Descending thoracic aortic mural ulceration is associated with postoperative spinal cord ischemia after branched endovascular aortic aneurysm repair.

OBJECTIVE: Paraplegia is one of the most feared complications after thoracoabdominal aortic aneurysm repair. The purpose of this study is to determine whether aortic thrombus characteristics are associated with spinal cord ischemia (SCI) after branched endovascular aneurysm repair (BEVAR). METHODS: From April 2011 to April 2020, 62 patients underwent elective BEVAR for thoracoabdominal aortic aneurysm and pararenal aortic aneurysms using a low-profile device and had a complete preoperative computed tomography angiography of the aorta from the sinotubular junction to the aortic bifurcation. Aortic thrombus was evaluated for thrombus thickness ≥5 mm, thrombus >2/3 of aortic circumference, and the presence of an ulcer-like thrombus. One point was assigned at each 5 mm axial image if all 3 criteria were met, resulting in a total "shaggy score" for the entire aorta. Data on demographics, procedural details, and outcomes were collected prospectively. All patients underwent a standard spinal cord protection protocol, including routine cerebrospinal fluid drainage. In July 2016, an insulin infusion protocol (IIP) was initiated to maintain postoperative blood glucose levels <120 mg/dL for 48 hours. The primary clinical end point was postoperative SCI. RESULTS: 10 (16%) patients developed postoperative SCI: 6 with transient paraparesis, 2 with persistent paraparesis, and 2 with persistent paraplegia. Patients with SCI were older, had higher shaggy scores, and were less likely to have been on an IIP. There were no significant differences in demographics, aneurysm type, or operative parameters. In a logistic multivariate regression model for SCI, age (odds ratio [OR]: 1.2 [1.1-1.4], P = .02) and shaggy score (OR: 1.2 [1.1-1.4], P = .02) were independently associated with increased risk of SCI, whereas treatment with the IIP was associated with lower risk of SCI (OR: 0.04 [0.006-0.50], P = .05). Of the individual components of the shaggy score, higher descending thoracic aortic ulcer scores were the most strongly associated with postoperative SCI (P = .009). CONCLUSIONS: Preoperative characterization of aortic wall thrombus is an important adjunctive tool for individualized clinical decision-making and patient counseling about the risk of SCI after BEVAR.

Iliac artery calcification score stratifies mortality risk estimation in patients with chronic limb-threatening ischemia undergoing revascularization.

OBJECTIVE: Patients with chronic limb-threatening ischemia (CLTI) are at high risk for adverse limb outcomes and mortality. Using the Vascular Quality Initiative (VQI) prediction model to estimate mortality after revascularization can assist with clinical decision-making. We aimed to improve the discrimination of the 2-year VQI risk calculator by incorporating a common iliac artery (CIA) calcification score based on computed tomography scans. METHODS: This was a retrospective analysis of patients who underwent infrainguinal revascularization for CLTI from January 2011 to June 2020 and had a computed tomography scan of the abdomen/pelvis 2 years before or up to 6 months after revascularization. CIA calcium morphology, circumference, and length were scored. Bilateral scores were summed for the total calcium burden (CB) score, which was trichotomized (mild, 0-15; moderate, 16-19; severe, 20-22). The VQI CLTI model was used to categorize patients as low, medium, or high risk for mortality. RESULTS: A total of 131 patients with a mean age of 69±12 years were included in the study, and 86 (66%) were men. CB scores were mild in 52 (40%), moderate in 26 (20%), and severe in 53 (40%) patients. Older patients (P = .0002) and those with coronary artery disease (P = .06) had higher CB scores. Patients with severe CB scores were more likely to undergo infrainguinal bypass compared with those with mild or moderate CB scores (P = .006). The 2-year VQI mortality risk was calculated to be low in 102 (78%), medium in 23 (18%), and high in 6 (4.6%) patients. In the "low-risk" VQI mortality subgroup, 46 (45%) patients had mild, 18 (18%) had moderate, and 38 (37%) had severe CB scores, and patients with severe CB scores had significantly higher risk of mortality compared with those with mild or moderate scores (hazard ratio, 2.5; 95% confidence interval, 1.2-5.1; P = .01). In this "low-risk" VQI mortality subgroup, CB score further stratified the risk of mortality (P = .04). CONCLUSIONS: Higher total CIA calcification was significantly associated with mortality in patients undergoing infrainguinal revascularization for CLTI, and preoperative assessment of CIA calcification may help with perioperative risk stratification and guide clinical decision making in this population.

