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Carotid endarterectomy (CEA) and carotid artery stenting (CAS) prevent stroke in selected patients. However, each intervention carries a risk of perioperative complications including stroke or death (S/D). We aimed to determine the relationship between operator volume, hospital volume, and the perioperative risk of S/D in carotid revascularization in Australia and New Zealand. Retrospective analysis was performed on prospectively collected data extracted from the Australasian Vascular Audit between 2010 and 2017. Annual caseload volume was analyzed in quintiles (Q) using multivariate regression to assess its impact on perioperative S/D. Carotid endarterectomy procedures (n = 16 765) demonstrated higher S/D rates for lower-volume operators (2.21% for Q1-Q3 [1-17 annual cases] vs 1.76% for Q4-Q5 [18-61 annual cases]; odds ratio [OR]: 1.28; 95% CI: 1.001-1.64; P = .049). Carotid artery stenting procedures (n = 1350) also demonstrated higher S/D rates for lower-volume operators (2.63% for Q1-Q3 [1-11 annual cases] vs 0.37% for Q4-Q5 [12-31 annual cases]; OR: 6.11; 95% CI: 1.27-29.33; P = .024). No significant hospital volume-outcome effect was observed for either procedure. An inverse relationship was demonstrated between operator volume and perioperative S/D rates following CEA and CAS. Consideration of minimum operator thresholds, restructuring of services and networked referral pathways of care in Australia and New Zealand, would likely result in improved patient outcomes.

Background: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) reduce the risk of stroke in patients with severe carotid stenosis. The aim was to compare contemporary treatment trends and outcomes after CEA and CAS between states of Australia., Methods: A retrospective analysis was conducted on data from the Australasian Vascular Audit between 2010 and 2017. The primary endpoint was perioperative stroke or death (S/D). We also analysed stroke and death independently and revascularization rates per 100 000 population., Results: A total of 15 413 patients underwent carotid revascularization (CEA 14 070; CAS 1343). S/D rates were similar for CEA and CAS (1.9% versus 1.8%; P = 0.37; symptomatic 2.1% versus 2.3%; P = 0.12; asymptomatic 1.5% versus 1.1%; P = 0.67). Patients ≥80 years (2.7% versus 1.7%; P = 0.01), those who had shunts (2.2% versus 1.7%; P = 0.03) or surgery in teaching hospitals (2.6% versus 1.4%; P = 0.02) had higher rates of S/D after CEA. Patients whose proceduralist used a cerebral protection device had lower S/D rates after CAS for symptomatic disease (4.8% versus 2.2%; P = 0.03). There was a wide variation in practice between states, where CAS as a proportion of total carotid procedures ranged from 0% to 17%, and a wide variation in outcomes, with rates of S/D varying between 1.4-6.6% for CEA and 0-6.7% after CAS., Conclusion: Outcomes after CAS are equivalent to CEA when performed by vascular surgeons, however significant variation exists for both choice of revascularization procedure and perioperative outcomes between states. Further investigation is needed to determine whether clinical care pathways should be revised to achieve consistency and quality of outcomes., (© 2021 Royal Australasian College of Surgeons.)

Objectives: The aim of this study was to perform a long-term evaluation of an everolimus eluting, bioresorbable vascular scaffold (BVS) in the treatment of de novo atherosclerotic disease within crural arteries., Methods: A prospective, single-arm study was performed enrolling patients with chronic lower limb ischemia between 2013 and 2018., Results: Fifty-five limbs in 48 patients (56% male; mean age 82.1 ± 8.0 years, range 65-97) were treated for critical limb ischemia (72.7%) or severe claudication (27.3%). Seventy-one scaffolds were used to treat 61 lesions with a mean length of 20.1 ± 10.8 mm. During a mean follow-up period of 35.2 ± 20.4 months, 22 (45.8%) patients had died. No late or very-late scaffold thrombosis was observed. Overall, clinical improvement was observed in 90.9% and a limb-salvage rate of 100% was observed. Binary restenosis was detected in 11/71(15.5%) scaffolds. Primary patency and freedom from clinically driven target lesion revascularization rates at 12, 24, 36, 48, and 60 months were 90.8% (95% confidence interval 80.7-95.8), 90.8% (80.7-95.8), 79.7% (65.8-88.4), 76.3% (61.1-86.2), 72.3% (55.5-83.4) and 97.2% (89.2-99.3), 97.2% (89.2-99.3), 90.7% (78.7-96.1), 90.7% (78.7-96.1), and 90.7% (78.7-96.1), respectively., Conclusions: This long-term study shows excellent rates of patency and freedom from target lesion revascularization using the absorb BVS below-the-knee. This proof of concept study lays the foundation for the next generation of BVS to be evaluated in infrapopliteal arteries., (© 2020 Wiley Periodicals LLC.)

Introduction: The native arteriovenous fistula may remain immature despite adequate arterial inflow after formation. This may occur when the puncturable vein segment (cannulation zone) is too small to be reliably punctured, occluded or too deep under the skin for needle access. We performed stenting (stent-assisted maturation) of arteriovenous fistulas with an immature cannulation zone, allowing for a large subcutaneous channel which could then be immediately punctured for dialysis., Methods: We performed a retrospective review of 49 patients (mean age was 58.7 ± 16.09 (12-83) years, mean arteriovenous fistula age of 162.6 ± 27.28 days) with end-stage renal failure who underwent balloon dilatation and bare-metal stent implantation (1.6 ± 0.67 (1-3) stents, median diameter and length of 8 (5-14) mm and 80 (40-150) mm, respectively) through their cannulation zone (forced maturation). Radiocephalic (35 arteriovenous fistulas), brachiocephalic (10 arteriovenous fistulas) and autogenous loop arteriovenous fistulas (4 arteriovenous fistulas) were included with 30 patients (61.2%) having an inadequate cannulation zone venous diameter, 9 patients (18.4%) having an absent cannulation zone and 10 patients (20.4%) having a patent cannulation zone deeper than 1 cm which was not reliably puncturable. The study was conducted over 9 years (January 2008-December 2016) with implantation of the SMART ® stent and Absolute Pro ® stent in 61.2% and 38.8%, respectively. Long-term outcomes including primary useable segmental and access circuit patency as well as assisted primary access circuit patency, rate of re-intervention, technical success and complications were analysed., Results: At 6 months, 12 months and 4 years, respectively, cannulation zone primary patency was 84.4%, 74.4% and 56.1% and access circuit primary patency was 62.2%, 45.3% and 23.2%; however, assisted primary access circuit patency was 95.6%, 91.1% and 83.8%, achieved with an endovascular re-intervention rate of 0.53 procedures/year with only four thrombosed circuits occurring., Discussion: Forced maturation using nitinol stents allows for long-term haemodialysis access with a low rate of re-intervention.

