Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease.

Antiamyloid antibodies have been used to reduce cerebral amyloid-beta (Aß) load in patients with Alzheimer's disease. We applied focused ultrasound with each of six monthly aducanumab infusions to temporarily open the blood-brain barrier with the goal of enhancing amyloid removal in selected brain regions in three participants over a period of 6 months. The reduction in the level of Aß was numerically greater in regions treated with focused ultrasound than in the homologous regions in the contralateral hemisphere that were not treated with focused ultrasound, as measured by fluorine-18 florbetaben positron-emission tomography. Cognitive tests and safety evaluations were conducted over a period of 30 to 180 days after treatment. (Funded by the Harry T. Mangurian, Jr. Foundation and the West Virginia University Rockefeller Neuroscience Institute.).

Surveillance duplex ultrasound prompted interventions after carotid endarterectomy.

OBJECTIVE: Current societal guidelines recommend duplex ultrasound (DUS) surveillance beyond 30 days after carotid endarterectomy (CEA) for patients with risk factors for restenosis or who underwent primary closure. However, the appropriate duration of this surveillance has not yet been identified, and the rate at which DUS surveillance prompts intervention is unknown. Multiple calls for decreasing health care spending that does not provide value, including unnecessary testing, have been made. The purpose of this study was to examine the rate of intervention prompted by surveillance DUS on the ipsilateral or contralateral carotid artery after CEA and determine the value of continued surveillance by determining the rate of DUS-prompted intervention. METHODS: A single-center, retrospective chart review of all patients older than 18 years who had undergone CEA from August 2009 to July 2022 was performed. Patients with at least one postoperative duplex in our Intersocietal Accreditation Council-accredited ultrasound lab were included. Exclusion criteria were patients with incomplete medical charts or patients who underwent a concomitant procedure. The primary end point was return to the operating room for subsequent intervention based on abnormal surveillance DUS findings. Secondary end points were the number of postoperative surveillance duplexes, duration of surveillance, and incidence of perioperative stroke. The study participant data were queried for patients who had a diagnosis of stroke that occurred following their procedure. RESULTS: A total 767 patients, accounting for 771 procedures, were included in this study, which resulted in 2145 ultrasound scans. A total of 40 (5.2%) patients required 44 subsequent interventions that were prompted by DUS surveillance scans. The average number of ultrasound scans per patient was 2.8 (range: 0-14), and the average duration of surveillance was 26.4 months (range: 0-155 months). Of the 767 patients, 669 (87.2%) had a unilateral CEA. A total of 62 of 767 (8.1%) patients had planned endarterectomies on the contralateral side based on initial imaging, not prompted by interval DUS surveillance scans. Of 767 patients, 28 (3.7%) patients who underwent CEA had a subsequent procedure for progression of contralateral disease, which was prompted by duplex surveillance scans. The average duration between index CEA and intervention on contralateral carotid was 29.57 months (range: 3-81 months). A total of 11 patients, accounting for 12 procedures, underwent a subsequent procedure for restenosis of their ipsilateral carotid, prompted by duplex surveillance scans. The average duration between index CEA and reintervention on the ipsilateral carotid was 17.9 months (range: 4-70 months). Three of 767 (0.4%) patients in total were identified as having a perioperative stroke. CONCLUSIONS: The overall rate of ipsilateral reintervention after CEA is low. A small percentage of patients will progress their contralateral disease, ultimately requiring surgical intervention. These data suggest that regular duplex surveillance after CEA is warranted for patients with at least moderate contralateral disease; however, the yield is low for ipsilateral restenosis after 36 months based on this single institution study. Further study is needed to better delineate which patients need follow-up to decrease unnecessary testing while still targeting patients most at risk of restenosis or contralateral progression of disease.

Mortality analysis of endovascular aneurysm sealing versus endovascular aneurysm repair.

