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Abstract Background Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM) patients. Treatment effects with improved left ventricular (LV) ejection fraction (EF) have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful. Methods This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR) to the relative risk (RR) of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM) and 63-70% (lower half of the normal range for TM). Results A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p < 0.001) and the higher EF stratum (EF 63-70%, RR 0.893 p = 0.001). Conclusion These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.

Purpose: To determine the effect of stent coverage of the external carotid artery (ECA) after carotid artery stenting (CAS) compared to eversion endarterectomy of the ECA after carotid endarterectomy (CEA).Methods: The records of 101 CAS and 165 CEA procedures performed over 2 years were reviewed. Duplex velocities and history and physical examinations were taken prior to the procedure, at 1 month, and at 6-month intervals subsequently. CAS was performed by extending the stent across the internal carotid artery (ICA) lesion into the common carotid artery (CCA) thereby covering the ECA. CEA was performed with eversion endarterectomy of the ECA.Results: The mean peak systolic velocities (PSV) in the ICA pre-CAS and pre-CEA were 361 and 352 cm/s, respectively. In terms of CAS, there was a significant increase in ECA velocities versus baseline at 12 (p = 0.009), 18 (p = 0.00001), and 24 (p = 0.005) months. In the CEA group, there was a significant decrease in ECA velocities versus baseline at 1 (p = 0.01) and 6 (p = 0.004) months. There were 2 occluded ECAs in follow-up in the CAS group and none in the CEA group. No significant differences were noted when comparing preprocedural ICA or ECA velocities. However, at the 1-, 6-, and 12-month intervals, the ECA velocities in the CAS group were significantly higher than in the CEA group (p = 0.03, p = 0.001, and p = 0.0004, respectively). There were no neurological symptoms in any patients during the study period.Conclusion: Although progressive stenosis of the ECA is noted during CAS, the ECA usually does not occlude. Furthermore, there are no associated neurological symptoms. Thus, apprehension for progressive ECA occlusion should not be a contraindication to CAS. In addition, concern for ECA coverage should not deter stent extension from the ICA to the CCA during CAS. [ABSTRACT FROM AUTHOR]

A high index of suspicion for popliteal aneurysms must be present when evaluating a popliteal mass. Though typically pulsatile, in the presence of chronic thrombosis, the absence of a pulse may make the diagnosis even more difficult. A case is presented that illustrates this point, where an 83-year-old man presents following the biopsy of what turned out to be a very large popliteal aneurysm. In the presence of chronic thrombosis and adequate collateral flow, decompression and ligation of any feeding vessels is typically sufficient. These patients must be followed lifelong for the development of other associated aneurysms. [ABSTRACT FROM AUTHOR]

Incidence of type 2 diabetes has greatly increased in the US, with over 90 percent having type 2. A cross-sectional, self-report survey was conducted for the purpose of assessing characteristics associated with self-management of type 2 diabetes (attitudes, certain behaviors, and perceived knowledge) among low-income Caucasian and African-American adults enrolled in the Food Stamp Nutrition Education Program (FSNEP). At the time of the study, almost 11 percent of FSNEP adult participants (457 individuals) throughout the state had type 2 diabetes. Among 196 subjects interviewed for the study, 86 were Caucasian (44%) and 100 (51%) were African-American. Results indicated that over three-fourths of subjects had been counseled on diet and exercise, but less that half were following dietary recommendations and only one-fourth were getting adequate exercise. No significant differences were found between the two race groups on assessed characteristics or among subjects grouped by place of residence (p < or = 0.01). Significant correlations were found among subjects' characteristics, including perceived health status, perceived knowledge of diabetes, attitudes towards diabetes, meal-plan adherence, perceived barriers to physical activity, and reported diabetes control (p < or = 0.0001). Findings imply that (a) self-management education for type 2 diabetes does not need to be different for African-Americans vs. Caucasians in southern states and (b) best disease control is achieved when those with type 2 diabetes have a high degree of knowledge of diabetes, positive attitudes, good meal plan adherence, and few perceived barriers to physical activity. [ABSTRACT FROM AUTHOR]

