Sex, Endothelial Cell Functions, and Peripheral Artery Disease.

Peripheral artery disease (PAD) is caused by blocked arteries due to atherosclerosis and/or thrombosis which reduce blood flow to the lower limbs. It results in major morbidity, including ischemic limb, claudication, and amputation, with patients also suffering a heightened risk of heart attack, stroke, and death. Recent studies suggest women have a higher prevalence of PAD than men, and with worse outcomes after intervention. In addition to a potential unconscious bias faced by women with PAD in the health system, with underdiagnosis, and lower rates of guideline-based therapy, fundamental biological differences between men and women may be important. In this review, we highlight sexual dimorphisms in endothelial cell functions and how they may impact PAD pathophysiology in women. Understanding sex-specific mechanisms in PAD is essential for the development of new therapies and personalized care for patients with PAD.

A hidden problem: peripheral artery disease in women.

Peripheral artery disease (PAD) has a huge social and economic burden and is an important contributor to the global health burden. Sex differences in PAD are apparent, with recent data suggesting equal if not greater prevalence in women, and women having worse clinical outcomes. Why this occurs is not clear. To identify underlying reasons for gender inequalities in PAD, we executed a deeper exploration through a social constructive perspective. A scoping review was conducted using the World Health Organization model for analysis of gender-related needs in healthcare. Complex interacting factors, including biological, clinical, and societal variables, were reviewed to highlight gender-related inequities in the diagnosis, treatment, and management of PAD. Current gaps in knowledge were identified and insights into future directions aimed at improving these inequalities were discussed. Our findings highlight the multi-level complexities that need to be considered for strategies to improve gender-related needs in PAD healthcare.

Factors associated with successful median arcuate ligament release in an international, multi-institutional cohort.

OBJECTIVE: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure. METHODS: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium. Data on open, laparoscopic, and robotic MALR performed from 2000 to 2020 were gathered. The primary outcome was treatment failure, defined as no improvement in median arcuate ligament syndrome symptoms after MALR or symptom recurrence between MALR and the last clinical follow-up. RESULTS: For 516 patients treated at 24 institutions, open, laparoscopic, and robotic MALR had been performed in 227 (44.0%), 235 (45.5%), and 54 (10.5%) patients, respectively. Perioperative complications (ileus, cardiac, and wound complications; readmissions; unplanned procedures) occurred in 19.2% (open, 30.0%; laparoscopic, 8.9%; robotic, 18.5%; P < .001). The median follow-up was 1.59 years (interquartile range, 0.38-4.35 years). For the 488 patients with follow-up data available, 287 (58.8%) had had full relief, 119 (24.4%) had had partial relief, and 82 (16.8%) had derived no benefit from MALR. The 1- and 3-year freedom from treatment failure for the overall cohort was 63.8% (95% confidence interval [CI], 59.0%-68.3%) and 51.9% (95% CI, 46.1%-57.3%), respectively. The factors associated with an increased hazard of treatment failure on multivariable analysis included robotic MALR (hazard ratio [HR], 1.73; 95% CI, 1.16-2.59; P = .007), a history of gastroparesis (HR, 1.83; 95% CI, 1.09-3.09; P = .023), abdominal cancer (HR, 10.3; 95% CI, 3.06-34.6; P < .001), dysphagia and/or odynophagia (HR, 2.44; 95% CI, 1.27-4.69; P = .008), no relief from a celiac plexus block (HR, 2.18; 95% CI, 1.00-4.72; P = .049), and an increasing number of preoperative pain locations (HR, 1.12 per location; 95% CI, 1.00-1.25; P = .042). The factors associated with a lower hazard included increasing age (HR, 0.99 per increasing year; 95% CI, 0.98-1.0; P = .012) and an increasing number of preoperative diagnostic gastrointestinal studies (HR, 0.84 per study; 95% CI, 0.74-0.96; P = .012) Open and laparoscopic MALR resulted in similar long-term freedom from treatment failure. No radiographic parameters were associated with differences in treatment failure. CONCLUSIONS: No difference was found in long-term failure after open vs laparoscopic MALR; however, open release was associated with higher perioperative morbidity. These results support the use of a preoperative celiac plexus block to aid in patient selection. Operative candidates for MALR should be counseled regarding the factors associated with treatment failure and the relatively high overall rate of treatment failure.

Aortic graft explants - A single institution analysis of incidence and outcomes.

