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Background: Inadvertent intra-arterial injection of sclerosants is an uncommon adverse event of both ultrasound-guided and direct vision sclerotherapy. This complication can result in significant tissue or limb loss and significant long-term morbidity. Objectives: To provide recommendations for diagnosis and immediate management of an unintentional intra-arterial injection of sclerosing agents. Methods: An international and multidisciplinary expert panel representing the endorsing societies and relevant specialities reviewed the published biomedical, scientific and legal literature and developed the consensus-based recommendations. Results: Actual and suspected cases of an intra-arterial sclerosant injection should be immediately transferred to a facility with a vascular/interventional unit. Digital Subtraction Angiography (DSA) is the key investigation to confirm the diagnosis and help select the appropriate intra-arterial therapy for tissue ischaemia. Emergency endovascular intervention will be required to manage the risk of major limb ischaemia. This includes intra-arterial administration of vasodilators to reduce vasospasm, and anticoagulants and thrombolytic agents to mitigate thrombosis. Mechanical thrombectomy, other endovascular interventions and even open surgery may be required. Lumbar sympathetic block may be considered but has a high risk of bleeding. Systemic anti-inflammatory agents, anticoagulants, and platelet inhibitors and modifiers would complement the intra-arterial endovascular procedures. For risk of minor ischaemia, systemic oral anti-inflammatory agents, anticoagulants, vasodilators and antiplatelet treatments are recommended. Conclusion: Inadvertent intra-arterial injection is an adverse event of both ultrasound-guided and direct vision sclerotherapy. Medical practitioners performing sclerotherapy must ensure completion of a course of formal training (specialty or subspecialty training, or equivalent recognition) in the management of venous and lymphatic disorders (phlebology), and be personally proficient in the use of duplex ultrasound in vascular (both arterial and venous) applications, to diagnose and provide image guidance to venous procedure. Expertise in diagnosis and immediate management of an intra-arterial injection is essential for all practitioners performing sclerotherapy. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semi-urgent (to be attended to within 30–90 days), example highly symptomatic chronic venous disease, and (4) discretionary/non-urgent- (to be seen within 6–12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Cholesterol crystals have been shown to cause inflammation, and ultimately atherosclerotic lesions through the activation of the NLRP3 inflammasome. As cholesterol crystals have also been found in the walls of patients with abdominal aortic aneurysms (AAA), it is possible that the NLRP3 inflammasome is involved in AAA and genetic variability within this protein complex could alter disease risk. The primary objective of this study was to assess whether there is genetic evidence for a role of the NLRP3 inflammasome in AAA by testing for association of AAA with functional single nucleotide polymorphisms (SNPs) in the CARD8 and NLRP3 genes. Methods: AAA patients (n =1151) and controls (n =727) were genotyped for CARD8 SNP rs2043211 and NLRP3 SNP rs35829419 using TaqMan SNP assays. IL1-β, C-reactive protein (CRP), and lipoprotein (a) [Lp(a)] were measured in the plasma of a subset of study participants. The Kruskal–Wallis Rank test was conducted to test for differences in mean concentration of IL1-β, CRP and Lp(a). Logistic regression was used to test for interaction between CARD8 and NLRP3. Results: Significantly higher mean concentration of plasma IL1-β was observed in study participants who were homozygous for the common C allele of NLRP3 rs35829419 (p =0.010). Interaction between rs2043211 and rs35829419 was observed in this dataset (χ 2 =6.22; p =0.044), which strengthened when adjusted for age, gender, smoking, diabetes, hypertension, and dyslipidemia (χ 2 =14.75; p =0.012); and separately for NOD2 genotype (χ 2 =14.06; p =0.015). Conclusion: Our finding suggests genetic variability within the NLRP3 inflammasome may be important in the pathophysiology of AAA. [Copyright &y& Elsevier]

The purpose of this study was to lest the hypothesis that cost, as well as frequency of infection, could be used to demonstrate a difference in the performance of prophylactic antibiotics. In a prospective, randomized, double-blind study, 1003 patients undergoing abdominal surgery were given 1 g of intravenous ceftriaxone (R) or cefotaxime (C) at induction of anesthesia, and an additional 500 mg of metronidazole for colorectal surgery. Infection was checked for during the hospital stay and at 30 days postoperatively. The inpatient, outpatient, and community costs of infection were prospectively collected. The frequency of wound infection fur appendectomies when additional metronidazole was not administered was greater with cefotaxime (R 6%, C 18%, p ≤ 0.05), but the cost of infection was the same (average cost R &dollar;994 ± SD &dollar; 1101, C &dollar;878 ± &dollar;1318). For all other procedures, the frequency of wound infection was similar (R 8%, C 10%), but the cost was less with ceftriaxone (R &dollar;887 ± &dollar;1743, C &dollar;2995 ± &dollar;6592, P &lt: 0.05). Ceftriaxone decreased the frequency but not the cost of chest and urinary infection (frequency R 6%, C 11%, p < 0.02, cost R &dollar;1273 ± 2338, C &dollar;1615 ± 4083). Differences in both the frequency and cost of all infection are also presented. Ceftriaxone decreased either the frequency or the cost of different postoperative infections. The cost of infection can increase the discriminatory power of trials comparing antibiotic effectiveness. [ABSTRACT FROM AUTHOR]