Acute mesenteric ischemia continues to be a highly morbid diagnosis with a high mortality rate. Percutaneous management of mesenteric ischemia is being more widely applied. Its utility is limited, though, for patients who present with an acute abdomen from ischemic bowel. The authors report a novel combination of open and endovascular techniques via a retrograde superior mesenteric artery (SMA) approach to treat acute mesenteric ischemia in the setting of an acute abdomen. [ABSTRACT FROM AUTHOR]

Background: Postoperative carotid endarterectomy (CEA) patch infection is a rare but well-recognized complication of CEA. It is important for otolaryngologists to be aware of the presentation and challenges in its diagnosis., Methods: Patients who presented with a neck mass or hemorrhage and a known prior history of carotid endarterectomy with synthetic patch reconstruction were worked up with ultrasound, CT, or MRI imaging. In one case, fine needle aspiration biopsy was performed. Ultimately, all patients were taken to the operating room for neck exploration., Results: Of the three patients presented in this case series, two presented with a chronic neck mass, two-to-three years after carotid endarterectomy. One patient presented acutely with hemorrhage from the carotid endarterectomy site. Carotid patch infection was diagnosed after neck exploration in all cases. Vascular surgery was consulted intra-operatively to perform definitive vascular repair., Conclusions: Infected carotid patch should be suspected in patients with a history of prior CEA, as many of the presenting complaints may resemble or mimic pathology managed by otolaryngology. The onset of symptoms can be perioperative or very delayed. A multidisciplinary approach with vascular surgery and infectious disease is required for appropriate management of these patients., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

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., Competing Interests: Disclosures None., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

In response to the COVID-19 pandemic, nonemergent surgery was postponed in efforts to limit disease spread. To determine whether these changes affected vascular integrated resident (VR) and fellow (VF) operative volume, Accreditation Council for Graduate Medical Education (ACGME) case log data was reviewed. Case volume and standard deviation for each major category was for graduates of 2020 and 2021 were compared to the year prior to the pandemic, 2019. There were only 3 significant changes when comparing 2020/2021 to the prepandemic baseline of 2019, with increase in abdominal obstructive cases for VRs (8.1 in 2021 vs 5.9 in 2019, P = .021), an increase in upper extremity cases for VFs (18.9 in 2021 from 15.8 in 2019, P = .029), and a decrease in venous cases for VFs (39.6 in 2021 from 48.4 in 2019, P = .011). Postponing nonemergent surgery did not translate to significant changes in operative cases for graduating VRs and VFs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Surgical education has evolved over time to incorporate supplemental modalities of training beyond the operating room. Even with the utility of simulation software and didactic education, there is still a need to provide surgical residents with experience in live tissue dissection and tissue handling while maintaining patient safety. In our program, after two clinical years, residents participate in a year of translational research which uses porcine models for complex open abdominal procedures. During the porcine surgeries, our residents are guided by the supervising attending to perform key portions of the procedure typically reserved for those more senior trainees. We found in a survey that research residents after two clinical years found this experience with large animal surgeries helped them better navigate anatomic structures and would recommend this to future trainees. We believe this dual-purpose research-training model provides a valuable resource that can be adapted to other programs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: [details omitted for double-anonymized peer review].

