Role of Anticoagulation in Nonagenarian Patients with Acute Limb Ischemia.

BACKGROUND: Preoperative anticoagulant therapy is known to have a positive impact on the prognosis of patients with acute limb ischemia (ALI). However, little is known about its efficacy in elderly patients. We aimed to investigate the potential effect of anticoagulation in nonagenarian patients managed for ALI. METHODS: Between January 2015 and December 2021, we identified all nonagenarian patients managed for ALI at a single center. Long-term anticoagulation and hemostasis parameters (prothrombin rate, activated partial thromboplastin time [APTT], platelet count) measured on admission were reviewed. The primary end point was mortality at 30-day mortality (D30) in patients with or without long-term anticoagulation therapy. We also studied the effect of these factors on the occurrence of revascularization failure in operated patients (initial failure, ischemic recurrence during hospitalization, necrosis requiring major amputation). RESULTS: A total of 68 nonagenarian patients were managed for ALI, with a mean age of 93.8 years (from 90-107 years), 76.5% of whom were women. Of these patients, 47 (69%) were managed surgically. Long-term anticoagulation therapy was associated with better survival at D30, both in nonoperated (P < 0.01) and operated (P < 0.05) patients. In operated patients, the absence of long-term anticoagulation therapy was associated with the occurrence of revascularization failure (P < 0.05). In operated patients, survival to D30 and successful revascularization were associated with a longer APTT (P < 0,05). We were able to observe the survival of 4 patients contraindicated for surgery and treated with a single medical therapy (intravenous unfractionated heparin). CONCLUSIONS: Anticoagulation appears to have an impact on the survival and postoperative prognosis of nonagenarian patients with ALI. In addition, curative anticoagulation therapy may be an alternative treatment when surgery is contraindicated in this frail population.

Automatic Measurement of Vascular Calcifications in Patients with Aorto-Iliac Occlusive Disease to Predict the Risk of Re-intervention After Endovascular Repair.

BACKGROUND: There is currently a lack of consensus and tools to easily measure vascular calcification using computed tomography angiography (CTA). The aim of this study was to develop a fully automatic software to measure calcifications and to evaluate the interest as predictive factor in patients with aorto-iliac occlusive disease. METHODS: This study retrospectively included 171 patients who had endovascular repair of an aorto-iliac occlusive lesion at the University Hospital of Nice between January 2011 and December 2019. Calcifications volumes were measured from CTA using an automatic method consisting in three sequential steps: image pre-processing, lumen segmentation using expert system, and deep learning algorithms and segmentation of calcifications. Calcification volumes were measured in the infrarenal abdominal aorta and the iliac arterial segments, corresponding to the common and the external iliac arteries. RESULTS: Among 171 patients included with a mean age of 65 years, the revascularization was performed on the native external and internal iliac arteries in, respectively: 83 patients (48.5%), 107 (62.3%), and 7 (4.1%). The mean volumes of calcifications were 2,759 mm3 in the infrarenal abdominal aorta, 1,821 mm3 and 1,795 mm3 in the right and left iliac arteries, respectively. For a mean follow-up of 39 months, target lesion re-intervention was performed in 55 patients (32.2%). These patients had higher volume of calcifications in the right and left iliac arteries, compared with patients who did not have a re-intervention (2,274 mm3 vs. 1,606 mm3, P = 0.0319 and 2,278 vs. 1,567 mm3, P = 0.0213). CONCLUSIONS: The development of a fully automatic software would be useful to facilitate the measurement of vascular calcifications and possibly better inform the prognosis of patients.

Diabetes-Induced Changes in Macrophage Biology Might Lead to Reduced Risk for Abdominal Aortic Aneurysm Development.