Staged autogenous to prosthetic hemodialysis access creation strategy to maximize forearm options.

OBJECTIVE: When an adequate cephalic vein is not available for fistula construction, surgeons often turn to basilic vein or prosthetic constructions. Single-stage forearm prosthetic hemodialysis accesses are associated with poor durability, and upper arm non-autogenous access options are often limited by axillary outflow failure, which inevitably drives transition to the contralateral arm or lower extremity. We hypothesized that initial creation of a modest flow proximal forearm arterial-venous anastomosis to dilate ("develop") inflow and outflow vessels, followed by a planned second-stage procedure to create a cannulation zone with a prosthetic graft in the forearm, would result in reliable and durable hemodialysis access in patients with limited options. METHODS: We performed an institutional cohort study from 2017 to 2021 using a prospectively maintained database supplemented with adjudicated chart review. Patients without traditional autogenous hemodialysis access options in the forearm underwent an initial non-wrist arterial-venous anastomosis creation in the forearm as a first stage, followed by a second-stage interposition graft sewn to the existing inflow and venous outflow segments to create a useable cannulation zone in the forearm while leveraging vascular development. Outcomes included time from second-stage access creation to loss of primary and secondary patency, frequency of subsequent interventions, and perioperative complications. RESULTS: The cohort included 23 patients; first-stage radial artery-based (74%) configurations were more common than brachial artery-based (26%). Mean age was 63 years (standard deviation, 14 years), and 65% were female. Median follow-up was 340 days (interquartile range [IQR], 169-701 days). Median time to cannulation from second-stage procedure was 28 days (IQR, 18-53 days). Primary, primary assisted, and secondary patency at 1 year was 16.7% (95% confidence interval [CI], 5.3%-45.8%), 34.6% (95% CI, 15.2%-66.2%), and 95.7% (95% CI, 81.3%-99.7%), respectively. Subsequent interventions occurred at a rate of 3.02 (IQR, 1.0-4.97) per person-year, with endovascular thrombectomy with or without angioplasty/stenting (70.9%) being the most common. There were no cases of steal syndrome. Infection occurred in two cases and were managed with antibiotics alone. CONCLUSIONS: For patients without adequate distal autogenous access options, staged prosthetic graft placement in the forearm offers few short-term complications and excellent durability with active surveillance while strategically preserving the upper arm for future constructions.

Examining the Development of Operative Autonomy in Vascular Surgery Training and When Trainees and Program Directors Agree and Disagree.

BACKGROUND: Lack of autonomy in the operating room (OR) during general surgery residency is a major contributing factor to low confidence operating independently after graduation. Although attempts to address decreased autonomy and development of entrustment in the OR are being made in general surgery programs, this issue has not been examined thoroughly in vascular surgery. We sought to determine barriers and opportunities for developing operative autonomy during vascular surgery training by surveying program directors (PDs) and trainees (integrated residents and fellows) in U.S. vascular surgery training programs. METHODS: An anonymous electronic survey was sent via email to all PDs (n = 155) and trainees (n = 516) in United States vascular surgery training programs. Demographics, academic characteristics, and responses regarding factors impacting the development of entrustment were collected. RESULTS: Thirty-five PDs and 100 trainees completed the survey (22.5% and 19.4% response rate, respectively). Sixty percent of trainees were integrated residents and 40% were fellows. Twenty percent of PDs and 33% of trainees were female, and 5% of all PDs and trainees were from underrepresented minorities. The single most positive factor affecting the development of autonomy according to trainees and PDs is familiarity of the faculty with the trainee. Both PDs and trainees thought the trainee's preparation for the case positively affected development of autonomy; however, more PDs believed that involvement with preoperative preparation in particular (marking the patient, consenting the patient, filling out a history and physical, prepping and draping the patient) was important (P < 0.05). PDs believed that duty-hour limitations negatively affected the trainee's ability to develop autonomy in the OR, whereas more trainees believed that hospital or OR efficiency policies played a negative role (P < 0.05). Finally, compared with trainees, PDs believed that the appropriate amount of time for safe struggle before the attending should take over the case was when OR efficiency was compromised or at any moment the trainee is unsure of themselves (P < 0.05); trainees believed that the attending should take over the case after the limit of their skill set or troubleshooting ability was reached (P < 0.05). CONCLUSIONS: Familiarity of the attending physician with the trainee is an important positive factor for development of entrustment and autonomy in vascular surgery trainees. Duty-hour limitations and belief of the need for hospital efficiency may negatively impact operative independence of trainees. An open discussion about balancing OR efficiency and trainees' safe struggle is essential to address the growth of independent operative skills in vascular surgery trainees.