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Abdominal Aortic Aneurysm (AAA) is a highly morbid condition and is the 11th leading cause of death in the United States. Treatment options are limited to operative interventions, with minimal non-operative options. Prior literature has demonstrated a benefit to the use of mesenchymal stem cells (MSCs) in attenuating AAA formation. We demonstrate the utility of MSCs in treating AAA in swine, focusing on the mechanical and structural characteristics of aortic tissue after treatment., Methods: 16 Yorkshire pigs underwent retroperitoneal exposure of the infrarenal aorta, with subsequent induction of AAA with peri-adventitial elastase and collagenase. A 1 × 4 cm piece of Gelfoam, an absorbable gelatin-based hemostatic agent, was soaked in media or human MSCs and placed directly on the vessel for control and experimental animals. At postoperative day 21, animals were sacrificed and the infrarenal aorta at this location was harvested for analysis. Tensile strength was measured using a tensiometer, from which Young's modulus and maximum strain were calculated., Results: All animals survived the surgery and post-operative course. Young's elastic modulus for the aneurysm control group was 15.83 ± 1.61 compared to 22.13 ± 2.34 for the stem cell treated segment, p  = 0.0316. There was no significant difference in the peak stress between groups., Conclusions: This is the first study to demonstrate the mechanical effects of stem cell therapy on a model of AAA in swine. Young's modulus, which characterizes the intrinsic capacity of a tissue to withstand stress, was greater in the animals treated with MSCs compared to control animals with aneurysms. This methodology can be utilized in future large animal models to develop cell and drug-based therapies for AAA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

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 × 10 6 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Biological systems employ multimetallic assemblies to achieve a range of functions. Here we demonstrate the preparation of metal-organic cages that contain either homobimetallic or heterobimetallic vertices. These vertices are constructed using 2-formyl-6-diphenylphosphinopyridine, which forms ligands that readily bridge between a pair of metal centers, thus enforcing the formation of bimetallic coordination motifs. Two pseudo-octahedral homometallic M I 12 L 4 cages (M I = Cu I or Ag I ) were prepared, with a head-to-head configuration of their vertices confirmed by X-ray crystallography and multinuclear NMR for Ag I . The phosphino-pyridine subcomponent also enabled the formation of a class of octanuclear Cd II 4 Cu I 4 L 4 tetrahedral cages, representing an initial example of self-assembled cages containing well-defined heterobimetallic vertices.

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., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Social media offers potential for educator professional learning, but platforms' for-profit nature complicates this practice, especially for professional learning around justice-oriented pedagogies. This exploratory study investigated 551 publicly available Instagram posts shared by 11 purposefully sampled, justice-oriented education influencers over an 8-week period as the COVID-19 pandemic and renewed activism for racial justice unfolded in the United States. Qualitative analysis of post content indicated these influencers offered pandemic-related support, while also illustrating, enacting, and engaging culturally relevant and sustaining pedagogies. However, promotional content was abundantly layered within posts and a cohesive message of how to enact culturally sustaining pedagogies was largely absent. Reflecting some of the paradoxes of learning via social media, our findings suggest there is some opportunity for justice-oriented professional learning from social media, however education influencers' content is limited by platforms' opaque algorithms and for-profit business models, which govern what influencers post and what followers see., (© Association for Educational Communications & Technology 2022.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Autologous fat transplantation is a versatile tool in reconstructive surgery. Adipose-derived stem cells (ASCs) increase survival of fat grafts and thus are increasingly used for breast reconstruction in breast cancer patients. However, radiation and/or chemotherapy have been proposed to inhibit soft tissue regeneration in wound healing thus suggesting alteration in stem cell pathways. Therefore, elucidating effects of radiation and chemotherapy on ASCs is critical if one desires to enhance the survival of fat grafts in patients. This review outlines our work evaluating the function and recoverability of ASCs from radiation or chemotherapy patients, focusing specifically on their availability as a source of autologous stem cells for fat grafting and breast reconstruction in cancer patients. Even though evidence suggests radiation and chemotherapy negatively influence ASCs at the cellular level, the efficiency of the isolation and differentiation capacity did not appear influenced in patients after receiving chemotherapy treatment, although fat from radiated patients exhibited significantly altered ASC differentiation into endothelial-like cells. Further, the in vitro growth rates of patient's ASCs do not differ significantly before or after treatment. Taken together, these studies suggest ASCs as an important new tool for grafting and reconstruction even when radiation and chemotherapy treatment are involved., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