: BackgroundAlthough ceftriaxone (R) and cefotaxime (C) are highly effective antibiotics, few studies have directly compared their prophylactic efficacy.: MethodsIn a prospective, randomized, double blind study of 1,013 patients undergoing abdominal surgery, the prophylactic use of ceftriaxone and cefotaxime were compared. Intravenous cephalosporin, 1 g, was given at induction of anesthesia, with intravenous metronidazole, 500 mg, also being given for colorectal surgery.: ResultsThe difference in wound infection (R 8%, C 12%, P <0.05) was due to appendicectomies not receiving metronidazole, (R 6%, C 18%, P <0.03) and was no longer present when these cases were excluded from analysis (R 8%, C 10%). Of note chest and urinary tract infection (R 6%, C 11%, P <0.02) and “any” infection (R 20%, C 27%, P <0.05) were reduced with ceftriaxone.: ConclusionsBoth antibiotics provide comparable wound prophylaxis as long as metronidazole is added for colorectal and appendiceal surgery. Ceftriaxone may be more versatile having the additional apparent benefits of reducing other postoperative infections, being less dependent on metronidazole as an adjunct and providing a more effective prophylactic cover against Staphylococcus aureus. [Copyright &y& Elsevier]

Examines the incidence of acute colonic pseudo-obstruction cases among the total number of patients with acute colonic obstructions that were admitted at the Dunedin Hospital in New Zealand between 1988 and 1996. Potential etiological factors; Line of treatment used in the hospital; Hospital's experience with colonoscopic decompression.

Peripheral arterial disease (PAD) is characterized by lower limb atherosclerosis impairing blood supply and causing walking-induced leg pain or claudication. Adherence to traditional exercise training programs is poor due to these symptoms despite exercise being a mainstay of conservative treatment. Heat therapy improves many cardiovascular health outcomes, so this study tested if this was a viable alternative cardiovascular therapy for PAD patients. Volunteers with PAD were randomized to 12 wk of heat (n = 11; mean age 76 ± 8 yr, BMI 28.7 ± 3.5 kg/m2, 4 females) or exercise (n = 11; 74 ± 10 yr, 28.5 ± 6.8 kg/m2, 3 females). Heat involved spa bathing at ~39°C, 3-5 days/wk for ≤30 min, followed by ≤30 min of callisthenics. Exercise involved ≤90 min of supervised walking and gym-based exercise, 1-2 days/wk. Following the interventions, total walking distance during a 6-min walk test increased (from ~350 m) by 41 m (95% CI: [13, 69], P = 0.006) regardless of group, and pain-free walking distance increased (from ~170 m) by 43 m ([22, 63], P < 0.001). Systolic blood pressure was reduced more following heat (-7 mmHg, [-4, -10], P < 0.001) than following exercise (-3 mmHg, [0, -6], P = 0.078), and diastolic and mean arterial pressure decreased by 4 mmHg in both groups (P = 0.002). There were no significant changes in blood volume, ankle-brachial index, or measures of vascular health. There were no differences in the improvement in functional or blood pressure outcomes between heat and exercise in individuals with PAD. [ABSTRACT FROM AUTHOR]

Epidemiological evidence has highlighted a strong relationship between cardiorespiratory fitness and surgical outcomes; specifically, fitter patients possess heightened resilience to withstand the surgical stress response. This narrative review draws on exercise and surgical physiology research to discuss and hypothesise the potential mechanisms by which higher fitness affords perioperative benefit. A higher fitness, as indicated by higher peak rate of oxygen consumption and ability to sustain metabolic homeostasis (i.e. higher anaerobic threshold) is beneficial postoperatively when metabolic demands are increased. However, the associated adaptations with higher fitness, and the related participation in regular exercise or physical activity, might also underpin the observed perioperative benefit through a process of hormesis, a protective adaptive response to the moderate and intermittent stress of exercise. Potential mediators discussed include greater antioxidant capacity, metabolic flexibility, glycaemic control, lean body mass, and improved mood. [ABSTRACT FROM AUTHOR]