Type 2 diabetes patients are less likely to develop an abdominal aortic aneurysm (AAA). Since macrophages play a crucial role in AAA development, we hypothesized that this decrease in AAA risk in diabetic patients might be due to diabetes-induced changes in macrophage biology. To test this hypothesis, we treated primary macrophages obtained from healthy human volunteers with serum from non-diabetic vs. diabetic AAA patients and observed differences in extracellular acidification and the expression of genes involved in glycolysis and lipid oxidation. These results suggest an increase in metabolism in macrophages treated with serum from diabetic AAA patients. Since serum samples used did not differ in glucose content, these changes are not likely to be caused by differences in glycemia. Macrophage functions have been shown to be linked to their metabolism. In line with this, our data suggest that this increase in macrophage metabolism is accompanied by a shift towards an anti-inflammatory state. Together, these results support a model where diabetes-induced changes in metabolism in macrophages might lead to a reduced risk for AAA development.

Mycotic aortic and left iliac ruptured aneurysm due to Escherichia Coli: a case report and literature overview.

Mycotic aneurysm is a life-threatening disease often caused by Salmonella, Staphylococci and Streptococci species. Interestingly, Escherichia Coli (E. Coli) is described as a rare causative agent. We report the case of a patient who developed a mycotic aortic and ruptured left iliac aneurysm due to E. Coli. The patient developed a secondary aortic graft infection due to a mesenteric ischemia with fecal peritonitis. A literature overview of the current knowledge on mycotic aortic aneurysms specifically due to E. Coli is discussed including the clinical characteristics of patients, the management of the disease and the post-operative outcomes.

Plasmatic osteopontin and vascular access dysfunction in hemodialysis patients: a cross-sectional, case-control study (The OSMOSIS Study).

BACKGROUND AND AIMS: Despite close follow-up of patients with native arteriovenous fistulas (AVFs), up to 10% experience thrombosis each year. The OSMOSIS Study (Osteopontin as a Marker of Stenosis) tested the hypothesis that the systemic osteopontin level, a pro-inflammatory mediator related to vascular remodelling and intimal hyperplasia, increases in AVF stenosis, and may be used in clinical surveillance. METHODS: Our cross-sectional study compared the level of plasmatic osteopontin (pOPN) between patients with a well-functioning AVF (control group) and patients who required revision of their AVF due to stenosis (stenosis group). Blood samples were collected before dialysis (control group) or before intervention (stenosis group) from the AVF arm, and from the opposite arm as a within-subject control. pOPN level was measured by enzyme-linked immunosorbent assay. RESULTS: A total of 76 patients were included in the study. Baseline characteristics were similar between the groups (mean age, 70 years; men, 63%; AVF duration, 39 months), apart from prevalence of type 2 diabetes (T2D) (control group, 33%; stenosis group, 57%; p = 0.04). pOPN levels were similar between the AVF arm and the contralateral arm (551 ± 42 ng/mL vs. 521 ± 41 ng/mL, respectively, p = 0.11, paired t-test). Patients in the stenosis group displayed a higher pOPN level than patients in the control group (650.2 ± 59.8 ng/mL vs. 460.5 ± 61.2, respectively, p = 0.03; two-way ANOVA). T2D was not identified as an associated factor in a multivariate analysis (p = 0.50). CONCLUSIONS: The level of pOPN in hemodialysis patients was associated with the presence of AVF stenosis requiring intervention. Thus, its potential as a diagnostic biomarker should be assessed in a vascular access surveillance program.

Prevalence of Thoracic Aortic Aneurysms in Patients with Degenerative Abdominal Aortic Aneurysms: Results from the Prospective ACTA Study.

