Objectives: Resolvins have been shown to attenuate inflammation, while NETosis, the process of neutrophils releasing neutrophil extracellular traps (NETs), produces increased inflammation. It is hypothesized that treatment of animals with resolvin D1 (RvD1) would reduce abdominal aortic aneurysm (AAA) formation by inhibiting NETosis. Methods: Wild-type (WT) 8–12-week old C57BL/6 male mice (n=47) and apolipoproteinE deficient (ApoE-/) mice (n=20) were used in two models to demonstrate the effects of RvD1 on AAA growth. In the topical elastase AAA model, WT mice were divided into three groups: (1) Deactivated elastase control group: sham surgery was performed using deactivated elastase and mice were intravenously injected with phosphate buffered saline (PBS) once a day until harvest. (2) Elastase group: active elastase was used to induce AAA and mice were injected with PBS daily until harvest. (3) RvD1 treated group: AAA was induced and mice were injected with RvD1 daily until harvest. In the angiotensin II (Ang II) induced AAA model, ApoE−/− mice were fed high fat diet and implanted with osmotic infusion pumps containing Ang II (1000ng/kg/min). The Ang II model was divided into two groups: (1) Ang II control group: Ang II was delivered and mice were injected with PBS daily until harvest. (2) RvD1 treated group: Ang II was delivered and mice were injected with RvD1 daily until harvest. On postoperative days 3, 14, or 28, aortic and blood samples were collected for western blot, histology, cytokine array, enzyme-linked immunosorbent assay, and gelatin zymography after aortic diameter measurement. Results: Day 14 RvD1 treated group demonstrated 42% reduced AAA diameter compared to elastase group (p<0.001). On postoperative day 3, RvD1 treated group showed decreased levels of NETosis markers citrullinated histone H3 (p=0.04) and neutrophil elastase (p=0.002) compared to the Elastase group. Among important cytokines involved in AAA formation, interleukin (IL) 1β was down-regulated (p=0.02), while IL-10, a protective cytokine, was upregulated (p=0.01) in the RvD1 treated group. Active matrix metalloproteinase 2 (MMP2) also decreased in the RvD1 treated group (p= 0.03). The RvD1 treated group in the Ang II AAA model, a second model, demonstrated reduced AAA diameter compared to Ang II control group on day 28 (p<0.046). RvD1 treated group showed decreased levels of citrullinated histone H3 on day 3 (p=0.002). Cytokines INF-γ, IL-1β, CXCL-10, MCP-1, and RANTES were all decreased on day 28 (p<0.05). Conclusion: Resolvin D1-mediated inhibition of NETosis may represent a future medical treatment for the attenuation of AAA growth.
This study of bariatric surgery patients at our institution identified several independent predictors of postoperative fracture. Additionally, these long-term data demonstrate patients who had bariatric surgery are at a significantly increased risk of bone fracture compared to a propensity-matched control group. Future efforts need to focus on nutrient screening and risk modification to reduce the impact of this long-term complication.
A reproducible model of aortic aneurysm rupture was developed with a high incidence of abdominal and thoracic aortic aneurysm. This model should enable further studies investigating the pathogenesis of aortic rupture, as well as allow for targeted strategies to prevent human aortic aneurysm rupture.
Objectives: Major Adverse Limb Events (MALE) and Major Adverse Cardiovascular Events (MACE) at 30 days provide standardized metrics for comparison and have been adopted by the Society for Vascular Surgery’s Objective Performance Goals for critical limb ischemia. However, MALE and MACE have not been widely adopted within the claudication population, and the comparative outcomes after lower extremity bypass (LEB) and infrainguinal endovascular intervention (IEI) remain unclear. The purpose of this study was to compare MALE and MACE after LEB and IEI in a contemporary national cohort and to determine predictors of MALE and MACE after revascularization for claudication. Methods: A national dataset of LEB and IEI performed for claudication was obtained using National Surgical Quality Improvement Program vascular-targeted participant use files from 2011-2014. Patients were stratified by LEB versus IEI and compared by appropriate univariate analysis. The primary outcomes were MALE (defined as untreated loss of patency, reintervention on the index arterial segment, or amputation of the index limb) and MACE (defined as stroke, myocardial infarction or death). Multivariable logistic regression was used to identify predictors of MALE and MACE. Results: A total of 3,925 infrainguinal revascularization procedures (2155 LEB and 1770 IEI) were performed for claudication. There was no difference in 30-day MALE between LEB and IEI (4.0% vs. 3.2%, P=.17). On multivariable logistic regression, predictors of 30-day MALE included tibial revascularization (OR 2.2, P<.0001) and prior LEB on the same arterial segment (OR 1.8, P=.004). LEB had significantly higher 30-day MACE (2.0% vs. 1.0%, P=.01) but similar mortality (0.5% vs. 0.4%, P=.6). Predictors of MACE included LEB vs IEI (OR 2.1, P=.01), chronic obstructive pulmonary disease (OR=2.2, P=.01), dialysis dependence (OR=4.4, P=.003) and diabetes (OR=1.9, P=.02). Conclusions: In this large national cohort, LEB and IEI for claudication are associated with similar 30-day MALE. Tibial revascularization and revascularization after prior failed bypass predict MALE in claudicants and should therefore be undertaken with caution. LEB was associated with higher 30-day MACE but comparable 30-day mortality compared to IEI. Patients with ESRD, COPD, and diabetes are high risk for MACE. The risk of 30-day MACE after LEB should be weighed against the longer-term outcomes of LEB vs IEI and conservative management, particularly in these higher risk patients. This analysis helps define contemporary 30-day outcomes after infrainguinal revascularization performed for claudication and serves as a baseline to which the short term outcomes of future treatments can be compared.