BACKGROUND: Endovascular aneurysm sealing (EVAS), using the Nellix endovascular aneurysm sealing system, has been associated with high reintervention and migration rates. However, prior reports have suggested that EVAS might be related to a lower all-cause mortality compared with endovascular aneurysm repair (EVAR). In the present study, we examined the 5-year all-cause mortality trends after EVAS and EVAR. METHODS: We compared the 333 EVAS patients in the EVAS-1 Nellix U.S. investigational device exemption trial with 16,497 infrarenal EVAR controls from the Vascular Quality Initiative, treated between 2014 and 2016, after applying the exclusion criteria from the investigational device exemption trial (ie, hemodialysis, creatinine >2.0 mg/dL, rupture). As a secondary analysis, we stratified the patients by aneurysm diameter (<5.5 cm and ≥5.5 cm). We calculated propensity scores after adjusting for demographics, comorbidities, and anatomic characteristics and applied inverse probability weighting to compare the risk-adjusted long-term mortality using Kaplan-Meier and Cox regression analyses. RESULTS: After weighting, the EVAS group had experienced similar 5-year mortality compared with the controls from the Vascular Quality Initiative (EVAS vs EVAR, 18% vs 14%; hazard ratio [HR], 1.1; 95% confidence interval [CI], 0.71-1.7; P = .70). The subgroup analysis demonstrated that for patients with an aneurysm diameter of <5.5 cm, EVAS was associated with higher 5-year mortality compared with EVAR (19% vs 11%; HR, 2.4; 95% CI, 1.7-4.7; P = .013). In patients with an aneurysm diameter of ≥5.5 cm, EVAS was associated with lower mortality within the first 2 years (2-year mortality: HR, 0.29; 95% CI, 0.13-0.62; P = .002). However, compared with EVAR, EVAS was associated with higher mortality between 2 and 5 years (HR, 1.9; 95% CI, 1.2-3.0; P = .005), with no mortality difference at 5 years (18% vs 17%; HR, 0.82; 95% CI, 0.4-1.4; P = .46). CONCLUSIONS: Within the overall population, EVAS was associated with similar 5-year mortality compared with EVAR. EVAS was associated with higher mortality for those with small aneurysms (<5.5 cm). For those with larger aneurysms (≥5.5 cm), EVAS was initially associated with lower mortality within the first 2 years, although this advantage was lost thereafter, with higher mortality after 2 years. Future studies are required to evaluate the specific causes of death and to elucidate the potential beneficial mechanism behind sac obliteration that leads to this potential initial survival benefit. This could help guide the development of future grafts with better proximal fixation and sealing that also incorporate sac obliteration.

Validating the Clinical Value of Temporal Artery Biopsy.

BACKGROUND: Giant cell arteritis (GCA) is a potentially devastating disease that may require treatment with high-dose steroids. Traditionally, diagnosis requires patients to meet at least 3 of 5 clinical criteria, one of which is a positive temporal artery biopsy (TAB). Vascular surgeons are often asked to perform TAB though it is not necessarily required for diagnosis or management. This study aimed to determine if TAB results altered management of patients with a concern for GCA by changing steroid use postoperatively in our health care system. METHODS: A retrospective review at a single-center tertiary care hospital was performed between 2007 and 2018. The inclusion criteria were patients greater than 18 years old with complete steroid treatment records who underwent a temporal artery biopsy due to concern for GCA. Steroid use and duration of treatment both pre- and post-operative were collected and analyzed. RESULTS: Eighty-three of 117 cases reviewed met inclusion criteria. Ninety-one percent (76) of patients had a negative biopsy. Twenty-nine percent (23) of negative biopsies met criteria for GCA prior to biopsy. Of those with a negative biopsy, steroids were continued in 68% (52) of patients after 30 days, 49% (37) after 90 days and 45% (34) after 180 days. Steroids were never started in 11% (6). One patient with a positive biopsy was discontinued on steroids due to intolerance. There was no statistically significant difference in duration of steroids between those with a positive and negative biopsy (average 610 and 787 days respectively; P = 0.682). Average follow up was 33 months. DISCUSSION: The duration of steroid use for patients with concern for GCA was not found to be altered by the performance of a TAB at our institution. Given the extremely low yield and absence of impact on steroid duration, TAB is not a useful diagnostic test at our institution. Similar reviews are recommended to determine the utility of TAB at other institutions that may differ in patient population or prescribing practices.

Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound.

The blood-brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer's disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions.

A forensic analysis of spin-off and downstream revenue in an academic vascular surgery practice: Unveiling the "vascular X-factor" in a tertiary health care system.

BACKGROUND: Owing to the high level of patient and operative complexity, vascular surgery represents a major driver for elevating case mix index within health care institutions. Although several specialty services are recruited in the care of these patients, it has been difficult to quantify the financial impact of these vascular patient across the health care enterprise. This study aims to quantify all revenues attributable to the introduction of vascular surgery patients within a tertiary health care system. METHODS: Billing data from 2017 to 2020 for all new vascular surgery patients entering a tertiary health care system were captured, and segregated by encounter type--inpatient versus outpatient. Within these major categories, vascular revenue streams were analyzed according to procedural pathology types, such as aneurysm, peripheral vascular disease, cerebrovascular, and venous. Subsequent revenues for nonvascular services were also captured for both inpatient and outpatient encounters that were tied to the initial vascular surgical encounter. Revenues attributable to vascular patients were analyzed and followed with respect to other hospital service lines. RESULTS: A total of 1115 new patients were introduced to the health care system for the first time by vascular surgery. These new patients generated more than $26 million in gross revenue and more than $10 million in contribution margin to the hospital during this time interval in aggregate. From a procedural standpoint, aortic surgery generated more than $7.4 million in revenue and $2.9 million in health system contribution margin. Peripheral vascular disease contributed $7.3 million and $2.6 million in revenue and contribution margins, respectively. Aortic surgery cases generated the highest margin per encounter encompassing the total sum of contributions. Subtracting all revenue attributable to vascular billing (spin-off), new patients brought in by vascular generated $9.6 million in revenue and $4.3 million in contribution margin from other service lines. Vascular access procedures produced the greatest spin-off margin per encounter at $10,985, and ancillary inpatient/outpatient generated the greatest number of spin-off encounters (n = 597) and revenue ($8,181,708). CONCLUSIONS: Patients introduced by a tertiary care vascular surgery program produce a significant revenue/margin for the parent health care system. When considering the fiscal health of a vascular program within a tertiary health care system, spin-off and downstream revenue should be considered in terms of overall value.

Intraoperative blood pressure lability carries a higher risk of headache after carotid endarterectomy.

OBJECTIVE: Cerebral hyperperfusion syndrome (CHS) is a rare but potentially devastating complication after carotid endarterectomies (CEA). Its symptoms range from new-onset unilateral headache (HA) to intracranial hemorrhage (ICH). Risk factors for CHS in the literature to date have not yet yielded a consensus. This study examines intraoperative and postoperative blood pressure variations as potential risk factors for HA. METHODS: A single-center retrospective review at a tertiary care center from January 2010 to November 2019 was performed. Inclusion criteria were all patients undergoing CEA for symptomatic or asymptomatic carotid disease. Patients with incomplete charts were excluded. Primary endpoints were new-onset unilateral HA or postoperative ICH. Data on intraoperative and postoperative mean arterial pressure (MAP), systolic blood pressure (SBP), the mode of endarterectomy, shunt placement, and contralateral carotid status were collected. RESULTS: There were 735 patients who met the inclusion criteria: 430 patients underwent modified eversion CEA (59%) and 305 patients for patch angioplasty (42%). The incidence of HA was 19% (n = 142) in our total cohort. Of the 19% with HA, 1.5% (n = 11) demonstrated no relief with analgesics and strict blood pressure control; noncontrast head computed tomography scans were performed subsequently. One patient (0.1%) had an ipsilateral ICH. Univariate analysis demonstrated that greater intraoperative MAP peak had the highest risk for HA (odds ratio [OR], 1.014; 95% confidence interval [CI], 1.007-1.022; P = .0002), followed by intraoperative MAP variability (OR, 1.011; 95% CI,1.005-1.018; P ≤ .0008), and peak intraoperative SBP (OR, 1.01; 95% CI, 1.004-1.015; P = .0011). An unpaired Student t test identified change in intraoperative MAP (P < .005), change in the SBP (P < .005), and peak SBP (P < .001) were significantly associated with HA. Interestingly, there was no significant difference between postoperative MAP variability and HA (P = .1). The mode of endarterectomy showed no statistically significant difference in risk for developing HA (OR, 1.165; 95%; 95% CI, 0.801-1.694; P = .42). CONCLUSIONS: Greater intraoperative variability in blood pressures are significantly associated with a higher risk of HA. Adhering to stricter intraoperative blood pressure parameters and limiting blood pressure variability may be beneficial at decreasing the incidence of CHS and its complications.

Treatment of Abdominal Aortic Aneurysm Utilizing Adipose-Derived Mesenchymal Stem Cells in a Porcine Model.

INTRODUCTION: The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop novel therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. We used a porcine model of aortic dilation to assess the ability of human adipose-derived mesenchymal stem cells (MSCs) to attenuate aortic dilation. MATERIALS AND METHODS: Twelve Yorkshire pigs received periadventitial injections (collagenase and elastase) into a 4-cm segment of infrarenal aorta. Animals were treated with either 1 × 106 MSCs placed onto Gelfoam or treated with media as a control. Aortic diameters were measured at the time of surgery and monitored at postoperative day (POD) 7 and 14 with ultrasound. Animals were sacrificed on POD 21. Aortic tissue was harvested for histopathological analyses and immunohistochemistry. Groups were compared with paired t-tests or Mann-Whitney U-tests. RESULTS: All animals survived until POD 21. The mean aortic diameter was reduced in the aortic dilation + MSC treatment group compared to aortic dilation control animals (1.10 ± 0.126 versus 1.48 cm ± 0.151, P < 0.001). Aortic media thickness was reduced in the aortic dilation group compared to the aortic dilation + MSC group (609.14 IQR 445.21-692.93 µm versus 643.55 IQR 560.91-733.88 µm, P = 0.0048). There was a significant decrease in the content of collagen and alpha-smooth muscle actin and elastin perturbation in the aortic dilation group as compared to the aortic dilation + MSC group. Immunohistochemistry demonstrated an increased level of vascular endothelial growth factor, tissue inhibitor of matrix metalloproteinase 1, and tissue inhibitor of matrix metalloproteinase 3 expression in the aorta of aortic dilation + MSC animals. CONCLUSIONS: Stem cell therapy suppressed the aortic dilation in a porcine model. Animals from the aortic dilation group showed more diseased gross features, histologic changes, and biochemical properties of the aorta compared to that of the aortic dilation + MSC treated animals. This novel finding should prompt further investigation into translatable drug and cell therapies for aneurysmal disease.

Blood-Brain Barrier Opening with MRI-guided Focused Ultrasound Elicits Meningeal Venous Permeability in Humans with Early Alzheimer Disease.

Background Opening of the blood-brain barrier (BBB) induced with MRI-guided focused ultrasound has been shown in experimental animal models to reduce amyloid-ß plaque burden, improve memory performance, and facilitate delivery of therapeutic agents to the brain. However, physiologic effects of this procedure in humans with Alzheimer disease (AD) require further investigation. Purpose To assess imaging effects of focused ultrasound-induced BBB opening in the hippocampus of human participants with early AD and to evaluate fluid flow patterns after BBB opening by using serial contrast-enhanced MRI. Materials and Methods Study participants with early AD recruited to a Health Insurance Portability and Accountability Act-compliant, prospective, ongoing phase II clinical trial (ClinicalTrials.gov identifier, NCT03671889) underwent three separate focused ultrasound-induced BBB opening procedures that used a 220-kHz transducer with a concomitant intravenous microbubble contrast agent administered at 2-week intervals targeting the hippocampus and entorhinal cortex between October 2018 and May 2019. Posttreatment effects and gadolinium-based contrast agent enhancement patterns were evaluated by using 3.0-T MRI. Results Three women (aged 61, 72, and 73 years) consecutively enrolled in the trial successfully completed repeated focused ultrasound-induced BBB opening of the hippocampus and entorhinal cortex. Postprocedure contrast enhancement was clearly identified within the targeted brain volumes, indicating immediate spatially precise BBB opening. Parenchymal enhancement resolved within 24 hours after all treatments, confirming BBB closure. Transient perivenous enhancement was consistently observed during the acute phase after BBB opening. Notably, contrast enhancement reappeared in the perivenular regions after BBB closure. This imaging marker is consistent with blood-meningeal barrier permeability and persisted for 24-48 hours before spontaneous resolution. No evidence of intracranial hemorrhage or other adverse effect was identified. Conclusion MRI-guided focused ultrasound-induced blood-brain barrier opening was safely performed in the hippocampi of three participants with Alzheimer disease without any adverse effects. Posttreatment MRI reveals a unique spatiotemporal contrast enhancement pattern that suggests a perivenular immunologic healing response downstream from targeted sites. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Klibanov in this issue.

Development of a Model for Abdominal Aortic Aneurysms in Swine.

INTRODUCTION: Producing a reliable large-animal model of AAA has proven challenging. We sought to create a reproducible swine model of AAA using enzymatic degradation of the aortic wall. METHODS: Twelve male Yorkshire swine received periadventitial injections of type 1 collagenase and porcine pancreatic elastase into a 4 cm segment of infrarenal aorta. Nine survived until postoperative day (POD) 21. Aortic growth was monitored at 7 and 14 days using ultrasound. The animals were euthanized on POD 21, and the suprarenal (control) and infrarenal aorta were harvested for analysis, after gross measurement of aortic diameter (AD). Tensile strength was measured and additional segments were collected for histopathological analysis. PCR of matrix metalloproteinases (MMP9) was conducted. Groups were compared with paired t-tests, or ANOVA, where appropriate. RESULTS: Average percent growth of AD at POD 21 for treated segments was 27% versus 4.5% for control tissue. The average difference in AD by subject, was 26.7% (P<0.001). Aortic medial thickness was decreased in treated tissue; 235 µm versus 645 µm (P<0.0001). Quantities of both medial elastin fibers, and smooth muscles cells were decreased in treated tissue; 1.8% compared to 9.9% (P<0.0001), and 24% versus 37.4%, respectively. Tensile strength was also decreased in treated tissue; 16.7 MPa versus 29.5 MPa (P=0.0002). A 12-fold increase in expression of MMP9 mRNA was also demonstrated in aneurysmal tissue (P=0.002) CONCLUSION: A reproducible, large-animal model of AAA, with anatomical, histopathological, and biomechanical properties that are clinically translatable, can be achieved with extraluminal enzymatic degradation.

Human Adipose Derived Stem Cells Enhance Healing in a Rat Model of Esophageal Injury with Stent.

BACKGROUND: Mesenchymal stem cells have been proven to promote cellular recruitment and remodeling during healing. Considering challenges encountered in the healing process of esophageal injury, we sought to evaluate the effect of human adipose derived stem cells (hASC) on esophageal injury with stent and to assess the feasibility of submucosal hASC injection as a mechanism of delivery. METHODS: An intrabdominal esophagotomy was created in rodents with placement of an expandable fully covered metal esophageal stent. A submucosal injection of 2 × 106 hASC was delivered in experimental animals. Animals were sacrificed on postoperative day 3 (POD3) or 7 (POD7). Macroscopic, immunohistochemical and immunofluorescence analyses were conducted to assess for markers of healing and viability of transplanted cells. RESULTS: hASC were identified within submucosal and muscular layers with proliferation demonstrated in respective areas on anti-Ki67 stained sections. Lower adhesion and abscess scores were observed in hASC specimens without significant statistical difference. Prevalence of submucosal collagen was increased in samples treated with hASC compared to control, with abundant collagen deposition demonstrated within the POD7 group. Granulation tissue at the site of esophageal injury was more prominent in tissue sections treated with hASC compared to control, with significantly higher density at POD3 (control 1.94 versus hASC 2.83, P < 0.01). CONCLUSIONS: Presence of hASC at the site of an esophageal injury may enhance wound healing predominantly through increased granulation and decreased inflammation in conjunction with esophageal stent placement. Targeted submucosal injection at the time of esophageal stent placement is an effective delivery method of hASC therapy.

Proper technical procedures improved outcomes in a retrospective analysis of EVAS FORWARD IDE trial 3-year results.

OBJECTIVE: Adverse outcomes observed late in the Nellix EndoVascular Aneurysm Sealing (EVAS) System (Endologix, Inc, Irvine, Calif) investigational device exemption trial prompted refinement of the anatomic instructions for use (IFU). This study aimed to investigate the association of procedural factors during Nellix endograft deployment and patient outcomes. METHODS: We retrospectively reviewed 1-month imaging of 333 patients enrolled in the prospective, multicenter EVAS investigational device exemption trial between January 2014 and September 2016. Initial observations of those patients who met revised anatomic IFU yet still experienced late adverse events suggested that inadequate seal and low graft placement were common among these patients. Key procedural variables identified from a univariate analysis were applied to construct four cohorts stratified by procedural technical performance (technically adequate [P+] or technically inadequate [P-]) and the revised anatomic indications for use (anatomically within IFU [A+] or anatomically outside of IFU [A-]) and to compare them for aneurysm-related outcomes. A logistic regression analysis was performed to identify significant predictors of sac expansion or migration. RESULTS: Proximal and distal seal zones and low graft placement were identified by logistic regression analysis as significant predictors of sac expansion or migration. Accordingly, acquisition of ≥10-mm proximal and distal seal zones and the position of the lowest stent within 10 mm of the lowest renal artery were clinically justified as thresholds for a technically adequate procedure. Patients who did not achieve these parameters were deemed to have a technically inadequate procedure. By use of the proposed procedural adequacy criteria and established anatomic criteria, patients were stratified into four cohorts: A+/P+ (n = 77), A+/P- (n = 54), A-/P+ (n = 71), and A-/P- (n = 131). Three-year estimates of freedom from migration of 10 mm were 98.6% in A+/P+, 95.9% in A+/P-, 85.8% in A-/P+, and 80.1% in A-/P-; freedom from type IA endoleak estimates were 98.6% in A+/P+, 100% in A+/P-, 96.4% in A-/ P+, and 90.3% in A-/P- cohorts. Freedom from sac expansion and secondary intervention were 96.9% and 90.6% in A+/P+, 86.0% and 93.6% in A+/P-, 87.1% and 83.1% in A-/P+, and 80.5% and 79.8% in A-/P- groups, respectively. Two early deaths (aneurysm-related mortality) on days 4 and 12 postoperatively were reported within the A+/P- group. Kaplan-Meier estimates of freedom from all-cause mortality and aneurysm-related mortality at 3 years were similar between cohorts. CONCLUSIONS: This post hoc analysis suggests that achieving a 10-mm proximal and distal seal with adequate positioning of the endograft with respect to the renal arteries is associated with improved patient outcomes.

Assessing trends, morbidity, and mortality in ruptured abdominal aortic aneurysm repair with 9 years of data from the National Surgical Quality Improvement Program.

BACKGROUND: The American College of Surgeons' National Quality Improvement Program (NSQIP) database can be used to assess trends and outcomes of ruptured abdominal aortic aneurysm (rAAA) repair. The purpose of this study is to examine the morbidity and mortality for ruptured endovascular (rEVAR) and ruptured open (rOPEN) aneurysm repair compared with elective endovascular (EVAR) and elective open (OPEN) aneurysm repair. METHODS: Ruptured and nonruptured abdominal aortic aneurysms were identified from the NSQIP database between 2008 and 2016. Data regarding demographics and comorbidities, 30-day mortality, and postoperative complications were collected for rEVAR, rOPEN, EVAR, and OPEN cases. RESULTS: There were 43,105 AAAs, 34,177 (79.28%) EVARs, and 8928 (20.71%) OPENs. There were 3806 rAAAs, 1843 (48.42%) rEVARs, and 1963 (51.58%) rOPENs. The incidence of rEVAR repair lagged behind EVAR considerably. Mortality for rOPEN was 575 (29.29%) and 344 (18.66%) for rEVAR. No difference between the ratio of men to women in rOPEN vs rEVAR was noted. There was a significant increase in mortality for women vs men undergoing rEVAR (P = .0362). No difference in mortality existed between women vs men undergoing rOPEN (P = .0639). There was no difference in the percentage of hypotensive cases undergoing rEVAR vs rOPEN (P =.1873). For all rAAAs with hypotension, rOPEN had an increased mortality compared to rEVAR (P = .0004). There were 20 (3.11%) rEVAR and 40 (8.00%) rOPEN cases with lower extremity ischemia. rOPEN conferred a significant increase in lower extremity ischemia (P = .0002). There were 46 (7.15%) rEVAR and 60 (12.00%) rOPEN cases of ischemic colitis. rOPEN had a significant increase in ischemic colitis (P = .0052). CONCLUSIONS: NSQIP data, over 9 years, demonstrate an increased morbidity and mortality associated with open vs endovascular repair of rAAAs. A great disparity exists between the proportion of rEVAR and rOPEN to EVAR and OPEN. The lagging use of endovascular repair of rAAAs must be further explored.

