Vascular calcification is associated with aging, type 2 diabetes, and atherosclerosis, and increases the risk of cardiovascular morbidity and mortality. It is an active, highly regulated process that resembles physiological bone formation. It has previously been established that pharmacological doses of metformin alleviate arterial calcification through adenosine monophosphate-activated protein kinase (AMPK)-activated autophagy, however the specific pathway remains elusive. In the present study we hypothesized that metformin protects against arterial calcification through the direct autophagic degradation of runt-related transcription factor 2 (Runx2). Calcification was blunted in vascular smooth muscle cells (VSMCs) by metformin in a dose-dependent manner (0.5-1.5 mM) compared to control cells (p < 0.01). VSMCs cultured under high-phosphate (Pi) conditions in the presence of metformin (1 mM) showed a significant increase in LC3 puncta following bafilomycin-A1 (Baf-A; 5 nM) treatment compared to control cells (p < 0.001). Furthermore, reduced expression of Runx2 was observed in the nuclei of metformin-treated calcifying VSMCs (p < 0.0001). Evaluation of the functional role of autophagy through Atg3 knockdown in VSMCs showed aggravated Pi-induced calcification (p < 0.0001), failure to induce autophagy (punctate LC3) (p < 0.001) and increased nuclear Runx2 expression (p < 0.0001) in VSMCs cultured under high Pi conditions in the presence of metformin (1 mM). Mechanistic studies employing three-way coimmunoprecipitation with Runx2, p62, and LC3 revealed that p62 binds to both LC3 and Runx2 upon metformin treatment in VSMCs. Furthermore, immunoblotting with LC3 revealed that Runx2 specifically binds with p62 and LC3-II in metformin-treated calcified VSMCs. Lastly, we investigated the importance of the autophagy pathway in vascular calcification in a clinical setting. Ex vivo clinical analyses of calcified diabetic lower limb artery tissues highlighted a negative association between Runx2 and LC3 in the vascular calcification process. These studies suggest that exploitation of metformin and its analogues may represent a novel therapeutic strategy for clinical intervention through the induction of AMPK/Autophagy Related 3 (Atg3)-dependent autophagy and the subsequent p62-mediated autophagic degradation of Runx2.

18F-NaF PET/MRI for Detection of Carotid Atheroma in Acute Neurovascular Syndrome.

Background MRI and fluorine 18-labeled sodium fluoride (18F-NaF) PET can be used to identify features of plaque instability, rupture, and disease activity, but large studies have not been performed. Purpose To evaluate the association between 18F-NaF activity and culprit carotid plaque in acute neurovascular syndrome. Materials and Methods In this prospective observational cohort study (October 2017 to January 2020), participants underwent 18F-NaF PET/MRI. An experienced clinician determined the culprit carotid artery based on symptoms and record review. 18F-NaF uptake was quantified using standardized uptake values and tissue-to-background ratios. Statistical significance was assessed with the Welch, χ2, Wilcoxon, or Fisher test. Multivariable models were used to evaluate the relationship between the imaging markers and the culprit versus nonculprit vessel. Results A total of 110 participants were evaluated (mean age, 68 years ± 10 [SD]; 70 men and 40 women). Of the 110, 34 (32%) had prior cerebrovascular disease, and 26 (24%) presented with amaurosis fugax, 54 (49%) with transient ischemic attack, and 30 (27%) with stroke. Compared with nonculprit carotids, culprit carotids had greater stenoses (≥50% stenosis: 30% vs 15% [P = .02]; ≥70% stenosis: 25% vs 4.5% [P < .001]) and had increased prevalence of MRI-derived adverse plaque features, including intraplaque hemorrhage (42% vs 23%; P = .004), necrotic core (36% vs 18%; P = .004), thrombus (7.3% vs 0%; P = .01), ulceration (18% vs 3.6%; P = .001), and higher 18F-NaF uptake (maximum tissue-to-background ratio, 1.38 [IQR, 1.12-1.82] vs 1.26 [IQR, 0.99-1.66], respectively; P = .04). Higher 18F-NaF uptake was positively associated with necrosis, intraplaque hemorrhage, ulceration, and calcification and inversely associated with fibrosis (P = .04 to P < .001). In multivariable analysis, carotid stenosis at or over 70% (odds ratio, 5.72 [95% CI: 2.2, 18]) and MRI-derived adverse plaque characteristics (odds ratio, 2.16 [95% CI: 1.2, 3.9]) were both associated with the culprit versus nonculprit carotid vessel. Conclusion Fluorine 18-labeled sodium fluoride PET/MRI characteristics were associated with the culprit carotid vessel in study participants with acute neurovascular syndrome. Clinical trial registration no. NCT03215550 and NCT03215563 © RSNA, 2022 Online supplemental material is available for this article.

