Reduced primary patency rate in diabetic patients after percutaneous intervention results from more frequent presentation with limb-threatening ischemia

ObjectiveAlthough patients with diabetes are at increased risk of amputation from peripheral vascular disease, excellent limb-salvage rates have been achieved with aggressive surgical revascularization. It is less clear whether patients with diabetes will fare as well as nondiabetics after undergoing percutaneous lower extremity revascularization, a modality which is becoming increasingly utilized for this disease process. This study aimed to assess differential outcomes in between diabetics and nondiabetics in lower extremity percutaneous interventions.MethodsWe retrospectively studied 291 patients with respect to patient variables, complications, and outcomes for percutaneous interventions performed for peripheral occlusive disease between 2002 and 2005. Tibial vessel run-off was assessed by angiography. Patency (assessed arterial duplex) was expressed by Kaplan-Meier method and log-rank analysis. Mean follow-up was 11.6 months (range 1 to 56 months).ResultsA total of 385 interventions for peripheral occlusive disease with claudication (52.2%), rest pain (16.4%), or tissue loss (31.4%) were analyzed, including 336 primary interventions and 49 reinterventions (mean patient age 73.9 years, 50.8% male). Comorbidities included diabetes mellitus (57.2%), chronic renal insufficiency (18.4%), hemodialysis (3.8%), hypertension (81.9%), hypercholesterolemia (57%), coronary artery disease (58%), tobacco use (63.2%). Diabetics were significantly more likely to be female (55.3% vs 40.8%), and suffer from CRI (23.5% vs 12.0%), a history of myocardial infarction (36.5% vs 18.0%), and <three-vessel tibial outflow (83.5% vs 71.8%), compared with nondiabetics, although all other comorbidities and lesion characteristics were equivalent between these groups. Overall primary patency (± SE) at 6, 12, and 18 months was 85 ± 2%, 63 ± 3% and 56 ± 4%, respectively. Patients with diabetes suffered reduced primary patency at 1 year compared with nondiabetics. For nondiabetics, primary patency was 88 ± 2%, 71 ± 4%, and 58 ± 4% at 6, 12, and 18 months, while for diabetics it was 82 ± 2%, 53 ± 4%, and 49 ± 4%, respectively (P = .05). Overall secondary patency at 6, 12, and 18 months was 88 ± 2%, 76 ± 3%, and 69 ± 3%, and did not vary by diabetes status. One-year limb salvage rate was 88.3% for patients with limb-threatening ischemia, which was also similar between diabetics and nondiabetics. While univariate analysis revealed that female gender, <three-vessel tibial outflow, and a history of tobacco use were all predictive of reduced primary patency (P < .05), none of these factors significantly impacted secondary patency or limb-salvage rate. Furthermore, only limb-threatening ischemia remained a significant predictor of outcome on multivariate analysis, suggesting that the poorer primary patency in diabetics is related primarily to their propensity to present with limb-threatening disease compared with nondiabetics.ConclusionPatients with diabetes demonstrate reduced primary patency rates after percutaneous treatment of lower extremity occlusive disease, most likely due to their advanced stage of disease at presentation. However, despite a higher reintervention rate, diabetics and others with risk factors predictive of reduced primary patency can attain equivalent short-term secondary patency and limb-salvage rates. Therefore, these patient characteristics should not be considered contraindications to endovascular therapy

Evaluation of pressure transmission and intra-aneurysmal contents after endovascular repair using the Trivascular Enovus expanded polytetrafluoroethylene stent graft in a canine model of abdominal aortic aneurysm

ObjectiveEndotension has been defined as persistently increased pressure within the excluded sac of an abdominal aortic aneurysm (AAA) resulting in increasing aneurysm size after endovascular repair in the absence of endoleak. Devices that use expanded polytetrafluoroethylene (ePTFE) have been associated with the development of endotension and continued AAA enlargement. In this study, intra-aneurysmal pressure and aneurysm content were evaluated after endovascular repair with the Enovus ePTFE stent graft in a canine model.MethodsProsthetic ePTFE aneurysms, each containing a solid-state, strain-gauge pressure transducer, were implanted in the infrarenal aorta of 13 mongrel dogs (25-35 kg). A second pressure transducer was inserted into the native aorta for systemic arterial pressure measurement. The stent graft was then deployed to exclude the aneurysm via distal aortic access. Comparison was made among three distinct stent grafts: the Trivascular Enovus (nonporous ePTFE; four animals), the original Gore Excluder (porous ePTFE; five animals), and the Medtronic AneuRx (Dacron; four animals). Daily systemic and intra-AAA pressures were measured for 4 weeks. Intra-aneurysmal pressures were indexed to simultaneously measured systemic pressures. After 4 weeks, the aorta, the prosthetic aneurysm, and its contents were harvested, photographed, and processed for histologic investigation with hematoxylin and eosin and Masson trichrome staining.ResultsWithin 24 hours after exclusion, the mean arterial pressure and pulse pressure within the AAA sac tapered to less than 20% of systemic pressure for all three stent graft types. Throughout the postoperative period, significantly lower indexed intra-aneurysmal pressures were present in the Enovus- and AneuRx-treated aneurysms as compared with those treated with the original Excluder stent graft (0.05 ± 0.04, 0.16 ± 0.06, and 0.06 ± 0.03 for the Enovus, Excluder, and AneuRx, respectively). Histologic analysis of the Enovus-treated aneurysms demonstrated intraluminal content characterized almost entirely by erythrocytes and infrequent white blood cells without the fibrin organization—characteristics of acute or chronic thrombus. This contrasted with the content of the Excluder-treated aneurysms, which contained poorly organized fibrin deposition suggestive of acute thrombus, and of the AneuRx-treated aneurysms, which demonstrated mature, well-organized collagenous connective tissue.ConclusionsExclusion of the AAA with the Enovus stent graft resulted in nearly complete elimination of intra-aneurysmal pressure in this model. Histologic analysis of the aneurysm content further suggested complete exclusion, including elimination of circulating clotting factors and fibroblasts responsible for thrombus formation and reorganization. Ultimately, clinical evaluation will be necessary to demonstrate the effectiveness of this stent graft in preventing the development of endotension.Clinical RelevanceEndovascular aneurysm repair is an effective method for the treatment of abdominal aortic aneurysm (AAA) subjected to the unique complications of endoleak and endotension, the indirect pressurization of a sac in the absence of endoleak. In our model, AAA exclusion with the Enovus stent graft results in inhibition of fluid and serum transudation into the AAA sac, a corresponding prompt pressure decay profile, and near-complete elimination of intra-aneurysmal pressure. With the advent of implantable wireless pressure transducers, this research can be readily translated to the clinical setting. Future intraoperative and postoperative studies may help elucidate the clinical significance of pressure decay profiles in identifying successful AAA exclusion and monitoring for the development of endotension and its clinical sequelae