Trends in the 10-year history of the vascular integrated residency match: More work, higher cost, same result.

OBJECTIVE: The purpose of this study was to examine trends in application submission, rank lists, and applicant quality for vascular surgery integrated residency. METHODS: The National Resident Matching Program Results and Data reports and the Electronic Residency Application Service Statistics from 2007 to 2017 were compiled and mined for trends in terms of application submission and the number of applicants a program needed to rank to fill all residency positions. Applicant pool depth and percentage of programs applied to were calculated. Outcome data from the National Resident Matching Program were reviewed for 2014 and 2016 for United States Medical Licensing Examination Step scores and experiences. RESULTS: During the last 10 years, the number of vascular surgery integrated residency spots rose from 9 to 60 per year. Most programs offer one spot per year; none offer more than two. The average number of applications received by programs rose from 17 applications in 2008 to 63.8 in 2017. The average rank list depth needed by programs to fill the spots has not increased (range, 2.5-5.1; standard deviation, 0.73). The proportional depth of the applicant pool decreased from 4.6 U.S. and Canadian applicants for every one residency spot in 2008 to 1.7 applicants for every one residency spot in 2017. Applicant quality metrics were available for 2 years (2014 and 2016). Step 1 scores (237/239), Step 2 scores (250/250), research experiences (3.7/4.2), and volunteer experiences (5.9/5.5) remained nearly unchanged. The number of contiguous ranks for matched applicants remained stable (12.3/12.8). CONCLUSIONS: The current system promotes multiple inefficiencies, resulting in application glut. Fewer applicants are flooding programs with an increasing number of applications. More money is being spent on Electronic Residency Application Service applications without changes in the number needed to rank by applicants or programs to achieve a match. There is no improvement in the quality of the applicant. Should these trends continue, they represent an unsustainable model for resident selection.

Locally Transplanted Adipose Stem Cells Reduce Anastomotic Leaks in Ischemic Colorectal Anastomoses: A Rat Model.

