Hypercholesterolemia impairs collateral artery enlargement by ten-eleven translocation 1-dependent hematopoietic stem cell autonomous mechanism in a murine model of limb ischemia.

Objective: The extent of collateral artery enlargement determines the risk of limb loss due to peripheral arterial disease. Hypercholesterolemia impairs collateral artery enlargement, but the underlying mechanism remains poorly characterized. This study tests the hypothesis that hypercholesterolemia impairs collateral artery enlargement through a ten-eleven translocation 1 (Tet1)-dependent hematopoietic stem cell (HSC)-autonomous mechanism that increases their differentiation into proinflammatory Ly6Chi monocytes and restricts their conversion into proangiogenic Ly6Clow monocytes. Methods: To test our hypothesis, we induced limb ischemia and generated chimeric mouse models by transplanting HSCs from either wild-type (WT) mice or hypercholesterolemic mice into lethally irradiated WT recipient mice. Results: We found that the lethally irradiated WT recipient mice reconstituted with HSCs from hypercholesterolemic mice displayed lower blood flow recovery and collateral artery enlargement that was nearly identical to that observed in hypercholesterolemic mice, despite the absence of hypercholesterolemia and consistent with an HSC-autonomous mechanism. We showed that hypercholesterolemia impairs collateral artery enlargement by a Tet1-dependent mechanism that increases HSC differentiation toward proinflammatory Ly6Chi monocytes and restricts the conversion of Ly6Chi monocytes into proangiogenic Ly6Clow monocytes. Moreover, Tet1 epigenetically reprograms monocyte gene expression within the HSCs. Restoration of Tet1 expression in HSCs of hypercholesterolemic mice restores WT collateral artery enlargement and blood flow recovery after induction of hindlimb ischemia. Conclusions: These results show that hypercholesterolemia impairs collateral artery enlargement by a novel Tet1-dependent HSC-autonomous mechanism that epigenetically reprograms monocyte gene expression within the HSCs.

Physical activity regulates the immune response to breast cancer by a hematopoietic stem cell-autonomous mechanism.

Physical activity is a modifiable lifestyle factor that is associated with a decreased risk for the development of breast cancer. While the exact mechanisms for the reduction in cancer risk due to physical activity are largely unknown, it is postulated that the biological reduction in cancer risk is driven by improvements in inflammation and immune function with exercise. Hematopoietic stem cells (HSCs) are the progenitor for all of the cells of the immune system and are involved in cancer immunosurveillance through differentiation into cytotoxic cell population. In this study, we investigate the role of physical activity (PA) in a spontaneously occurring model of breast cancer over time, with a focus on tumor incidence, circulating and tumor-infiltrating immune cells as well gene expression profiles of tumors and hematopoietic stem cells. Furthermore, we show that, in addition to a direct effect of PA on the immune cells of tumor-bearing mice, PA reduces the oxidative stress in HSCs of wildtype and tumor-bearing mice, and by doing so, alters the differentiation of the HSCs towards T cells in order to enhance cancer immunosurveillance.

A distinct class of hematopoietic stem cells develop from the human yellow bone marrow.

Aging and metabolic diseases are accompanied by systemic inflammation, but the mechanisms that induce this state are not known. We developed a human bone-marrow organoid system to explore mechanisms underlying metabolic-disease associated systemic inflammation. We find that a distinct type of hematopoietic stem cell (HSC) develops in the adipose-rich, yellow bone marrow, which is known to gradually replace the hematopoietic red marrow as we age and during metabolic disease. Unlike HSCs derived from the red bone marrow, HSCs derived from the yellow bone marrow have higher proliferation rates, increase myeloid differentiation, skew towards pro-inflammatory M1 macrophage differentiation, and express a distinct transcriptomic profile associated with responsiveness to wounding. Yellow marrow-derived HSCs express higher levels of the leptin receptor, which we find to be further increased in patients with type 2 diabetes. Our work demonstrates that the human long bone yellow marrow is a niche for a distinct class of HSCs which could underlie hematopoietic dysfunction during aging and metabolic disease processes suggesting a shared inflammaging mechanism.

Evolution of fenestrated/branched endovascular aortic aneurysm repair complexity and outcomes at an organized center for the treatment of complex aortic disease.

BACKGROUND: Fenestrated/branched endovascular aneurysm repair (F/BEVAR) volume has increased rapidly, with favorable outcomes at centers of excellence. We evaluated changes over time in F/BEVAR complexity and associated outcomes at a single-center complex aortic disease program. METHODS: Prospectively collected data of all F/BEVAR (definition: requiring ≥1 fenestration/branch), procedures performed in an institutional review board-approved registry and/or physician-sponsored investigational device exemption trial (IDE# G130210), were reviewed (11/2010-2/2019). Patients were stratified by surgery date into thirds: early experience, mid experience, and recent experience. Patient and operative characteristics, aneurysm morphology, device types, perioperative and midterm outcomes (survival, freedom from type I or III endoleak, target artery patency, freedom from reintervention), were compared across groups. RESULTS: For 252 consecutive F/BEVARs (early experience, n = 84, mid experience, n = 84, recent experience, n = 84), 194 (77%) company-manufactured custom-made devices, 11 (4.4%) company-manufactured off-the-shelf devices, and 47 (19%) physician-modified devices, were used to treat 5 (2.0%) common iliac, 97 (39%) juxtarenal, 31 (12%) pararenal, 116 (46%) thoracoabdominal, and 2 (0.8%) arch aneurysms. All patients had follow-up for 30-day events. The mean follow-up time for the entire cohort was 589 days (interquartile range, 149-813 days). On 1-year Kaplan-Meier analysis, survival was 88%, freedom from type I or III endoleak was 91%, and target vessel patency was 92%. When stratified by time period, significant differences included aneurysm extent (thoracoabdominal, 33% early experience, 40% mid experience, and 64% recent experience; P < .001) and target vessels per case (four-vessel case, 31% early experience, 39% mid experience, and 67% recent experience; P < .0001). There was no difference, but a trend toward improvement, in composite 30-day events (early experience, 39%; mid experience, 23%; recent experience, 27%; P = .05). On Kaplan-Meier analysis, there was no difference in survival (P = .19) or target artery patency (P = .6). There were differences in freedom from reintervention (P < .01) and from type I or III endoleak (P = .02), with more reinterventions in the early experience, and more endoleaks in the recent period. CONCLUSIONS: Despite increasing repair complexity, there has been no significant change in perioperative complications, overall survival, or target artery patency, with favorable outcomes overall. Type I or III endoleaks remain a significant limitation, with increased incidence as the number of branch arteries incorporated into the repairs has increased.

Hypercholesterolemia Accelerates the Aging Phenotypes of Hematopoietic Stem Cells by a Tet1-Dependent Pathway.

Hypercholesterolemia accelerates the phenotypes of aging in hematopoietic stem cells (HSCs). As yet, little is known about the underlying mechanism. We found that hypercholesterolemia downregulates Ten eleven translocation 1 (Tet1) in HSCs. The total HSC population was increased, while the long-term (LT) population, side population and reconstitution capacity of HSCs were significantly decreased in Tet1-/- mice. Expression of the Tet1 catalytic domain in HSCs effectively restored the LT population and reconstitution capacity of HSCs isolated from Tet1-/- mice. While Tet1 deficiency upregulated the expression of p19 and p21 in HSCs by decreasing the H3K27me3 modification, the restoration of Tet1 activity reduced the expression of p19, p21 and p27 by restoring the H3K27me3 and H3K36me3 modifications on these genes. These results indicate that Tet1 plays a critical role in maintaining the quiescence and reconstitution capacity of HSCs and that hypercholesterolemia accelerates HSC aging phenotypes by decreasing Tet1 expression in HSCs.

Acute Limb Ischemia in a 26-Year-Old Man Presenting with an Idiopathic Thrombosed Popliteal Artery Aneurysm.

Popliteal artery aneurysms (PAAs) are the most common peripheral arterial aneurysms and develop almost exclusively (>90%) in men who have a history of tobacco abuse at an average age of 65 years. Most PAAs are caused by chronic inflammation secondary to atherosclerotic disease; other nondegenerative causes of PAAs include arterial trauma, infection, Behçet's disease, medial fibromuscular dysplasia, or popliteal artery entrapment. Few case reports have been published on idiopathic congenital PAAs. We report a case of a 26-year-old man who presented with progressive claudication and subsequent acute limb ischemia due to the thrombosis of a large idiopathic PAA. Our case demonstrates that the differential diagnosis of young adult or pediatric patients presenting with signs of acute limb ischemia or claudication should include a symptomatic PAA.

Impact of acute kidney injury on long-term outcomes after fenestrated and branched endovascular aortic aneurysm repair.

OBJECTIVE: Acute kidney injury (AKI) has been identified as a common complication after fenestrated and branched endovascular aneurysm repair (F/BEVAR), occurring in 5% to 29% of patients. Predictors of AKI and its impact on long-term outcomes remain unknown. We sought to identify independent predictors of AKI and its effect on long-term survival after F/BEVAR. METHODS: A single-institution retrospective review of all consecutive F/BEVAR procedures was performed (November 2010-September 2018). Data were collected prospectively through an Institutional Review Board-approved registry and a physician-sponsored investigational device exemption clinical trial (G130210). AKI was defined as a decrease in estimated glomerular filtration rate by >30% from baseline, within 30 days postoperatively. The cohort was stratified according to whether a patient experienced AKI. Demographics, operative details, perioperative complications, and length of stay between groups were compared. The primary outcome, long-term survival, was assessed with Kaplan-Meier analysis and Cox proportional hazards modeling. Independent predictors of AKI were identified using logistic regression. RESULTS: Among 219 consecutive F/BEVAR patients, AKI occurred in 41 patients (19%) and was the most common 30-day complication observed. Whereas preoperative creatinine concentration, estimated glomerular filtration rate, and target renal artery stenosis >50% did not predict AKI, the occurrence of intraoperative complications did correlate with AKI (37% vs 7.3%; P < .01). By 30 days, AKI resolved in 7 (17%) patients, persisted without need for dialysis in 26 (64%), and progressed to dialysis in 5 (12%); the remaining 3 (7%) patients died. Survival at 30 days was significantly lower in the AKI group (92.7% vs 98.9%; P = .047), and this difference persisted at 1 year (68% vs 87%; log-rank, P <.01) and 3 years (44% vs 60%; log-rank, P = .04). On multivariable modeling, AKI increased the hazard of death nearly twofold (hazard ratio, 1.92; 95% confidence interval [CI], 1.11-3.23; P = .019). Independent predictors of AKI on multivariable logistic regression were intraoperative complications (odds ratio, 4.10; 95% CI, 1.61-10.42; P < .01) and increased operating room time (odds ratio, 1.56; 95% CI, 1.22-2.00; P < .01). CONCLUSIONS: In our 8-year experience of F/BEVAR, AKI was the most common postoperative complication observed in nearly 20% of patients. AKI after F/BEVAR is associated with decreased short- and long-term survival. Whether AKI is causative or just associated with decreased survival remains to be elucidated. Further study is needed to determine whether the independent predictors of AKI, including intraoperative complications and operating room time, are generalizable across all centers performing F/BEVAR and to investigate how we might further mitigate this common and serious complication.

Increasing the number of integrated vascular surgery residency positions is important to address the impending shortage of vascular surgeons in the United States.