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Endovascular retrieval of an irrigation cannula from the thoracic aorta following cardiac surgery: A case report

Introduction: Endovascular techniques to retrieve intravascular foreign bodies are a necessary component of the Vascular surgeon's skill set. We report the successful retrieval of an embolized irrigation cannula from the thoracic aorta following aortic valve replacement. Presentation of case: The patient is an 81 year old male who underwent coronary artery bypass grafting and aortic valve replacement. Prior to closure, the aortotomy was irrigated with heparinized saline using a syringe with an olive tip irrigation cannula. When the syringe was handed back to the nursing staff, the tip was noted to be missing but could not be found. Prior to closure of the sternum, the field was searched again for the tip and thus the chest was closed. The missing instrument then prompted an intraoperative chest radiograph that demonstrated a metal irrigation cannula superimposed on the cardiac silhouette. Additionally, a transesophageal echocardiogram was performed, which demonstrated the irrigation cannula within the descending thoracic aorta. Right common femoral artery was accessed and a thoracic aortogram was performed demonstrating the cannula to be lodged in the descending thoracic aorta. Intravascular ultrasound (IVUS) was performed to exclude an aortic abnormality preventing the caudad migration of the cannula. No aortic pathology was identified. A tri-lobed snare was used to grasp the cannula at its tip and withdrawn into the right external iliac artery. The cannula was successfully removed through a transverse arteriotomy in the distal right external iliac artery. The patient's postoperative course was uneventful. Conclusion: Endovascular retrieval of intravascular foreign bodies is minimally invasive, relatively simple, and carries minimal morbidity compared to conventional open surgical techniques. This unusual case demonstrates the importance of a working knowledge of techniques and instruments requisite for retrieval of intravascular foreign bodie

Genetic Risk Factors for Abdominal Aortic Aneurysms (AAA)

Abdominal aortic aneurysm (AAA) is a complex, multifactorial disease with a strong genetic component. About 20% of AAA patients have at least one relative with this condition. Since the first candidate gene studies were published 20 years ago, nearly 100 genetic association studies using single nucleotide polymorphisms (SNPs) in biologically relevant genes have been reported on AAA. The most significant results from candidate gene studies are for sortilin-1 (SORT1), interleukin 6 receptor (IL6R), and apolipoprotein(a) (LPA). Unbiased genome-wide approaches such as family-based DNA linkage studies and genome-wide association studies have been carried out by international consortia to identify susceptibility loci for AAA. The chromosomal regions in the human genome with the strongest supporting evidence of contribution to the genetic risk for AAA are: 1) CDKN2BAS gene (located on chromosome 9p21), also known as ANRIL, which encodes an antisense RNA that regulates expression of the cyclin-dependent kinase inhibitors CDKN2A and CDKN2B; 2) DAB2 interacting protein (DAB2IP; located on chromosome 9q33), which encodes an inhibitor of cell growth and survival; 3) low density lipoprotein receptor-related protein 1 (LRP1; located on chromosome 12q13.3), a plasma membrane receptor involved in vascular smooth muscle and macrophage endocytosis, 4) low density lipoprotein receptor (LDLR; located on chromosome 19p13.2), and 5) contactin-3 (CNTN3; located on chromosome 3p12.3), which demonstrated the strongest association in smokers and yet its function remains unclear. These five loci were identified in genome-wide association studies. Using a different approach, DNA linkage analysis with affected relative-pairs, two additional loci containing several plausible candidate genes, located on chromosomes 4q31 and 19q13, were discovered. On-going and future studies to find additional risk loci include large meta-analyses and whole genome sequencing. Furthermore, functional studies are needed to establish the mechanisms by which these genes contribute to AAA pathogenesis. In the long-term, these discoveries will result in important translational applications to the prevention, diagnosis and management of AAAs

Understanding the pathogenesis of abdominal aortic aneurysms

<div><p>An aortic aneurysm is a dilatation in which the aortic diameter is ≥3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50–80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation and oxidative stress. We expect that large genetic, genomic, epigenetic, proteomic and metabolomic studies will be undertaken by international consortia to identify additional risk factors and biomarkers, and to enhance our understanding of the pathobiology of AAA. Collaboration between different research groups will be important in overcoming the challenges to develop pharmacological treatments for AAA.</p></div

Update on Abdominal Aortic Aneurysm Research: From Clinical to Genetic Studies

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person’s risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks