Female and male patients have similar outcomes after transcarotid artery revascularization in prospective trials.

OBJECTIVE: Sex disparities in outcomes after carotid revascularization have long been a concern, with several studies demonstrating increased postoperative death and stroke for female patients after either carotid endarterectomy or transfemoral stenting. Adverse events after transfemoral stenting are higher in female patients, particularly in symptomatic cases. Our objective was to investigate outcomes after transcarotid artery revascularization (TCAR) stratified by patient sex hypothesizing that the results would be similar between males and females. METHODS: We analyzed prospectively collected data from the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER)1 (pivotal), ROADSTER2 (US Food and Drug Administration indicated postmarket), and ROADSTER Extended Access TCAR trials. All patients had verified carotid stenosis meeting criteria for intervention (≥80% for asymptomatic patients and ≥50% in patient with symptomatic disease), and were included based on anatomical or clinical high-risk criteria for carotid stenting. Neurological assessments (National Institutes of Health Stroke Scale, Modified Rankin Scale) were obtained before and within 24 hours from procedure end by an independent neurologist or National Institutes of Health Stroke Scale-certified nurse. Patients were stratified by sex (male vs female). Baseline demographics were compared using χ2 and Fisher's exact tests where appropriate; primary outcomes were combination stroke/death (S/D) and S/D/myocardial infarction (S/D/M) at 30 days, and secondary outcomes were the individual components of S/D/M. Univariate logistic regression was conducted. RESULTS: We included 910 patients for analysis (306 female [33.6%], 604 male [66.4%]). Female patients were more often <65 years old (20.6% vs 15%) or ≥80 years old (22.6% vs 20.2%) compared with males, and were more often of Black/African American ethnicity (7.5% vs 4.3%). There were no differences by sex in term of comorbidities, current or prior smoking status, prior stroke, symptomatic status, or prevalence of anatomical and/or clinical high-risk criteria. General anesthetic use, stent brands used, and procedure times did not differ by sex, although flow reversal times were longer in female patients (10.9 minutes male vs 12.4 minutes female; P = .01), as was more contrast used in procedures for female patients (43 mL male vs 48.9 mL female; P = .049). The 30-day S/D and S/D/M rates were similar between male and female patients (S/D, 2.7% male vs 1.6% female [P = .34]; S/D/M, 3.6% male vs 2.6% female [P = .41]), which did not differ when stratified by symptom status. Secondary outcomes did not differ by sex, including stroke rates at 30 days (2.2% male vs 1.6% female; P = .80), nor were differences seen with stratification by symptom status. Univariate analysis demonstrated that history of a prior ipsilateral stroke was associated with increased odds of S/D (odds ratio [OR], 4.19; P = .001) and S/D/M (OR, 2.78; P = .01), as was symptomatic presentation with increased odds for S/D (OR, 2.78; P = .02). CONCLUSIONS: Prospective TCAR trial data demonstrate exceptionally low rates of S/D/MI, which do not differ by patient sex.

Development of a biomarker panel for assessing cardiovascular risk in diabetic patients with chronic limb-threatening ischemia (CLTI): a prospective study.

BACKGROUND: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI. METHODS: In this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes' incidence was evaluated after 1, 3, 6 and 12 months. RESULTS: During the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events. CONCLUSIONS: Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER.

Current Medical Therapy and Revascularization in Peripheral Artery Disease of the Lower Limbs: Impacts on Subclinical Chronic Inflammation.

Peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CeVD) are characterized by atherosclerosis and inflammation as their underlying mechanisms. This paper aims to conduct a literature review on pharmacotherapy for PAD, specifically focusing on how different drug classes target pro-inflammatory pathways. The goal is to enhance the choice of therapeutic plans by considering their impact on the chronic subclinical inflammation that is associated with PAD development and progression. We conducted a comprehensive review of currently published original articles, narratives, systematic reviews, and meta-analyses. The aim was to explore the relationship between PAD and inflammation and evaluate the influence of current pharmacological and nonpharmacological interventions on the underlying chronic subclinical inflammation. Our findings indicate that the existing treatments have added anti-inflammatory properties that can potentially delay or prevent PAD progression and improve outcomes, independent of their effects on traditional risk factors. Although inflammation-targeted therapy in PAD shows promising potential, its benefits have not been definitively proven yet. However, it is crucial not to overlook the pleiotropic properties of the currently available treatments, as they may provide valuable insights for therapeutic strategies. Further studies focusing on the anti-inflammatory and immunomodulatory effects of these treatments could enhance our understanding of the mechanisms contributing to the residual risk in PAD and pave the way for the development of novel therapies.

Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population.

BACKGROUND: Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients. The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI). METHODS: We conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up. RESULTS: During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p < 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p < 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariable analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75). CONCLUSIONS: This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI.

Dietary Risk Factors and Eating Behaviors in Peripheral Arterial Disease (PAD).

Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE.

RETRACTED: Invited commentary.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and Author. This article has not been retracted for any ethics infringement but because the article on which it is commenting has been retracted.

Incidence of stent graft failure from type IIIB endoleak in contemporary endovascular abdominal aortic aneurysm repair.

BACKGROUND: Type IIIB endoleak from material failure can lead to aneurysmal sac enlargement and latent rupture after endovascular repair of abdominal aortic aneurysm. Long-term durability of the endovascular stent graft is largely unknown, and the complication rate from device failure due to material fatigue may be underappreciated. In addition, even with advancement in imaging techniques, recognition of type IIIB endoleak can be challenging, which can lead to delay in intervention. METHODS: A review of the literature was performed in PubMed and Google Scholar, yielding 23 articles with 46 case reports of type IIIB endoleak from various Food and Drug Administration-approved stent grafts after endovascular repair of infrarenal abdominal aortic aneurysm. RESULTS: The most common location of type IIIB endoleak occurred in the main body (34.8%), followed by the area of the flow divider (32.6%). Sac growth was identified in 63% (29/46) of cases. Diagnosis of the endoleak occurred an average of 54.3 months after the index operation. Endovascular repair was the primary approach for elective repair of type IIIB endoleak (61.3% vs 13.3%). Perioperative mortality was higher in ruptured or symptomatic patients compared with patients undergoing elective repair (33.3% vs 6.5%). CONCLUSIONS: The actual incidence of type IIIB endoleak is still lacking, and the etiology may be multifactorial. Therefore, suspicion of type IIIB endoleak requires appropriate imaging techniques and prompt intervention to reduce the perioperative mortality rate.

Update of Operative Log Data for Traditional versus Integrated Vascular Training Programs.

BACKGROUND: In 2006, the Accreditation Council for Graduate Medical Education (ACGME) approved an integrated 5-year vascular surgery residency program creating a 2-tiered system of training for vascular surgeons. The question remains if the new paradigm is equivalent to the traditional training. The true test of this may be looking at data from fully trained surgeons in their first years of practice. It is hard to obtain this data. There are surrogate methods that can be used. Operative experience of trainees is readily available as a substitute. The purpose of this study is to compare the operative experience of those graduating from the traditional (5 + 2) vascular training program with the integrated (0 + 5) program. METHODS: National operative case log data supplied by the ACGME was gathered and organized for vascular surgery residents graduating between 2013 and 2019. Mean case numbers were compared between integrated vascular residents and traditional vascular fellows (mean case numbers for vascular fellows included cases from their general surgery residencies). RESULTS: The 5 + 2 trainees performed an average of 35% more total procedures than the 0 + 5 trainees (1,662 ± 7 vs. 1,084 ± 12). The greater number of overall procedures performed by the 5 + 2 trainees was primarily realized by an increased number of abdominal (e.g., biliary, small/large intestine) cases. However, the 0 + 5 trainees performed 8% more vascular procedures (858 ± 10 vs. 794 ± 3). The greater number of vascular procedures performed by the 0 + 5 trainees was primarily realized by increased mean numbers of endovascular and venous procedure cases. CONCLUSIONS: The integrated 0 + 5 graduates performed more total vascular procedures than their 5 + 2 counterparts. The overall total operative experience remains greater for the traditional 5 + 2 graduates, given their additional 2 years of training. Further longitudinal studies will be needed to fully assess the effect of the newer integrated 0 + 5 training paradigm.