Intraluminal delivery of thrombospondin-2 small interfering RNA inhibits the vascular response to injury in a rat carotid balloon angioplasty model.

In an effort to inhibit the response to vascular injury that leads to intimal hyperplasia, this study investigated the in vivo efficacy of intraluminal delivery of thrombospondin-2 (TSP-2) small interfering RNA (siRNA). Common carotid artery (CCA) balloon angioplasty injury was performed in rats. Immediately after denudation, CCA was transfected intraluminally (15 min) with one of the following: polyethylenimine (PEI)+TSP-2 siRNA, saline, PEI only, or PEI+control siRNA. CCA was analyzed at 24 h or 21 d by using quantitative real-time PCR and immunohistochemistry. TSP-2 gene and protein expression were significantly up-regulated after endothelial denudation at 24 h and 21 d compared with contralateral untreated, nondenuded CCA. Treatment with PEI+TSP-2 siRNA significantly suppressed TSP-2 gene expression (3.1-fold) at 24 h and TSP-2 protein expression, cell proliferation, and collagen deposition up to 21 d. These changes could be attributed to changes in TGF-ß and matrix metalloproteinase-9, the downstream effectors of TSP-2. TSP-2 knockdown induced anti-inflammatory M2 macrophage polarization at 21 d; however, it did not significantly affect intima/media ratios. In summary, these data demonstrate effective siRNA transfection of the injured arterial wall and provide a clinically effective and translationally applicable therapeutic strategy that involves nonviral siRNA delivery to ameliorate the response to vascular injury.-Bodewes, T. C. F., Johnson, J. M., Auster, M., Huynh, C., Muralidharan, S., Contreras, M., LoGerfo, F. W., Pradhan-Nabzdyk, L. Intraluminal delivery of thrombospondin-2 small interfering RNA inhibits the vascular response to injury in a rat carotid balloon angioplasty model.

Effects of Mentorship on Graduating Vascular Surgery Trainees.

BACKGROUND: Mentorship within surgery, particularly vascular surgery, has not been extensively evaluated. This study sought to examine mentorship experiences in graduating vascular trainees (VTs). METHODS: An anonymous electronic survey examining current mentor relationships, ideal characteristics, academic productivity, and operative comfort level was emailed to all US graduating 2015 (n = 141) and 2016 (n = 144) VTs during their last year of training. A parallel survey was emailed to program/associate program directors (PDs) of all US vascular training programs (n = 169). RESULTS: Surveys were completed by 65 (38%) PDs and 62 (22%) VTs. Forty-three (69%) VTs identified a mentor with no difference in frequency of having a mentor noted among gender, type of training (fellowship/residency), or geographical region. The majority (41/43, 95%) recognized a vascular surgeon as their mentor; the mentor was assigned to 10 of 43 (23%) trainees and was their PD to 9 of 43 (21%). Ideal mentor characteristics, identified by VTs using 4-point Likert scales, were approachability, supportiveness, and accessibility (3.94, 3.76, and 3.74, respectively), while those of a good mentee were enthusiasm, ethical work, and commitment (3.79, 3.69, and 3.45, respectively). Trainees scored accessibility, approachability, compassion, and same gender significantly higher than PDs as characteristics of ideal mentors (P < 0.05). The majority of PDs thought mentorship increased access to research opportunities, professional networking, and job opportunities, but not operative skill (90%, 95%, 65%, and 18%, respectively). There was no difference between trainees with mentors and those without in terms of reported academic productivity or operative comfort level. Vascular fellows reported higher comfort than residents in open abdominal aortic aneurysm repair (3.32 vs. 2.73, P = 0.006), juxtarenal aneurysm repair (2.8 vs. 2.1, P = 0.02), and aorto-mesenteric bypass (2.57 vs. 1.93, P = 0.03), and neither group was comfortable performing carotid stenting or fenestrated endovascular aneurysm repairs. CONCLUSIONS: There is no difference in academic productivity or case comfort level between surgical trainees with mentors and those without. Possible benefits identified by PDs and trainees include professional networking and increased research and job opportunities. Mentors should be approachable, accessible, supportive, and ethical, while mentees should be enthusiastic, ethical, committed, and approachable. Vascular fellows feel more comfortable with open vascular operations than residents, and nether group feels comfortable with complex endovascular cases. More research is warranted.

Local delivery of decorin via hyaluronic acid microrods improves cardiac performance and ventricular remodeling after myocardial infarction.

Heart failure (HF) is a global public health burden and associated with significant morbidity and mortality. HF can result as a complication following myocardial infarction (MI), with cardiac fibrosis forming in the myocardium as a response to injury. The dense, avascular scar tissue that develops in the myocardium after injury following MI creates an inhospitable microenvironment that hinders cellular function, survival, and recruitment, thus severely limiting tissue regeneration. We have previously demonstrated the ability of hyaluronic acid (HA) polymer microrods to modulate fibroblast phenotype using discrete biophysical cues and to improve cardiac outcomes after implantation in rodent models of ischemia-reperfusion MI injury. Here, we developed a dual-pronged biochemical and biophysical therapeutic strategy leveraging bioactive microrods to more robustly attenuate cardiac fibrosis after acute myocardial injury. Incorporation of the anti-fibrotic proteoglycan decorin within microrods led to sustained release of decorin over one month in vitro and after implantation, resulted in marked improvement in cardiac function and ventricular remodeling, along with decreased fibrosis and cardiomyocyte hypertrophy. Together, this body of work aims to contribute important knowledge to help develop rationally designed engineered biomaterials that may be used to successfully treat cardiovascular diseases.

Local decorin delivery via hyaluronic acid microrods improves cardiac performance, ventricular remodeling after myocardial infarction.

Heart failure (HF) remains a global public health burden and often results following myocardial infarction (MI). Following injury, cardiac fibrosis forms in the myocardium which greatly hinders cellular function, survival, and recruitment, thus severely limits tissue regeneration. Here, we leverage biophysical microstructural cues made of hyaluronic acid (HA) loaded with the anti-fibrotic proteoglycan decorin to more robustly attenuate cardiac fibrosis after acute myocardial injury. Microrods showed decorin incorporation throughout the entirety of the hydrogel structures and exhibited first-order release kinetics in vitro. Intramyocardial injections of saline (n = 5), microrods (n = 7), decorin microrods (n = 10), and free decorin (n = 4) were performed in male rat models of ischemia-reperfusion MI to evaluate therapeutic effects on cardiac remodeling and function. Echocardiographic analysis demonstrated that rats treated with decorin microrods (5.21% ± 4.29%) exhibited significantly increased change in ejection fraction (EF) at 8 weeks post-MI compared to rats treated with saline (-4.18% ± 2.78%, p < 0.001) and free decorin (-3.42% ± 1.86%, p < 0.01). Trends in reduced end diastolic volume were also identified in decorin microrod-treated groups compared to those treated with saline, microrods, and free decorin, indicating favorable ventricular remodeling. Quantitative analysis of histology and immunofluorescence staining showed that treatment with decorin microrods reduced cardiac fibrosis (p < 0.05) and cardiomyocyte hypertrophy (p < 0.05) at 8 weeks post-MI compared to saline control. Together, this work aims to contribute important knowledge to guide rationally designed biomaterial development that may be used to successfully treat cardiovascular diseases.

The role of a Coronavirus disease 2019 pharmacist: an Australian perspective.

The coronavirus disease 2019 (COVID-19) pandemic has greatly impacted healthcare services around the world. Pharmacists are front-line healthcare professionals and integral members of the healthcare team. The deployment of a specialized 'COVID pharmacist' within our institution has demonstrated that the skills of the pharmacist can be adapted, expanded and utilized to alleviate the pressure of doctor shortages, reduce healthcare worker exposure to infected patients, contribute to therapeutic decisions and work collaboratively to tackle the challenges faced during this pandemic. This commentary details an Australian hospital pharmacy response to the COVID-19 pandemic, describing the unique clinical and practical contributions made by a specialized COVID pharmacist in our institution.