Teaching traditionally asserts that the arterial pressure pulse is dampened across the capillary bed to the extent that pulsatility is nonexistent in the venous circulation of the lower limbs. Herein, we present evidence of transmission of arterial pulsations across the capillary network into perforator veins in the lower limbs of healthy, heat-stressed humans. Perforator veins are connections from the superficial veins that drain into the deep veins. When assessed using ultrasound at rest, they infrequently demonstrate flow, and a pulsatile flow waveform is not described. We investigated perforator vein pulsatility in 10 young, healthy volunteers who underwent passive heating by þ2°C core body temperature via a hot-water-perfused suit, and 5 who also underwent active heating by þ2°C via low-intensity cycling while wearing the hot-water-perfused suit. At þ0.5°C increments in temperature, blood velocity in an ankle perforator vein was measured using duplex ultrasound. In all perforators with heating, sustained flow was demonstrated, with a pulsatile waveform that was synchronous with the cardiac cycle. The maximum velocity was 30 ± 13 cm/s with passive heating and approximately half with active heating (P = 0.04). The small veins of the skin at the ankle also demonstrated increased perfusion with pulsatility, seen with low-velocity microvascular imaging technology. We consider explanations for this pulsatility and conclude that it is propagated from the arterial inflow through the skin microcirculation as a result of increased dilatation and flow volume and that this is a normal response to increased skin blood flow. [ABSTRACT FROM AUTHOR]

Background: New Zealand, like Australia, has a widely dispersed population in towns at long distances from the main centres. We set out to estimate the in-hospital mortality rate for ruptured abdominal aortic aneurysms in New Zealand and identify factors associated with mortality. Methods: Data were gathered prospectively as part of the Vascular Society of New Zealand’s continuous audit programme of all member surgeons. Data collection was validated by random record audit. In-hospital mortality of ruptured abdominal aortic aneurysms, defined as death during hospital admission irrespective of cause, was determined for the period 1993–2005. Along with other performance indicators, differences in outcomes were assessed to take into account the trend over the time period, hospital size and number of non-operative admissions. Results: Of the 740 patients admitted with a mean age of 73.9 ± 8.5 years, 78% were men and 17.8% were declined an operation. The in-hospital mortality was 48.3% and the operative mortality was 37.8%. With univariate analysis increasing patient age, American Society of Anesthesiology score, hospital size and female sex were predictors of in-hospital mortality. Only age and American Society of Anesthesiology score were independent predictors of operative mortality. Women were less likely to have surgery. Conclusion: Over the past 13 years in-hospital mortality of ruptured abdominal aortic aneurysms in New Zealand remained unchanged. In provincial hospitals the operative outcomes were satisfactory, but the reported number not offered surgery was higher. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a prominent risk factor for peripheral artery disease (PAD). Yet, the mechanistic link between diabetes and PAD remains unclear. This study proposes that dysregulation of the endogenous hormone ghrelin, a potent modulator of vascular function, underpins the causal link between diabetes and PAD. Moreover, this study aimed to demonstrate the therapeutic potential of exogenous ghrelin in a diabetic mouse model of PAD. Standard ELISA analysis was used to quantify and compare circulating levels of ghrelin between (i) human diabetic patients with or without PAD (clinic) and (ii) db/db diabetic and non-diabetic mice (lab). Db/db mice underwent unilateral hindlimb ischaemia (HLI) for 14 days and treated with or without exogenous ghrelin (150 µg/kg/day.) Subsequently vascular reparation, angiogenesis, hindlimb perfusion, structure and function were assessed using laser Doppler imaging, micro-CT, microangiography, and protein and micro-RNA (miRNA) analysis. We further examined hindlimb perfusion recovery of ghrelin KO mice to determine whether an impaired vascular response to HLI is linked to ghrelin dysregulation in diabetes. Patients with PAD, with or without diabetes, had significantly lower circulating levels of endogenous ghrelin, compared to healthy individuals. Diabetic db/db mice had ghrelin levels that were only 7% of non-diabetic mice. The vascular reparative capacity of diabetic db/db mice in response to HLI was impaired compared to non-diabetic mice and, importantly, comparable to ghrelin KO mice. Daily therapeutic treatment of db/db mice with ghrelin for 14 days post HLI, stimulated angiogenesis, and improved skeletal muscle architecture and cell survival, which was associated with an increase in pro-angiogenic miRNAs-126 and -132. These findings unmask an important role for endogenous ghrelin in vascular repair following limb ischemia, which appears to be downregulated in diabetic patients. Moreover, these results implicate exogenous ghrelin as a potential novel therapy to enhance perfusion in patients with lower limb PAD, especially in diabetics. [ABSTRACT FROM AUTHOR]