Assessing carotid plaque neovascularity and calcifications in patients prior to endarterectomy.

OBJECTIVE: The objective was to use two ultrasound image and signal processing techniques (MicroPure and superb microvascular imaging [SMI]; Toshiba Medical, Tokyo, Japan) to investigate carotid plaque calcification and intraplaque neovascularity flow as biomarkers for plaque vulnerability in patients before endarterectomy. METHODS: Thirty patients, with preoperative computed tomography angiography and scheduled for carotid endarterectomy, were enrolled in an institutional review board-approved study. Bilateral grayscale, power Doppler, SMI and MicroPure imaging of the carotids were performed using an Aplio 500 Platinum scanner (Toshiba). MicroPure combines nonlinear imaging and speckle suppression to mark calcifications as white spots in a blue overlay, and SMI uses clutter suppression to extract microvascular flow signals. Readers counted calcifications and scored them as present or absent; intraplaque neovascularity was scored on a 4-point scale by ultrasound imaging as well as by pathology (as the reference). MicroPure and SMI assessments were compared with conventional ultrasound examination and computed tomography angiography with pathology as the reference standard. RESULTS: Owing to technical difficulties and cancelled operations, 57 carotids were studied; endarterectomies yielded 28 specimens. Intraplaque neovascularization was detected by SMI in significantly more plagues than by power Doppler (41 vs 22 out 57 examined plaques or 72% vs 39%; P < .0001). There was no statistical difference between either reader compared with pathology (P > .37). Sensitivity specificity and accuracy for detecting intraplaque neovascularity based on color SMI and PDI were 84% (95% confidence interval [CI], 64%-96%), 33% (95% CI, 1%-91%), 79% (95% CI, 59%-92%), and 52% (95% CI, 31%-72%), 100% (95% CI, 23%-100%), and 57% (95% CI, 37%-76%), respectively. MicroPure did not correlate with any measures of intraplaque flow (P > .13). CONCLUSIONS: SMI may have potential for providing evidence of plaque vulnerability. MicroPure appears less useful in carotid applications.

Functional Popliteal Artery Entrapment Syndrome: A Review of Diagnosis and Management.

BACKGROUND: Functional popliteal artery entrapment syndrome (FPAES) results from hypertrophied gastrocnemius, soleus, and/or plantaris muscles, without an identifiable anatomic abnormality. Historically, FPAES has been managed with surgical myotomy or myomectomy. Herein, we review the literature to evaluate the results of surgery along with a newer treatment (botulinum toxin A injection) for this rare form of claudication. METHODS: A literature search in PubMed, Cochrane, and Ovid for studies reporting incidence and management of FPAES yielded 3391 publications; 2804 articles were excluded based on initially established exclusion criteria. Ultimately, data were extracted from six articles, from which the number of patients, demographic information, preoperative workup, surgical treatment details, follow-up imaging, and results of treatment were obtained. RESULTS: A total of 133 patients were studied. Mean age was 26 years; 57% were female, and noninvasive testing revealed bilateral findings in 39%. Treatment involved surgical myotomy/myomectomy (98; five studies) and botulinum toxin injection (35; two studies). Adjunctive vascular reconstruction was performed in eight of the surgical cases. Patients with FPAES who underwent surgical management were evaluated subjectively for symptomatic improvement, and some patients had duplex ultrasounds in follow-up averaging 25.6 months. Three of 98 patients (3%) had recurrent symptoms, and seven (7%) underwent revision surgical procedures. Complications in the surgical management group included seroma/hematoma (4%, 4/98) and infection (2%, 2/98). For the botulinum toxin treatment group, improvement of symptoms was achieved in 66% of patients at an average follow-up time of ten months. Most patients treated with botulinum toxin did not undergo imaging in follow-up. No complications were reported. CONCLUSIONS: This review suggests FPAES may be treated successfully with surgical myotomy/myomectomy plus adjunctive vascular reconstruction if necessary. Botulinum toxin A injection may be useful as a diagnostic and therapeutic measure for FPAES.