Delivery of targeted gene therapies using a hybrid cryogel-coated prosthetic vascular graft.

OBJECTIVES: The success of prosthetic vascular grafts in the management of peripheral arterial disease is frequently limited by the development of anastomotic neointimal hyperplasia (ANIH), with the host response to prosthetic grafts beginning soon after implantation. To address this, we combine a platform of polyethylene terephthalate (PET) fabric with an applied cryogel layer containing biologic agents to create a bioactive prosthetic graft system, with the ability to deliver therapeutics targeting modulators of the ANIH-associated transcriptome response, along with antithrombotic agents. METHODS: Hybrid graft materials were synthesized by cryopolymerization of methacrylated alginate and heparin onto electrospun (ePET), knitted PET (kPET), or woven PET (wPET). Arg-Gly-Asp (RGD) peptides were added to increase cell adhesion. Scanning electron microscopy (SEM) was used to study the microstructure at 1 day, and 2, 4, and 8 weeks. Physical properties such as swelling ratio, pore connectivity, shape recovery, and stiffness were evaluated. Human aortic endothelial cell (HAoEC) adherence was visualized using confocal microscopy after 24 hours and proliferation was evaluated with a resazurin-based assay for 7 days. Confocal microscopy was used to assess delivery of adeno-associated virus (AAV-GFP) after incubation of hybrid grafts with HAoECs. Heparin activity of the materials was measured using an anti-Xa assay. RESULTS: SEM demonstrated large interconnected pores throughout the entire structure for all graft types, with minimal degradation of the cryogel after 8 weeks. Hybrid materials showed a trend towards increased shape recovery, increased stiffness, decreased swelling ratio, and no difference in pore connectivity. HAoECs incorporated, adhered, and proliferated over 7 days on all materials. HAoECs were successfully transduced with AAV-GFP from the hybrid graft materials. Anti-Xa assay confirmed continued activity of heparin from all materials for over 7 days. CONCLUSIONS: We have developed a bioactive prosthetic graft system with a cryogel coating capable of delivering biologic agents with antithrombotic activity. By applying the cryogel and selected agents onto PET prior to graft implantation, this study sets the stage for the system to be individualized and tailored to the patient, with bioengineering and targeted gene therapy strategies dovetailing to create an improved prosthetic graft adaptable to emerging knowledge and technologies.

Symptomatic Delayed Aortic Dissection After Superior Mesenteric Artery Stenting for Chronic Mesenteric Ischemia.

Chronic mesenteric ischemia most commonly occurs secondary to atherosclerotic disease of the mesenteric arteries. Patients are often older than 60 years and can present with postprandial abdominal pain, nausea, diarrhea, and significant weight loss. Symptomatic disease has traditionally been managed with open surgical repair, but endovascular strategies, such as percutaneous angioplasty and stenting, have emerged as the mainstays of therapy. Complications from stenting include plaque embolization, thrombosis, perforation, or dissection of the mesenteric arteries. We present a patient with symptomatic acute aortic dissection 18 months after celiac and superior mesenteric artery stent placement for chronic mesenteric ischemia.

Endovascular stent graft exclusion of a thoracic arteriovenous malformation in a patient with Cobb syndrome.

Cobb syndrome is a rare neurocutaneous disorder characterized by spinal vascular abnormalities in association with a vascular lesion of the skin at the same metamere. Patients present after the onset of symptoms such as paraplegia, back pain, and, less commonly, fatigue due to heart failure. Available treatment options to date have included neurosurgical resection and endovascular embolization. We present a patient with Cobb syndrome with a progressively symptomatic arteriovenous malformation involving the thoracic vertebrae and left hemithorax, with extensive blood supply from the T3 to T10 intercostal arteries, and demonstrate successful endovascular thoracic stent graft placement and coil embolization.

Nanopore-Based Target Sequence Detection.