Objective: Hospital and surgeon operative caseload is thought to be associated with peri-operative mortality following the non-elective repair of aortic aneurysms; however, whether such an association exists within the Australian healthcare setting is unknown., Methods: The Australasian Vascular Audit was interrogated to identify patients undergoing non-elective (emergency [EMG] or semi-urgent [URG]) aortic aneurysm repair between 2010 and 2016, as well as their treating surgeon and hospital. Hierarchal logistic regression modelling was used to assess the impact of caseload on outcomes after both endovascular (EVAR) and open surgical repair (OSR)., Results: Volume counts were determined from 14 262 patients (4 121 OSR and 10 141 EVAR). After exclusion of elective procedures and duplicates, 1 153 EVAR (570 EMG and 583 URG) and 1 245 OSR (946 EMG and 299 URG) non-elective cases remained for the analysis. Crude mortality was 24.0% following OSR (EMG 29.2%; URG 7.7%) and 7.5% following EVAR (EMG 12.6%; URG 2.4%). Univariable analysis demonstrated an association between OSR mortality and hospital volume (quintile [Q] 1: 25.3%, Q2: 27.8%, Q3: 23.9%, Q4: 27.0%, Q5: 16.2%; p = .030), but not surgeon (Q1: 25.2%, Q2: 27.4%, Q3: 26.0%, Q4: 21.4%, Q5: 19.5%, p = .32). Multivariable analysis confirmed this association (odds ratio (OR) [95% CI]; Q1 vs 5: 1.91 [1.13-3.21], Q2 vs. 5: 2.01[1.24-3.25], Q3 vs. 5: 1.41 [0.86-2.29], Q4 vs. 5: 1.92 [1.17-3.15]; p = .020). The difference was most pronounced in the EMG OSR group [Q1 - 3 vs. 4-5] (OR 1.63 [1.07-2.48]; p = .020). Mortality after EVAR was not associated with either hospital (Q1: 6.3%, Q2: 10%, Q3: 6.8%, Q4: 4.5%, Q5: 10%; p = .14) or surgeon volume (Q1: 9.3%, Q2: 5.7%, Q3: 8.1%, Q4: 7.0%, Q5: 7.3%; p = .67)., Conclusion: There is an inverse correlation between hospital volume and peri-operative mortality following EMG open repair of aortic aneurysm. These data support restructuring Australian pathways of care to direct suspected ruptured aneurysm to institutions that reach a minimum volume threshold., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Patients with incurable lung cancer often present with debilitating symptoms that require urgent palliative radiotherapy. Volumetric modulated arc therapy (VMAT) provides several dosimetric advantages compared to basic non-conformal techniques, but involves complex planning resulting in a slower turn-around time for treatment. A simplified planning technique known as 'rapid VMAT' was developed with an aim to deliver palliative treatment to patients within 48 hours. The purpose of this study was to prospectively compare the dosimetric quality of rapid VMAT plans to standard VMAT plans. Fourteen consecutive rapid VMAT cases were re-planned de novo as per standard VMAT planning guidelines. Planning target volume (PTV) and organs at risk (OARs) were then compared. PTV coverage and dose to OARs including the spinal canal, lung, heart, and esophagus were similar between rapid and standard VMAT. Each plan was ready for treatment within 48 hours of the CT simulation. This study describes an expedited process for which palliative radiotherapy can be delivered to lung tumors with a similar robust quality that is provided for curative intent VMAT radiotherapy plans., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Mak et al.)

Objective The goal of this survey-based study is to explore patients' knowledge of and expectations for radiologists in the outpatient setting.  Materials and Methods A comprehensive survey was distributed to adult patients undergoing knee magnetic resonance imaging (MRI) over a one-year period from September 2015 through August 2016 at an urban, quaternary care academic medical center. Results The survey results demonstrate that only a subset of patients undergoing knee MRI at the institution during the survey period are aware of the role of the radiologist, which is a well-documented fact described in the literature. Approximately one-third of patients expected to meet the radiologist during their visit to the department of radiology to undergo a knee MRI. The vast majority of patients surveyed wanted to be able to contact the person who read their exam, but only one patient actually contacted the radiologist during the study period.  Conclusion While the vast majority of surveyed patients wanted to be able to contact the person who read their knee MRI, only one patient actually did reach out to the radiologist to discuss findings. However, six of 36 follow-up respondents reported that they had contacted the person "who interpreted/read your exam:" two in person, one by email, three by phone, and one by other. Survey results demonstrated that only a subset of patients correctly understood the role of the radiologist (46% in the 1 st  survey and 63% in the 2 nd  survey, which does not represent a statistically significant difference), which suggests that perhaps the patients did have a conversation with a member of the radiology department staff whom they believed was actually the radiologist. The fact that patients expressed a desire to communicate with the person reading their reports, but then did not take advantage of the opportunity to contact the radiologist, suggests that the issue is more complicated than just a lack of a pathway for communication between patients and radiologists. Perhaps the lack of a clear understanding of the role of the radiologist hinders patients from contacting radiologists, as they feel uncertain as to whom they are actually attempting to reach. Or perhaps patients are sufficiently reassured by having a means through which they could contact the radiologist and do not require the actual communication in order to feel comfortable. There remains a significant amount of work to be done in understanding the barriers in patient-radiologist communications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Phillips et al.)

The aim of this study was to assess the effect of exercise intensity on the thermal sensory function of active and inactive limbs. In a randomised and counterbalanced manner, 13 healthy young male participants (25 ± 6 years, 1.8 ± 0.1 m, 77 ± 6 kg) conducted: (1) 30-min low-intensity (50% heart rate maximum, HRmax; LOW) and (2) 30-min high-intensity (80% HRmax; HIGH) cycling exercises, and (3) 30 min of seated rest (CONTROL). Before, immediately after, and 1 h after, each intervention, thermal sensory functions of the non-dominant dorsal forearm and posterior calf were examined by increasing local skin temperature (1 °C/s) to assess perceptual heat sensitivity and pain thresholds. Relative to pre-exercise, forearm heat sensitivity thresholds were increased immediately and 1 hr after HIGH, but there were no changes after LOW exercise or during CONTROL (main effect of trial; p = 0.017). Relative to pre-exercise, calf heat sensitivity thresholds were not changed after LOW or HIGH exercise or during CONTROL (main effect of trial; p = 0.629). There were no changes in calf (main effect of trial; p = 0.528) or forearm (main effect of trial; p = 0.088) heat pain thresholds after exercise in either LOW or HIGH or CONTROL. These results suggest that cutaneous thermal sensitivity function of an inactive limb is only reduced after higher intensity exercise but is not changed in a previously active limb after exercise. Exercise does not affect heat pain sensitivity in either active or inactive limbs.

Purpose: To report the risk of all-cause mortality after treatment with paclitaxel-coated devices vs uncoated controls in patients with chronic limb-threatening ischemia (CLTI)., Materials and Methods: A search of the PubMed, Embase, Cochrane, CINAHL, DARE, and PROSPERO databases was made on 5 November 2019 to identify randomized controlled trials (RCT) using intention-to-treat analysis to compare a paclitaxel-coated device to an uncoated device in PAD patients having clinical follow-up of at least 6 months. Half of the study population had to have CLTI or extractable data on the CLTI subgroup if <50%. The search identified 11 trials having 1450 patients randomized to a paclitaxel-coated device (n=866) or an uncoated control (n=584). There were 1367 (94.3%) patients with CLTI (range 10-429). The single endpoint was all-cause mortality, which was analyzed by pooling the mortality data in a DerSimonian and Laird random effects model. Summary statistics are expressed as relative risk ratios (RR) with a 95% confidence interval (CI)., Results: The mean follow-up was 25.6 months (range 6-60); 10 of 11 studies reported a minimum 12-month follow-up. There were 161 (18.6%) deaths among 866 subjects in the paclitaxel device group and 116 deaths among 584 (19.9%) subjects in the non-coated control group (RR 0.93, 95% CI 0.78 to 1.12, p=0.45)., Conclusion: There was no observed difference in short- to midterm mortality among a pooled patient population of predominately CLTI patients treated with paclitaxel-coated balloons or stents compared with uncoated controls.

Background and Objective: The use of patient-specific CFD modelling for arteriovenous fistulae (AVF) has shown great clinical potential for improving surveillance, yet the use of imaging modes such as MRI and CT for the 3D geometry acquisition presents high costs and exposure risks, preventing regular use. We have developed an ultrasound based procedure to bypass these limitations., Methods: A scanning procedure and processing pipeline was developed specifically for CFD modelling of AVFs, using a freehand ultrasound setup combining B-mode scanning with 3D probe motion tracking. The scanning procedure involves sweeping along the vasculature to create a high density stack of B-mode frames containing the lumen geometry. This stack is converted into a continuous volume and transient flow waveforms are recorded at the boundaries, synchronised with ECG and automatically digitised, forming realistic boundary conditions for the CFD models. This is demonstrated on a diseased patient-specific AVF., Results: The three scans obtained using this procedure varied in geometry and flow behaviour, with regions of disease located in the first two scans. The outcome of the second procedure seen in the third scan indicated successful restoration with no sites of disease and higher flow. The models gave insight into the lumenal changes in diameter for both the artery and vein segments, as well as characterising hemodynamic behaviours in both the diseased and restored states. Vascular segment resistances obtained from the CFD models indicate a significant reduction once disease was removed, resulting in much higher flows enabling the patient to resume dialysis., Conclusion: The methodology described in this study allowed for a multifaceted analysis and high level tracking in terms of both geometry and flow behaviours for a patient case, demonstrating significant clinical utility and practicality, as well as enabling further research into vascular disease progression in AVFs through longitudinal analysis., (Copyright © 2019. Published by Elsevier B.V.)