This study investigated whether microvenous reflux can be detected in limbs with chronic venous disease using superb microvascular imaging (SMI) and colour Doppler imaging. Participants with venous disease (limbs, n = 26) and without venous disease (limbs, n = 10) were studied. The skin in the medial gaiter region was imaged using both SMI and colour Doppler to identify reflux in the small vessels in response to distal augmentation. The diameters and depths of responsive vessels were measured. In limbs with venous disease, reflux in response to provocation was visualised with SMI in a greater number of vessels (12/26 versus 4/26) and smaller vessels than with colour Doppler. Reflux in the superficial skin veins was demonstrated in one control participant (1/10) using SMI and in none using colour Doppler (0/10). Our study indicates that microvenous reflux is demonstrable in limbs with venous disease and that SMI is more sensitive than colour Doppler. [ABSTRACT FROM AUTHOR]

Background Highly trained vascular sonographers make up a significant cost of abdominal aortic aneurysm (AAA) ultrasound screening. However, they are over-trained for this very limited task. Others have reported that health workers (e.g. emergency room staff and nurses) with far less training may be able to perform these scans. The national AAA screening programme in the UK uses staff with limited training. Whether individuals without a health professional qualification could be trained to perform the scan accurately to improve cost-effectiveness is not known. We aimed to investigate whether a short, well-supervised course in ultrasonography could train novices to detect AAA for screening purposes. Methods Three novices were trained by an experienced sonographer for 15 days to perform abdominal aortic ultrasound examinations and detect AAA using a portable ultrasound system. The examination included four anterior-posterior aortic measurements: a maximal diameter in the coronal plane and three diameters of the suprarenal, mid and distal infrarenal aorta in the transverse plane. The novices independently scanned 215 subjects following training; experienced sonographers repeated the measurements on the same subject in the same session. Using Bland-Altman plots and CUSUM analysis, the novices' and experienced sonographers' accuracy and efficiency measurements were compared. Factors influencing performance were recorded. Results The novices measured the maximal coronal aortic diameter accurately, to within 0.46-0.52 cm of the true diameter; 85-97% of their coronal measurements were within 0.5 cm of the assessors; kappa statistic and Bland-Altman plots show a high agreement with the assessor's measurements. However, the novices' measurements of the three diameters in the transverse plane were outside clinically acceptable limits. Assuming a referral policy for a second scan for scans recorded as 'difficult', only one novice missed a 3.13 cm aneurysm. A CUSUM quality improvement analysis demonstrated substantial improvements in the scanning efficiency of the novices with continued scanning experience. Conclusion This study showed that novices could be trained to screen for AAA over 15 days. However, the need for continuing quality improvement is critical, especially in more technically demanding cases. Measuring the maximal infrarenal diameter instead of specific segmental diameters may be more appropriate for AAA screening using novices. [ABSTRACT FROM AUTHOR]

Anti-Mü llerian hormone (AMH) is a gonadal hormone present in the blood in men and pre-menopausal women. AMH regulates male sexual differentiation but has no putative function in adulthood. In recent studies, high AMH levels are associated with absence of cardiovascular disease in men and smaller atherosclerotic burden in monkeys. Mechanistically, AMH has downstream convergence with known regulators of the cardiovascular system, while the specific receptor for AMH is present in murine aorta and the human heart. Our primary objective was to examine whether AMH levels in healthy men correlated with the physical characteristics of their aorta. Our secondary aim was to document whether men with distinct vascular disorders expressed different levels of AMH. Serum AMH assayed by ELISA in 153 men (54-93 years) free from vascular disease inversely correlated with the ultrasonographic diameters of the distal- (r=K0.22, P=0.006) and mid-infrarenal aorta (r=K0.26, P=0.008). This association was similar in magnitude but opposite to that of body surface area (largest known determinant of aortic diameter) and independent of known cardiovascular risk factors. This relationship is specific to AMH, as inhibin B, a Sertoli cell hormone-like AMH, did not correlate with aortic diameter (r=K0.04, P=0.66) despite partially correlating with AMH. Among men with known vascular disease, higher AMH levels were associated with varicose vein disease, while men with higher levels ofAMH were underrepresented in the abdominal aortic aneurysm relative to the healthy cohort. These findings identify AMH as a novel putative regulator of the cardiovascular system. [ABSTRACT FROM AUTHOR]

