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.

Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial.

Introduction: While current treatments for substance use disorder (SUD) are beneficial, success rates remain low and treatment outcomes are complicated by co-occurring SUDs, many of which are without available medication treatments. Research involving neuromodulation for SUD has recently gained momentum. This study evaluated two doses (60 and 90 W) of Low Intensity Focused Ultrasound (LIFU), targeting the bilateral nucleus accumbens (NAc), in individuals with SUD. Methods: Four participants (three male), who were receiving comprehensive outpatient treatment for opioid use disorder at the time of enrollment and who also had a history of excessive non-opioid substance use, completed this pilot study. After confirming eligibility, these participants received 10 min sham LIFU followed by 20 min active LIFU (10 min to left then right NAc). Outcomes were the safety, tolerability, and feasibility during the LIFU procedure and throughout the 90-day follow-up. Outcomes also included the impact of LIFU on cue-induced substance craving, assessed via Visual Analog Scale (VAS), both acutely (pre-, during and post-procedure) and during the 90-day follow-up. Daily craving ratings (without cues) were also obtained for one-week prior to and one-week following LIFU. Results: Both LIFU doses were safe and well-tolerated based on reported adverse events and MRI scans revealed no structural changes (0 min, 24 h, and 1-week post-procedure). For the two participants receiving "enhanced" (90 W) LIFU, VAS craving ratings revealed active LIFU attenuated craving for participants' primary substances of choice relative to sham sonication. For these participants, reductions were also noted in daily VAS craving ratings (0 = no craving; 10 = most craving ever) across the week following LIFU relative to pre-LIFU; Participant #3 pre- vs. post-LIFU: opioids (3.6 ± 0.6 vs. 1.9 ± 0.4), heroin (4.2 ± 0.8 vs. 1.9 ± 0.4), methamphetamine (3.2 ± 0.4 vs. 0.0 ± 0.0), cocaine (2.4 ± 0.6 vs. 0.0 ± 0.0), benzodiazepines (2.8 ± 0.5 vs. 0.0 ± 0.0), alcohol (6.0 ± 0.7 vs. 2.7 ± 0.8), and nicotine (5.6 ± 1.5 vs. 3.1 ± 0.7); Participant #4: alcohol (3.5 ± 1.3 vs. 0.0 ± 0.0) and nicotine (5.0 ± 1.8 vs. 1.2 ± 0.8) (all p's < 0.05). Furthermore, relative to screening, longitudinal reductions in cue-induced craving for several substances persisted during the 90-day post-LIFU follow-up evaluation for all participants. Discussion: In conclusion, LIFU targeting the NAc was safe and acutely reduced substance craving during the LIFU procedure, and potentially had longer-term impact on craving reductions. While early observations are promising, NAc LIFU requires further investigation in a controlled trial to assess the impact on substance craving and ultimately substance use and relapse.

Guanidinoacetate N-methyltransferase deficiency: Case report and brief review of the literature.

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a rare autosomal recessive disorder characterized by a decrease in creatine synthesis, resulting in cerebral creatine deficiency syndrome (CCDS). GAMT deficiency is caused by mutations in the GAMT gene located on chromosome 19, which impairs the conversion of guanidinoacetic acid (GAA) to creatine. The resulting accumulation of the toxic metabolite GAA and the lack of creatine lead to various symptoms, including global developmental delays, behavioral issues, and epilepsy. The gold standard for diagnosis of GAMT deficiency is genetic testing. Treatment options for GAMT deficiency include creatine supplementation, ornithine supplementation, arginine restriction, and sodium benzoate supplementation. These treatment options have been shown to improve movement disorders and epileptic symptoms, but their impact on intellectual and speech development is limited. Early intervention has shown promising results in normalizing neurological development in a minor subgroup of patients. Therefore, there is a growing need for newborn screening techniques to detect GAMT deficiency early and prevent permanent neurological delays. Here we report a case of GAMT deficiency with emphasis on imaging presentation. Our case showed reduced brain parenchyma creatine stores on MR Spectroscopy, which may provide an avenue to aid in early diagnosis.

Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer's disease.