OBJECTIVES: Explantation of both endovascular endovascular aneurysm repair and open aortic grafts is a procedure associated with high peri-operative risk, and the current study sought to determine the outcomes and trends over time in these patients. METHODS: This study examined data from all patients undergoing explant of an aortic graft (both open and endovascular) between January 2004 and December 2020 at a single centre. Variables analysed included comorbidities, duration to and indication for explantation, type of revascularization, in-hospital complications and mortality, duration of hospital and ICU stay, and out-patient mortality. RESULTS: Of 688 open and 1352 EVARs performed, 46 patients underwent 48 explants. Five were open grafts and 43 were endografts, equating to an explant rate of 0.73% of open and 3.18% EVARs. Average time to explant was 70 months, with patients presenting electively having a significantly longer duration to representation than those presenting emergently (51 vs 44 months, p=0.003). Indication for explant was endoleak in 70%, infection in 23%, and occlusion in 6%. Of the endoleaks, 61% of were Type 1, 22% Type II, 11% Type IV, and 6% Type V. On representation, 17 patients (35%) were symptomatic. Overall mortality rate was 8.3%, with a trend for higher mortality in emergent than elective presentations (11.8 vs 6.5%, p=0.55). There was no change in explant rate over time. CONCLUSIONS: Elective aortic graft explantation is associated with low mortality, despite its complexity and patient comorbidities. Patients presenting with symptoms suffered higher mortality and a longer post-operative course, suggesting that aortic graft explantation should be considered sooner rather than later, rather than persisting with repeated endovascular management.

Endothelial cell dysfunction: Implications for the pathogenesis of peripheral artery disease.

Peripheral artery disease (PAD) is caused by occluded or narrowed arteries that reduce blood flow to the lower limbs. The treatment focuses on lifestyle changes, management of modifiable risk factors and vascular surgery. In this review we focus on how Endothelial Cell (EC) dysfunction contributes to PAD pathophysiology and describe the largely untapped potential of correcting endothelial dysfunction. Moreover, we describe current treatments and clinical trials which improve EC dysfunction and offer insights into where future research efforts could be made. Endothelial dysfunction could represent a target for PAD therapy.

Use of Suture-Mediated Closure Devices for Closure of Punctures in Prosthetic Patches or Grafts is Associated With High Rates of Technical Success and Low Complication Rates.

OBJECTIVES: Despite the increasing use of endovascular techniques in the management of peripheral vascular disease, there is little data on the safety of percutaneous closure devices in punctures of synthetic vascular material. Our paper sought to address this paucity in the literature by reviewing the incidence of complications occurring in patients in whom the ProGlide device was utilised to achieve haemostasis post-percutaneous puncture of vascular patches and graft materials. METHODS: A retrospective review of patient records was conducted at a tertiary referral centre. Patients who had undergone percutaneous punctures of prosthetic bypass grafts or patch angioplasties between January 2011 and December 2020 were identified from a prospectively collected database. Medical records and post-procedural imaging were reviewed to assess the occurrence of post-procedural complications such as pseudoaneurysms, puncture site stenosis and further interventions for access complications. RESULTS: A total of 73 punctures of prosthetic material were performed in 42 patients, of which 39 utilised ProGlides. Median age of included patients was 72 years. There was male predominance in the cohort (69.8%), and most punctures (87.3%) were through polyurethane patches. Device success rate was 95%, and no patients required open repair. There was a low incidence of complications, with no patients developing pseudoaneurysms, arteriovenous fistulas, ischaemic limbs or > 50% stenosis when either manual pressure or the ProGlide device was used to achieve haemostasis. Furthermore, there were no returns to theatre or further interventions performed for access site complications. CONCLUSION: The use of the ProGlide closure device has a low incidence of complications and its safety appears to be equivalent to manual compression when used to achieve haemostasis in percutaneous punctures of synthetic vascular material in select patients. To our knowledge, this is the only article to date to assess the safety of the ProGlide in this setting.

Successful Management of a Large Internal Carotid Artery Aneurysm via Open Resection.