Abstract: Background: This study aimed to investigate whether the endogenous active levels of MMP-9 or tissue inhibitor of metalloproteinases-1 (TIMP-1) were related to indices of diastolic dysfunction (DD) in the setting of contemporary treatment of coronary artery disease (CAD). Methods and results: We prospectively studied 116 patients with CAD and preserved left ventricular LV systolic function (ejection fraction≥45%). All patients were free of heart failure symptoms at recruitment and underwent percutaneous intervention (PCI) of culprit lesions. Demographic and angiographic characteristics were collected. Plasma samples were analysed for the active form of MMP-9 and TIMP-1 using enzyme-linked immunosorbent assay-based isoform sensitive assays. Conventional and tissue Doppler-echocardiographic assessment of diastolic filling was undertaken with measurements of maximal early (E) and late (A) transmitral velocities in diastole, E/A ratio, E-wave deceleration time, isovolumic relaxation time, peak systolic (S), diastolic (D) and atrial reversal velocities of pulmonary venous flow, S/D fraction, time difference between A and duration of atrial reversal flow, early diastolic peak velocities of the lateral mitral annulus (E′) and E/E′. Active MMP-9 level was higher in patients with more severe phases of DD (normal [n=22]: median 0.57ng/ml; mild [n=19] 0.83ng/ml; mild-moderate [n=41] 0.64ng/ml; moderate or severe [n=34] 1.63ng/ml; p<0.0001 for trend). Three month post-PCI elevated levels of active MMP-9 had an adjusted odds ratio of 11.2 (2.3–56.0, p<0.004) for association with moderate or severe DD. Conclusion: Elevated active MMP-9 level is associated with more severe DD in patients with CAD and preserved systolic function, which may indicate abnormal extracellular matrix metabolism in myocardial ischaemia. [Copyright &y& Elsevier]

The Sertoli cells of the testes secrete anti-Müllerian hormone (Müllerian inhibiting Substance, AMH) and inhibin B (InhB). AMH triggers the degeneration of the uterine precursor in male embryos, whereas InhB is part of the gonadal-pituitary axis for the regulation of sperm production in adults. However, both hormones are also putative regulators of homeostasis, and age-related changes in these hormones may therefore be important to the health status of elderly men. The levels of AMH in elderly men are unknown, with limited information being available about age-related changes in InhB. We have therefore used ELISAs to measure Sertoli cell hormone levels in 3 cohorts of community-dwelling men in New Zealand. In total, 615 men were examined, 493 of which were aged 65 or older. Serum AMH and InhB levels inversely correlated with age in men older than 50 years (p<0.001) but not in the younger men. A minority of elderly men had undetectable levels of AMH and InhB. The variation in hormone levels between similarly aged men increased with the age of men. AMH and InhB partially correlated with each other as expected (r = 0.48, p<0.001). However, the ratio of the two Sertoli hormones varied significantly between men, with this variation increasing with age. Elderly men selected for the absence of cardiovascular disease had AMH levels similar to those of young men whereas their InhB levels did not differ from aged-matched controls. These data suggests that Sertoli cell number and function changes with age, but with the extent and nature of the changes varying between men. [ABSTRACT FROM AUTHOR]

In the past the saphenofemoral junction (SFJ) for the surgeon was regarded as a simple conduit to be obliterated. With modern ultrasound we can distinguish the components of this complex structure and examine their haemodynamic function and suggest more haemodynamically-focused interventions. Despite this, there are no ultrasound studies describing the components of the normal SFJ and their haemodynamic significance. Patients attending our vascular laboratory with suspected deep vein thrombosis were screened and the SFJ in 75 limbs with no physiological or haemodynamic abnormalities were examined. The terminal (TV) and preterminal (PTV) valve morphology and the distance from the SFJ were assessed. The number of tributaries and their position relative to these valves was also examined. TV and PTVs were identified on ultrasound in all 75 limbs. TVs were found at a mean distance of 0.4 cm (range 0-1.2 cm) from the SFJ. Nearly a third of all limbs had at least one tributary vein identified superior to the TV. The greater the distance to the TV, the greater the number of tributary veins one should expect to find superior to the TV. PTV location was more variable. PTVs were identified at a mean distance of 3.1 cm (range 0.4-8.7 cm), giving rise to a large number of configurations of tributary veins in the intervalve space. This study characterizes the ultrasound appearances of the normal SFJ and compares these with reported anatomical studies. Valves can be consistently identified whereas the number and location of the tributaries are very variable. This should inform planning of haemodynamically-focused treatment at the SFJ. [ABSTRACT FROM AUTHOR]