A randomized clinical trial evaluating negative pressure therapy to decrease vascular groin incision complications.

OBJECTIVE: Vascular groin incision complications contribute significantly to patients' morbidity and rising health care costs. Negative pressure therapy over the closed incision decreases the infection rate in cardiac and orthopedic procedures. This study prospectively evaluated negative pressure therapy as a means to decrease wound complications and associated health care costs. METHODS: This was a randomized, prospective, single-institution study of 119 femoral incisions closed primarily after elective vascular surgery including both inflow (eg, aortofemoral) and outflow (eg, femoral-popliteal bypass) procedures. Incisions were categorized as high risk for wound complications on the basis of body mass index >30 kg/m2, pannus, reoperation, prosthetic graft, poor nutrition, immunosuppression, or hemoglobin A1c >8% and randomized 1:1 to standard gauze (n = 60) dressing vs negative pressure therapy (Prevena [Acelity, San Antonio, Tex], n = 59). Wound complication rate, length of stay (LOS), reoperation, readmission, and variable hospital costs were determined during 30 days. Statistical analysis was performed using χ2 test along with a two-sample unpaired t-test for continuous variables. RESULTS: There were no significant demographic differences (age, sex, risk factors for wound complication) between the two high-risk groups. In low-risk controls, the major wound complication rate was 4.8% (involving one infection in 21 incisions), resulting in a 3.8-day LOS, 4.8% reoperation, 4.8% readmission rate, and $17,599 in average variable cost. For high-risk controls, there was a significant increase in major wound complications to 25% (including all 12 infections in 60 incisions), LOS (10.6 days), reoperation (18.3%), readmission (16.7%), and costs ($36,537). Finally, negative pressure therapy significantly reduced major wound complications to 8.5% (including five of six infections in 59 incisions; P < .001), reoperation (8.5%; P < .05), and readmission (6.8%; P < .04) but not LOS (10.6 days). The average variable cost was reduced ($30,492), yielding an average savings of $6045 per patient (P = .11). CONCLUSIONS: This study suggests that negative pressure therapy significantly reduces the major wound complication, reoperation, and readmission rates for patients at high risk for groin wound complications. Furthermore, this therapy may lead to a reduction in hospital costs. Negative pressure therapy for all groin incisions considered at high risk for wound complications is recommended.

Temporary Reversal of Blood Flow During Transcarotid Artery Revascularization Does Not Change Brain Electrical Activity in Lead-In Cases of the ROADSTER 1 Multicenter Trial.

PURPOSE: To evaluate any intraoperative electroencephalographic (EEG) changes accompanying reversed flow with the ENROUTE Transcarotid Neuroprotection System during transcarotid artery revascularization (TCAR). METHODS: A post hoc analysis was performed of the first 81 consecutive lead-in patients (mean age 72.8±8 years; 61 men) enrolled in the ROADSTER 1 trial at 5 participating institutions. All patients had high-grade carotid artery stenosis [53 (59.3%) left sided; 12 (14.8%) contralateral occlusions] and high-risk criteria for carotid endarterectomy. A third had symptoms of either stroke (13, 16.0%) or transient ischemic attack (14, 17.3%). This subset of early patients underwent EEG monitoring to detect any cerebral changes during reversed flow as an added safety measure mandated by the ROADSTER 1 trial protocol. RESULTS: Mean flow reversal time was 12.9±8.2 minutes. The goal mean arterial pressure during reversed flow was 100 mm Hg, but 7 (8.6%) patients suffered hypotension. One (1.2%) patient had slight EEG changes secondary to blood pressure fluctuation; these resolved with blood pressure elevation. No other EEG changes were noted. One (1.2%) patient had a postoperative stroke and another (1.2%) had postoperative myocardial infarction (MI), leading to 2.5% 30-day stroke/death/MI rate. CONCLUSION: Temporary reversal of blood flow during TCAR is a safe maneuver and does not cause cerebral ischemia in the vast majority of patients, including those with contralateral carotid occlusion. Carotid stenting performed with reversed blood flow mitigates cerebral embolization and periprocedural stroke without concern for brain ischemia.