Background: Several studies have reported worse outcomes in women compared to men after endovascular aneurysm repair (EVAR). This study aimed to evaluate sex-specific short-term and 5-year outcomes after EVAR., Methods: A total of 409 consecutive patients underwent elective EVAR from 2004 to 2017 at two tertiary hospitals in Western Australia. Baseline, intraoperative, and postoperative variables were examined retrospectively according to sex. The primary outcome was 30-day mortality (death within 30 days after EVAR). Secondary outcomes were 30-day composite endpoint, length of stay after EVAR, 5-year survival, freedom from reintervention, residual aneurysm size after EVAR, and major adverse event rate at 5-year follow-up., Results: A cohort of 409 patients, comprising 57 women (14%) and 352 men (86%), was analysed. Female patients were older (median age, 76.8 versus 73.5 years, p =0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p =0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p =0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p =0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p =0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p =0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p =0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%., Conclusion: This study found no significant differences in 30-day and 5-year outcomes between female and male patients treated with EVAR, implying that EVAR remains a safe treatment choice for female patients., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Bibombe P. Mwipatayi et al.)

Introduction: High flow rates may develop in arteriovenous fistula (AVF), resulting in clinical syndromes of steal, aneurysmal fistula, or high-output cardiac failure. Various techniques with varying success have been advocated to treat this difficult problem. We present a hemodynamically validated novel banding technique., Methods: We designed a computational fluid dynamic (CFD) model of the native high-flow AVF and tested various juxta-anastomotic venous diameters to determine the effect on AVF blood flow and pressure. We translated this principle in our banding technique, wherein adjustable banding was performed in conjunction with ultrasound-guided brachial artery flow measurement to determine the optimal band diameter. Polyurethane patch was used to fashion the adjustable band. Patient demographics, AVF flow parameters pre- and postintervention, operative intervention, and ultrasound follow-up data were collected prospectively., Results: Our CFD testing demonstrated that the band diameter needed to achieve optimal distal blood pressure and preserve AVF flow depending on blood pressure, end capillary pressure, venous pressure, and vascular diameters. Five patients subsequently underwent dynamic banding of symptomatic high-flow AVF. Mean brachial artery blood flow rates pre- and postbanding were 2964 mL/min (confidence interval [CI]: 1487-4440 mL/min) and 1099 mL/min (CI: 571.7-1627 mL/min), respectively ( P = .01). All patients had symptomatic improvement, and at a mean follow-up of 1 year, this benefit was sustained with no AVF thrombosis or loss., Conclusion: Adjustable dynamic band using ultrasound-guided brachial artery flow shows promising results in producing accurate AVF blood flow reduction with sustained efficacy in the short term for patients with symptomatic high-flow AVF.

Purpose: We report short-term patency outcomes of a proof of concept study conducted to determine the efficacy of drug-eluting stent (DES) for the treatment of arteriovenous fistula (AVF) stenosis in hemodialysis patients., Materials and Methods: This is a single-center, retrospective observational study involving 10 patients with AVF dysfunction treated with DESs between January 2017 and December 2017. The primary outcome was AVF patency confirmed by sonographic and clinical assessment at 1 month and 6 to 9 months after treatment., Results: A total of 12 DESs were deployed in 10 patients with dysfunctional AVF (radiocephalic: 7, brachiocephalic: 3). During the early follow up (mean: 28.6 days), primary access circuit and DES patency was 100%, with an average volume flow rate of 886.4 mL/min. Nine patients were available for short-term follow up (mean: 202.4 days; 1 unrelated death), with a mean volume flow rate of 1,048.9 mL/min. The primary DES patency was 7/9 (77.8%), and 3 patients required angioplasty at other parts of the circuit (primary access circuit patency: 4/9 [44.4%]). The assisted primary access circuit patency was 77.8%. In 2 patients, the ultrasound revealed that the DESs were thrombosed without any antecedent stenosis; they were salvaged with angioplasty. Both patients previously underwent 2 DESs implanted and recently stopped dual antiplatelet therapy. B-mode sonographic assessment at all timepoints showed minimal intimal ingrowth on the stent struts., Conclusion: This study demonstrates acceptable short-term patency for DESs in the treatment of AVF stenosis. Dual antiplatelet therapy is probably mandatory in the short term., Competing Interests: CONFLICTS OF INTEREST The authors have nothing to disclose., (Copyright © 2019, The Korean Society for Vascular Surgery.)

Purpose: To report the risk of all-cause mortality in patients who underwent dialysis access treatment using paclitaxel-coated devices compared with percutaneous transluminal angioplasty (PTA) with an uncoated balloon. Materials and Methods: A systematic review and meta-analysis of randomized controlled trials were performed to investigate the mortality outcomes associated with paclitaxel-coated devices in the treatment of patients with a failing dialysis access (last search date February 28, 2019). The primary endpoint was all-cause mortality. This analysis included 8 studies comparing paclitaxel-coated balloon (PCB) angioplasty (n=327) and PTA (n=331) in the treatment of failing dialysis access. None investigated paclitaxel-coated stents. Mortality data were pooled using a random effects model. Statistical heterogeneity was evaluated with a chi-square test and the I 2 statistic. Summary statistics are expressed as relative risk ratios (RR) with a 95% confidence interval (CI). Results: At the pooled mean follow-up of 13.5 months (median 12, range 6-24) all-cause mortality was similar in the PCB group (13.8%) compared with PTA (11.2%; RR 1.26, 95% CI 0.85 to 1.89, p=0.25; I 2 =0%). Subgroup analysis, stratified according to length of follow-up, confirmed that there were no statistically significant differences in mortality at short- and midterm follow-up [6-month (8 studies): 5.2% vs 4.8%, RR 1.24, 95% CI 0.62 to 2.47, p=0.55; 12-month (6 studies): 6.3% vs 6.0%, RR 1.06, 95% CI 0.43 to 2.63, p=0.90; and 24-month (3 studies): 19.0% vs 13.5%, RR 1.38, 95% CI 0.90 to 2.12, p=0.14). Conclusion: The analysis found no difference in short- to midterm mortality among patients treated with a drug-coated balloon compared with PTA. With proven benefit and no evidence of harm, the authors recommend ongoing use of PCB for the failing dialysis access.