OBJECTIVE: The demand for vascular surgeons is expected to far exceed the current supply. In an attempt to decrease the training duration and to address the impending shortage, integrated vascular surgery residencies were approved and have expanded nationally. Meanwhile, vascular fellowships have continued to matriculate approximately 120 trainees annually. We sought to evaluate the supply and demand for integrated vascular residency positions as well as changes in the quality of applicants. METHODS: We conducted a retrospective review of national data compiled by the Association of American Medical Colleges and the National Resident Matching Program regarding integrated vascular surgery residency programs (2008-2015) and fellowships (2007-2016). Variables reviewed included the total number of applicants, sex, U.S. vs international medical school enrollment, applications per program, and applicants per position. In addition, we conducted a retrospective review of applicants to the University of Massachusetts Medical School integrated vascular surgery residency program from 2008 to 2015 to examine these variables and United States Medical Licensing Examination Step 1 and Step 2 CK scores over time. RESULTS: The number of vascular surgery integrated residency positions increased from 4 in 2008 to 56 in 2015. Concurrently, the number of integrated residency applicants grew from 112 in 2008 to 434 in 2015. This increase has been predominantly driven by a 575% increase in U.S. graduate applicants and a 170% increase in women applicants. The percentage of international medical graduates has decreased by 17% during the study period. The total number of applicants per residency position increased from 5.9 to 7.8. Meanwhile, the number of vascular surgery fellowship positions remained stable with an applicant to position ratio near 1:1. At the University of Massachusetts Medical School, the mean United States Medical Licensing Examination Step 1 (226 to 235) and Step 2 CK (237 to 243) scores among integrated residency applicants have improved annually and typically exceed the national average among U.S. applicants who have matched in their preferred specialty. CONCLUSIONS: Since the approval of a primary certificate in vascular surgery and the subsequent rollout of integrated vascular residency programs, the number of residency programs and the quality of residency applicants have continued to increase. Demand from medical school applicants vastly outweighs the current supply of training positions by eightfold. In contrast, demand from fellowship applicants matches the supply of fellowship positions. The matriculation of additional trainees must be met with continued expansion of the integrated vascular surgery residency pathway to manage future public health needs.

Reinterventions after fenestrated or branched endovascular aortic aneurysm repair.

OBJECTIVE: Reinterventions after fenestrated or branched endovascular aneurysm repair (F/B-EVAR) are sometimes necessary to maintain aneurysm exclusion or endograft and target artery patency. These reinterventions are nontrivial, potentially associated with morbidity, mortality, and resource utilization. Whereas rates, types, and outcomes of reintervention after infrarenal EVAR have been well described, they have not been well described for F/B-EVAR. We sought to characterize the morbidity, mortality, and resource utilization due to reinterventions after F/B-EVAR. METHODS: All F/B-EVAR variables collected prospectively through a single-institution, Institutional Review Board-approved registry, which included patients enrolled in a physician-sponsored investigational device exemption trial (G130210), were reviewed (November 2010-December 2016). Reinterventions were defined as any procedure that was aneurysm related, device related, or target artery related. For patients with more than one reintervention, each intervention occurrence was treated as a discrete event. Reintervention type, indication, timing (perioperative, days 0-30; short term, days 31-180; midterm, >180 days), inpatient/outpatient, length of stay, and morbidity/mortality were recorded. Reintervention success was defined as resolution of the indication. RESULTS: Among 123 consecutive F/B-EVARs (mean follow-up, 25 months), 32 patients (25%) underwent 54 reinterventions (one reintervention, 20 (63%) patients; two reinterventions, 6 (19%) patients; three reinterventions, 4 (13%) patients; four reinterventions, 1 (3.1%) patient; and six reinterventions, 1 (3.1%) patient). The most frequent indications were type III endoleaks (n = 15 [28%]), target artery occlusions (n = 7 [13%]), and stenoses (n = 6 [11%]). These were performed in the perioperative, short-term, and midterm time frames 17%, 41%, and 43% of the time, respectively. Reinterventions were percutaneous (67%), inpatient procedures (61%), with median length of stay of 5 days. Of the 32 reintervention patients, 4 experienced access site complications and 4 died <30 days after reintervention (3 were adjudicated as not aneurysm related/not reintervention related). In 31 of 32 (97%) patients, reintervention success was achieved. CONCLUSIONS: Reinterventions after F/B-EVAR were necessary in 26% of patients, most commonly for type III endoleaks and target artery complications. Whereas all but one reintervention was successful, many of these required complex procedures with significant morbidity and mortality. Development of strategies to eliminate type III endoleaks by improving component junction integrity and to ensure target artery primary patency are key next steps in the evolution of F/B-EVAR.

Type 2 diabetes impairs the ability of skeletal muscle pericytes to augment postischemic neovascularization in db/db mice.

