The most common and significant morbidity and mortality of vascular surgical procedures remain coronary artery disease, arrhythmia, and heart failure. Cardiac evaluation and medical optimization provide the groundwork for best medical practice in an otherwise high-risk surgical population. The goal of this study is to review the most current literature and guidelines for evaluating patients prior to vascular surgical interventions. From this, we have made our own recommendations regarding both the preoperative and perioperative management of vascular surgical patients.Risk stratification using a modified Lee index may be best to assess perioperative cardiac risk. Coronary revascularization should be reserved for those patients with significant coronary disease irrespective of symptoms. β-blockers, statins, and antiplatelet agents should be considered for all patients with peripheral vascular disease.The preoperative management of vascular surgical patients requires a complete understanding of the patient's medical history as it relates to their perioperative cardiac risk. Overwhelming data support the use of medical therapy as adjunct to minimize or prevent the risk of future cardiovascular events. As vascular surgery transitions to the outpatient setting, further studies will be required to better elucidate cardiac evaluation in this patient population.

Purpose of review The most common and significant morbidity and mortality of vascular surgical procedures remain coronary artery disease, arrhythmia, and heart failure. Cardiac evaluation and medical optimization provide the groundwork for best medical practice in an otherwise high-risk surgical population. The goal of this study is to review the most current literature and guidelines for evaluating patients prior to vascular surgical interventions. From this, we have made our own recommendations regarding both the preoperative and perioperative management of vascular surgical patients. Recent findings Risk stratification using a modified Lee index may be best to assess perioperative cardiac risk. Coronary revascularization should be reserved for those patients with significant coronary disease irrespective of symptoms. beta-blockers, statins, and antiplatelet agents should be considered for all patients with peripheral vascular disease. Summary The preoperative management of vascular surgical patients requires a complete understanding of the patient's medical history as it relates to their perioperative cardiac risk. Overwhelming data support the use of medical therapy as adjunct to minimize or prevent the risk of future cardiovascular events. As vascular surgery transitions to the outpatient setting, further studies will be required to better elucidate cardiac evaluation in this patient population.

Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host's ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection.

Bisphenol A (BPA) is a high-production volume chemical classified as an environmental estrogen and used primarily in the plastics industry. BPA's increased usage correlates with rising BPA levels in people and a corresponding increase in the incidence of asthma. Due to limited studies, the contribution of maternal BPA exposure to allergic asthma pathogenesis is unclear. Using two established mouse models of allergic asthma, we examined whether developmental exposure to BPA alters hallmarks of allergic lung inflammation in adult offspring. Pregnant C57BL/6 dams were gavaged with 0, 0.5, 5, 50, or 500 μg BPA/kg/day from gestational day 6 until postnatal day 21. To induce allergic inflammation, adult offspring were mucosally sensitized with inhaled ovalbumin containing low-dose lipopolysaccharide or ip sensitized using ovalbumin with alum followed by ovalbumin aerosol challenge. In the mucosal sensitization model, female offspring that were maternally exposed to ≥ 50 μg BPA/kg/day displayed enhanced airway lymphocytic and lung inflammation, compared with offspring of control dams. Peritoneally sensitized, female offspring exposed to ≤ 50 μg BPA/kg/day presented dampened lung eosinophilia, compared with vehicle controls. Male offspring did not exhibit these differences in either sensitization model. Our data demonstrate that maternal exposure to BPA has subtle and qualitatively different effects on allergic inflammation, which are critically dependent upon route of allergen sensitization and sex. However, these subtle, yet persistent changes due to developmental exposure to BPA did not lead to significant differences in overall airway responsiveness, suggesting that early life exposure to BPA does not exacerbate allergic inflammation into adulthood.

The biological effects of acute particulate air pollution exposure in host innate immunity remain obscure and have relied largely on in vitro models. We hypothesized that single acute exposure to ambient or engineered particulate matter (PM) in the absence of other secondary stimuli would activate lung dendritic cells (DC) in vivo and provide information on the early immunological events of PM exposure and DC activation in a mouse model naïve to prior PM exposure. Activation of purified lung DC was studied following oropharyngeal instillation of ambient particulate matter (APM). We compared the effects of APM exposure with that of diesel-enriched PM (DEP), carbon black particles (CBP) and silver nanoparticles (AgP). We found that PM species induced variable cellular infiltration in the lungs and only APM exposure induced eosinophilic infiltration. Both APM and DEP activated pulmonary DC and promoted a Th2-type cytokine response from naïve CD4+ T cells ex vivo. Cultures of primary peribronchial lymph node cells from mice exposed to APM and DEP also displayed a Th2-type immune response ex vivo. We conclude that exposure of the lower airway to various PM species induces differential immunological responses and immunomodulation of DC subsets. Environmental APM and DEP activated DC in vivo and provoked a Th2 response ex vivo. By contrast, CBP and AgP induced altered lung tissue barrier integrity but failed to stimulate CD4+ T cells as effectively. Our work suggests that respirable pollutants activate the innate immune response with enhanced DC activation, pulmonary inflammation and Th2-immune responsiveness.