Glyphosate is a broad-spectrum herbicide that is used worldwide. It represents a potential harm to surface water, and when commercially mixed with surfactants, its uptake is greatly magnified. The most well-known glyphosate-based product is Roundup. This herbicide is potentially an endocrine disruptor and many studies have shown the cytotoxicity potential of glyphosate-based herbicides. In breast cancer (BC) cell lines it has been demonstrated that glyphosate can induce cellular proliferation via estrogen receptors. Therefore, we aimed to identify gene expression changes in ER+ and ER- BC cell lines treated with Roundup and AMPA, to address changes in canonical pathways that would be related or not with the ER pathway, which we believe could interfere with cell proliferation. Using the Human Transcriptome Arrays 2.0, we identified gene expression changes in MCF-7 and MDA-MB-468 exposed to low concentrations and short exposure time to Roundup Original and AMPA. The results showed that at low concentration (0.05% Roundup) and short exposure (48h), both cell lines suffered deregulation of 11 canonical pathways, the most important being cell cycle and DNA damage repair pathways. Enrichment analysis showed similar results, except that MDA-MB-468 altered mainly metabolic processes. In contrast, 48h 10mM AMPA showed fewer differentially expressed genes, but also mainly related with metabolic processes. Our findings suggest that Roundup affects survival due to cell cycle deregulation and metabolism changes that may alter mitochondrial oxygen consumption, increase ROS levels, induce hypoxia, damage DNA repair, cause mutation accumulation and ultimately cell death. To our knowledge, this is the first study to analyze the effects of Roundup and AMPA on gene expression in triple negative BC cells. Therefore, we conclude that both compounds can cause cellular damage at low doses in a relatively short period of time in these two models, mainly affecting cell cycle and DNA repair., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To determine the clinical outcomes in hemodialysis patients after implantation of a Supera stent to treat juxta-anastomotic stenosis in radiocephalic arteriovenous fistulas (AVF)., Materials and Methods: A single-center retrospective study was conducted of 42 consecutive patients (mean age 66.7 years, range 40-84; 26 men) who had a failing AVF due to juxta-anastomotic stenosis treated with the interwoven Supera stent between February 2014 and February 2018. A third of the patients had previous juxta-anastomotic intervention (either balloon angioplasty or open surgical revision)., Results: The stent was inserted successfully in all patients. Overall mean follow-up was 12.2±8.2 months (range 3.8-38.3). Juxta-anastomotic segment primary patency estimates at 6 and 12 months were 92.5% and 59.8%, respectively, with assisted primary patency rates of 97.5% and 92.9%. Reintervention (elective drug-coated balloon angioplasty) occurred at a rate of 0.31 procedures/year. Two AVFs thrombosed during the 1-year follow-up and were revascularized using balloon angioplasty. Ultrasound measurements of brachial artery flow rates increased significantly from 543.5±96.72 mL/min (range 430-644) before intervention to 919.2±355.9 mL/min (range 200-1600) after intervention (p=0.047). Arterial pressures on hemodialysis improved from -142.3±24.9 mm Hg (range -100 to -180) to -123.4±21.9 mm Hg (range -100 to -184; p=0.051). No AVFs were lost or abandoned during the follow-up period., Conclusion: The interwoven Supera stent is a promising treatment for failing AVFs with juxta-anastomotic stenosis. Encouraging 1-year primary and assisted primary patency was demonstrated, with a low reintervention rate. This treatment facilitates long-term maintenance of AVF vascular accesses.

Introduction: Endovascular treatment below-the-knee is safe and effective but limited by poor patency. Coronary drug-eluting stents (DES) may play a role in providing mechanical scaffolding and deliver anti-proliferative drug to the site of vascular barotrauma to reduce the incidence of restenosis. Our aim was to evaluate and compare the use of contemporary DES with standard endovascular-therapies for atherosclerotic disease of infrapopliteal arteries., Evidence Acquisition: We performed a meta-analysis of randomized controlled trials comparing DES with conventional treatment for symptomatic peripheral artery disease (search date 30 August 2017). The primary endpoint was primary patency. Secondary endpoints were freedom from target lesion revascularization (TLR), major amputation, sustained Rutherford class improvement and mortality., Evidence Synthesis: We identified 7 trials enrolling 801 randomly assigned patients (392 DES, 409 control). At the median follow-up of 12-months DES improved rates of primary patency (OR 3.49, 95%CI 2.38-5.12, I2=0%, P<0.00001), freedom from TLR (OR 2.19, 95%CI 1.30-3.69, I2=38%, P=0.003), major amputation (OR 0.56, 95%CI 0.31-0.99, I2=0%, P=0.049), and Rutherford class improvement (OR 1.62, 95%CI 1.01-2.59, I2=65%, P=0.046), but not mortality (OR 1.05, 95%CI 0.68-1.62; I2 =0%, P=0.91) compared to control. Subgroup analysis of primary patency favoured DES coated in sirolimus analogues compared to paclitaxel (Test for subgroup differences, Chi2=6.51, df=1, P=0.01, I2=84.6%)., Conclusions: At midterm follow-up DES significantly improved rates of primary patency, re-intervention, Rutherford class improvement and major amputation for the treatment of atherosclerotic disease of infrapopliteal arteries compared to control therapy, with no effect on patient survival. Stents coated in sirolimus analogues were more effective than paclitaxel.

Objectives: Operative caseload is thought to be associated with peri-operative mortality following intact aortic aneurysm repair. The aim was to study that association in the Australian setting, which has a unique healthcare provision system and geographical population distribution., Methods: The Australasian Vascular Audit database was used to capture volume measurements for both individual surgeon and hospital and to separate it into quintiles (1, lowest, to 5, highest) for endovascular (EVAR), open surgical repair (OSR), and subgroups of repair types between 2010 and 2016. Multivariable logistic regression modelling was used to assess the impact of caseload volumes on in hospital mortality after adjustment for confounders., Results: Volume counts were determined from 14,262 aneurysm repair procedures (4121 OSR, 10,106 EVAR). After exclusions, 2181 OSR (161 complex, 2020 standard) and 7547 EVAR (6198 standard, 1135 complex, 214 thoracic (TEVAR)) elective cases were available for volume analysis. Unadjusted mortality after EVAR was unaffected by either surgeon (Quintile 1, 1.0%; Quintile 5, 0.9%; p = .28) or hospital volume (Quintile 1, 0.8%; Quintile 5, 1.3%; p = .47). However, univariable analysis of the TEVAR subgroup revealed a significant correlation with hospital volume (Quintiles 1-2 vs. Quintiles 3-5; p = .02). Univariable analysis for OSR demonstrated a marginal, non-significant value for surgeon (Quintile 1, 4.0%; Quintile 5, 3.6%; p = .06), but not hospital volume (Quintile 1, 4.7%; Quintile 5, 4.0%; p = .67). After adjustment for confounders hospital volume remained a significant predictor of peri-operative TEVAR mortality (Quintile 1-2 vs. 3-5; OR 5.62, 95% CI 1.27-24.83; p = .02) and surgeon volume a predictor following standard OSR (Quintile 1-2 vs. Quintile 3-5; OR 2.15, 95% CI 1.21-3.83; p = .01)., Conclusions: There is an inverse correlation between both surgeon volume of open aortic aneurysm repair, hospital volume of thoracic endovascular aneurysm repair and in hospital mortality. These findings suggest that in Australia TEVAR should be performed by high volume hospitals and OSR by high volume surgeons., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Introduction: The easily-imaged retinal microvasculature may reflect the brain microvasculature and therefore be related to dementia., Methods: In a population-based study of 12,482 adults aged 50-73 years (22% African American), we estimated the relationship of retinal characteristics from fundus photography (1993-1995) with incident all-cause dementia (1993-1995 to 2011-2013) and with etiologic subtype of dementia/mild cognitive impairment (2011-13)., Results: A total of 1259 (10%) participants developed dementia over a mean 15.6 years. Moderate/severe (vs. no) retinopathy (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.36-2.55) and central retinal arteriolar equivalent (narrowest quartile vs. widest three quartiles; HR, 1.26; 95% CI: 1.09-1.45) were associated with all-cause dementia. Results were qualitatively stronger (but not statistically significantly different) in participants with diabetes. Retinopathy was associated with a joint outcome of cerebrovascular-related, but not Alzheimer's disease-related, dementia/mild cognitive impairment (HR, 2.29; 95% CI: 1.24-4.23)., Discussion: Exploration of measures in the eye may provide surrogate indices of microvascular lesions relevant to dementia., (Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background: Vascular endothelial growth factor (VEGF) is commonly overexpressed in a variety of tumor types including lung cancer. As a key regulator of angiogenesis, it promotes tumor survival, growth, and metastasis through the activation of the downstream protein kinase B (AKT) and extracellular signal-regulated kinase (ERK 1/2) activation. The VEGF promoter contains a 36 bp guanine-rich sequence (VEGFq) which is capable of forming quadruplex (four-stranded) DNA. This sequence has been implicated in the down-regulation of both basal and inducible VEGF expression and represents an ideal target for inhibition of VEGF expression., Results: Our experiments demonstrate sequence-specific interaction between a G-rich quadruplex-forming oligonucleotide encoding a portion of the VEGFq sequence and its double stranded target sequence, suggesting that this G-rich oligonucleotide binds specifically to its complementary C-rich sequence in the genomic VEGF promoter by strand invasion. We show that treatment of A549 non-small lung cancer cells (NSCLC) with this oligonucleotide results in decreased VEGF expression and growth inhibition. The VEGFq oligonucleotide inhibits proliferation and invasion by decreasing VEGF mRNA/protein expression and subsequent ERK 1/2 and AKT activation. Furthermore, the VEGFq oligonucleotide is abundantly taken into cells, localized in the cytoplasm/nucleus, inherently stable in serum and intracellularly, and has no effect on non-transformed cells. Suppression of VEGF expression induces cytoplasmic accumulation of autophagic vacuoles and increased expression of LC3B, suggesting that VEGFq may induce autophagic cell death., Conclusion: Our data strongly suggest that the G-rich VEGFq oligonucleotide binds specifically to the C-rich strand of the genomic VEGF promoter, via strand invasion, stabilizing the quadruplex structure formed by the genomic G-rich sequence, resulting in transcriptional inhibition. Strand invading oligonucleotides represent a new approach to specifically inhibit VEGF expression that avoids many of the problems which have plagued the therapeutic use of oligonucleotides. This is a novel approach to specific inhibition of gene expression., Competing Interests: The authors have declared that no competing interests exist.

Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α 4 β 7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches.

Background: Annually in the US, over 100,000 pregnant women with overt type 2 diabetes give birth. Strict maternal glycemic control is the key to optimizing infant outcomes. Medical treatment of type 2 diabetes in pregnancy is generally restricted to insulin, as data on the safety and efficacy of oral hypoglycemic agents in pregnancy are limited. However, over one-third of infants born to women with type 2 diabetes experience an adverse outcome, such as premature delivery, large-for-gestational age, hypoglycemia, hyperbilirubinemia, or birth trauma, suggesting that current treatment regimens fall short of optimizing outcomes. Metformin is the pharmacologic treatment of choice for type 2 diabetes outside of pregnancy. Metformin is favored over insulin because it results in less weight gain, fewer hypoglycemic episodes, and is administered orally rather than injected. However, metformin is not typically used for treatment of type 2 diabetes complicating pregnancy, mainly because no large clinical studies have been conducted to examine its use in this context., Methods/design: This is a randomized double-blind multi-center clinical trial of insulin plus metformin versus insulin plus placebo for the treatment of type 2 diabetes complicating pregnancy. A total of 1200 women with type 2 diabetes will be randomized between 10 weeks 0 days' and 20 weeks 6 days' gestation and followed until 30 days after delivery. Neonate outcomes will be followed until 30 days of age. The primary aim is to compare the effect of insulin and metformin versus insulin and placebo on composite adverse neonatal outcomes, comprising perinatal mortality, preterm delivery, neonatal hypoglycemia, hyperbilirubinemia, large-for-gestational age small for gestational age, low birth weight, and/or birth trauma. Key secondary aims are to compare treatment groups for neonatal fat mass and rate of maternal hypoglycemia. Additional aims are to assess the side effects and safety of insulin and metformin among pregnant women with overt type 2 diabetes and to compare gestational weight gain among women treated with metformin plus insulin versus insulin alone., Discussion: Successful completion of this study will result in high-quality, contemporary evidence for management of overt type 2 diabetes complicating pregnancy to improve neonatal outcomes., Trial Registration: NCT02932475 (05/17/2016).

Purpose: To investigate the midterm performance of the everolimus-eluting Absorb bioresorbable vascular scaffold (BVS) for the treatment of symptomatic infrapopliteal atherosclerotic disease., Methods: A single-center study prospectively enrolled 48 symptomatic patients (mean age 82.1±8.0 years; 27 men) between September 2013 and February 2018 to evaluate the Absorb everolimus-eluting BVS system in distal popliteal and tibial lesions. Mean lesion length was 20.1±10.8 mm. Following predilation, up to 2 BVS were implanted in target lesions in 55 limbs. Clinical and duplex ultrasound follow-up was performed at 1, 3, 6, 12, 24, 36, and 48 months to determine 30-day morbidity and midterm Kaplan-Meier estimates of binary restenosis, clinically-driven target lesion revascularization (CD-TLR), amputation, and mortality., Results: Seventy-one scaffolds were implanted to treat 61 lesions. Technical success was achieved in all patients, with no amputation, death, or target limb bypass surgery within 30 days of the index procedure. There was 1 early thrombotic occlusion of 2 BVS in a previously anticoagulated patient not given antiplatelet medication after the procedure. During a mean follow-up of 24.0±15.3 months, 11 (23%) patients died; the remaining 37 were available for follow-up. Binary restenosis (50%-75%) was detected in 6 (8%) scaffolds. Primary patency estimates at 12, 24, and 36 months were 92.2%, 90.3%, and 81.1%; freedom from CD-TLR estimates were 97.2%, 97.2%, and 87.3% at the same time points. No late scaffold thrombosis has been observed. The majority of the 55 limbs (51, 93%) were clinically improved; 4 (7%) were unchanged. Thirty-six (92%) of 39 limbs treated for tissue loss achieved complete wound healing, with no major amputation (limb salvage 100%)., Conclusion: Midterm follow-up demonstrates excellent safety, patency, and freedom from CD-TLR rates using the Absorb bioresorbable vascular scaffold below the knee.

Introduction: Hearing impairment is highly prevalent and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders study is a multicenter randomized controlled trial to determine efficacy of hearing treatment in reducing cognitive decline in older adults. Clinicaltrials.gov Identifier: NCT03243422., Methods: Eight hundred fifty participants without dementia aged 70 to 84 years with mild-to-moderate hearing impairment recruited from four United States field sites and randomized 1:1 to a best-practices hearing intervention or health education control. Primary study outcome is 3-year change in global cognitive function. Secondary outcomes include domain-specific cognitive decline, incident dementia, brain structural changes on magnetic resonance imaging, health-related quality of life, physical and social function, and physical activity., Results: Trial enrollment began January 4, 2018 and is ongoing., Discussion: When completed in 2022, Aging and Cognitive Health Evaluation in Elders study should provide definitive evidence of the effect of hearing treatment versus education control on cognitive decline in community-dwelling older adults with mild-to-moderate hearing impairment.

Purpose: To compare the total initial treatment costs for open surgery, endovascular revascularization, and primary major amputation within a single-payer healthcare system., Methods: A multicenter, retrospective analysis was undertaken to evaluate 1138 patients with symptomatic peripheral artery disease (PAD) who underwent 1017 endovascular procedures, 86 open surgeries, and 35 major amputations between 2013 and 2016. A cost-mix analysis was performed on individual patient data generated for selected diagnosis-related groups. Mean costs are presented with the 95% confidence interval (CI)., Results: There was no intergroup difference in demographics or private health insurance status. However, the amputation group had a higher proportion of emergency procedures (68.6% vs 13.3% vs 27.9%, p<0.001) and critical limb ischemia (88.6% vs 35.9% vs 37.2%, p<0.001) compared with the endovascular therapy and open surgery groups, respectively. The endovascular revascularization group spent less time in hospital and used fewer intensive care unit (ICU) resources compared with the open surgery and major amputation groups (hospital length of stay: 3.4 vs 10.0 vs 20.2 days, p<0.01; ICU: 2.4 vs 22.6 vs 54.6 hours, p<0.01), respectively. While mean prosthetic and device costs were higher in the endovascular group [AUD$2770 vs AUD$1658 (open) and AUD$1219 (amputation), p<0.01], substantial disparities were observed in costs associated with longer operating theater times, length of stay, and ICU utilization, which resulted in significantly higher costs in the open and amputation groups. After adjusting for confounders, the AUD$18,396 (95% CI AUD$16,436 to AUD$20,356) mean cost per admission for the endovascular revascularization group was significantly less (p<0.001) than the open surgery (AUD$31,908, 95% CI AUD$28,285 to AUD$35,530) and major amputation groups (AUD$43,033, 95% CI AUD$37,706 to AUD$48,361)., Conclusion: Endovascular revascularization procedures for PAD cost the health payer less compared with open surgery and primary amputation. While devices used to deliver contemporary endovascular therapy are more expensive, the reduction in bed days, ICU utilization, and related hospital resources results in a significantly lower mean total cost per admission for the initial treatment.