BACKGROUND: Anastomotic leakage remains a dreaded complication after colorectal surgery. Stem-cell-based therapies have been shown to increase angiogenesis and cell proliferation. OBJECTIVE: The purpose of this research was to investigate the use of adipose-derived stem cells on the healing of ischemic colonic anastomoses in a rat model. DESIGN: This is an animal research study using xenotransplantation. SETTINGS: Male Wistar rats (300-400 g, n = 48) were purchased from a licensed breeder. PATIENTS: Adipose stem cells were isolated from the subcutaneous fat of healthy human donors. INTERVENTIONS: The rats underwent laparotomy with creation of an ischemic colorectal anastomosis created by ligation of mesenteric vessels. The animals were divided into 3 groups: control group with an ischemic anastomosis, vehicle-only group in which the ischemic anastomosis was treated with an absorbable gelatin sponge, and a treatment group in which the ischemic anastomosis was treated with an absorbable gelatin sponge plus adipose stem cells. Animals were killed at postoperative days 3 and 7. MAIN OUTCOME MEASURES: Anastomotic leakage was defined as the finding of feculent peritonitis or perianastomotic abscess on necropsy. Rat mRNA expression was measured using real-time polymerase chain reaction. RESULTS: Adipose-derived stem cells significantly decreased anastomotic leakage when compared with control at both postoperative days 3 (25.0% vs 87.5%; p = 0.02) and 7 (25.0% vs 87.5%; p = 0.02). The use of an absorbable gelatin sponge alone had no effect on anastomotic leakage when compared with control and postoperative days 3 or 7. We found that stem cell-treated animals had a 5.9-fold and 7.4-fold increase in the expression of vascular endothelial growth factor when compared with control at 3 and 7 days; however, this difference was not statistically significant when compared with the absorbable gelatin sponge group. LIMITATIONS: This is a preclinical animal research study using xenotransplantation of cultured stem cells. CONCLUSIONS: Locally transplanted adipose stem cells enhance the healing of ischemic colorectal anastomoses and may be a novel strategy for reducing the risk of anastomotic leakage in colorectal surgery. See Video Abstract at http://links.lww.com/DCR/B203. EL TRANSPLANTE LOCAL DE CÉLULAS MADRE ADIPOSAS REDUCE LA FUGA ANASTOMÓTICA EN LAS SUTURAS COLORRECTALES ISQUÉMICAS: MODELO EN RATAS: Las fugas anastomóticas son una complicación pusilánime después de toda cirugía colorrectal. Se ha demostrado que el tratamiento con células madre aumenta la angiogénesis y la proliferación celular.Investigar el uso de células madre derivadas de tejido adiposo en la cicatrización de una anastomosis colónica isquémica basada en ratas como modelo.Estudio de investigación en animales utilizando xenotrasplantes.Adquisición de típicas ratas de laboratorio raza Wistar, todas machos (300-400 g, n = 48) de un criadero autorizado.Aislamiento de células madre de tipo adiposo del tejido celular subcutáneo en donantes humanos sanos.Las ratas se sometieron a laparotomía con la creación de una anastomosis colorrectal isquémica obtenida mediante ligadura controlada de los vasos mesentéricos correspondientes. Los animales se dividieron en tres grupos: grupo de control con anastomosis isquémica, grupo de vehículo único en el que la anastomosis isquémica se trató con una esponja de gelatina absorbible, y un grupo de tratamiento en el que la anastomosis isquémica se trató con una esponja de gelatina absorbible asociada a un vástago adiposo de células madre. Los animales fueron sacrificados el POD3 y el POD7.La fuga anastomótica fué definida como el hallazgo de peritonitis fecaloidea o absceso perianastomótico a la necropsia. La expresión de RNAm de las ratas se midió usando PCR en tiempo real.Las células madre derivadas de tejido adiposo disminuyeron significativamente la fuga anastomótica en comparación con el grupo control tanto en el POD3 (25% frente a 87.5%, p = 0.02) como en el POD7 (25% frente a 87.5%, p = 0.02). El uso de una esponja de gelatina absorbible sola, no tuvo efecto sobre la fuga anastomótica en comparación con los controles el POD3 o el POD7. Descubrimos que los animales tratados con células madre adiposas tenían un aumento de 5,9 y 7,4 veces en la expresión de VEGF en comparación con el control a los 3 y 7 días, respectivamente; sin embargo, esta diferencia no fue estadísticamente significativa en comparación con el grupo de esponja de gelatina absorbible.Este es un estudio preclínico de investigación en animales que utiliza xenotrasplantes de células madre adiposas cultivadas.Las células madre de tipo adiposo trasplantadas localmente mejoran la cicatrisación en casos de anastomosis colorrectales isquémicas, y podrían convertirse en una nueva estrategia para reducir el riesgo de fugas anastomóticas en casos de cirugía colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B203. (Traducción-Dr Xavier Delgadillo).

Poly-Specialty Application Practices of Medical Students Applying to Integrated Vascular Surgery Residency.

BACKGROUND: It is not uncommon for medical students seeking surgical residencies to apply to and rank two or more surgical specialties. Level of interest in a specialty is consistently cited as one of the most important factors for program directors when evaluating applicants for 0 + 5 integrated vascular surgery (IVS) programs. The purpose of this study was to examine trends in poly-specialty application submission to IVS and poly-specialty ranking of IVS to determine the percentage of applicants to IVS residencies with vascular surgery as their true preference. METHODS: Electronic Residency Application Service (ERAS) statistics for noninternational medical graduates from 2011 to 2017 were mined for trends in poly-specialty applications between IVS and other surgical disciplines. The poly-specialty application percentage, range, and standard deviation were determined. The National Resident Match Program (NRMP) results and data from 2011 to 2018 were also used to identify those U.S. seniors who ranked IVS programs as their preferred choice, defined as ranking vascular as the only choice or the first-choice specialty. This was compared with those who ranked a specialty other than vascular surgery first but had vascular surgery listed on their rank list. These data were also collected for applicants to orthopedic surgery, neurosurgery, otolaryngology, obstetrics and gynecology, integrated cardiothoracic surgery, and integrated plastic surgery. RESULTS: Between 2011 and 2017, applicants who submitted ERAS applications to IVS most often poly-specialty applied to IVS and general surgery (87%) followed by IVS and the following: preliminary surgery (71%), plastic surgery (22%), orthopedic surgery (19%), neurosurgery (17%), otolaryngology (16%), obstetrics and gynecology (12%), and urology (3%). The percentage of the applicant pool submitting rank lists with multiple specialties fell over the study period from 94% in 2011 to 67% in 2018. Between 2011 and 2018, an average of 14% of IVS applicants (n = 463), who submitted rank lists to the NRMP, ranked a specialty other than vascular as their true preference (range 7-23 SD 5). Only integrated cardiothoracic surgery had a higher percentage of applicants listing a different specialty as their true preference at 25% (range 18-36 SD 7). Nearly all (97-99%) applicants to orthopedic surgery, neurosurgery, otolaryngology, obstetrics and gynecology, and plastic surgery applied to that specialty as their true preference. CONCLUSIONS: IVS residency applicants were most likely to apply for poly-specialty via the ERAS to general surgery and IVS. Compared to the other surgical specialties, those who submitted rank lists to the NRMP listing integrated cardiothoracic and IVS had the highest likelihood of ranking another specialty higher. Care must be taken when evaluating applications to IVS residencies to determine the applicant's level of interest in vascular surgery as a career.