Abstract: Background: Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized. Methods: Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IMPROVE study (n = 3427) using the Illumina 200k Metabochip was performed. Single nucleotide polymorphisms (SNPs) that met array-wide significance were taken forward for analysis in three further studies (n = 5704), and tested for association with Abdominal Aortic Aneurysm (AAA). Results: rs3768445 on Chromosome 1q24.3, in a cluster of protein coding genes (DNM3, PIGC, C1orf105) was associated with larger ICCAD in the IMPROVE study. For each copy of the rare allele carried, ICCAD was on average 0.13 mm greater (95% CI 0.08–0.18 mm, P = 8.2 × 10−8). A proxy SNP (rs4916251, R 2 = 0.99) did not, however, show association with ICCAD in three follow-up studies (P for replication = 0.29). There was evidence of interaction between carotid intima-media thickness (CIMT) and rs4916251 on ICCAD in two of the cohorts studies suggesting that it plays a role in the remodelling response to atherosclerosis. In meta-analysis of 5 case–control studies pooling data from 5007 cases and 43,630 controls, rs4916251 was associated with presence of AAA 1.10, 95% CI 1.03–1.17, p = 2.8 × 10−3, I 2 = 18.8, Q = 0.30). A proxy SNP, rs4916251 was also associated with increased expression of PIGC in aortic tissue, suggesting that this may the mechanism by which this locus affects vascular remodelling. Conclusions: Common variation at 1q24.3 is associated with expansive vascular remodelling and risk of AAA. These findings support a hypothesis that pathways involved in systemic vascular remodelling play a role in AAA development. [Copyright &y& Elsevier]

Objectives: The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background: It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods: The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n e] = 9,396); peripheral arterial disease (n e = 5,215); abdominal aortic aneurysm (n e = 4,572); venous thromboembolism (n e = 4,607); intracranial aneurysm (n e = 1,328); CAD (n e = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results: LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 × 10–4), peripheral artery disease (OR: 1.47; p = 2.9 × 10–14), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 × 10–5), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 × 10–12). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (–1.58 years/allele; p = 8.2 × 10–8) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions: LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. [Copyright &y& Elsevier]

Abstract: Objective: The role of transforming growth factor (TGF)-beta in abdominal aortic aneurysm (AAA) is controversial. The aim of this study was to assess the association of single nucleotide polymorphisms (SNPs) within TGFBR1 and TGFBR2 with AAA and infrarenal aortic diameter by combining data from previously published studies. Methods: We performed a meta-analysis using individual subject data from three independent case-control groups from Western Australia (n =1675), New Zealand (n =1209), and the Netherlands (n =1636) with 610, 601, and 693 cases of AAA (maximum infrarenal aortic diameter ≥30mm), respectively. Data were available for two TGFBR1 (rs10819634, rs1571590) and six TGFBR2 (rs304839, rs1346907, rs1036095, rs9831477, rs9843143, rs764522) SNPs. Results: There was marked heterogeneity between studies. The G alleles of the TGFBR2 rs764522 and rs1036095 SNPs were associated with AAA under a recessive model (OR=1.69, 95% CI 1.28–2.25, P <0.001 and OR=1.59, 95% CI 1.23–2.07, P <0.001) when a fixed effects model was used. Both associations remained significant after adjustment for multiple testing. Conclusion: This study suggests that two common genetic polymorphisms in TGFBR2 are associated with the risk of developing AAA although this association was mainly driven by findings in the Netherlands group and marked between study heterogeneity was detected. [Copyright &y& Elsevier]

Male gender and family history are risk factors for abdominal aortic aneurysm (AAA). We hypothesized that genes involved in sex hormones might be important in AAA. We investigated the association of aortic diameter with single-nucleotide polymorphisms (SNPs) in genes determining circulating sex hormones and their action. We genotyped 74 tagging SNPs across four genes (steroid 5α reductase, subfamily A, polypeptide 1 (SRD5A1), cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1), androgen receptor (AR) and estrogen receptor 2 (ESR2)) related to sex hormone production and action in 1711 men, 640 of whom had an AAA. One genotype was also assessed in an independent cohort of 782 men, of whom 513 had large AAAs. Associations were assessed adjusting for other risk factors for AAA. One SNP in CYP19A1 was strongly associated with aortic diameter. Subjects who had the rare homozygote genotype (TT) for CYP19A1g.49412370C>T (SNP ID rs1961177), had an increased aortic diameter (coefficient 5.058, SE 1.394, P=0.0003, under a recessive model). This SNP was not associated with aortic diameter in an independent cohort, which included patients with larger AAAs. Our findings do not support an important role of genetic polymorphisms in genes determining sex hormones in aortic dilatation in men. The association of one SNP in CYPA9A1 with small but not large AAA may suggest differences between AAA formation and progression. This SNP warrants further investigation in another large population, including patients with small AAAs. [ABSTRACT FROM AUTHOR]