Arterial protocol including prophylactic distal perfusion catheter decreases limb ischemia complications in patients undergoing extracorporeal membrane oxygenation.

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation (ECMO) is a salvage therapy in patients with severe cardiopulmonary failure. Owing to the large size of the cannulas inserted via the femoral vessels (≤24-F) required for adequate oxygenation, this procedure could result in significant limb ischemic complications (10%-70%). This study evaluates the results of a distal limb perfusion arterial protocol designed to reduce associated complications. METHODS: We conducted a retrospective institutional review board-approved review of consecutive patients requiring ECMO via femoral cannulation (July 2010-January 2015). To prevent arterial ischemia, a distal perfusion catheter (DPC) was placed antegrade into the superficial femoral artery and connected to the ECMO circuit. Limb perfusion was monitored via near-infrared spectroscopy (NIRS) placed on both calves. Decannulation involved open repair, patch angioplasty, and femoral thrombectomy as needed. RESULTS: A total of 91 patients were placed on ECMO via femoral arterial cannula (16-F to 24-F) for a mean duration of 9 days (range, 1-40 days). A percutaneous DPC was inserted prophylactically at the time of cannulation in 55 of 91 patients, without subsequent ischemia. Of the remaining 36 patients without initial DPC placement, 12 (33% without DPC) developed ipsilateral limb ischemia related to arterial insufficiency, as detected by NIRS and clinical findings. In these patients, the placement of a DPC (n = 7) with or without a fasciotomy, or with a fasciotomy alone (n = 4), resulted in limb salvage; only one patient required subsequent amputation. After decannulation (n = 7), no patients had further evidence of limb ischemia. Risk factors for the development of limb ischemia identified by categorical analysis included lack of DPC at time of cannulation and ECMO cannula size of less than 20-Fr. There was a trend toward younger patient age. Overall ECMO survival rate was 42%, whereas survival in patients with limb ischemia was only 25%. CONCLUSIONS: Limb ischemia complications from ECMO may be decreased by prophylactic placement of an antegrade DPC. Without DPC, continuous monitoring using NIRS may identify limb ischemia, which can be treated subsequently with DPC and or fasciotomy.

Autologous human plasma in stem cell culture and cryopreservation in the creation of a tissue-engineered vascular graft.

OBJECTIVE: Previous work demonstrated the effectiveness of autologous adipose-derived stem cells (ASCs) as endothelial cell (EC) substitutes in vascular tissue engineering. We further this work toward clinical translation by evaluating ASC function after (1) replacement of fetal bovine serum (FBS) with autologous human plasma (HP) in culture and (2) cryopreservation. METHODS: Human ASCs and plasma, isolated from periumbilical fat and peripheral blood, respectively, were collected from the same donors. ASCs were differentiated in endothelial growth medium supplemented with FBS (2%) vs HP (2%). Proliferation was measured by growth curves and MTT assay. Endothelial differentiation was measured by quantitative polymerase chain reaction, assessment of acetylated low-density lipoprotein uptake, and cord formation after plating on Matrigel (BD Biosciences, San Jose, Calif). Similar studies were conducted before and after cryopreservation of ASCs and included assessment of cell retention on the luminal surface of a vascular graft. RESULTS: ASCs expanded in HP-supplemented medium showed (1) similar proliferation to FBS-cultured ASCs, (2) consistent differentiation toward an EC lineage (increases in CD31, von Willebrand factor, and CD144 message; acetylated low-density lipoprotein uptake; and cord formation on Matrigel), and (3) retention on the luminal surface after seeding and subsequent flow conditioning. Cryopreservation did not significantly alter ASC viability, proliferation, acquisition of endothelial characteristics, or retention after seeding onto a vascular graft. CONCLUSIONS: This study suggests that (1) replacement of FBS with autologous HP--a step necessary for the translation of this technology into human use--does not significantly impair proliferation or endothelial differentiation of ASCs used as EC substitutes and (2) ASCs are tolerant to cryopreservation in terms of maintaining EC characteristics and retention on a vascular graft.

Atypical Mycotic Aortic Aneurysms.