Open extent IV thoracoabdominal aneurysm repair: 22-year experience of the Scottish National Service.

BACKGROUND: Since 1999, the Scottish National Service for Thoracoabdominal Aneurysms has offered repair of thoracoabdominal aneurysms (TAAAs) to a population of 5.5 million people. The open operation most commonly performed by the service is the extent IV TAAA repair. METHODS: All extent IV open TAAA repairs performed at the Scottish National Service for TAAAs from June 1999 until April 2021 were evaluated for clinical features, technical details, and clinical outcomes. The primary outcome measure was 30-day mortality; secondary outcomes included short-term (90 days, 6 months, 1 and 2 years) and long-term (5 and 10 years) survival, perioperative complications, and reintervention. Survival was assessed using Kaplan-Meier analysis. RESULTS: Some 248 patients underwent extent IV TAAA repair, with elective surgery in 204 (82.3 per cent). A totally abdominal transperitoneal approach was used for all patients, with a median visceral ischaemia time of 40 (i.q.r. 35-48) min. Overall, 18 patients (7.3 per cent) died within 30 days. The proportion of patients surviving at 90 days, 6 months, 1, 2, 5, and 10 years was 0.91, 0.90, 0.89, 0.85, 0.72, and 0.41, respectively. Ten patients (4.0 per cent) required a reintervention while in hospital, four (1.6 per cent) experienced permanent spinal cord ischaemia, 19 (7.9 per cent) required temporary renal replacement therapy (RRT), and four (1.6 per cent) required permanent RRT. CONCLUSION: Open extent IV TAAA repair performed in a high-volume national centre is associated with favourable short- and long-term survival, and acceptable complication rates.

Assessment of different quantification metrics of [18F]-NaF PET/CT images of patients with abdominal aortic aneurysm.

BACKGROUND: We aim to assess the spill-in effect and the benefit in quantitative accuracy for [18F]-NaF PET/CT imaging of abdominal aortic aneurysms (AAA) using the background correction (BC) technique. METHODS: Seventy-two datasets of patients diagnosed with AAA were reconstructed with ordered subset expectation maximization algorithm incorporating point spread function (PSF). Spill-in effect was investigated for the entire aneurysm (AAA), and part of the aneurysm excluding the region close to the bone (AAAexc). Quantifications of PSF and PSF+BC images using different thresholds (% of max. SUV in target regions-of-interest) to derive target-to-background (TBR) values (TBRmax, TBR90, TBR70 and TBR50) were compared at 3 and 10 iterations. RESULTS: TBR differences were observed between AAA and AAAexc due to spill-in effect from the bone into the aneurysm. TBRmax showed the highest sensitivity to the spill-in effect while TBR50 showed the least. The spill-in effect was reduced at 10 iterations compared to 3 iterations, but at the expense of reduced contrast-to-noise ratio (CNR). TBR50 yielded the best trade-off between increased CNR and reduced spill-in effect. PSF+BC method reduced TBR sensitivity to spill-in effect, especially at 3 iterations, compared to PSF (P-value ≤ 0.05). CONCLUSION: TBR50 is robust metric for reduced spill-in and increased CNR.

Editor's Choice - Systematic Review and Meta-Analysis of Wound Adjuncts for the Prevention of Groin Wound Surgical Site Infection in Arterial Surgery.

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 - 0.51; p < .001, GRADE strength of evidence: moderate). Local antibiotics did not reduce groin SSIs (OR 0.60 95% CI 0.30 - 1.21 p = .15, GRADE strength: low). Subcuticular sutures (vs. transdermal sutures or clips) reduced groin SSI rates (OR 0.33, 95% CI 0.17 - 0.65, p = .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.

Iterative reconstruction incorporating background correction improves quantification of [18F]-NaF PET/CT images of patients with abdominal aortic aneurysm.