Peripheral artery disease is an atherosclerotic occlusive disease that causes limb ischemia and has few effective noninterventional treatments. Stem cell therapy is promising, but concomitant diabetes may limit its effectiveness. We evaluated the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization in wild-type and type 2 diabetic (T2DM) mice. Wild-type C57BL/6J and leptin receptor spontaneous mutation db/db T2DM mice underwent unilateral femoral artery excision to induce limb ischemia. Twenty-four hours after ischemia induction, CD45-CD34-CD146+ skeletal muscle pericytes or vehicle controls were transplanted into ischemic hindlimb muscles. At postoperative day 28, pericyte transplantation augmented blood flow recovery in wild-type mice (79.3 ± 5% vs. 61.9 ± 5%; P = 0.04), but not in T2DM mice (48.6% vs. 46.3 ± 5%; P = 0.51). Pericyte transplantation augmented collateral artery enlargement in wild-type (26.7 ± 2 µm vs. 22.3 ± 1 µm, P = 0.03), but not T2DM mice (20.4 ± 1.4 µm vs. 18.5 ± 1.2 µm, P = 0.14). Pericyte incorporation into collateral arteries was higher in wild-type than in T2DM mice ( P = 0.002). Unexpectedly, pericytes differentiated into Schwann cells in vivo. In vitro, Insulin increased Nox2 expression and decreased tubular formation capacity in human pericytes. These insulin-induced effects were reversed by N-acetylcysteine antioxidant treatment. In conclusion, T2DM impairs the ability of pericytes to augment neovascularization via decreased collateral artery enlargement and impaired engraftment into collateral arteries, potentially via hyperinsulinemia-induced oxidant stress. While pericytes show promise as a unique form of stem cell therapy to increase postischemic neovascularization, characterizing the molecular mechanisms by which T2DM impairs their function is essential to achieve their therapeutic potential.

Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages.

People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1, PU.1, and Klf4. This HSC-autonomous mechanism reduces the number of wound macrophages and skews their polarization towards M1 macrophages. These findings reveal a novel inflammatory mechanism by which a metabolic disorder induces an epigenetic mechanism in HSCs, which predetermines the gene expression of terminally differentiated inflammatory cells that controls their number and function.

Fenestrated endovascular aortic aneurysm repair using physician-modified endovascular grafts versus company-manufactured devices.

OBJECTIVE: Fenestrated endografts are customized, patient-specific endovascular devices with potential to reduce morbidity and mortality of complex aortic aneurysm repair. With approval from the U.S. Food and Drug Administration, our center began performing fenestrated endovascular aneurysm repair through a physician-sponsored investigational device exemption (IDE #G130210), using both physician-modified endografts (PMEGs) and company-manufactured devices (CMDs). Because these techniques are associated with specific advantages and disadvantages, we sought to investigate differences in outcomes between PMEG and CMD cases. METHODS: A single-institution retrospective review of all fenestrated endovascular aneurysm repairs was performed. The cohort was analyzed by device type (PMEG or CMD) after matching of cases on the basis of (1) number of target vessels intended for treatment, (2) extent of aneurysm, (3) aneurysm diameter, (4) device configuration, and (5) date of operation. Outcomes of ruptures, common iliac artery aneurysms, and aortic arch aneurysms were excluded. Demographics, operative details, perioperative complications, length of stay, and reinterventions were compared. For patients with >1 year of follow-up time, survival, type I or type III endoleak rate, target artery patency, and reintervention rate were estimated using the Kaplan-Meier method. RESULTS: Between November 30, 2010, and July 30, 2016, 82 patients were identified and matched. The cohort included 41 PMEG and 41 CMD patients who underwent repair of 38 juxtarenal (PMEG, 17; CMD, 21; P = .38), 14 pararenal (PMEG, 6; CMD, 8; P = .56), and 30 thoracoabdominal type I to type IV (PMEG, 18; CMD, 12; P = .17) aneurysms. There were significant differences in presentation requiring urgent aneurysm repair (PMEG, 9; CMD, 0; P = .002), total fluoroscopy time (PMEG, 76 minutes; CMD, 61 minutes; P = .02), volume of contrast material used (PMEG, 88 mL; CMD, 70 mL; P = .02), in-operating room to out-of-operating room time (PMEG, 391 minutes; CMD, 319 minutes; P = .001), incision to surgery end time (PMEG, 276 minutes; CMD, 224 minutes; P = .002), and 1-year reintervention rate (PMEG, 37%; CMD, 13%; log-rank P = .04). No differences in perioperative complications, overall length of stay, type I or type III endoleak, or survival were observed between PMEG and CMD. For the entire cohort including both PMEG and CMD, the overall rate of any 30-day postoperative complication was 39%, and the Kaplan-Meier estimate of survival at 1 year was 86%. CONCLUSIONS: In this single-institution experience of fenestrated endovascular aneurysm repair, the primary differences between PMEG and CMD related only to operative metrics and the need for postoperative reinterventions. No statistically significant advantage was found for one approach over the other; we therefore cannot conclude that one approach is better than the other. Both remain viable options that may compare favorably with open repair of complex aortic aneurysms. Further studies are necessary to determine whether this relative equivalence represents a type II error or lack of long-term durability data or whether true equivalence between PMEG and CMD approaches exists.