Mycotic aortic aneurysms are rare occurrences and such aneurysms associated with Streptococcus pneumoniae are seldom seen in the current antibiotic era. We present the unusual case of a 68-year-old healthy female with a Streptococcal mycotic abdominal aortic aneurysm of unknown etiology treated with antibiotics and open surgical intervention. Postoperative imaging revealed multiple new thoracic mycotic aortic aneurysms for which she was treated with thoracic endovascular aortic repair. Sequential abdominal and thoracic Streptococcal mycotic aortic aneurysms treated with a combination of open and endovascular surgery demonstrate a unique and rare case.

The first assessment of operative logs for traditional vascular fellowship track versus integrated vascular training programs.

OBJECTIVE: As vascular surgery training paradigms evolve, one measure of success is operative experience. This study assessed the initial operative experience of those graduating from new integrated programs (0+5) vs those from the traditional programs (5+2). METHODS: National operative case log data supplied by the Accreditation Council for Graduate Medical Education was compiled for vascular surgical residents graduating between 2010 and 2013. Mean case numbers for the 0+5 residents were compared with those for the 5+2 residents (experience from their general surgery residency plus vascular fellowship) for total vascular operations, open vascular operations, endovascular procedures, and total operative experience. RESULTS: The 5+2 trainees performed significantly more procedures than the 0+5 trainees (mean, 1605 vs 1015); however, they performed 12% less vascular procedures (mean, 758 vs 851). No significant differences in total number of open vascular operations (mean, 404 vs 411) or specific open operations for cerebral vascular disease, aneurysm, peripheral obstruction, and access were found. The increase in vascular procedures logged by 0+5 trainees was realized by a 24% increase in endovascular procedures, mainly involving diagnostic arteriography, caval filter placement, and balloon angioplasty. No significant differences were seen in endovascular aneurysm repair (mean, 63 vs 60) and stent placement (mean, 59 vs 60). CONCLUSIONS: This report summarizes the first data available for the 0+5 trainee operative experience. Compared with the traditional 5+2 trainees, the 0+5 trainees have (1) equivalent open vascular training and (2) overall superior endovascular training, although this was accounted via an increase in minor procedures. The overall operative experience remains greater for the 5+2 trainees secondary to 2 extra years of training. Further longitudinal studies will be needed to fully characterize the effect of the new 0+5 training paradigm.

In vitro effects of tamoxifen on adipose-derived stem cells.

In breast reconstructive procedures, adipose-derived stem cells (ASCs) that are present in clinical fat grafting isolates are considered to play the main role in improving wound healing. In patients following chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. However, it is unclear if tamoxifen (TAM) as the most widely used hormonal therapeutic agent for breast cancer treatment, affects the ASCs and ultimately wound healing. This study evaluated whether TAM exposure to in vitro human ASCs modulate cellular functions. Human ASCs were isolated and treated with TAM at various concentrations. The effects of TAM on cell cycle, cell viability and proliferation rates of ASCs were examined by growth curves, MTT assay and BrdU incorporation, respectively. Annexin V and JC-1 Mitochondrial Membrane Potential assays were used to analyze ASC apoptosis rates. ASCs were cultured in derivative-specific differentiation media with or without TAM (5 uM) for 3 weeks. Adipogenic and osteogenic differentiation levels were measured by quantitative RT-PCR and histological staining. TAM has cytotoxic effects on human ASCs through apoptosis and inhibition of proliferation in dose- and time-dependent manners. TAM treatment significantly down-regulates the capacity of ASCs for adipogenic and osteogenic differentiation (p<0.05 vs. control), and inhibit the ability of the ASCs to subsequently formed cords in Matrigel. This study is the first findings to our knowledge that demonstrated that TAM inhibited ASC proliferation and multi-lineage ASC differentiation rates. These results may provide insight into the role of TAM with associated poor soft tissue wound healing and decreased fat graft survival in cancer patients receiving TAM.

Posterior tibial vein aneurysm presenting as tarsal tunnel syndrome.