In clinical decision making, myocardial viability is defined as myocardium in acute or chronic coronary artery disease and other conditions with contractile dysfunction but maintained metabolic and electrical function, having the potential to improve dysfunction upon revascularization or other therapy. Several pathophysiological conditions may coexist to explain this phenomenon. Cardiac imaging may allow identification of myocardial viability through different principles, with the purpose of prediction of therapeutic response and selection for treatment. This expert consensus document reviews current insight into the underlying pathophysiology and available methods for assessing viability. In particular the document reviews contemporary viability imaging techniques, including stress echocardiography, single photon emission computed tomography, positron emission tomography, cardiovascular magnetic resonance, and computed tomography and provides clinical recommendations for how to standardize these methods in terms of acquisition and interpretation. Finally, it presents clinical scenarios where viability assessment is clinically useful., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: The ambulatory arterial stiffness index (AASI) obtained during ambulatory blood pressure monitoring (ABPM) has been cited as an independent predictor of major adverse cardiovascular events (MACEs) including cardiovascular death, stroke and worsening chronic kidney disease (CKD) among mixed-sex adult populations. This study aimed to determine the relationship between AASI and MACE and its predictive precision in women., Methods: This work follows the guidelines of the STROBE initiative for cohort studies. This was a retrospective single-center observational study of adult women (aged 18 - 75 years), who underwent 24-h ABPM for the diagnosis of hypertension or its control. The primary endpoint was a composite MACE of cardiovascular death, acute limb ischemia, stroke, acute coronary syndrome (ACS), or progression to stage V CKD., Results: A total of 219 women aged 57.4 ± 13.3 years were followed up for a median (interquartile range (IQR)) of 25.5 (18.3 - 31.3) months. Overall, 16 (7.3%) patients suffered one or more MACE events. AASI was significantly higher in patients with known coronary artery disease (CAD), diabetes mellitus, peripheral vascular disease (PVD), heart failure, previous stroke, or transient ischemic attack (TIA). AASI was a significant predictor of MACE (area under the curve: 0.78; P < 0.001) with an optimal cut-off of ≥ 0.56. On Kaplan-Meier analysis AASI ≥ 0.56 was significantly associated with MACE (log-rank test, P < 0.001). The only independent predictors of MACE on Cox proportional hazard analysis were diabetes mellitus, low high-density lipoprotein (HDL) levels, cumulative AASI values, or AASI ≥ 0.56., Conclusions: An AASI of ≥ 0.56 is an independent predictor of MACE in women. A further validation study in a larger cohort of women is recommended., Competing Interests: We have no conflict of interest to declare., (Copyright 2021, Boos et al.)

A bis-urea-functionalized ditopic subcomponent assembled with 2-formylpyridine and Fe II , resulting in a dynamic library of metal-organic assemblies: an irregular Fe II 4 L 6 structure and three Fe II 2 L 3 stereoisomers: left- and right-handed helicates and a meso-structure. This library reconfigured in response to the addition of monosaccharide derivatives, which served as guests for specific library members, and the rate of saccharide mutarotation was also enhanced by the library. The (P) enantiomer of the Fe II 2 L 3 helical structure bound β-D-glucose selectively over α-D-glucose. As a consequence, the library collapsed into the (P)-Fe II 2 L 3 helicate following glucose addition. The α-D-glucose was likewise transformed into the β-D-anomer during equilibration and binding. Thus, β-D-glucose and (P)-3 amplified each other in the product mixture, as metal-organic and saccharide libraries geared together into a single equilibrating system., (© 2020 Wiley-VCH GmbH.)

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., (© 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier Inc.)

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., (© 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019. Published by Elsevier Inc.)

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).

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., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Here we describe the formation of a trigonal prismatic cage, utilizing 2-formyl-1,8-naphthyridine subcomponents to bind pairs of silver(I) ions in close proximity. This cage is the first example of a new class of subcomponent self-assembled polyhedral structures having bimetallic vertices, as opposed to the single metal centers that typically serve as structural elements within such cages. Our new cage self-assembles around a pair of anionic templates, which are shown by crystallographic and solution-phase data to bind within the central cavity of the structure. Many different anions serve as competent templates and guests. Elongated dianions, such as the strong oxidizing agent peroxysulfate, also serve to template and bind within the cavity of the prism. The principle of using subcomponents that have more than one spatially close, but nonchelating, binding site may thus allow access to other higher-order structures with multimetallic vertices.