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 × 10−10. In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 × 10−5), peripheral arterial disease (OR = 1.14, P = 3.9 × 10−5) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases—that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Abdominal Aortic Aneurysm (AAA) has a strong genetic predisposition. Transforming growth factor beta 1 (TGF-β1) is a causal factor in ascending aortic dilatation; however, a role in AAA pathology is unclear. The aim of the study was to determine whether genes coding TGF-β and its binding protein are associated with the presence and expansion of AAA. Methods: Four geographically distinct case control studies, totaling 1890 AAA cases and 3785 controls, were genotyped and compared to the presence, size and growth rate of AAA. 26 single nucleotide polymorphisms (SNPs) in 5 genes were genotyped in the UK cohort and the result was replicated in 3 independent cohorts. Results: No associations between genotypes or haplotypes and the presence of AAA disease were confirmed. Five SNPs in Latent TGF-β Binding Protein (LTBP4) and an allelic variant of TGFB3 were associated with a significant decrease in AAA growth (p ≤0.02), in the UK cohort. Altered growth was demonstrated in carriers of two common haplotypes of LTBP4 (+0.38mm/year, p =0.003; −0.41mm/year, p =0.02, per haplotype copy) and a single haplotype of TGFB3 (−0.53mm/year, p =0.05). This association with AAA growth could not be demonstrated in two other independent cohorts. Meta-analysis of AAA size and growth rates in larger AAA (≥45mm), in all four cohorts, demonstrated a significant association with the LTBP4 21011A>T genotype (a 2% decrease in AAA diameter, or a 0.53mm/year reduction in AAA growth rate, per T allele [p =0.03, p =0.01]). Conclusion: This study suggests that the LTBP4 gene may contribute to AAA progression. [Copyright &y& Elsevier]

Background: Abdominal aortic aneurysm (AAA) is an important cause of mortality for the aged, a group that has been denied surgery in the past for fear of peri-operative mortality. Is this attitude still justified? Methods: Analysis of prospectively gathered data from a vascular database. Results: 10.9% of all open AAA operations were in patients older than 79 years with an 8% mortality cate compared to 3% for younger patients. For fit elderly patients with ASA scores less than 3, mortality was just under 4%. Renal failure and wound dehiscence were more common in the elderly. Conclusion: When endovascular repair is not possible in a fit elderly patient, open surgery can be performed with acceptable results. [ABSTRACT FROM AUTHOR]

The ability to predict who will develop perioperative complications remains difficult because the etiology of adverse events is multifactorial. This study examines the preoperative and postoperative ability of the surgeon to predict complications and assesses the significance of a change in prediction. This was a prospective study of 1013 patients. The surgeon assessed the risk of a major complication on a 100-mm visual analog scale (VAS) immediately before and after surgery. When the VAS score was changed, the surgeon was asked to document why. Patients were assessed up to 30 days postoperatively. Surgeons made a meaningful preoperative prediction of major complications (median score = 27mm vs. 19mm, p < 0.01), with an area under the receiver operating characteristic curve of 0.74 for mortality, 0.67 for major complications, and 0.63 for all complications. A change in the VAS score postoperatively was due to technical reasons in 74% of stated cases. An increased VAS score identified significantly more complications, but the improvement in the discrimination was small. When included in a multivariate model for predicting postoperative complications, the surgeon’s VAS score functioned as an independent predictive variable and improved the predictive ability, goodness of fit, and discrimination of the model. Clinical assessment of risk by the surgeon using a VAS score independently improves the prediction of perioperative complications. Including the unique contribution of the surgeon’s clinical assessment should be considered in models designed to predict the risk of surgery. [ABSTRACT FROM AUTHOR]

Background: Wound infection occurs when bacterial contamination overcomes the hosts’ defences against bacterial growth. Wound categories are a measurement of wound contamination. The American Society of Anesthesiologists (ASA) classification of physical status may be an effective indirect measurement of the hosts’ defence against infection. This study examines the association between the ASA score of physical status and wound infection. Methods: A retrospective review of a prospective study of antibiotic prophylaxis was carried out. Patients with a documented ASA score who received optimal prophylactic antibiotics were included. The anaesthetist scored the ASA classification of physical status in theatre. Other risk factors for wound infection were also documented. Patients were assessed up to 30 days postoperatively. Results: Of 1013 patients there were 483 with a documented ASA score. One hundred and one may not have received optimal prophylaxis, leaving a database of 382 patients. There were 36 wound infections (9.4%). Both the ASA classification of physical status ( P = 0.002) and the wound categories ( P = 0.034) significantly predicted wound infection. The duration of surgery, patient’s age, acuteness of surgery and the organ system being operated on did not predict wound infection. On logistic regression analysis the ASA score was the strongest predictor of wound infection. Conclusion: When effective prophylactic antibiotics were used the ASA classification of physical status was the most significant predictor of wound infection. [ABSTRACT FROM AUTHOR]