The purpose of the study was to describe conditions and dynamics in the lives of high-risk, low-income, Southern United States prenatal-interconceptional women ( n = 37) in a home visiting program that promoted maternal health literacy progression. In the Life Course Health Development (LCHD) Model, conditions were risk and protective factors that impacted health. Dynamics drove the complex, epigenetic relationships between risk and protective factors. Maternal health literacy promotion helped participants address conditions and dynamics to create positive life changes. This research was a retrospective, mixed methods study of women's service records documenting care from prenatal admission to 24 months post-delivery. The Life Skills Progression Instrument (LSP) was scored to measure maternal health literacy progression. Ethnographic content analysis of visit notes triangulated with quantitative data enabled specificity of critical data elements. Subsequently, a complementary focus group was conducted with the Registered Nurse Case Managers (RNCM). Severe social conditions included devastating poverty, low educational achievement, transient housing, unstable relationships, incarceration, lack of continuous health insurance, and shortage of health care providers. Dynamics included severe psycho-social stressors, domestic violence, lack of employment, low income, low self-esteem and self-expectations, and social/family restraints upon women's intended positive changes. An important protective factor was the consistent, stable, evidence-informed relationship with the RNCM. Findings from the focus group discussion supported content analysis results.

Background: Management of vascular access for haemodialysis is a leading cause of morbidity and hospitalization in patients with end-stage renal disease. We sought to evaluate the change in admission and procedural outcomes before and after the establishment of a vascular surgeon-led comprehensive renal vascular access clinic (RVAC)., Method: A retrospective clinical study was conducted after an RVAC was established in January 2013, with retrospective database created for the 24-month period prior to and after., Results: The number of inpatient encounters for haemodialysis vascular access care fell over identical time periods before (n = 193) and after (n = 164) the RVAC was established. This reduction was associated with a significant decrease in length of stay (from 10.71 to 3.14 days; P = 0.0056) and thrombosed access procedures (from 32 to 16; P = 0.048). The proportion of emergency procedures fell (from 54.5 to 25.4%; P = 0.002) with a trend towards less arteriovenous fistula formations in the latter group (from 75 to 49; P = 0.099). There was also a trend towards fewer procedures in the latter group (from 195 to 151; P = 0.22). A case-mix costing analysis showed an estimated reduction in mean admission cost from $25 883.15 to $9332.81 for those 2-year periods, equating to a saving of $3.46 million associated with the introduction of the clinic., Conclusion: The establishment of an RVAC has led to a variety of objective performance outcome improvements, including a decrease in hospital admission, length of stay, revision and emergency surgeries, with associated cost saving. It reflects positive outcomes observed in other surgical specialties' clinics., (© 2016 Royal Australasian College of Surgeons.)

Purpose The present study aimed to determine the safety and efficacy of a drug-coated balloon inflated within a thin-strut self-expanding bare-metal stent in patients with severe and complex femoropopliteal occlusive disease. Methods This prospective study used the Pulsar-self-expanding stent and Passeo-18 Lux drug-coated balloon in patients with severe and complex femoropopliteal occlusive disease. The primary endpoint was the 12-month primary patency, and the secondary endpoints included 24-month primary patency, assisted primary patency, secondary patency, and clinically associated target lesion revascularisation. Results The study included 44 patients (51 limbs). The mean age of the patients was 67.6 ± 10.2 years, with 73% men. Chronic limb severity was classified as Rutherford Category III in 41% of the patients, stage IV in 31%, and stage V in 27%. Lesions were predominantly Trans-Atlantic Inter-Society Consensus (TASC 2007) D (51%) and C (45%), with 32 (63%) chronic total occlusions. Procedural success was obtained in all cases. The mean lesion length was 200 ± 74.55 mm (95% CI = 167.09-208.01) with a mean number of stents per limb used of 1.57 ± 0.70 (95% CI = 1.37-1.76). Distal embolisation occurred in two patients. The primary patency rates at the 12- and 24-month follow-up were 94% (95% CI = 82.9-98.1) and 88% (95% CI = 75.7-94.5), respectively. The assisted primary was 94% (95% CI = 82.9-98.1) and secondary patency was 96% (95% CI = 85.2-99.0) at 24-month follow-up. The cumulative stent fracture rate at the 24-month follow-up was 10%. Freedom from clinically driven target lesion revascularisation was 94% (95% CI = 83-98%) at 12-month follow-up and 88% (95% CI = 76-94%) at 24-month follow-up, with two patients requiring a bypass graft. Conclusion Our novel approach involving the combination of a thin-strut bare-metal stent and a drug-coated balloon may be safe and effective, with sustainable and promising clinical outcomes up to 24 months after treatment.

AS1411 is an antiproliferative DNA aptamer, which binds the ubiquitous protein, nucleolin. In this study, we show that constitutive overexpression of nucleolin confers increased sensitivity to the growth inhibitory effects of AS1411. HeLa cells overexpressing nucleolin have an increased growth rate and invasiveness relative to control cells. Nucleolin overexpressing cells demonstrate increased growth inhibition in response to the AS1411 treatment, which correlates with increased apoptosis and cell cycle arrest, when compared to non-transfected cells. AS1411 induces nucleolin expression at the RNA and protein level in HeLa cells, suggesting a feedback loop with important implications for the clinical use of AS1411.

Aims and Objectives: To critically synthesise research related to the transition of registered nurses into new areas of clinical practice., Background: Global workforce shortages and rising healthcare demands have encouraged registered nurses to move into new clinical settings. While a body of literature reports on the transition of newly qualified nurses, evidence surrounding the transition of more experienced registered nurses to new clinical areas remains poorly explored., Design: An integrative review was conducted, guided by Whittemore and Knafl (Journal of Advanced Nursing, 52, 2005, 546) framework., Methods: An electronic database search was conducted for papers published between 1996-2016. Papers were then subjected to a methodological quality appraisal, with findings synthesised using thematic analysis into core themes., Results: Ten articles met the inclusion criteria. Three themes emerged, namely Support, Professional Development and Emotional Impact. These themes suggest that transitioning nurses experience challenges in adapting to new clinical areas and developing necessary skills. Such challenges prompted various emotional and physical responses. While formal and informal support systems were regarded as valuable by transitioning nurses, they were inconsistent across the new clinical areas., Conclusions: There is some evidence to highlight the initial shock and emotional stress experienced by registered nurses during transition to a new clinical area. However, the influence of formal and informal support systems for such registered nurses is far from conclusive. Further research is needed, to examine registered nurse transition into a variety of clinical areas to inform workforce support, policy and practices., Relevance to Clinical Practice: The demand of health care is growing while global shortages of nursing workforce remain. To ensure retention and enhance the transition experience of registered nurses, it is important for nurse leaders, managers and policymakers to understand the transition experience and factors that impact this experience., (© 2017 John Wiley & Sons Ltd.)