The cavities of artificial receptors are defined by how their components fit together. The encapsulation of specific molecules can thus be engineered by considering geometric principles; however, intermolecular interactions and steric fit scale with receptor size, such that the ability to bind multiple guests from a specific class of compounds remains a current challenge. By employing metal-organic self-assembly, we have prepared a triangular prism from two different ligands that is capable of binding more than 20 different natural products, drugs, and steroid derivatives within its prolate cavity. Encapsulation inflates the host, enhancing its ability to bind other guests in peripheral pockets and thus enabling our system to bind combinations of different drug and natural product cargoes in different locations simultaneously. This new mode of entropically favorable self-assembly thus enables central encapsulation to amplify guest-binding events around the periphery of an artificial receptor.

Background: Adipose-derived stem cells (ASCs) assisted lipotransfer have been considered to facilitate the survival of fat grafts. However, emerging evidence of insufficient vascularization is another obstacle for fat graft survival in cell-assisted lipotransfer., Objectives: This study evaluated if endothelial phenotype ASCs with fat lipoaspirate improves survival and neovascularization in fat transplantation., Methods: ASCs were isolated from human periumbilical fat tissue and cultured in endothelial growth medium for 2 weeks. Fat lipoaspirate was mixed with fresh adipose stroma vascular fraction (SVF), endothelial differentiated ASCs (EC/ASCs), and fat lipoaspirate alone. Three fat mixtures were subcutaneously injected into the adult male Sprague-Dawley rat's dorsum at 3 locations. At 8 weeks after transplantation, the grafted fat lipoaspirates were harvested, and the extracted fat was evaluated using photographic, survival weights measurements and histological examination. Neo-vascularization was quantified by immunofluorescence and real-time RT-PCR., Results: Grafts from the EC/ASC assisted group had a higher survival rate, morphologic integrity, and most uniform lipid droplets. They also revealed less inflammation and fibrosis with increased number of vessels by histological and immunofluorescence analysis. Quantitative RT-PCR analysis indicated that the expression levels of EC-specific markers of CD31 and vWF were higher in the EC/ASC group compared with in the control and fat with SVF transplants., Conclusions: These results indicated that co-implantation of fat lipoaspirate with ASCs differentiated toward an endothelial phenotype improves both survival and neovascularization of the transplanted fat lipoaspirate, which might provide benefits and represents a promising strategy for clinical application in autologous fat transplantation.

Introduction: Neoadjuvant chemotherapy prior to lumpectomy or mastectomy for breast cancer challenges wound healing. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has been shown to work synergistically with paclitaxel in vitro and in preclinical studies. In addition, our laboratory has demonstrated that SAHA treatment decreases paclitaxel-associated stem cell toxicity, modulates inflammatory response, and promotes wound healing in injured fibroblast cells. Our goal was to determine if combined SAHA and paclitaxel treatment would improve wound healing in an in vivo full-thickness murine model, without altering antitumor effect., Methods: Thirty-two nude athymic mice received intraperitoneal injections of paclitaxel (20 mg/kg), SAHA (25 mg/kg), paclitaxel + SAHA (20 mg/kg + 25 mg/kg), or no treatment for 2 weeks prior to surgery. Under general anesthesia, 8-mm full-thickness dorsal wounds were created in all animals, and a silicone splint was attached to minimize wound contraction. The wounds were measured twice a week with a surgical caliper until healing was complete. To evaluate the in vivo effect of drug treatment, 16 athymic nude mice with MDA-MB-231 xenografts received the treatments described previously, following which tumor volumes were compared between groups., Results: Average wound healing time was prolonged in mice treated with paclitaxel (20 ± 1.9 days), and combination SAHA + paclitaxel therapy improved average wound healing time (17.0 ± 1.8 days). In the xenograft model, the antitumor effect of SAHA and paclitaxel (average tumor volume 43.9 ± 34.1 mm) was greater than paclitaxel alone (105.8 ± 73.8 mm)., Conclusions: The addition of SAHA to taxane chemotherapy improves the therapeutic effect on triple-negative breast cancer while decreasing the detrimental effect of paclitaxel on wound healing. This may have substantial implications on improving outcomes in breast reconstruction following chemotherapy.