Background: There is a paucity of literature regarding thoracic endovascular aneurysm repair (TEVAR) in women. We report our institutional experience with TEVAR. Methods: Retrospective chart review was performed from 2004 to 2008. TEVAR was performed in 59 patients; 29 (49%) were female. Results: Mean age was 73.5 years. Mean thoracic aortic aneurysm (TAA) diameter was larger for women (5.9 cm vs 4.7 cm). A trend toward an increase in paraplegia was noted in women, 10.3% vs 4.8%. This may be related to increase in length of aortic coverage in women, 18.2 cm vs 15.2 cm (P < .05). Conclusion: TEVAR in women is safe and effective. The length of aortic coverage is greater in women, which may be related to larger aneurysms and more diffuse disease. This may be associated with a concerning increase in postoperative paraplegia. Women undergoing TEVAR should be considered for prophylactic maneuvers to prevent spinal cord ischemia (SCI), including minimizing length of coverage.

BACKGROUND:Preoperative evaluation and perioperative management of cardiac disease in patients undergoing vascular surgery (VS) is important for patients and vascular surgeons. Recent evidence has emerged that has allowed us to develop contemporary paradigms for evaluating and managing coronary artery disease in VS patients perioperatively. METHODS:The utility of stress testing, the role of preoperative coronary revascularization, the optimal use of beta-blockers and statins, and the role of antiplatelet therapy in VS patients were reviewed in the literature. RESULTS:The revised Lee cardiac risk index, based on the number of risk factors (high-risk surgery, ischemic heart disease, congestive heart failure, cerebrovascular disease, insulin-dependent diabetes mellitus, renal failure, hypertension, and age >75) quantitates cardiac risk. Stress testing is not predictive of myocardial ischemia/infarction (MI) or death and is only recommended in patients with unstable angina or an active arrhythmia. Stress testing for patients with 0 to 2 risk factors delays VS up to 3 weeks. In high-risk patients (>or=3 risk factors), it helps to identify patients who may develop myocardial ischemia and would benefit from a 30-day period to optimize medical therapy before VS. Stress testing and coronary catheterization do not predict which coronary artery to revascularize to prevent MI or death. Revascularization does not decrease MI or death rates at 1 month or 6 years. Although beta-blocker treatment decreases cardiac risk with VS, timing and dosage (titration) influence outcomes, improper usage may increase stroke and death rate, and not all VS patients should be taking these drugs. Patients with >or=1 risk factor should be considered to begin a low dose beta-blocker 1 month before VS. Preoperative statin use sharply decreases MI, stroke, and death perioperatively and long-term postoperatively. CONCLUSION:Routine stress testing should not be performed before VS. The Lee index should be used to stratify risk in patients undergoing VS. Patients with >or=3 risk factors or active cardiac conditions should undergo stress testing, if VS can be delayed. All VS patients, except those with 0 risk factors, should be considered for a beta-blocker (bisoprolol, 2.5-5 mg/d started 1 month before VS, titrated to a pulse <70 beats/min and a systolic blood pressure >or=120 mm Hg). Intermediate risk factors may not require aggressive heart rate control but simply maintenance on a low-dose beta-blocker. Statins should be started (ideally 30 days) before all VS using long-acting formulations such as fluvastatin (80 mg/d) for patients unable to take oral medication.

Dendritic cells (DC) are potent professional antigen-presenting cells that drive primary immune responses to infections or other agonists perceived as ‘dangerous’. Muc1 is the only cell surface mucin or MUC gene product that is expressed in DC. Unlike other members of this glycoprotein family, Muc1 possesses a unique cytosolic region capable of signal transduction and attenuating toll-like receptor (TLR) activation. The expression and function of Muc1 has been intensively investigated on epithelial and tumor cells, but relatively little is known about its function on DC. We hypothesized that Muc1 would influence in vitro generation and primary DC activation in response to the TLR4 and TLR5 ligands lipopolysaccharide and flagellin. Compared with Muc1+/+ DC, we found that Muc1–/– DC were constitutively activated, as determined by higher expression of co-stimulatory molecules (CD40, CD80 and CD86), greater secretion of immunoregulatory cytokines (TNF-α and VEGF), and better stimulation of allogeneic naïve CD4+ T cell proliferation. After activation by either LPS or flagellin and co-culture with allogeneic CD4+ T cells, Muc1–/– DC also induced greater secretion of TNF-α and IFN-γ compared to similarly activated Muc1+/+ DC. Taken together, our results indicate that deletion of Muc1 promotes a heightened functional response of DC in response to TLR4 and TLR5 signaling pathways, and suggests a previously under-appreciated role for Muc1 in regulating innate immune responses of DC.