Background: Independent risk factors such as age, loss of consciousness, elevated serum creatinine, low hemoglobin, and electrocardiogram evidence of ischemia have previously been shown to predict mortality after ruptured abdominal aortic aneurysm (rAAA). With an aging Australian population, we sought to determine if patients presenting with rAAA now had more predictive risk factors for mortality and whether these factors remain predictive of mortality., Methods: The records of all patients presenting with rAAA between January 1985 to December 1993 (past era, group 1) and January 2007 to December 2011 (modern era, group 2) were retrieved. A database of independent risk factors, repair method, and mortality was constructed. Comparisons were made between the 2 groups, where a P value of < 0.05 was considered statistically significant., Results: Hundred and eighty-eight patients presented with rAAA in the past era, of which 154 were then prepared for repair. 60 patients presented in the modern group, in which 38 patients were then prepared for repair. Proportionally, more patients in the modern era group were rejected for surgery compared to the past era group, (22/60 vs. 34/188; P = 0.004) Rejection was based on both medical comorbidities as well as patient/family and surgeon preferences. The in-hospital mortality rate for patients undergoing repair remained unchanged between the groups at 39%. Age was the only predictive factor that differed between the modern and past era groups (median age: 81 vs. 72 respectively, P < 0.001). However, this equated to more risk factors per patient in the modern group compared to the past era (2 vs. 1, respectively, P < 0.001). When stratified by 0, 1, 2, and 3 + risk factors present, there was a trend toward lower mortality in the modern group per strata. Univariate and multivariate analysis of the risk factors in the modern group demonstrated that low blood hemoglobin was the only risk factor independently predictive of mortality in the modern group., Conclusions: Patients in the modern era group are older and presenting with more predictive risk factors for mortality after rAAA. This has seen an increased rate of rejection for surgery. However, mortality rates following rAAA repair remain unchanged. These results suggest that the previously identified predictive risk factors need to be adjusted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To describe relevant technical details with which to facilitate safe and effective use of the Absorb coronary bioresorbable vascular scaffold (BVS) in lower extremity arteries., Technique: The Absorb BVS is a balloon-expandable, poly-l-lactide structure covered in a poly-d,l-lactide bioresorbable polymer that contains the antiproliferative drug everolimus. As a polymeric structure, it has a number of unique physical, handling, and imaging properties that may differ from metallic stents and pose a challenge to the interventionist. Attention must be paid to lesion selection, preparation, scaffold sizing, deployment, and postdilation to achieve optimal outcomes. A detailed description of these issues and deployment techniques is offered based on experience using this BVS in below-the-knee arteries., Conclusion: The Absorb BVS may have application in the infrapopliteal circulation; however, its unique properties warrant careful consideration before use in the lower limb.

Purpose: To report the use of adjunctive venography for the treatment of superficial venous reflux., Methods: Two hundred consecutive patients (mean age 60.9 years, range 33-86; 128 women) with chronic venous disease underwent saphenous or perforator vein ablation in 268 limbs (305 venous trunks) guided by adjunctive venography and fluoroscopy in addition to ultrasound between October 2010 and May 2016. Intraprocedural venograms were independently evaluated by 2 vascular specialists to identify the presence of venous anomalies and the need for fluoroscopy-guided maneuvers to successfully complete venous ablation. Intraprocedural venography results were compared with preoperative venous duplex scan reports to ascertain if the duplex study could be of value in identifying preoperatively any anatomical variants that may pose a technical challenge to the operator., Results: In this cohort, 542 venograms (2.0/limb) were performed with a mean duration of 4.9±9.1 minutes (range 1-48). Two thirds of patients (132, 66%) had anomalies or abnormalities within the target vein; more than a third (88, 44%) required an endovascular maneuver to successfully complete the ablation and 17% (34) of cases were impossible to complete without adjunctive fluoroscopic guidance. Per-patient comparison of intraprocedural venography with preoperative venous duplex reports identified 21 (11%) patients with abnormalities detected on ultrasound (23 anomalies) compared with 123 (64%) on venography (193 anomalies). This gave ultrasound a 17.1% sensitivity, 100% specificity and positive predictive value, and 40.7% negative predictive value., Conclusion: Venography is a valuable addition to ultrasound to facilitate complete ablation of insufficient saphenous veins in selected patients with complex anatomy.

Background and Purpose: To study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines., Material and Methods: Objective xerostomia was assessed in 121 patients (n Cohort1 =55; n Cohort2 =66) treated to 70Gy@2Gy in 2006-2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (p HL )). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmean contra , Dmean ipsi ) were estimated from the generated dose-response curves., Results: The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11-12months) in Cohort1/Cohort2. Risk of xerostomia at 3months increased for higher Dmean contra and Dmean ipsi (Cohort1: 0.17·Dmean contra +0.11·Dmean ipsi -8.13; AUC=0.90±0.05; p=0.0002±0.002; p HL =0.22±0.23; Cohort2: AUC=0.81; p<0.0001; p HL =0.27). The identified minimum Dmean contra thresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmean contra =12/19Gy; Dmean contra , Dmean ipsi =16, 25/20, 26Gy)., Conclusions: Increased Dmean contra and Dmean ipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmean contra to below 20Gy, while keeping Dmean ipsi to around 25Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The arterial resistive index, also referred to as the resistive index (RI) or Pourcelot Index, is a measure of pulsatile blood flow. Previous studies have demonstrated the usefulness of the RI as a predictor of allograft outcomes based on RI measurement in the later stages after transplantation. However, there is little evidence of the predictive value of "immediate" RI measurement within 24 hours after transplantation., Methods: We performed a retrospective cohort study of 305 adult renal transplants carried out between 2003 and 2013. The associations between immediate RI measurement (within 24 hours after transplantation) and donor, recipient, and surgical factors were analyzed. In addition, the correlations between immediate RI measurement and renal allograft outcomes, including delayed graft function (DGF) and transplant failure (TF), also were evaluated., Results: From a cohort of 305 patients, 52 were excluded on the basis of on confounding factors. Of the remaining 253 patients, the mean age was 48.4 years, 57.5% were male, and approximately one-third had diabetes. Two hundred twenty-six patients had an RI < 0.8, whereas only 27 had an RI ≥ 0.8. Significant associations were found between elevated RI (≥0.8) and both DGF (odds ratio = 3.22, P = .006) and TF (odds ratio = 3.54, P = .008)., Conclusions: Immediate RI measurement after renal transplantation is a strong predictor of both DGF and TF., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