Hypercholesterolemia Increases Colorectal Cancer Incidence by Reducing Production of NKT and γδ T Cells from Hematopoietic Stem Cells.

Obesity will soon surpass smoking as the most preventable cause of cancer. Hypercholesterolemia, a common comorbidity of obesity, has been shown to increase cancer risk, especially colorectal cancer. However, the mechanism by which hypercholesterolemia or any metabolic disorder increases cancer risk remains unknown. In this study, we show that hypercholesterolemia increases the incidence and pathologic severity of colorectal neoplasia in two independent mouse models. Hypocholesterolemia induced an oxidant stress-dependent increase in miR101c, which downregulated Tet1 in hematopoietic stem cells (HSC), resulting in reduced expression of genes critical to natural killer T cell (NKT) and γδ T-cell differentiation. These effects reduced the number and function of terminally differentiated NKT and γδ T cells in the thymus, the colon submucosa, and during early tumorigenesis. These results suggest a novel mechanism by which a metabolic disorder induces epigenetic changes to reduce lineage priming of HSC toward immune cells, thereby compromising immunosurveillance against cancer. Cancer Res; 77(9); 2351-62. ©2017 AACR.

Trends in use of the only Food and Drug Administration-approved commercially available fenestrated endovascular aneurysm repair device in the United States.

BACKGROUND: Fenestrated endografts are customized, patient-specific, endovascular devices with potential to significantly reduce morbidity and mortality of short-neck infrarenal and juxtarenal abdominal aortic aneurysm repair. The Zenith fenestrated endovascular graft (ZFEN) for abdominal aortic aneurysms (Cook Medical, Bloomington, Ind), Food and Drug Administration-approved in 2012, remains the only fenestrated device available in the United States. This technology is among the most technically complex catheter-based procedures and, therefore, inherently associated with serious risk for device-related complications. We sought to define patterns of physician and hospital adoption of ZFEN. METHODS: Deidentified datasets containing numbers of physicians trained, orders by physicians and hospitals, and designs (fenestration/scallop configuration) was provided for U.S. ZFEN devices ordered (April 2012-August 2015). We evaluated the number of physicians trained, the number of devices ordered, hospital characteristics, and fenestration/scallop design configurations. Cook Medical assembled the datasets but played no role in study design, analysis, or interpretation of data. RESULTS: Between April 2012 and August 2015, 553 physicians attended formal ZFEN training sessions, 388 (70%) of whom ordered a total of 2669 devices. An increase in orders per month (nine in June 2012 and 91 in August 2015, 911% growth; P < .001) and in number of physicians ordering per month (eight in June 2012 and 62 in August 2015, 675% growth; P < .001) was observed. Teaching hospitals, representing all U.S. regions (Midwest 927, 35%; South 799, 30%; Northeast 547, 20%; West 396, 15%), accounted for 1703 (64%) ZFEN orders. Of 553 trained physicians, 165 (30%) ordered no devices, 116 (21%) ordered 1 device, 144 (26%) ordered 2-5 devices, 61 (11%) ordered 6-10 devices, 39 (7%) ordered 11-20, and 28 (5%) ordered >20 devices. For physicians contributing >6 months of data (n = 336), the average number of devices ordered per year was three (standard deviation, 4); 272 (81%) ordered ≤ 5 devices/year, 15 (4.5%) ordered 11-20 devices/year, and 3 (0.9%) ordered >20 devices/year. Of devices with design details available (2618 of 2669; 98%), most common designs were 2 small fenestrations/1 scallop (1443; 55%), 2 small fenestrations/1 large fenestration (568; 22%), 1 small fenestration/1 scallop (173, 6.6%), and 2 small fenestrations (169; 6.5%). The average number of target vessels incorporated in each design was 2.7/device; 2071 (79%) incorporated three, 398 (15%) incorporated two. CONCLUSIONS: Since 2012, ZFEN has demonstrated a ninefold increase in monthly orders, with 553 physicians trained. Unlike the experience of rapid dissemination seen with infrarenal endografts, only 28 (5%) physicians have ordered >20, whereas 165 (30%) have ordered none, and 272 (81%) ordered ≤ 5 devices/year. Assuming that volume, in general, correlates with outcomes, this adoption pattern raises questions whether fenestrated technology should be regionalized to high-volume centers.