BACKGROUND: Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening is under investigation as a therapeutic modality for neurodegeneration, yet its effects in humans are incompletely understood. Here, we assessed physiologic responses to FUS administered in multifocal brain sites of persons with Alzheimer's disease (AD). METHODS: At a tertiary neuroscience institute, eight participants with AD (mean age 65, 38% F) enrolled in a phase 2 clinical trial underwent three successive targeted BBB opening procedures at 2 week intervals using a 220 kHz FUS transducer in combination with systemically administered microbubbles. In all, 77 treatment sites were evaluated and encompassed hippocampal, frontal, and parietal brain regions. Post-FUS imaging changes, including susceptibility effects and spatiotemporal gadolinium-based contrast agent enhancement patterns, were analyzed using serial 3.0-Tesla MRI. RESULTS: Post-FUS MRI revealed expected intraparenchymal contrast extravasation due to BBB opening at all targeted brain sites. Immediately upon BBB opening, hyperconcentration of intravenously-administered contrast tracer was consistently observed around intracerebral veins. Following BBB closure, within 24-48 h of FUS intervention, permeabilization of intraparenchymal veins was observed and persisted for up to one week. Notably, extraparenchymal meningeal venous permeabilization and associated CSF effusions were also elicited and persisted up to 11 days post FUS treatment, prior to complete spontaneous resolution in all participants. Mild susceptibility effects were detected, however no overt intracranial hemorrhage or other serious adverse effects occurred in any participant. CONCLUSIONS: FUS-mediated BBB opening is safely and reproducibly achieved in multifocal brain regions of persons with AD. Post-FUS tracer enhancement phenomena suggest the existence of a brain-wide perivenous fluid efflux pathway in humans and demonstrate reactive physiological changes involving these conduit spaces in the delayed, subacute phase following BBB disruption. The delayed reactive venous and perivenous changes are consistent with a dynamic, zonal exudative response to upstream capillary manipulation. Further preclinical and clinical investigations of these FUS-related imaging phenomena and of intracerebral perivenous compartment changes are needed to elucidate physiology of this pathway as well as biological effects of FUS administered with and without adjuvant neurotherapeutics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03671889, registered 9/14/2018.

Operative Case Volume for Vascular Integrated Residents and Fellows Following the Elective Surgery Shutdown due to COVID-19.

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.

Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy.

Patients with metastatic breast cancer have high and continually increasing rates of brain metastases. During the course of the disease, brain metastases can occur in up to 30% of these patients. In most cases, brain metastases are diagnosed after significant disease progression. The blood-tumor barrier increases the difficulty of treating brain metastasis by preventing accumulation of chemotherapy within metastases at therapeutically effective concentrations. Traditional therapies, such as surgical resection, radiotherapy, and chemotherapy, have poor efficacy, as reflected by a low median survival rate of 5-8% after post-diagnosis. Low-intensity focused ultrasound (LiFUS) is a new treatment for enhancing drug accumulation within the brain and brain malignancies. In this study, we elucidate the effect of clinical LiFUS combined with chemotherapy on tumor survival and progression in a preclinical model of triple-negative breast cancer metastasis to the brain. LiFUS significantly increased the tumor accumulation of 14C-AIB and Texas Red compared to controls (p< 0.01). LiFUS-mediated opening of the BTB is size-dependent, which is consistent with our previous studies. Mice receiving LiFUS with combinatorial Doxil and paclitaxel showed a significant increase in median survival (60 days) compared to other groups. LiFUS plus combinatorial chemotherapy of paclitaxel and Doxil also showed the slowest progression of tumor burden compared to chemotherapy alone or individual chemotherapy and LiFUS combinations. This study shows that combining LiFUS with timed combinatorial chemotherapeutic treatment is a potential strategy for improving drug delivery to brain metastases.

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.

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.

Utilization Large Animal Research as an Adjunct for Surgical Education Increases Perceived Resident Confidence.

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.

Focused ultrasound-mediated blood-brain barrier opening in Alzheimer's disease: long-term safety, imaging, and cognitive outcomes.