Background: The Nellix System (Endologix, Inc, Irvine, Calif) for endovascular aneurysm sealing (EVAS) is a novel approach to abdominal aortic aneurysm treatment and conceptually different from endovascular aneurysm repair, whereby polymer is employed to fill and actively manage the abdominal aortic aneurysm sac. One-year safety and effectiveness results of the Nellix pivotal trial demonstrated encouraging outcomes with very low morbidity and mortality and high procedural and treatment success. Two-year imaging revealed a signal of migration, leading to a field safety notification issued by the manufacturer on October 21, 2016, and a dedicated root cause analysis, resulting in refinements to the instructions for use (IFU). We report the 2-year results of the investigational device exemption pivotal trial stratified according to the new and original criteria for selection of patients., Methods: Comprehensive engineering evaluations, statistical analyses, and clinical assessments were conducted looking at patients enrolled in the pivotal trial (N = 150), roll-in cohort (N = 29), and continued access program (N = 154). All patients in all cohorts were treated on-IFU at the time of enrollment. Logistic regression models supported the mechanism that migration with Nellix is associated with a small aortic flow lumen relative to a large aneurysm thrombus burden and large aortic neck diameters. Based on these findings, refinements to the IFU criteria were applied, excluding patients with a thrombus index (maximum aneurysm sac/maximum flow lumen diameter) >1.4, aortic neck diameter >28 mm, and aortic neck conicity (>10% diameter change along the infrarenal neck) and requiring a 10-mm distal seal zone in the iliac artery., Results: Freedom from all-cause mortality at 2 years was 94%. Patient outcomes were then stratified on the refined morphologic criteria and analyzed retrospectively. Two-year freedom from composite endoleak was high among both cohorts (95% on-IFU vs 92% off-IFU). Freedom from migration was 97.7% on-IFU vs 93.2% off-IFU (P = .0125). Freedom from aneurysm enlargement was 98.1% on-IFU vs 93.5% off-IFU (P value is not available because of failure of log-rank test assumptions). Composite freedom from migration, type IA endoleak, or aneurysm expansion was 95.9% among the on-IFU cohort vs 85.1% in the off-IFU cohort (P = .0017)., Conclusions: Consistent with the introduction of a novel therapy, the presentation of failure modes of EVAS over time was inevitable. Using detailed imaging as well as engineering and statistical analysis, we were able to understand risk factors for adverse events specific to EVAS and defined those patients best suited for Nellix. With this EVAS-specific approach to defining IFU, on-IFU patients were identified as those with large aneurysms with little thrombus that would be prone to type II endoleaks and sac expansion with traditional devices. When treated with Nellix, these patients were predicted to experience exceptional results, especially with regard to a low composite endoleak rate and low all-cause mortality., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Chronic wounds are a common surgical problem exacerbated by diabetes and ischemia. Although adipose-derived stem cells (ASCs) have shown promise as a wound healing therapy, their function and proliferation are hindered in diabetes. This study examines the ability of the human umbilical vein endothelial cell (HUVEC) secretome to reverse the deleterious effects of high glucose concentrations on ASCs through priming, thereby enhancing their ability to participate in angiogenesis and wound healing., Methods: Institutional review board-approved human ASCs were cultured in M199 medium with or without glucose (30 mmol/L). HUVEC were grown in 30 mmol/L glucose-containing M199 medium; the resulting conditioned medium (HUVEC-CM) was collected every 3 days and used to prime ASCs. An aliquot of HUVEC-CM was heated (85°C for 30 minutes) to produce thermal denaturation of protein. Viability, proliferation, and endothelial differentiation were measured by MTT assays, growth