Outcomes of fenestrated and branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms.

BACKGROUND: More than 80% of infrarenal aortic aneurysms are treated by endovascular repair. However, adoption of fenestrated and branched endovascular repair for complex aortic aneurysms has been limited, despite high morbidity and mortality associated with open repair. There are few published reports of consecutive outcomes, inclusive of all fenestrated and branched endovascular repairs, starting from the inception of a complex aortic aneurysm program. Therefore, we examined a single center's consecutive experience of fenestrated and branched endovascular repair of complex aortic aneurysms. METHODS: This is a single-center, prospective, observational cohort study evaluating 30-day and 1-year outcomes in all consecutive patients who underwent fenestrated and branched endovascular repair of complex aortic aneurysms (definition: requiring one or more fenestrations or branches). Data were collected prospectively through an Institutional Review Board-approved registry and a physician-sponsored investigational device exemption clinical trial (G130210). RESULTS: We performed 100 consecutive complex endovascular aortic aneurysm repairs (November 2010 to March 2016) using 58 (58%) commercially manufactured custom-made devices and 42 (42%) physician-modified devices to treat 4 (4%) common iliac, 42 (42%) juxtarenal, 18 (18%) pararenal, and 36 (36%) thoracoabdominal aneurysms (type I, n = 1; type II, n = 4; type III, n = 12; type IV, n = 18; arch, n = 1). The repairs included 309 fenestrations, branches, and scallops (average of 3.1 branch arteries/case). All patients had 30-day follow-up for 30-day event rates: three (3%) deaths; six (6%) target artery occlusions; five (5%) progressions to dialysis; eight (8%) access complications; one (1%) paraparesis; one (1%) bowel ischemia; and no instances of myocardial infarction, paralysis, or stroke. Of 10 type I or type III endoleaks, 8 resolved (7 with secondary intervention, 1 without intervention). Mean follow-up time was 563 days (interquartile range, 156-862), with three (3%) patients lost to follow-up. On 1-year Kaplan-Meier analysis, survival was 87%, freedom from type I or type III endoleak was 97%, target vessel patency was 92%, and freedom from aortic rupture was 100%. Average lengths of intensive care unit stay and inpatient stay were 1.4 days (standard deviation, 3.3) and 3.6 days (standard deviation, 3.6), respectively. CONCLUSIONS: These results show that complex aortic aneurysms can now be treated with minimally invasive fenestrated and branched endovascular repair. Endovascular technologies will likely continue to play an increasingly important role in the management of patients with complex aortic aneurysm disease.

An intensive vascular surgical skills and simulation course for vascular trainees improves procedural knowledge and self-rated procedural competence.