Background: Limited health resources necessitate prioritization for access to elective cholecystectomy in New Zealand. We aimed to develop and validate a patient questionnaire for determining the effect of gallstone disease on quality of life (QOL) and evaluate its potential role in appraising prioritization and outcomes from surgery. Methods: The Otago gallstones condition-specific questionnaire (CSQ) was designed based on review of published reports, structural equation modelling, input from experts and patient feedback. Fifty-four patients with symptomatic gallstone disease completed the CSQ including a single question asking about global condition impact, along with other QOL measures: the Gallstone Impact Checklist and the Short Form-36 Health Survey. Validity and reliability of the CSQ were assessed using standard psychometric criteria and patient acceptance was explored in a semistructured interview. Patients’ priority status for surgery was determined by two participating surgeons and resulting scores were correlated with the QOL measures. Results: Average CSQ completion time was 2.7 (range 1–5) min and patients found its content concise and comprehensive. Validity was supported through high correlations with the Gallstone Impact Checklist ( r = 0.74), the global condition impact ( r = 0.69) and related dimensions of the Short Form-36 Health Survey. CSQ questions showed satisfactory internal consistency (Cronbach’s α = 0.94) and reproducibility (ICC = 0.93, where ICC is intraclass coefficient). Of all the QOL measures, the CSQ was the most clinically relevant, showing the strongest relationship with surgeon-rated priority ( r = 0.62). Conclusions: Evidence is provided to support the validity of the CSQ for assessing the effect of gallstone disease on QOL. The CSQ could be particularly valuable in aiding priority decisions surgeons make and may be useful in tracking subsequent outcomes. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Recent reports have suggested a reproducible association between the rs11121615 SNP, located within an intron of the castor zinc finger 1 (CASZ1) gene, and varicose veins. This study aimed to determine if this variant is also differentially associated with the various clinical classifications of chronic venous disease (CVD). The rs11121615 SNP was genotyped in two independent cohorts from New Zealand (n = 1876 controls /1606 CVD cases) and the Netherlands (n = 1626/2966). Participants were clinically assessed using well-established CVD criteria. The association between the rs11121615 C-allele and varicose veins was validated in both cohorts. This was strongest in those with higher clinical severity classes and was not significant in those with non-varicose vein CVD. Functional analysis of the rs11121615 variant demonstrated that the risk allele was associated with increased enhancer activity. This study demonstrates that the CASZ1 gene associated C-allele of rs11121615 has a significant, reproducible, association with CVD (CEAP C ≥ 2 meta-odds ratio 1.31, 95% CI 1.27–1.34, P = 1 × 10−98, PHet = 0.25), but not with non-varicose vein (CEAP C1, telangiectasia or reticular veins) forms of venous disease. The effect size of this association therefore appears to be susceptible to influence by phenotypic heterogeneity, particularly if a cohort includes a large number of cases with lower severity CVD. [ABSTRACT FROM AUTHOR]

Background: Highly trained vascular sonographers make up a significant cost of abdominal aortic aneurysm (AAA) ultrasound screening. However, they are over-trained for this very limited task. Others have reported that health workers (e.g. emergency room staff and nurses) with far less training may be able to perform these scans. The national AAA screening programme in the UK uses staff with limited training. Whether individuals without a health professional qualification could be trained to perform the scan accurately to improve cost-effectiveness is not known. We aimed to investigate whether a short, well-supervised course in ultrasonography could train novices to detect AAA for screening purposes.Methods: Three novices were trained by an experienced sonographer for 15 days to perform abdominal aortic ultrasound examinations and detect AAA using a portable ultrasound system. The examination included four anterior-posterior aortic measurements: a maximal diameter in the coronal plane and three diameters of the suprarenal, mid and distal infrarenal aorta in the transverse plane. The novices independently scanned 215 subjects following training; experienced sonographers repeated the measurements on the same subject in the same session. Using Bland-Altman plots and CUSUM analysis, the novices' and experienced sonographers' accuracy and efficiency measurements were compared. Factors influencing performance were recorded.Results: The novices measured the maximal coronal aortic diameter accurately, to within 0.46-0.52 cm of the true diameter; 85-97% of their coronal measurements were within 0.5 cm of the assessors; kappa statistic and Bland-Altman plots show a high agreement with the assessor's measurements. However, the novices' measurements of the three diameters in the transverse plane were outside clinically acceptable limits. Assuming a referral policy for a second scan for scans recorded as 'difficult', only one novice missed a 3.13 cm aneurysm.A CUSUM quality improvement analysis demonstrated substantial improvements in the scanning efficiency of the novices with continued scanning experience.Conclusion: This study showed that novices could be trained to screen for AAA over 15 days. However, the need for continuing quality improvement is critical, especially in more technically demanding cases. Measuring the maximal infrarenal diameter instead of specific segmental diameters may be more appropriate for AAA screening using novices. [ABSTRACT FROM AUTHOR]