BACKGROUND Extracranial carotid artery aneurysms are rare pathologies associated with an increased risk of neurological events and cranial nerve dysfunction. While they often require prompt intervention, the preferred surgical management remains unclear due to the rarity of this pathology, with described surgical and endovascular techniques having unique benefit and risk profiles in the current literature. CASE REPORT We report an interesting case of an internal carotid artery aneurysm successfully managed via open resection in a female patient in her 70s. Our patient, who was otherwise well, initially presented with an isolated episode of dysarthria associated with hypertension. Her pathology was identified on routine work-up for a presumed neurological event in the setting of her symptoms, and the patient referred to our center for definitive surgical management given the associated risk of embolic events. Under our care, the patient underwent an open resection of the ICA aneurysm with primary repair of the vessel. Her intra-operative and post-operative courses were unremarkable, and the patient remained well with no neurological deficits at follow-up at 4 months. CONCLUSIONS Our case demonstrates that select patients presenting with internal carotid artery aneurysms and tortuous internal carotid arteries, who may be otherwise ineligible for endovascular treatment, may be amenable to resection of the aneurysm followed by primary repair of the vessel, negating the requirement for interposition grafts.

Changing patterns in Australian and New Zealand: vascular surgery during COVID-19.

BACKGROUND: Early government-mandated restrictions in Australia and New Zealand contributed to a successful public health outcome during the COVID-19 pandemic, including an unprecedented temporary cancellation of all non-urgent elective surgical procedures. This study describes the change in vascular surgery services across Australia and New Zealand before and during the COVID-19 restrictions. METHODS: De-identified data from the Australia and New Zealand Society for Vascular Surgery Australasian Vascular Audit from January 2015 to September 2020 was obtained. Vascular surgery procedure numbers from January to September of 2020 (study period) was compared to the corresponding months between 2015 and 2019 (pre-study period). The volume of procedures, both elective and emergency, were compared. Subgroup analyses included procedures categorized by operation type and location. RESULTS: There was a 11% decrease in total vascular procedures, 22% decrease in elective procedures, and a 14% increase in emergency procedures, comparing the study and pre-study periods. There was a large increase in all revascularization procedures for critical limb ischemia and no change in acute limb ischemia interventions, without a concomitant rise in major or minor all-cause amputation. There was a decrease in interventions for abdominal aortic aneurysm and carotid artery disease, driven by a fall in elective procedures, while volume for dialysis access remained the same. Change in procedural volume varied by state with the largest decrease noted in NSW and Victoria. CONCLUSIONS: The COVID-19 pandemic reduced vascular surgery procedures across Australia and New Zealand with a decrease in elective operations and an increase in emergency operations.

Early outcomes using dedicated venous stents in the upper limb of patients with venous thoracic outlet syndrome: A single centre experience.

INTRODUCTION: Surgical management of Venous Thoracic Outlet Syndrome (vTOS) is based upon resection of the first rib. The optimal method to treat any residual venous scarring however remains unclear. The purpose of this study was to evaluate a single quaternary centre's early and mid-term outcomes following endovascular reconstruction of the axillo-subclavian vein using dedicated venous stents in patients with VTOS. METHODOLOGY: A retrospective analysis of patients at Royal Prince Alfred Hospital, who underwent upper limb deep venous stenting as an adjunct in the treatment of vTOS was performed. All patients between 2012 and 2017 were included. Stent patency was assessed with duplex ultrasonography. All re-interventions and their indications were recorded. RESULTS: A total of 24 limbs in 21 patients (13 female, median age 44 yrs) were treated with dedicated venous stents between 2012 and 2017. All patients had resection of their first rib using a transaxillary approach. Nine patients initially presented with an acute DVT and underwent thrombolysis. In three of these patients a venous stent was placed before rib resection following completion of lysis. In the remainder, the median time for stent placement following surgery was 64 days. Median follow-up from stent insertion was 50 months. Primary, primary-assisted and secondary patency at 24 months was 55%, 95% and 100% respectively with one patient lost during follow-up. There were no major complications. A total of 14 re-interventions were performed on these patients. Three patients reported residual symptoms following stenting including heaviness (n = 1), bluish discolouration (n = 1) and prominent veins on the chest (n = 1) with the remainder asymptomatic. CONCLUSION: In this single centre study, endovascular reconstruction using dedicated venous stents appears to be an effective and safe method to reconstruct a damaged subclavian vein following rib resection in patients with vTOS.

The Gore Global Registry for Endovascular Aortic Treatment: Objectives and Design.