The promise of portable diagnostic devices relies on three basic requirements: comparable sensitivity to established platforms, inexpensive manufacturing and cost of operations, and the ability to survive rugged field conditions. Solid state nanopores can meet all these requirements, but to achieve high manufacturing yields at low costs, assays must be tolerant to fabrication imperfections and to nanopore enlargement during operation. This paper presents a model for molecular engineering techniques that meets these goals with the aim of detecting target sequences within DNA. In contrast to methods that require precise geometries, we demonstrate detection using a range of pore geometries. As a result, our assay model tolerates any pore-forming method and in-situ pore enlargement. Using peptide nucleic acid (PNA) probes modified for conjugation with synthetic bulk-adding molecules, pores ranging 15-50 nm in diameter are shown to detect individual PNA-bound DNA. Detection of the CFTRΔF508 gene mutation, a codon deletion responsible for ∼66% of all cystic fibrosis chromosomes, is demonstrated with a 26-36 nm pore size range by using a size-enhanced PNA probe. A mathematical framework for assessing the statistical significance of detection is also presented.

Immune Checkpoint Inhibitors: New Insights and Current Place in Cancer Therapy.

The treatment of cancer has largely relied on killing tumor cells with nonspecific cytotoxic therapies and radiotherapy. This approach, however, has limitations including severe systemic toxicities, bystander effects on normal cells, recurrence of drug-resistant tumor cells, and the inability to target micrometastases or subclinical disease. An increased understanding of the critical role of the immune system in cancer development and progression has led to new treatment strategies using various immunotherapies. It is now recognized that established tumors have numerous mechanisms of suppressing the antitumor immune response including production of inhibitory cytokines, recruitment of immunosuppressive immune cells, and upregulation of coinhibitory receptors known as immune checkpoints. This review focuses on the immune checkpoint inhibitors, a novel class of immunotherapy first approved in 2011. Our objective is to highlight similarities and differences among the three immune checkpoint inhibitors approved by the U.S. Food and Drug Administration-ipilimumab, pembrolizumab, and nivolumab-to facilitate therapeutic decision making. We conducted a review of the published literature and conference proceedings and present a critical appraisal of the clinical evidence supporting their use in the treatment of metastatic melanoma and advanced squamous non-small cell lung cancer (NSCLC). We also compare and contrast their current place in cancer therapy and patterns of immune-related toxicities, and discuss the role of dual immune checkpoint inhibition and strategies for the management of immune-related adverse events. The immune checkpoint inhibitors have demonstrated a dramatic improvement in overall survival in patients with advanced melanoma and squamous NSCLC, along with acceptable toxicity profiles. These agents have a clear role in the first-line treatment of advanced melanoma and in the second-line treatment of advanced squamous NSCLC.

Axillary Lymph Node Burden in Invasive Breast Cancer: A Comparison of the Predictive Value of Ultrasound-Guided Needle Biopsy and Sentinel Lymph Node Biopsy.

BACKGROUND: Recent studies suggest that axillary lymph node dissection (ALND) may be omitted in select breast cancer patients with a positive sentinel lymph node biopsy (SLNB). As we trend away from ALND, we must understand the burden of axillary disease among various patient subgroups. For patients with positive nodes determined using ultrasound-guided needle biopsy (USNB), there are no data regarding the extent of axillary disease. PATIENTS AND METHODS: An institutional breast cancer registry was retrospectively reviewed to identify women with invasive cancer and a positive USNB/SLNB who had completion ALND. For statistical analysis, we used χ(2) and 1-way analysis of variance. RESULTS: One hundred ninety-nine USNB-positive (USNB(+)) patients and 434 SLNB(+) patients were eligible for the study. Positive USNB patients were significantly older, had larger tumors, and were more likely to be estrogen receptor-negative/progesterone receptor-negative and HER2/neu(+) than SLNB(+) patients. USNB(+) patients had much higher rates of N2 (33.2% vs. 12.4%; P < .05) and N3 (17.1% vs. 3.9%; P < .05) disease compared with SLNB(+) patients. Higher axillary disease burden was demonstrated in USNB patients who were clinically node negative and those who met Z11 criteria. CONCLUSION: Patients with invasive breast cancer with a positive node on USNB have a significantly greater burden of axillary disease compared with patients with a positive SLNB. USNB(+) patients represent a distinct patient population and further research is required to determine if these patients can be safely exempted from axillary dissection.