Tarsal tunnel syndrome is a compressive neuropathy of the posterior tibial nerve within the tarsal tunnel. Its etiology varies, including space occupying lesions, trauma, inflammation, anatomic deformity, iatrogenic injury, and idiopathic and systemic causes. Herein, we describe a 46-year-old man who presented with left foot pain. Work up revealed a venous aneurysm impinging on the posterior tibial nerve. Following resection of the aneurysm and lysis of the nerve, his symptoms were alleviated. Review of the literature reveals an association between venous disease and tarsal tunnel syndrome; however, this report represents the first case of venous aneurysm causing symptomatic compression of the nerve.

Sphingosine-1-phosphate promotes the differentiation of adipose-derived stem cells into endothelial nitric oxide synthase (eNOS) expressing endothelial-like cells.

BACKGROUND: Adipose tissue provides a readily available source of autologous stem cells. Adipose-derived stem cells (ASCs) have been proposed as a source for endothelial cell substitutes for lining the luminal surface of tissue engineered bypass grafts. Endothelial nitric oxide synthase (eNOS) is a key protein in endothelial cell function. Currently, endothelial differentiation from ASCs is limited by poor eNOS expression. The goal of this study was to investigate the role of three molecules, sphingosine-1-phosphate (S1P), bradykinin, and prostaglandin-E1 (PGE1) in ASC endothelial differentiation. Endothelial differentiation markers (CD31, vWF and eNOS) were used to evaluate the level of ASCs differentiation capability. RESULTS: ASCs demonstrated differentiation capability toward to adipose, osteocyte and endothelial like cell phenotypes. Bradykinin, S1P and PGE were used to promote differentiation of ASCs to an endothelial phenotype. Real-time PCR showed that all three molecules induced significantly greater expression of endothelial differentiation markers CD31, vWF and eNOS than untreated cells. Among the three molecules, S1P showed the highest up-regulation on endothelial differentiation markers. Immunostaining confirmed presence of more eNOS in cells treated with S1P than the other groups. Cell growth measurements by MTT assay, cell counting and EdU DNA incorporation suggest that S1P promotes cell growth during ASCs endothelial differentiation. The S1P1 receptor was expressed in ASC-differentiated endothelial cells and S1P induced up-regulation of PI3K. CONCLUSIONS: S1P up-regulates endothelial cell markers including eNOS in ASCs differentiated to endothelial like cells. This up-regulation appears to be mediated by the up-regulation of PI3K via S1P1 receptor. ASCs treated with S1P offer promising use as endothelial cell substitutes for tissue engineered vascular grafts and vascular networks.

Endothelial differentiation of diabetic adipose-derived stem cells.

BACKGROUND: Diabetic (DM) patients frequently lack autologous vascular tissue required for revascularization procedures and dialysis access creation. We have developed a tissue-engineered graft that uses adipose-derived stem cells (ASC) as endothelial cell substitutes. Here, we compare DM versus nondiabetic (NDM) ASC in terms of isolation efficiency, proliferation, commitment toward endothelial lineage, and seeding onto the luminal surface of a graft. METHODS: ASC were isolated from liposuction specimens of vascular surgery patients. Proliferation was assessed by constructing growth curves over 14 d. ASC were differentiated in endothelial growth medium (EGM2). Endothelial commitment was assessed by measuring endothelial cell-specific gene expression (CD31, von Willebrand factor) and by cord formation on Matrigel. Finally, ASC were seeded onto a vascular scaffold, flow conditioned, and imaged with confocal microscopy. RESULTS: Diabetes did not alter ASC isolation efficiency (224,028 ± 20,231 cells/g adipose for DM (n = 53) versus 259,345 ± 15,441 cells/g adipose for NDM (n = 145; P = 0.21). Growth curves for DM (n = 6) and NDM (n = 6) also appeared similar. After culture in EGM2, upregulation of CD31 and von Willebrand factor message was observed in NDM; these markers were found within the primary cultures of DM but no upregulation was observed after culture in EGM2. Both groups exhibited similar cord formation on Matrigel and retention to vascular scaffolds. CONCLUSIONS: Isolation and proliferation studies suggest that adipose is a promising source of stem cells for tissue engineering in the DM population. The angiogenic potential of DM ASC appears intact; however, differences in acquisition of endothelial cell markers suggest that differentiation may be inhibited or delayed by diabetes.