BACKGROUND: A confounding issue in [18F]-NaF PET/CT imaging of abdominal aortic aneurysms (AAA) is the spill in contamination from the bone into the aneurysm. This study investigates and corrects for this spill in contamination using the background correction (BC) technique without the need to manually exclude the part of the AAA region close to the bone. METHODS: Seventy-two (72) datasets of patients with AAA were reconstructed with the standard ordered subset expectation maximization (OSEM) algorithm incorporating point spread function (PSF) modelling. The spill in effect in the aneurysm was investigated using two target regions of interest (ROIs): one covering the entire aneurysm (AAA), and the other covering the aneurysm but excluding the part close to the bone (AAAexc). ROI analysis was performed by comparing the maximum SUV in the target ROI (SUVmax(T)), the corrected cSUVmax (SUVmax(T) - SUVmean(B)) and the target-to-blood ratio (TBR = SUVmax(T)/SUVmean(B)) with respect to the mean SUV in the right atrium region. RESULTS: There is a statistically significant higher [18F]-NaF uptake in the aneurysm than normal aorta and this is not correlated with the aneurysm size. There is also a significant difference in aneurysm uptake for OSEM and OSEM + PSF (but not OSEM + PSF + BC) when quantifying with AAA and AAAexc due to the spill in from the bone. This spill in effect depends on proximity of the aneurysms to the bone as close aneurysms suffer more from spill in than farther ones. CONCLUSION: The background correction (OSEM + PSF + BC) technique provided more robust AAA quantitative assessments regardless of the AAA ROI delineation method, and thus it can be considered as an effective spill in correction method for [18F]-NaF AAA studies.

Improved identification of abdominal aortic aneurysm using the Kernelized Expectation Maximization algorithm.

Abdominal aortic aneurysm (AAA) monitoring and risk of rupture is currently assumed to be correlated with the aneurysm diameter. Aneurysm growth, however, has been demonstrated to be unpredictable. Using PET to measure uptake of [18F]-NaF in calcified lesions of the abdominal aorta has been shown to be useful for identifying AAA and to predict its growth. The PET low spatial resolution, however, can affect the accuracy of the diagnosis. Advanced edge-preserving reconstruction algorithms can overcome this issue. The kernel method has been demonstrated to provide noise suppression while retaining emission and edge information. Nevertheless, these findings were obtained using simulations, phantoms and a limited amount of patient data. In this study, the authors aim to investigate the usefulness of the anatomically guided kernelized expectation maximization (KEM) and the hybrid KEM (HKEM) methods and to judge the statistical significance of the related improvements. Sixty-one datasets of patients with AAA and 11 from control patients were reconstructed with ordered subsets expectation maximization (OSEM), HKEM and KEM and the analysis was carried out using the target-to-blood-pool ratio, and a series of statistical tests. The results show that all algorithms have similar diagnostic power, but HKEM and KEM can significantly recover uptake of lesions and improve the accuracy of the diagnosis by up to 22% compared to OSEM. The same improvements are likely to be obtained in clinical applications based on the quantification of small lesions, like for example cancer. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 1'.

Effectiveness of revascularisation of the ulcerated foot in patients with diabetes and peripheral artery disease: A systematic review.

In patients with diabetes, foot ulceration and peripheral artery disease (PAD), it is often difficult to determine whether, when and how to revascularise the affected lower extremity. The presence of PAD is a major risk factor for non-healing and yet clinical outcomes of revascularisation are not necessarily related to technical success. The International Working Group of the Diabetic Foot updated systematic review on the effectiveness of revascularisation of the ulcerated foot in patients with diabetes and PAD is comprised of 64 studies describing >13 000 patients. Amongst 60 case series and 4 non-randomised controlled studies, we summarised clinically relevant outcomes and found them to be broadly similar between patients treated with open vs endovascular therapy. Following endovascular revascularisation, the 1 year and 2 year limb salvage rates were 80% (IQR 78-82%) and 78% (IQR 75-83%), whereas open therapy was associated with rates of 85% (IQR 80-90%) at 1 year and 87% (IQR 85-88%) at 2 years, however these results were based on a varying combination of studies and cannot therefore be interpreted as cumulative. Overall, wound healing was achieved in a median of 60% of patients (IQR 50-69%) at 1 year in those treated by endovascular or surgical therapy, and the major amputation rate of endovascular vs open therapy was 2% vs 5% at 30 days, 10% vs 9% at 1 year and 13% vs 9% at 2 years. For both strategies, overall mortality was found to be high, with 2% (1-6%) perioperative (or 30 day) mortality, rising sharply to 13% (9-23%) at 1 year, 29% (19-48%) at 2 years and 47% (39-71%) at 5 years. Both the angiosome concept (revascularisation directly to the area of tissue loss via its main feeding artery) or indirect revascularisation through collaterals, appear to be equally effective strategies for restoring perfusion. Overall, the available data do not allow us to recommend one method of revascularisation over the other and more studies are required to determine the best revascularisation approach in diabetic foot ulceration.

Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: A systematic review.

Clinical outcomes of patients with diabetes, foot ulceration, and peripheral artery disease (PAD) are difficult to predict. The prediction of important clinical outcomes, such as wound healing and major amputation, would be a valuable tool to help guide management and target interventions for limb salvage. Despite the existence of a number of classification tools, no consensus exists as to the most useful bedside tests with which to predict outcome. We here present an updated systematic review from the International Working Group of the Diabetic Foot, comprising 15 studies published between 1980 and 2018 describing almost 6800 patients with diabetes and foot ulceration. Clinical examination findings as well as six non-invasive bedside tests were evaluated for their ability to predict wound healing and amputation. The most useful tests to inform on the probability of healing were skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg, or TcPO2  ≥ 25 mmHg. With these thresholds, all of these tests increased the probability of healing by greater than 25% in at least one study. To predict major amputation, the most useful tests were ankle pressure < 50 mmHg, ABI < 0.5, toe pressure < 30 mmHg, and TcPO2  < 25 mmHg, which increased the probability of major amputation by greater than 25%. These indicative values may be used as a guide when deciding which patients are at highest risk for poor outcomes and should therefore be evaluated for revascularization at an early stage. However, this should always be considered within the wider context of important co-existing factors such as infection, wound characteristics, and other comorbidities.

Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: A systematic review.

The accurate identification of peripheral artery disease (PAD) in patients with diabetes and foot ulceration is important, in order to inform timely management and to plan intervention including revascularisation. A variety of non-invasive tests are available to diagnose PAD at the bedside, but there is no consensus as to the most useful test, or the accuracy of these bedside investigations when compared to reference imaging tests such as magnetic resonance angiography, computed tomography angiography, digital subtraction angiography or colour duplex ultrasound. Members of the International Working Group of the Diabetic Foot updated our previous systematic review, to include all eligible studies published between 1980 and 2018. Some 15 380 titles were screened, resulting in 15 eligible studies (comprising 1563 patients, of which >80% in each study had diabetes) that evaluated an index bedside test for PAD against a reference imaging test. The primary endpoints were positive likelihood ratio (PLR) and negative likelihood ratio (NLR). We found that the most commonly evaluated test parameter was ankle brachial index (ABI) <0.9, which may be useful to suggest the presence of PAD (PLR 6.5) but an ABI value between 0.9 and 1.3 does not rule out PAD (NLR 0.31). A toe brachial index >0.75 makes the diagnosis of PAD less likely (NLR 0.14-0.24), whereas pulse oximetry may be used to suggest the presence of PAD (if toe saturation < 2% lower than finger saturation; PLR 17.23-30) or render PAD less likely (NLR 0.2-0.27). We found that the presence of triphasic tibial waveforms has the best performance value for excluding a diagnosis of PAD (NLR 0.09-0.28), but was evaluated in only two studies. In addition, we found that beside clinical examination (including palpation of foot pulses) cannot reliably exclude PAD (NLR 0.75), as evaluated in one study. Overall, the quality of data is generally poor and there is insufficient evidence to recommend one bedside test over another. While there have been six additional publications in the last 4 years that met our inclusion criteria, more robust evidence is required to achieve consensus on the most useful non-invasive bedside test to diagnose PAD.

Definitions and criteria for diabetic foot disease.

Multiple disciplines are involved in the management of diabetic foot disease, and a common vocabulary is essential for clear communication. Based on the systematic reviews of the literature that form the basis of the International Working Group on the Diabetic Foot (IWGDF) Guidelines, the IWGDF has developed a set of definitions and criteria for diabetic foot disease. This document describes these definitions and criteria. We suggest these definitions be used consistently in both clinical practice and research to facilitate clear communication between professionals.