OBJECTIVE: MRI-guided low-intensity focused ultrasound (FUS) has been shown to reversibly open the blood-brain barrier (BBB), with the potential to deliver therapeutic agents noninvasively to target brain regions in patients with Alzheimer's disease (AD) and other neurodegenerative conditions. Previously, the authors reported the short-term safety and feasibility of FUS BBB opening of the hippocampus and entorhinal cortex (EC) in patients with AD. Given the need to treat larger brain regions beyond the hippocampus and EC, brain volumes and locations treated with FUS have now expanded. To evaluate any potential adverse consequences of BBB opening on disease progression, the authors report safety, imaging, and clinical outcomes among participants with mild AD at 6-12 months after FUS treatment targeted to the hippocampus, frontal lobe, and parietal lobe. METHODS: In this open-label trial, participants with mild AD underwent MRI-guided FUS sonication to open the BBB in ß-amyloid positive regions of the hippocampus, EC, frontal lobe, and parietal lobe. Participants underwent 3 separate FUS treatment sessions performed 2 weeks apart. Outcome assessments included safety, imaging, neurological, cognitive, and florbetaben ß-amyloid PET. RESULTS: Ten participants (range 55-76 years old) completed 30 separate FUS treatments at 2 participating institutions, with 6-12 months of follow-up. All participants had immediate BBB opening after FUS and BBB closure within 24-48 hours. All FUS treatments were well tolerated, with no serious adverse events related to the procedure. All 10 participants had a minimum of 6 months of follow-up, and 7 participants had a follow-up out to 1 year. Changes in the Alzheimer's Disease Assessment Scale-cognitive and Mini-Mental State Examination scores were comparable to those in controls from the Alzheimer's Disease Neuroimaging Initiative. PET scans demonstrated an average ß-amyloid plaque of 14% in the Centiloid scale in the FUS-treated regions. CONCLUSIONS: This study is the largest cohort of participants with mild AD who received FUS treatment, and has the longest follow-up to date. Safety was demonstrated in conjunction with reversible and repeated BBB opening in multiple cortical and deep brain locations, with a concomitant reduction of ß-amyloid. There was no apparent cognitive worsening beyond expectations up to 1 year after FUS treatment, suggesting that the BBB opening treatment in multiple brain regions did not adversely influence AD progression. Further studies are needed to determine the clinical significance of these findings. FUS offers a unique opportunity to decrease amyloid plaque burden as well as the potential to deliver targeted therapeutics to multiple brain regions in patients with neurodegenerative disorders.

Impact of adipose-derived stem cells on aortic tensile strength in a model of abdominal aortic aneurysm.

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.

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model.

BACKGROUND: Systemic drug delivery to the central nervous system is limited by presence of the blood-brain barrier (BBB). Low intensity focused ultrasound (LiFUS) is a non-invasive technique to disrupt the BBB, though there is a lack of understanding of the relationship between LiFUS parameters, such as cavitation dose, time of sonication, microbubble dose, and the time course and magnitude of BBB disruption. Discrepancies in these data arise from experimentation with modified, clinically untranslatable transducers and inconsistent parameters for sonication. In this report, we characterize microbubble and cavitation doses as LiFUS variables as they pertain to the time course and size of BBB opening with a clinical Insightec FUS system. METHODS: Female Nu/Nu athymic mice were exposed to LiFUS using the ExAblate Neuro system (v7.4, Insightec, Haifa, Israel) following target verification with magnetic resonance imaging (MRI). Microbubble and cavitation doses ranged from 4-400 µL/kg, and 0.1-1.5 cavitation dose, respectively. The time course and magnitude of BBB opening was evaluated using fluorescent tracers, ranging in size from 105-10,000 Da, administered intravenously at different times pre- or post-LiFUS. Quantitative autoradiography and fluorescence microscopy were used to quantify tracer accumulation in brain. RESULTS: We observed a microbubble and cavitation dose dependent increase in tracer uptake within brain after LiFUS. Tracer accumulation was size dependent, with 14C-AIB (100 Da) accumulating to a greater degree than larger markers (~ 625 Da-10 kDa). Our data suggest opening of the BBB via LiFUS is time dependent and biphasic. Accumulation of solutes was highest when administered prior to LiFUS mediated disruption (2-fivefold increases), but was also significantly elevated at 6 h post treatment for both 14C-AIB and Texas Red. CONCLUSION: The magnitude of LiFUS mediated BBB opening correlates with concentration of microbubbles, cavitation dose as well as time of tracer administration post-sonication. These data help define the window of maximal BBB opening and applicable sonication parameters on a clinically translatable and commercially available FUS system that can be used to improve passive permeability and accumulation of therapeutics targeting the brain.

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.

Instagramming for Justice: The Potentials and Pitfalls of Culturally Relevant Professional Learning on Instagram.

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.

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.

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.

Effects of radiation and chemotherapy on adipose stem cells: Implications for use in fat grafting in cancer patients.

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.