Objective: Few large animal models exist for the study of aortic aneurysms. βaminopropionitrile (BAPN) is a compound known to cause aortic aneurysms by inhibiting lysyl oxidase, a collagen cross-linking enzyme. It is hypothesized that BAPN plus aneurysm induction surgery would result in significant aneurysm formation in swine with biologic properties similar to human disease. Methods: Initial experiments were performed in uncastrated male swine not treated with BAPN (surgery alone). Subsequently, uncastrated male swine were fed BAPN (0.15 grams/kilogram) for 7 days before undergoing surgery: the infrarenal aorta was circumferentially dissected and measured, balloon dilated, perfused with elastase (500 units) and Type 1 collagenase (8000 units), with extraluminal elastase application. In the BAPN groups, daily BAPN feedings continued until swine harvest at postoperative days 7, 14, and 28. Results: Swine undergoing surgery alone (n=12) had significantly less dilation at 28 days compared with BAPN + surgery swine (51.9±29.2% (0-100%) vs. 113.5±30.2% (52.9-146.2%); p<0.0003). Mean aortic dilation in animals undergoing treatment with surgery and BAPN was 86.9%±47.4% (range, 55.6-157.1%), 105.4%±58.1% (50-133.3%), and 113.5%±30.2% (52.9-146.2%) at 7, 14, and 28 days, respectively. In the BAPN + surgery group, significant elastolysis was present at all time points, while aortic wall collagen content was not significantly different. Smooth muscle cells were significantly depleted at 14 and 28 days, and M1 macrophages were increased at 14 and 28 days (p<0.05, all). Matrix metalloproteinase 2 was elevated at 7 days
Background Total abdominal colectomy (TAC) is the standard surgical treatment of Clostridium difficile infection (CDI). An alternative therapy, loop ileostomy and colonic lavage (IL), was described in 2011, but the results have never been validated. Methods Patients treated surgically for CDI between April 2011 and June 2015 were included. Bivariable analysis was used to compare 30-day mortality, 1-year mortality, CDI recurrence, colon preservation and ileostomy reversal. Results Ten IL patients and thirteen TAC patients were identified. 30-day mortality (30% vs 23%, p = 1.0) and 1-year mortality (40% vs 46%, p = 1.0) were similar. Four IL and three TAC patients (57% vs 30%, p = 0.35) experienced recurrent CDI. All six surviving IL patients had successful colon preservation; five underwent ileostomy reversal compared to three in the TAC group (83% vs 43%, p = 0.27). Conclusions Although IL allowed colon preservation and return of intestinal continuity in most patients, IL did not decrease mortality or recurrent CDI when compared to TAC.
Objective Lower extremity bypass (LEB) has traditionally been the gold standard in the treatment of critical limb ischemia (CLI). Infrainguinal endovascular intervention (IEI) has become more commonly performed than LEB but comparative outcomes are limited. We sought to compare rates of Major Adverse Limb Events (MALE) and Major Adverse Cardiovascular Events (MACE) after LEB and EI in a propensity score matched, national cohort of patients with CLI. Methods The National Surgical Quality Improvement Program (NSQIP) Vascular Targeted Files (2011–2014) for LEB and IEI were merged. CLI patients were identified by ischemic rest pain and/or tissue loss. Patients were matched on a 1:1 basis for propensity to undergo LEB or IEI. Primary outcomes were 30-day MALE and MACE. Within the propensity matched cohort multivariate logistic regression was used to identify independent predictors of MALE and MACE. Results A total of 13,294 LEB and IEI were identified with 8,066 cases performed for CLI. Propensity matching identified 3,848 cases (1,924 per group). There were no differences in preoperative variables between the propensity matched LEB and IEI groups (all P>.05). At 30 days, rates of MALE were significantly lower in the LEB group (9.2% LEB vs IEI 12.2%, P=.003). On multivariate logistic regression, bypass with single segment saphenous vein vs IEI (OR 0.7 [0.54, 0.92], P=.01), and bypass with alternative conduit (prosthetic/spliced vein/composite) vs IEI (OR 0.7 [0.56, 0.98], P=.04), antiplatelet therapy (OR 0.8 [0.58, 1.00], P=.049), and statin therapy (OR 0.8 [0.62, 0.99], P=.04) were protective against MALE while infrageniculate intervention (OR 1.4 [1.09, 1.72], P=.01) and a history of prior bypass of the same arterial segment (OR 1.8 [1.41, 2.41], P<.0001) were predictive. Rates of 30-day MACE were not significantly different (4.9% LEB vs 3.7% IEI, P=.07) between the groups. Independent predictors of MACE included age (OR 1.02 [1.01, 1.04], P=.01), steroid use (OR 1.8 [1.08, 2.99], P=.03), congestive heart failure (OR 1.7 [1.00,1.96], P=.02), beta-blocker use (OR 1.6 [1.09, 1.43], P=.01), dialysis (OR 2.3 [1.55,3.45], P<.0001), totally dependent functional status (OR 3.1 [1.25, 7.58], P=.02), and suboptimal conduit for LEB compared to IEI (OR 1.6 [1.08, 2.36], P=.02). Conclusions Within this large, propensity-matched, national cohort, LEB predicted lower risk-adjusted 30-day MALE compared to IEI. Furthermore, there was no difference in 30-day MACE between the groups despite higher inherent risk with open surgical procedures. Therefore, the present study supports the effectiveness and primacy of LEB for revascularization in CLI.
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