Guidelines on diagnosis, prognosis, and management of peripheral artery disease in patients with foot ulcers and diabetes (IWGDF 2019 update).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This guideline is on the diagnosis, prognosis, and management of peripheral artery disease (PAD) in patients with foot ulcers and diabetes and updates the previous IWGDF Guideline. Up to 50% of patients with diabetes and foot ulceration have concurrent PAD, which confers a significantly elevated risk of adverse limb events and cardiovascular disease. We know that the diagnosis, prognosis, and treatment of these patients are markedly different to patients with diabetes who do not have PAD and yet there are few good quality studies addressing this important subset of patients. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to devise clinical questions and critically important outcomes in the patient-intervention-comparison-outcome (PICO) format, to conduct a systematic review of the medical-scientific literature, and to write recommendations and their rationale. The recommendations are based on the quality of evidence found in the systematic review, expert opinion where evidence was not available, and a weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to the intervention. We here present the updated 2019 guidelines on diagnosis, prognosis, and management of PAD in patients with a foot ulcer and diabetes, and we suggest some key future topics of particular research interest.

Role of Vascular Smooth Muscle Cell Phenotypic Switching and Calcification in Aortic Aneurysm Formation.

Aortic aneurysm is a vascular disease whereby the ECM (extracellular matrix) of a blood vessel degenerates, leading to dilation and eventually vessel wall rupture. Recently, it was shown that calcification of the vessel wall is involved in both the initiation and progression of aneurysms. Changes in aortic wall structure that lead to aneurysm formation and vascular calcification are actively mediated by vascular smooth muscle cells. Vascular smooth muscle cells in a healthy vessel wall are termed contractile as they maintain vascular tone and remain quiescent. However, in pathological conditions they can dedifferentiate into a synthetic phenotype, whereby they secrete extracellular vesicles, proliferate, and migrate to repair injury. This process is called phenotypic switching and is often the first step in vascular pathology. Additionally, healthy vascular smooth muscle cells synthesize VKDPs (vitamin K-dependent proteins), which are involved in inhibition of vascular calcification. The metabolism of these proteins is known to be disrupted in vascular pathologies. In this review, we summarize the current literature on vascular smooth muscle cell phenotypic switching and vascular calcification in relation to aneurysm. Moreover, we address the role of vitamin K and VKDPs that are involved in vascular calcification and aneurysm. Visual Overview- An online visual overview is available for this article.

Biomechanical Assessment Predicts Aneurysm Related Events in Patients with Abdominal Aortic Aneurysm.

OBJECTIVE: To test whether aneurysm biomechanical ratio (ABR; a dimensionless ratio of wall stress and wall strength) can predict aneurysm related events. METHODS: In a prospective multicentre clinical study of 295 patients with an abdominal aortic aneurysm (AAA; diameter ≥ 40 mm), three dimensional reconstruction and computational biomechanical analyses were used to compute ABR at baseline. Participants were followed for at least two years and the primary end point was the composite of aneurysm rupture or repair. RESULTS: The majority were male (87%), current or former smokers (86%), most (72%) had hypertension (mean ± standard deviation [SD] systolic blood pressure 140 ± 22 mmHg), and mean ± SD baseline diameter was 49.0 ± 6.9 mm. Mean ± SD ABR was 0.49 ± 0.27. Participants were followed up for a mean ± SD of 848 ± 379 days and rupture (n = 13) or repair (n = 102) occurred in 115 (39%) cases. The number of repairs increased across tertiles of ABR: low (n = 24), medium (n = 34), and high ABR (n = 44) (p = .010). Rupture or repair occurred more frequently in those with higher ABR (log rank p = .009) and ABR was independently predictive of this outcome after adjusting for diameter and other clinical risk factors, including sex and smoking (hazard ratio 1.41; 95% confidence interval 1.09-1.83 [p = .010]). CONCLUSION: It has been shown that biomechanical ABR is a strong independent predictor of AAA rupture or repair in a model incorporating known risk factors, including diameter. Determining ABR at baseline could help guide the management of patients with AAA.