Endovascular Aneurysm Sealing is Associated with Higher Medium-Term Survival than Traditional EVAR.

BACKGROUND: Endovascular aneurysm repair (EVAR) is the dominant treatment modality for abdominal aortic aneurysm (AAA). Periprocedural risks are low, and cardiovascular events are the principle determinants of long-term survival. Recently, the concept of endovascular aneurysm sealing (EVAS) has been introduced into clinical investigation. In previous cohort studies, EVAS has been associated with a lower all-cause mortality than expected despite device issues. We used a propensity weighted approach to investigate whether EVAS was associated with lower all-cause mortality after aneurysm repair. METHODS: We compared 333 patients in the Nellix United States Investigational Device Exemption trial to 15,431 controls from the Vascular Quality Initiative between 2014 and 2016 after applying the exclusion criteria from the investigational device exemption (hemodialysis, creatinine > 2.0 mg/dL, or rupture). We calculated propensity scores and applied inverse probability weighting to compare risk adjusted medium-term survival using Kaplan-Meier and Cox regression. RESULTS: After weighting, patients treated with the Nellix EVAS system experienced higher 3-year survival than controls from the Vascular Quality Initiative (93% vs. 88%, respectively). This corresponded to a 41% lower risk of mortality for EVAS compared with EVAR (HR 0.59 [0.38-0.92], P = 0.02). Subgroup analysis demonstrated that the association between EVAS and higher survival was strongest in the subgroup of patients with aneurysms over 5.5 cm (P for interaction < 0.001). In this subgroup, EVAS patients experienced half the rate of mortality as those patients treated with EVAR, with 3-year survival of 92% compared with 86% (HR 0.5 [0.3-0.9], P = 0.02). CONCLUSIONS: In this select group of patients, EVAS was associated with higher medium-term survival than traditional EVAR. Although issues with the device have recently surfaced, this exploratory analysis shows that the concept of sac sealing may hold promise. Further study is needed to confirm this finding and determine whether EVAS is associated with lower rates of cardiovascular events.

Transformative instruction or old wine in new skins? Exploring how and why educators use HyperDocs.

HyperDocs are interactive, digital teaching and learning materials created, disseminated, and remixed by educators. To date, HyperDocs have not been the subject of published, peer-reviewed research. To address this research gap, we engaged in exploratory, primarily qualitative research to systematically examine how and why teachers use HyperDocs. We used an online survey to gather data on educators' (N = 261) uses of and perceptions regarding HyperDocs. Analysis suggested a wide range of definitions of, purposes for, and approaches to HyperDoc use, indicating that educators are adapting HyperDocs to their practice in myriad ways. Consistent with the openness and flexibility in finding, remixing, and using HyperDocs, educators identified a number of benefits of using these tools in their practice, including changes in student engagement and learning, shifts in instructional design and delivery, and changes in their own support and dispositions. Analysis of examples of HyperDocs shared by a subset of participants suggested some mismatch between rhetoric about HyperDocs and what was actually incorporated into them. We discuss these findings in relation to the work of educators and the future of research on HyperDocs and other crowdsourced teaching and learning initiatives.

Multiscale modeling and cinematic visualization of photosynthetic energy conversion processes from electronic to cell scales.

Conversion of sunlight into chemical energy, namely photosynthesis, is the primary energy source of life on Earth. A visualization depicting this process, based on multiscale computational models from electronic to cell scales, is presented in the form of an excerpt from the fulldome show Birth of Planet Earth. This accessible visual narrative shows a lay audience, including children, how the energy of sunlight is captured, converted, and stored through a chain of proteins to power living cells. The visualization is the result of a multi-year collaboration among biophysicists, visualization scientists, and artists, which, in turn, is based on a decade-long experimental-computational collaboration on structural and functional modeling that produced an atomic detail description of a bacterial bioenergetic organelle, the chromatophore. Software advancements necessitated by this project have led to significant performance and feature advances, including hardware-accelerated cinematic ray tracing and instanced visualizations for efficient cell-scale modeling. The energy conversion steps depicted feature an integration of function from electronic to cell levels, spanning nearly 12 orders of magnitude in time scales. This atomic detail description uniquely enables a modern retelling of one of humanity's earliest stories-the interplay between light and life.

How and why are educators using Instagram?

Social media are commonplace in many educators' lives, but their Instagram activities have received no prior attention in the empirical literature. We therefore created and disseminated a survey regarding educators' Instagram use. Analyses of 841 responses suggested participants were generally intensive users of Instagram who engaged in the exchange of both professional knowledge and wisdom, as well as affective support. In addition to identifying benefits to Instagram use, some participants offered critiques of Instagram's professional utility. We discuss the implications of these findings for educators' work in a digital era and the future of research on educators' social media activities.