Staged endovascular repair of an abdominal aortic aneurysm adjacent to a chronic high-flow iliocaval traumatic arteriovenous fistula

Large-vessel chronic traumatic arteriovenous fistulas are a rare complication after trauma. Delayed presentation can consist of one or more features of high-output cardiac failure, pulsatile abdominal mass, bruit, limb ischemia, and venous congestion. We describe a patient with a complex iliocaval fistula secondary to a remote gunshot wound associated with a large 8.5-cm aortic aneurysm. Informed consent of the patient was obtained for publication of the case

XIAP antagonist embelin inhibited proliferation of cholangiocarcinoma cells.

Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP) impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 cells. Assessment of nuclear morphology demonstrated a concentration-dependent increase in nuclear staining. Interestingly, embelin induced nuclear morphology changes as a single agent, independent of the addition of TNF-related apoptosis inducing ligand (TRAIL). However, caspase activity assays revealed that increasing embelin concentrations resulted in slight inhibition of caspase activity, not activation. In addition, the use of a pan-caspase inhibitor did not prevent nuclear morphology changes. Finally, embelin treatment of cholangiocarcinoma cells did not induce DNA fragmentation or PARP cleavage. Apoptosis does not appear to contribute to the effects of embelin on cholangiocarcinoma cells. Instead, embelin caused inhibition of cell proliferation and cell cycle analysis indicated that embelin increased the number of cells in S and G2/M phase. Our results demonstrate that embelin decreased proliferation in cholangiocarcinoma cell lines. Embelin treatment resulted in decreased XIAP protein expression, but did not induce or enhance apoptosis. Thus, in cholangiocarcinoma cells the mechanism of action of embelin may not be dependent on apoptosis

XIAP Antagonist Embelin Inhibited Proliferation of Cholangiocarcinoma Cells

Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP) impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 cells. Assessment of nuclear morphology demonstrated a concentrationdependent increase in nuclear staining. Interestingly, embelin induced nuclear morphology changes as a single agent, independent of the addition of TNF-related apoptosis inducing ligand (TRAIL). However, caspase activity assays revealed that increasing embelin concentrations resulted in slight inhibition of caspase activity, not activation. In addition, the use of a pan-caspase inhibitor did not prevent nuclear morphology changes. Finally, embelin treatment of cholangiocarcinoma cells did not induce DNA fragmentation or PARP cleavage. Apoptosis does not appear to contribute to the effects of embelin on cholangiocarcinoma cells. Instead, embelin caused inhibition of cell proliferation and cell cycle analysis indicated that embelin increased the number of cells in S and G2/M phase. Our results demonstrate that embelin decreased proliferation in cholangiocarcinoma cell lines. Embelin treatment resulted in decreased XIAP protein expression, but did not induce or enhance apoptosis. Thus, in cholangiocarcinoma cells the mechanism of action of embelin may not be dependent on apoptosis

XIAP antagonist embelin inhibited proliferation of cholangiocarcinoma cells.

Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP) impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 cells. Assessment of nuclear morphology demonstrated a concentration-dependent increase in nuclear staining. Interestingly, embelin induced nuclear morphology changes as a single agent, independent of the addition of TNF-related apoptosis inducing ligand (TRAIL). However, caspase activity assays revealed that increasing embelin concentrations resulted in slight inhibition of caspase activity, not activation. In addition, the use of a pan-caspase inhibitor did not prevent nuclear morphology changes. Finally, embelin treatment of cholangiocarcinoma cells did not induce DNA fragmentation or PARP cleavage. Apoptosis does not appear to contribute to the effects of embelin on cholangiocarcinoma cells. Instead, embelin caused inhibition of cell proliferation and cell cycle analysis indicated that embelin increased the number of cells in S and G2/M phase. Our results demonstrate that embelin decreased proliferation in cholangiocarcinoma cell lines. Embelin treatment resulted in decreased XIAP protein expression, but did not induce or enhance apoptosis. Thus, in cholangiocarcinoma cells the mechanism of action of embelin may not be dependent on apoptosis

Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation

Introduction The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth. Methods Peripheral blood was collected from patients previously diagnosed with abdominal aortic aneurysm or presenting for their U.S. Preventive Task Force-recommended abdominal aortic aneurysm screening. Plasma and circulating peripheral blood mononuclear cells were isolated using Ficoll density centrifugation. Circulating plasma inflammatory and regulatory cytokines were assessed with enzyme-linked immunosorbent assays. CD4+ cell phenotyping was performed using flow cytometric analysis and expressed as a proportion of total CD4+ cells. To determine the circulating antibody to self-antigen response, a modified enzyme-linked immunosorbent assay was performed against antibodies to collagen type V and elastin fragments. Results Peripheral blood was isolated from 266 patients without diabetes mellitus (n=182), with diabetes mellitus not treated with metformin (n=34), and with diabetes mellitus actively taking metformin (n=50) from 2015 to 2017. We found no differences in the expression of Tr1, Th17, and Treg CD4+ fractions within diabetics ± metformin. When comparing inflammatory cytokines, we detected no differences in IL-1β, IL-6, IL-17, IL-23, IFN-γ, and TNF-α. Conversely, no differences were observed pertaining to the expression to regulatory cytokines IL-4, IL-10, IL-13, TSG-6, or TGF-β. Lastly, no differences in expression of collagen type V and elastin fragment antigen and/or antibodies were detected with metformin use in diabetics. Conclusion Metformin in diabetics at-risk for abdominal aortic aneurysm or diagnosed with abdominal aortic aneurysm does not seem to alter the peripheral inflammatory environment

Cryopreserved Homografts in Infected Infrainguinal Fields Are Associated with Frequent Reinterventions and Poor Amputation-Free Survival

Background Single-length saphenous vein continues to be the conduit of choice in infected-field critical limb ischemia. However, half of these individuals have inadequate vein secondary to previous use or chronic venous disease. We reviewed our outcomes of infected-field infrainguinal bypasses performed with cryopreserved homografts (CHs), a widely accepted alternative to autogenous vein in this setting. Methods This is a retrospective, institutional descriptive analysis of infected-field infrainguinal revascularizations between 2012 and 2015. Results Twenty-four operations were performed in the same number of patients for limb ischemia with signs of active infection. The mean age of the cohort examined was 62.5 ± 14.4 (standard deviation) years. Mean Society of Vascular Surgery risk score was 3.9 with a baseline Rutherford's chronic ischemia score of 4.3 at presentation. Emergent procedures constituted 29% of cases, and the remainder cases were urgent procedures. The CH bypass captured was a reoperative procedure in all but one of the patients. Culture positivity was present in 75% of cases with Staphylococcus aureus (29%), the most commonly isolated organism. Thirty-day mortality and major adverse cardiovascular events were both 4%. Amputation-free survival (AFS) was 75% at 30 days. Similarly, 30-day reintervention was 38% with debridement (43%) and bleeding (29%), the most common indications. Average duration of follow-up was 27.9 ± 20.4 months (range: 0.5–60.4). Mean length of stay was 14.8 days. Reinfection requiring an additional procedure or antibiotic regimen separate from the index antibiotic course was 13%. Primary patency and AFS at 1 year was 50% and 58%, respectively. Primary patency and AFS at 2 years was 38% and 52%, respectively. Limb salvage at 1 and 2 years was 70% and 65%, respectively. Fifteen patients (63%) required reintervention during the follow-up period with 40% of those subjects undergoing multiple procedures. Conclusions CHs remain a marginal salvage conduit in the setting of infection and no autogenous choices. Therefore, clinicians should individualize usage of this high-cost product in highly selected patients only

Perioperative Outcomes are Adversely Affected by Poor Pretransfer Adherence to Acute Limb Ischemia Practice Guidelines

Objectives The accepted treatment for acute limb ischemia (ALI) is immediate systemic anticoagulation and timely reperfusion to restore blood flow. In this study, we describe the retrospective assessment of pretransfer management decisions by referring hospitals to an academic tertiary care facility and its impact on perioperative adverse events. Methods A retrospective analysis of ALI patients transferred to us via our Level I Vascular Emergency program from 2010 to 2013 was performed. Patient demographics, comorbidities, Rutherford ischemia classification, time to anticoagulation, and time to reperfusion were tabulated and analyzed for correlation to incidence of major adverse limb events (MALE), mortality, and bypass patency in the perioperative period (30-day postoperative). All time intervals were calculated from the onset of symptoms and categorized into three subcohorts (48 hrs). Results Eighty-seven patients with an average age of 64.0 (± 16.2) years presented to outlying hospitals and was transferred to us with lower extremity ALI. The mean delay from symptom onset to initial referring physician evaluation was 18.3 hrs. At that time of evaluation, 53.8% had Rutherford class IIA ischemia and 36.3% had class IIB ischemia. Seventy-six (87.4%) patients were started on heparin previous to transfer. However, only 44 (57.9%) patients reached therapeutic levels as measured by activated partial thromboplastin time (aPTT) prior to definitive revascularization. A delay of anticoagulation initiation >48 hrs from symptom onset was associated with increased 30-day reintervention rates compared with the <6 hrs group (66.7% vs. 23.5%; p<0.05). However, time to reperfusion had no statistically significant impact on MALE, 30-day mortality, or 30-day interventional patency in our small cohorts. Additionally, patients with a previous revascularization had a higher 30-day reintervention rate (46.5%; p<0.05). Conclusions The practice of timely therapeutic anticoagulation of patients referred for ALI from community facilities occurs less frequently than expected and is associated with an increased perioperative reintervention rate