Core Outcomes for Colorectal Cancer Surgery: A Consensus Study.

BACKGROUND: Colorectal cancer (CRC) is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs); however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard "core" set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery. METHODS AND FINDINGS: The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals) from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods). Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78%) centers, including 90 professionals, and 97 out of 267 (35%) patients. Second round response rates were high for all stakeholders (>80%). Analysis of responses lead to 45 and 23 outcome domains being retained after the first and second surveys, respectively. Consensus meetings generated agreement on a 12 domain COS. This constituted five perioperative outcome domains (including anastomotic leak), four quality of life outcome domains (including fecal urgency and incontinence), and three oncological outcome domains (including long-term survival). CONCLUSION: This study used robust consensus methodology to develop a core outcome set for use in colorectal cancer surgical trials. It is now necessary to validate the use of this set in research practice.

Assessment of foot perfusion in patients with a diabetic foot ulcer.

Assessment of foot perfusion is a vital step in the management of patients with diabetic foot ulceration, in order to understand the risk of amputation and likelihood of wound healing. Underlying peripheral artery disease is a common finding in patients with foot ulceration and is associated with poor outcomes. Assessment of foot perfusion should therefore focus on identifying the presence of peripheral artery disease and to subsequently estimate the effect this may have on wound healing. Assessment of perfusion can be difficult because of the often complex, diffuse and distal nature of peripheral artery disease in patients with diabetes, as well as poor collateralisation and heavy vascular calcification. Conventional methods of assessing tissue perfusion in the peripheral circulation may be unreliable in patients with diabetes, and it may therefore be difficult to determine the extent to which poor perfusion contributes to foot ulceration. Anatomical data obtained on cross-sectional imaging is important but must be combined with measurements of tissue perfusion (such as transcutaneous oxygen tension) in order to understand the global and regional perfusion deficit present in a patient with diabetic foot ulceration. Ankle-brachial pressure index is routinely used to screen for peripheral artery disease, but its use in patients with diabetes is limited in the presence of neuropathy and medial arterial calcification. Toe pressure index may be more useful because of the relative sparing of pedal arteries from medial calcification but may not always be possible in patients with ulceration. Fluorescence angiography is a non-invasive technique that can provide rapid quantitative information about regional tissue perfusion; capillaroscopy, iontophoresis and hyperspectral imaging may also be useful in assessing physiological perfusion but are not widely available. There may be a future role for specialized perfusion imaging of these patients, including magnetic resonance imaging techniques, single-photon emission computed tomography and PET-based molecular imaging; however, these novel techniques require further validation and are unlikely to become standard practice in the near future.

Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T.

BACKGROUND: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems. METHODS: Twenty volunteers were recruited: 10 imaged each at 1.5 T and 3 T. T2* and late gadolinium enhanced (LGE) MRI was conducted at baseline with further T2* imaging conducted approximately 24 h after USPIO infusion (ferumoxytol, 4 mg/kg). Regions of interest were selected in the myocardium and compared to other tissues. RESULTS: Following administration, USPIO was detected by changes in R2* from baseline (1/T2*) at 24 h in myocardium, skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and myocardium, kidney, liver, spleen, blood and bone at 3 T (p < 0.05 for all). Myocardial changes in R2* due to USPIO were 26.5 ± 7.3 s-1 at 1.5 T, and 37.2 ± 9.6 s-1 at 3 T (p < 0.0001 for both). Tissues showing greatest ferumoxytol enhancement were the reticuloendothelial system: the liver, spleen and bone marrow (216.3 ± 32.6 s-1, 336.3 ± 60.3 s-1, 69.9 ± 79.9 s-1; p < 0.0001, p < 0.0001, p = ns respectively at 1.5 T, and 275.6 ± 69.9 s-1, 463.9 ± 136.7 s-1, 417.9 ± 370.3 s-1; p < 0.0001, p < 0.0001, p < 0.01 respectively at 3 T). CONCLUSION: Ferumoxytol-enhanced MRI is feasible at both 1.5 T and 3 T. Careful data selection and dose administration, along with refinements to echo-time acquisition, post-processing and analysis techniques are essential to ensure reliable and robust quantification of tissue enhancement. TRIAL REGISTRATION: ClinicalTrials.gov Identifier - NCT02319278 . Registered 03.12.2014.