BACKGROUND: Surgical skills and simulation courses are emerging to meet the demand for vascular simulation training for vascular surgical skills, but their educational effect has not yet been described. We sought to determine the effect of an intensive vascular surgical skills and simulation course on the procedural knowledge and self-rated procedural competence of vascular trainees and to assess participant feedback regarding the course. METHODS: Participants underwent a 1.5-day course covering open and endovascular procedures on high-fidelity simulators and cadavers. Before and after the course, participants completed a written test that assessed procedural knowledge concerning index open vascular and endovascular procedures. Participants also assessed their own procedural competence in open and endovascular procedures on a 5-point Likert scale (1: no ability to perform, 5: performs independently). Scores before and after the course were compared among postgraduate year (PGY) 1-2 and PGY 3-7 trainees. Participants completed a survey to rate the relevance and realism of open and endovascular simulations. RESULTS: Fifty-eight vascular integrated residents and vascular fellows (PGY 1-7) completed the course and all assessments. After course participation, procedural knowledge scores were significantly improved among PGY 1-2 residents (50% correct before vs 59% after; P < .0001) and PGY 3-7 residents (52% correct before vs 63% after; P = .003). Self-rated procedural competence was significantly improved among PGY 1-2 (2.2 ± 0.1 before vs 3.1 ± 0.1 after; P < .0001) and PGY 3-7 (3.0 ± 0.1 before vs 3.7 ± 0.1 after; P ≤ .0001). Self-rated procedural competence significantly improved for both endovascular (2.4 ± 0.1 before vs 3.3 ± 0.1 after; P < .0001) and open procedures (2.7 ± 0.1 before vs 3.5 ± 0.1 after; P < .0001). More than 93% of participants reported they were "satisfied" or "very satisfied" with the relevance and realism of the open and endovascular simulations. All participants reported they would recommend the course to other trainees. CONCLUSIONS: This intensive vascular surgical skills and simulation course improved procedural knowledge concerning index open vascular and endovascular procedures among PGY 1-2 and PGY 3-7 trainees. The course also improved self-rated procedural competence across all levels of training for open and endovascular procedures. Trainees rated the value of a surgical skills and simulation course highly. These results support strong consideration for the implementation of similar intensive simulation and surgical skills courses with ongoing objective assessment of their educational effect.

Contemporary Management of Acute Aortic Occlusion Has Evolved but Outcomes Have Not Significantly Improved.

BACKGROUND: Most existing series of acute aortic occlusion (AAO) predate the changes in surgical and endovascular therapy of the last 2 decades. We examined the contemporary management and outcomes of AAO. METHODS: We reviewed consecutive patients with AAO at a tertiary referral center from 2004 to 2012. Outcomes were stratified and compared according to etiology and procedure performed. RESULTS: AAO in 29 patients was due to in situ thrombosis in 21 (72%) and embolism in 8 (28%) patients. Vascular patients with embolism were on average older (77 ± 7 vs. 66 ± 12 years, P = 0.02) and had higher rates of atrial fibrillation (100% vs. 20%, P = 0.0002) and congestive heart failure (75% vs. 0%, P = 0.0001) in comparison with those with in situ thrombosis. Neurologic deficit was present in 16 (55%) patients. Six patients (21%) presented with bilateral paresis/paralysis secondary to spinal cord or lumbosacral plexus ischemia, and primary neurologic etiology was investigated before vascular consultation was obtained in 4 of these 6 patients. Of the 29 patients, 28 (97%) underwent revascularization including transfemoral embolectomy (n = 6), transperitoneal aortoiliac thrombectomy (n = 2), axillobifemoral bypass (n = 10), aortobifemoral bypass (n = 6), and endovascular therapy including thrombolysis, angioplasty ± stenting (n = 4). In-hospital mortality was 31% and did not vary significantly according to etiology (embolism 38% vs. in situ thrombosis 29%, P = 0.67). In-hospital mortality varied widely according to procedure (transfemoral embolectomy 50%, aortoiliac thrombectomy 100%, axillobifemoral bypass 30%, aortobifemoral bypass 0%, and endovascular therapy 25%, P = 0.08). Major morbidity (59%), length of stay (8.6 ± 8.0 days), and discharge to a rehabilitation facility (50%) did not vary by etiology or procedure. At a media follow-up of 361 ± 460 days (range 3-2014), overall survival was 42%. There were no amputations among 20 survivors of initial hospitalization. CONCLUSIONS: AAO is now more commonly caused by in situ thrombosis rather than embolism. A high index of suspicion for AAO is required for prompt diagnosis and treatment, particularly when patients present with profound lower extremity neurologic deficit. In comparison with previous reports, the contemporary management of AAO includes increased use of axillobifemoral bypass and now involves endovascular revascularization, although a variety of open surgical procedures are utilized. However, the in-hospital mortality and morbidity of AAO has not decreased significantly over the last 2 decades and mid-term survival remains limited. Further study is required to identify strategies that improve outcomes after AAO.