Clinical and Laboratory characteristics of patients with COVID-19 Infection and Deep Venous Thrombosis

Objective: Early reports suggest that patients with novel coronavirus disease-2019 (COVID-19) infection carry a significant risk of altered coagulation with an increased risk for venous thromboembolic events. This report investigates the relationship of significant COVID-19 infection and deep venous thrombosis (DVT) as reflected in the patient clinical and laboratory characteristics. Methods: We reviewed the demographics, clinical presentation, laboratory and radiologic evaluations, results of venous duplex imaging and mortality of COVID-19-positive patients (18-89 years) admitted to the Indiana University Academic Health Center. Using oxygen saturation, radiologic findings, and need for advanced respiratory therapies, patients were classified into mild, moderate, or severe categories of COVID-19 infection. A descriptive analysis was performed using univariate and bivariate Fisher's exact and Wilcoxon rank-sum tests to examine the distribution of patient characteristics and compare the DVT outcomes. A multivariable logistic regression model was used to estimate the adjusted odds ratio of experiencing DVT and a receiver operating curve analysis to identify the optimal cutoff for d-dimer to predict DVT in this COVID-19 cohort. Time to the diagnosis of DVT from admission was analyzed using log-rank test and Kaplan-Meier plots. Results: Our study included 71 unique COVID-19-positive patients (mean age, 61 years) categorized as having 3% mild, 14% moderate, and 83% severe infection and evaluated with 107 venous duplex studies. DVT was identified in 47.8% of patients (37% of examinations) at an average of 5.9 days after admission. Patients with DVT were predominantly male (67%; P = .032) with proximal venous involvement (29% upper and 39% in the lower extremities with 55% of the latter demonstrating bilateral involvement). Patients with DVT had a significantly higher mean d-dimer of 5447 ± 7032 ng/mL (P = .0101), and alkaline phosphatase of 110 IU/L (P = .0095) than those without DVT. On multivariable analysis, elevated d-dimer (P = .038) and alkaline phosphatase (P = .021) were associated with risk for DVT, whereas age, sex, elevated C-reactive protein, and ferritin levels were not. A receiver operating curve analysis suggests an optimal d-dimer value of 2450 ng/mL cutoff with 70% sensitivity, 59.5% specificity, and 61% positive predictive value, and 68.8% negative predictive value. Conclusions: This study suggests that males with severe COVID-19 infection requiring hospitalization are at highest risk for developing DVT. Elevated d-dimers and alkaline phosphatase along with our multivariable model can alert the clinician to the increased risk of DVT requiring early evaluation and aggressive treatmen

The Drought Calculator: Decision Support Tool for Predicting Forage Growth During Drought

The Drought Calculator (DC), a spreadsheet-based decision support tool, was developed to help ranchers and range managers predict reductions in forage production due to drought. Forage growth potential (FGP), the fraction of historical average production, is predicted as a weighted average of monthly precipitation from January through June. We calibrated and evaluated the DC tool in the Great Plains of the United States, using FGP and precipitation data from Colorado (CO), North Dakota (ND), and Wyoming (WY). In CO, FGP was most sensitive to precipitation in April and May, in ND to precipitation in April and June, and in WY to precipitation in April, May, and June. Weights in these months ranged from 0.16 to 0.52. Prediction was better for CO and WY than for ND. When January-June precipitation was used, the tool correctly predicted 83% of the years with FGP reduced by drought for CO, 82% for WY, and only 67% for ND. Positive values of the True Skill Statistic (0.53 for CO, 0.42 for WY, and 0.17 for ND) indicate that FGP was classified as above or below average better than random selection. Predicting FGP earlier than April in CO and WY will require accurate forecasts of April-June precipitation. Use of the DC is most limited by insufficient forage data to determine the site-specific relationships between FGP and monthly precipitation. Even so, the decision tool is useful for discriminating drought effects on FGP classification being above or below the long term average, and it provides a quantitative prediction to producers for their destocking decisions in drought years.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202

Temporizing amplatzer closure of an aorto-enteric fistula associated with a blind aortic stump via a translumbar approach

We present a case of an aorto-enteric fistula (AEF) with chronic, persistent bleeding from a blind aortic stump managed by endovascular means. This novel approach may have extended the life of a patient who would otherwise have been subject to a high perioperative morbidity or persistent bleeding and death. While our patient ultimately expired, we believe this technique can be considered for temporization in highly-selected patients