BACKGROUND: The Global Registry for Endovascular Aortic Treatment (GREAT) is a prospective observational multicenter cohort registry that was initiated in November 2011. The aim of the GREAT is to collect contemporary real-world data on the performance of all Gore aortic endografts in the treatment of multiple aortic pathologies. The primary and secondary objectives, design, and future directions of the GREAT are described. METHODS: The GREAT aims to enroll 5000 consecutive patients with Gore thoracic and abdominal aortic endografts from multiple centers throughout the world. The GREAT has broad inclusion criteria with minimal exclusion criteria to reflect real-world practice such as including off-label use, nonstandard indications and devices deployed outside instruction for use. Follow-up will extend to 10 years providing major insights into the long-term durability and behavior of Gore aortic endografts. Primary end points include the incidence and timing of (1) endoleak of any type, (2) endograft migration and/or stent fracture, (3) endograft explantation, and (4) aortic rupture. Secondary end points include the following: (1) incidence of serious device events by pathology, (2) incidence of serious device events by aortic segment (ascending aorta, arch of aorta, descending thoracic aorta, abdominal aorta), (3) long-term survival by pathology, and (4) aorta-related mortality by pathology. RESULTS: As of June 2015, 2960 patients have been enrolled into the GREAT from 78 centers in Europe, the United States, Australia, New Zealand, and Brazil. The majority of patients and centers are from Europe and the United States. Completion of enrollment is anticipated to be in 2017 with interim results planned to be published during enrollment and on follow-up. CONCLUSIONS: Upon completion, the GREAT will be among the largest clinical registry to date of abdominal and thoracic aortic devices manufactured by a single sponsor. It will provide valuable real-world data on the use and durability of Gore aortic endografts in the treatment of a variety of aortic pathologies and devices deployed within and outside instruction for use.

Primary aortoenteric fistulae: the challenges in diagnosis and review of treatment.

Primary aortoenteric fistula (PAEF) is a potentially fatal condition which poses a considerable diagnostic challenge because of its infrequency and the nonspecific presentation. We report the case of a 61-year old woman who presented to her general practitioner with nonspecific and intermittent rectal bleeding, hematemesis, and weight loss. Four days later, she presented to the emergency department with worsening symptoms. The investigations revealed a new small 3.8-cm abdominal aortic aneurysm on computed axial tomography (CT), however, no evidence of a fistula was observed either on CT scan or endoscopy. Two days later, she became unstable requiring an emergency laparotomy and was taken to the operation theater for an en bloc resection of a segment of the aorta and duodenum with exclusion of the duodenum with an inline reconstruction of the aorta using a Dacron graft for a PAEF. The published data were reviewed to address the issues of optimal diagnostic methods and management of PAEF.

Studies of structure-activity relationship on plant polyphenol-induced suppression of human liver cancer cells.

PURPOSE: To study anticancer activities of 68 plant polyphenols with different backbone structures and various substitutions and to analyze the structure-activity relationships. METHODS: Antiproliferative activity of 68 plant polyphenols on human liver cancer cells were screened by the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide method. Structure-activity relationships were analyzed by comparison of their activities with selected structures. Cell cycle progression was assayed by flow cytometry analysis and apoptosis was analyzed by DNA fragment assay. RESULTS: Based on their backbone structures, 68 polyphenols were sub-classed to flavonoids (chalcones, flavanones, flavones and isoflavones), chromones and coumarins. The order of their potency to suppress the human liver cancer cells is chalcones > flavones > chromones > isoflavones > flavanones > coumarins. Chalcones comprise the most potent group with IC(50) values ranging from 21.69 to 197 microM. Top nine most potent chalcones in the group have hydroxylation at 2'-carbon position in B-ring. Flavones ranked second in their potencies. Quercetin, 4-hydroxyflavone and luteolin are three hydroxyflavones with highest potencies in this group. Their IC(50) values are 30.81, 39.29 and 71.17 microM, respectively. Chromones, isoflavones, flavanones and coumarins showed much lower potencies when compared to the first two groups with IC(50) ranges of 61 to >400, 131 to >400, 138 to >400 and 360.85 to >400 microM, respectively. In mechanistic studies, the most potent chalcone, 2,2'-dihydroxychalcone could induce G2/M arrest and then apoptosis of the cancer cells. CONCLUSIONS: An analysis of structure-activity relationship showed that following structures are required for their inhibitory potencies on human liver cancer cells: (1) of the six sub-classes of the polyphenols tested, the unique backbone structure of chalcones with a open C-ring; (2) within the chalcone group, hydroxyl substitution at 2'-carbon of B-ring; (3) hydroxyl substitution at 3'-carbon in B-ring of flavones. However, some other structures were found to decrease their potencies: e.g. substitutions by sugar moieties in flavones. These data are valuable for design and modification of new polyphenols, which could be potential antiproliferative agents of cancer cells.