G-quadruplex forming sequences are particularly enriched in the promoter regions of eukaryotic genes, especially of oncogenes. One of the most well studied G-quadruplex forming sequences is located in the nuclease hypersensitive element (NHE) III1 of the c-MYC promoter region. The oncoprotein c-MYC regulates a large array of genes which play important roles in growth regulation and metabolism. It is dysregulated in >70% of human cancers. The silencer NHEIII1 located upstream of the P1 promoter regulates up-to 80% of c-MYC transcription and includes a G-quadruplex structure (Pu27) that is required for promoter inhibition. We have identified, for the first time, a family of seventeen G-quadruplex-forming motifs with >90% identity with Pu27, located on different chromosomes throughout the human genome, some found near or within genes involved in stem cell maintenance or neural cell development. Notably, all members of the Pu27 family interact specifically with NHEIII1 sequence, in vitro. Crosslinking studies demonstrate that Pu27 oligonucleotide binds specifically to the C-rich strand of the NHEIII1 resulting in the G-quadruplex structure stabilization. Pu27 homologous sequences (Pu27-HS) significantly inhibit leukemic cell lines proliferation in culture. Exposure of U937 cells to the Pu27-HS induces cell growth inhibition associated with cell cycle arrest that is most likely due to downregulation of c-MYC expression at the RNA and/or protein levels. Expression of SOX2, another gene containing a Pu27-HS, was affected by Pu27-HS treatment as well. Our data suggest that the oligonucleotides encoding the Pu27 family target complementary DNA sequences in the genome, including those of the c-MYC and SOX2 promoters. This effect is most likely cell type and cell growth condition dependent. The presence of genomic G-quadruplex-forming sequences homologous to Pu27 of c-MYC silencer and the fact that they interact specifically with the parent sequence suggest a common regulatory mechanism for genes whose promoters contain these sequences., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The aim of this study was to investigate the midterm performance of an everolimus-eluting, bioresorbable vascular scaffold (Absorb, Abbott Vascular, Santa Clara, California) for the treatment of focal tibial and distal popliteal lesions., Background: Drug-eluting stents are used below the knee to improve technical success and durability, but the ongoing presence of a permanent metal scaffold may have deleterious effects on the local vessel., Methods: Tibial and distal popliteal angioplasty with scaffold placement was performed using an everolimus-eluting, bioresorbable scaffold (Absorb). Clinical and ultrasound follow-up was performed at 1, 3, 6, 12, and 24 months to detect binary restenosis and evaluate safety, restenosis, and clinical improvement., Results: Thirty-eight limbs in 33 patients were treated for critical limb ischemia (68.4%) or severe claudication (31.6%). Fifty scaffolds were used to treat a total of 43 lesions, with a mean length of 19.2 ± 11.6 mm. During a mean follow-up period of 12.0 ± 3.9 months, 5 patients died, and all others were available for follow-up. Among the 38 treated limbs, clinical improvement was present in 30 (79%). Binary restenosis was detected in 3 of 50 scaffolds (6%). Using the Kaplan-Meier method, rates of primary patency were 96% and 84.6% at 12 and 24 months, respectively, and rates of freedom from clinically driven target lesion revascularization were 96% and 96% at 12 and 24 months, respectively. Complete wound healing occurred in 64% of those treated for tissue loss, with no major amputation and a limb-salvage rate of 100%., Conclusions: Twelve-month follow-up demonstrated excellent safety, patency, and freedom from target lesion revascularization using the Absorb bioresorbable vascular scaffold below the knee., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

While the high prevalence of offending and victimisation among young people is well established, no study to date has compared official crime records of young people with mental illness with those without mental illness. This case linkage study sought to determine whether young people with a formal history of mental illness were more likely to have official histories of offending and victimisation than young people who had no recorded histories of mental illness. Results suggested that young people with a history of mental illness are particularly vulnerable to violence. While a weak association was established between violent offending and mental illness, a stronger relationship was found between victimisation and mental illness, especially violent victimisation. Consistent with literature regarding the victim-offender overlap, a history of offending placed young people at a substantially higher risk of victimisation. Implications of these results are discussed in the context of how public mental health services could better protect these vulnerable young people., (© 2016 The Australian and New Zealand Association of Psychiatry, Psychology and Law.)

Objective: The Covered vs Balloon Expandable Stent Trial (COBEST) is the first multicenter trial to investigate the patency of covered stents (CSs) and bare-metal stents (BMSs) in the treatment of aortoiliac arterial disease. The short-term results demonstrated that CSs were superior to BMSs in maintaining patency for TransAtlantic Inter-Society Consensus (TASC) C and D lesions at 18 months and were equivalent to BMSs for TASC B lesions. The current study was conducted to determine if the initial patency advantage of CSs over BMSs was sustained at the 5-year follow-up., Methods: A retrospective post hoc analysis of COBEST was performed. Originally, 125 patients with 168 iliac arteries were prospectively enrolled and randomly assigned to receive a CS or BMS. In this study, 77 of the 125 patients (61.6%; 119 limbs) were assessed at 60 months for the primary and secondary end points, with particular attention paid to the outcomes stratified according to TASC lesion severity. The primary end point was the rate of binary stenosis or freedom from stent occlusion of the treated area, as determined by ultrasound imaging or quantitative visual angiography., Results: The 5-year results of the COBEST showed that the CS had a significantly higher patency rate than the BMS at 18, 24, 48, and 60 months (95.1%, 82.1%, 79.9%, 74.7% for CS vs 73.9%, 70.9%, 63% and 62.5% for BMS; log-rank test, P = .01). On multivariate analysis, the type of stent used (hazard ratio [HR], 2.797; 95% confidence interval [CI], 1.471-5.318; P = .002) and the Rutherford classification (HR, 2.019; 95% CI, 1.278-3.191; P = .026) significantly affected the adjusted primary patency. On subgroup analysis, the CS showed significantly higher patency and a survival benefit compared with the BMS in TASC C and D lesions (HR, 8.639; 95% CI, 54.253-75.753; P = .003). Moreover, fewer patients received target limb revascularization in the CS group than in the BMS group (odds ratio, 2.32; 95% CI, 1.47-3.36; P = .02); however, there was no statistically significant difference in the rate of amputations between the groups., Conclusions: The 5-year results of the COBEST demonstrated that the CS has an enduring patency advantage over the BMS in both the short and long terms. Furthermore, the CS showed acceptable patency rates for the treatment of more severe TASC C and D lesions, and patients who received a CS required fewer revascularization procedures. However, the choice of stent did not affect the rate of major limb amputations., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

The last two decades have seen a revolution in the treatment of aortoiliac occlusive disease (AIOD). Acceptable safety and durability outcomes have now been realized with endovascular treatments, which is increasingly finding a place in the treatment of AIOD. Evolution of stent technologies and endovascular techniques is seeing an expansion of AIOD lesions indicated for primary endovascular treatment. The literature evidence basis is continuously evolving, and questions remain as to the optimal form of vessel treatment. Covered stents have been increasingly promoted for their long-term durability, particularly in extensive, challenging AIOD lesions. Here, we explore the seminal evidence basis for covered stents in the treatment of AIOD, and aim to provide a sound evidence based argument for their use.

Purpose: To evaluate the safety and midterm patency of the Supera interwoven nitinol stent in a real-world population and determine deployment and patient-related factors that may predispose to loss of patency., Methods: A retrospective analysis was conducted of 111 consecutive limbs from 97 patients (mean age 75.3 years; 68 men) with severe atherosclerotic disease of the superficial femoral and popliteal arteries that were treated with Supera stents between June 2012 and October 2014. Half the patients had claudication (56%); the remainder had rest pain (19%) and tissue loss (26%). Forty-eight (43%) lesions were chronic total occlusions, and more than half were classified as TransAtlantic Inter-Society Consensus C (22%) or D (30%)., Results: All 146 Supera stents (1.32 stents per limb) were deployed successfully, extending over a mean length of 175.5±130.5 mm to treat lesions averaging 151.5±127.1 mm long. At 30 days, Kaplan-Meier estimated freedom from death, target lesion revascularization, and amputation was 97.3%. Primary patency and freedom from clinically driven target lesion revascularization rates were 87.1% and 95.0% at 6 months, respectively, and 78.9% and 87.6% at 12 months, respectively. Four distinct mechanisms for failure were identified in the 13 limbs in which patency was lost; stent intussusception (n=4), compromised inflow or outflow (n=2), gross oversizing (n=1), and neoplastic thrombophilia (n=1); the cause of 5 occlusions could not be identified., Conclusion: In this heterogeneous group that included long and complex atheromatous femoropopliteal lesions, the Supera stent achieved excellent clinical and patency results at 1 year. Further improvement may be achieved through careful patient selection and the avoidance of deployment pitfalls., (© The Author(s) 2016.)

Background: Studies have suggested that people with intellectual disability are disproportionately involved in crime both as perpetrators and victims., Method: A case linkage design used three Australian contact-level databases, from disability services, public mental health services and police records. Rates of contact, and official records of victimisation and criminal charges were compared to those in a community sample without intellectual disability., Results: Although people with intellectual disability were significantly less likely to have an official record of victimisation and offending overall, their rates of violent and sexual victimisation and offending were significantly higher. The presence of comorbid mental illness considerably increased the likelihood of victimisation and offending; several sex differences were also noted., Conclusions: People with intellectual disability are at increased risk for both violent and sexual victimisation and offending. The presence of comorbid mental illness aggravates the risk of offending and victimisation. Future research should focus on a more nuanced exploration of the risks associated with intellectual disability and specific mental disorders and related indices of complexity.