curves, and quantitative polymerase chain reaction, respectively. A Matrigel assay was used to assess the ability of primed ASCs to participate in capillary-like tube formation. An Institutional Animal Care and Use Committee-approved in vivo murine model of diabetic and ischemic hindlimbs was used to evaluate the angiogenic potential of primed stem cells. Human ASCs were cultured with either control M199 or HUVEC-CM. Mice were randomized to a control group, an unprimed ASC group, or a HUVEC-primed ASC group. Cellular therapies were injected into the ischemic muscle. Thirty days later, slides were made. Microvessels were counted by three blinded observers., Results: MTT assays revealed that HUVEC-priming induced a 1.5 times increase in cell viability over diabetic controls. This promoting effect was lost with heated HUVEC-CM (P < .001), indicating that the active molecules are of protein origin. After 9 days, ASCs cultured in 30 mmol/L glucose solution showed a 14% reduction in growth from nondiabetic controls (P = .013) and exhibited atrophic morphology. Conversely, diabetic HUVEC-primed stem cells demonstrated a nearly four-fold increase in proliferation (P < .05) and took on a fusiform, endothelial-like phenotype. Polymerase chain reaction demonstrated enhanced expression of CD31 messenger RNA by 4.7-fold after 14 days in the HUVEC-primed group, and endothelial nitric oxide synthase messenger RNA messenger RNA was increased 20.1-fold from controls. Unlike unprimed controls, HUVEC-primed ASCs readily formed capillary-like tube networks on Matrigel. Diabetic mice that were injected with HUVEC-primed ASCs demonstrated greater vessel density than both controls (2.1-fold) and unprimed stem cell treatments (P < .001)., Conclusions: HUVECs secrete protein factors that significantly increase proliferation and endothelial differentiation of ASCs under diabetic conditions. Injection of ischemic hindlimbs in diabetic mice with HUVEC-primed ASCs leads to enhanced angiogenesis., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the civilian population. The purpose of this study was to examine the effect(s) of adipose-derived stem cell (ASC) treatment on cellular and functional recovery in TBI via both in vitro and in vivo methods., Methods: Cultured neuroblastoma cells, SH-SY5Y, were scratched to mimic TBI in an in vitro model. The effect of ASC-conditioned medium (CM) on cell death, mitochondrial function, and expression of inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin 1β [IL-1β], and IL-6), as well as apoptosis marker FAS, was measured. In our in vivo model, Sprague-Dawley rats underwent TBI via a frontal, closed-head injury model. Animals randomly received either intravenous human-derived ASCs or intravenous saline within 3 hours of injury and were compared with a sham group. Functional recovery was evaluated via accelerating Rotarod method. On post-TBI Day 3, brain tissue was harvested and assessed for cellular damage via enzyme-linked immunosorbent assay for TNF-α, as well as immunohistochemical staining for β-amyloid precursor protein (β-APP)., Results: Our in vitro data show that ASC treatment imparted reduced cell death (ratio to control: 1.21 ± 0.066 vs. 1.01 ± 0.056, p = 0.017), increased cell viability (ratio to control: 0.86 ± 0.009 vs. 1.09 ± 0.01, p = 0.0001), increased mitochondrial function (percentage of control: 78 ± 6% vs. 68 ± 3%), and significantly decreased levels of inflammatory cytokine IL-1β. In our in vivo study, compared with TBI alone, ASC-treated animals showed no difference in functional recovery, lower levels of expressed TNF-α (ratio to total protein, 0.47 ± 0.01 vs. 0.67 ± 0.04; p < 0.01), and lower levels of β-amyloid precursor protein (fluorescence ratio, 0.43 ± 0.05 vs. 0.69 ± 0.03; p < 0.01)., Conclusions: Adipose-derived stem cell treatment results in improved cell survival, decreased inflammatory marker release, and decreased evidence of neural injury. No difference in functional recovery was seen. These data suggest the potential for ASC treatment to aid in cellular protection and recovery in neural cells following TBI.