Oxidative stress plays an important role in immune regulation and dendritic cell (DC) maturation. Recent studies indicate that allergens, including ragweed extract (RWE), possess prooxidant activities, but how RWE interacts with DCs is not well understood. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a key transcription factor that regulates constitutive and coordinated induction of a battery of antioxidant genes. We hypothesized that RWE would activate DCs and that this response would be augmented in the absence of Nrf2. We generated bone marrow-derived DCs (BM-DCs) and isolated lung DCs from Nrf2(+/+) and Nrf2(-/-) mice and studied the effects of RWE on DCs in vitro. Under resting conditions, Nrf2(-/-) BM-DCs exhibited constitutively greater levels of inflammatory cytokines and costimulatory molecules than Nrf2(+/+) BM-DCs. Exposure to RWE impaired endocytic activity, significantly induced oxidative stress, and enhanced the expression of CD80, CD86, and MHCII in Nrf2(-/-) BM-DCs when compared with Nrf2(+/+) BM-DC, in association with reduced expression of Nrf2-regulated antioxidant genes. RWE significantly induced the secretion of inflammatory cytokines IL-6 and TNF-alpha in BM-DCs and lung DCs from Nrf2(-/-) mice than Nrf2(+/+) mice and significantly inhibited the secretion of IL-12 in Nrf2(+/+) BM-DCs and IL-18 in Nrf2(+/+) and Nrf2(-/-) BM-DCs. The stimulatory effects of RWE on DC activation were inhibited to varying degrees by the antioxidant N-acetyl cysteine. Our findings indicate that a defect in Nrf2-mediated signaling mechanisms alters the response of DCs to a common environmental allergen, which may contribute to the susceptibility to allergic diseases.

There is a paucity of literature regarding thoracic endovascular aneurysm repair (TEVAR) in women. We report our institutional experience with TEVAR in women. A retrospective chart review was performed. Case planning was done with CTa. Patients with small access vessels received a 10mm common iliac artery (CIA) conduit. Patients received a CTa 30-days post-operatively. Post-operative stroke was diagnosed clinically and by cerebral imaging. Spinal cord ischemia (SCI) was diagnosed clinically with negative cerebral imaging. TEVAR was performed in 51 patients for a variety of aortic pathologies; of these 29 (56%) were female. The mean age of women was 73.5 years. Mean TAA diameter was larger for women than for men (5.9 cm vs. 4.7 cm). TEVAR was performed more often on an urgent basis in women as compared to men (20.7% vs. 9.5%, p= NS). There was a trend towards pain as the predominant presenting symptom in women as compared to men (44.8% vs. 22.7%, p= NS). There was a statistically significant difference in the need for a CIA conduit in women compared to men (48.3% vs. 20.0%, p<0.05). This was not associated with an increase in peripheral ischemic complications or an increase length of stay (LOS). There were no differences in endoleak rate, stroke, or post-operative death. Although not statistically significant, there was a concerning trend towards an increase in paraplegia in women, 10.3% versus 4.8%. This may be related to the statistically significant increase in the total length of aortic coverage required in women compared to men, 18.2 cm versus 15.2 cm (p<0.05). Our data suggests that TEVAR in women is safe and effective. Women presented more frequently with indications for urgent intervention. As expected, women require a conduit more often due to smaller access vessel size, but this does not increase the rate of peripheral ischemic complications or LOS. The length of aortic coverage is greater in women than in men, and this may be related to their being treated for larger aneurysms and more advanced or diffuse disease. The increase in length of coverage appears to be associated with a concerning increase in postoperative paraplegia. Female patients undergoing TEVAR should be considered for prophylactic maneuvers to prevent SCI, including minimizing length of coverage.

Major histocompatability molecules (MHC) are involved in presentation of peptide antigens for recognition by the immune system. The density and stability of presented peptides is a critical parameter in determining the magnitude of the immune response. Increasing the half-life and density of an MHC class I-peptide complex should promote a stronger cytotoxic T lymphocyte (CTL) response to clinically important peptides, including those that exhibit low or suboptimal MHC class I binding affinity. We hypothesized that the covalent linkage of a known tumor antigen peptide to beta-2-microglobulin (beta2m) would increase peptide immunogenicity and, therefore, in vivo effectiveness as an antitumor vaccine in BALB/c mice. The iL3 peptide fusion protein (iL3-L12-hbeta2m) was developed based on the mutant iL3 peptide, derived from the L3 ribosomal protein, and expressed in the mutagenized murine fibroblastic tumor cell line, BCA34. The iL3-L12-beta2m and a negative control fusion protein utilizing the H-2K(d)-restricted NP(147-155) influenza peptide (NP-L12-hbeta2m) were both produced in E. coli for exogenous antigen presentation by dendritic cells. In vitro, the iL3-L12-hbeta2m protein was found to stabilize H-2K(d) over time on the surface of H-2K(d)-expressing target cells and sensitized them to peptide-specific CTL-mediated lysis. Furthermore, mice immunized with dendritic cells pulsed with the iL3-L12-hbeta2m protein rejected a challenge with BCA34 cells significantly more so than mice immunized with dendritic cells pulsed with free peptide and hbeta2m. We conclude that vaccines incorporating peptides covalently linked to beta2m may have future potential in the specific targeting of human malignancy.