OBJECTIVE: There are no recommendations for screening for thoracic aortic aneurysms (TAAs), even in patients with infrarenal abdominal aortic aneurysms (AAAs). The aims of this study were to determine the prevalence of TAAs in patients with AAAs and to analyse the risk factors for this association. METHODS: This was a multicentre prospective study. The Aortic Concomitant Thoracic and Abdominal Aneurysm (ACTA) study included 331 patients with infrarenal AAAs > 40 mm between September 2012 and May 2016. These patients were prospectively enrolled in three French academic hospitals. RESULTS: Patients were classified as having a normal, aneurysmal, or ectatic (non-normal, non-aneurysmal) thoracic aorta according to their maximum aortic diameter indexed by sex, age, and body surface area. Thoracic aortic ectasia (TAE) was defined as above or equal to the 90th percentile of normal aortic diameters according to gender and body surface area. Descending TAA was defined as ≥ 150% of the mean normal value, and ascending TAA as > 47 mm in men and 42 mm in women; 7.6% (n = 25) had either an ascending (seven cases; 2.2%) or descending aortic TAA (18 cases; 5.4%), and 54.6% (n = 181) had a TAE. Among the 25 patients with TAAs, five required surgery; two patients had TAAs related to penetrating aortic ulcers < 60 mm in diameter, and three had a TAA > 60 mm. In the multinomial regression analysis, atrial fibrillation (AF) (odds ratio [OR] 11.36, 95% confidence interval [CI] 2.18 - 59.13; p = .004) and mild aortic valvulopathy (OR 2.89, 1.04-8.05; p = .042) were independent factors associated with TAAs. Age (OR 1.06, CI 1.02 - 1.09; p = .003) and AF (OR 4.36, 1.21 - 15.61; p = .024) were independently associated with ectasia. CONCLUSION: This study confirmed that TAAs coexisting with AAAs are not rare, and one fifth of these TAAs are treated surgically. Systematic screening by imaging the whole aorta in patients with AAAs is clinically relevant and should lead to an effective prevention policy.

Hypoxia and hypoxia-inducible factors promote the development of neointimal hyperplasia in arteriovenous fistula.

KEY POINTS: Patients with end-stage renal failure need arteriovenous fistulas (AVF) to undergo dialysis. However, AVFs present a high rate of failure as a result of excessive venous thickness. Excessive venous thickness may be a consequence of surgical dissection and change in oxygen concentration within the venous wall. We show that venous cells adapt their metabolism and growth depending on oxygen concentration, and drugs targeting the hypoxic response pathway modulate this response in vitro. We used the same drugs on a mouse model of AVF and show that direct or indirect inhibition of the hypoxia-inducible factors (HIFs) help decrease excessive venous thickness. Hypoxia and HIFs can be targets of therapeutic drugs to prevent excessive venous thickness in patients undergoing AVF surgical creation. ABSTRACT: Because the oxygen concentration changes in the venous wall, surrounding tissue and the blood during surgical creation of arteriovenous fistula (AVF), we hypothesized that hypoxia could contribute to AVF failure as a result of neointimal hyperplasia. We postulated that modulation of the hypoxia-inducible factors (HIF) with pharmacological compounds could promote AVF maturation. Fibroblasts [normal human fibroblasts (NHF)], smooth muscle cells [human umbilical vein smooth muscle cells (HUVSMC)] and endothelial cells [human umbilical vein endothelial cells (HUVEC)], representing the three layers of the venous wall, were tested in vitro for proliferation, cell death, metabolism, reactive oxygen species production and migration after silencing of HIF1/2-α or after treatment with deferioxamine (DFO), everolimus (Eve), metformin (Met), N-acetyl-l-cysteine (NAC) and topoisomerase I (TOPO), which modulate HIF-α stability or activity. Compounds that were considered to most probably modify intimal hyperplasia were applied locally to the vessels in a mouse model of aortocaval fistula. We showed, in vitro, that NHF and HUVSMC can adapt their metabolism and thus their growth depending on oxygen concentration, whereas HUVEC appears to be less flexible. siHIF1/2α, DFO, Eve, Met, NAC and TOPO can modulate metabolism and proliferation depending on the cell type and the oxygen concentration. In vivo, siHIF1/2α, Eve and TOPO decreased neointimal hyperplasia by 32%-50%, 7 days after treatment. Within the vascular wall, hypoxia and HIF-1/2 mediate early failure of AVF. Local delivery of drugs targeting HIF-1/2 could inhibit neointimal hyperplasia in a mouse model of AVF. Such compounds may be delivered during the surgical procedure for AVF creation to prevent early AVF failure.

Vascular Calcifications are Associated with Increased Mortality in Patients with Acute Mesenteric Ischemia.

BACKGROUND: Vascular calcifications have been identified as predictors of mortality in several cardiovascular diseases but have not been investigated in context of acute mesenteric ischemia. The aim of this study was to investigate the impact of vascular calcifications in patients with acute mesenteric ischemia. METHODS: Patients admitted for an acute mesenteric ischemia were retrospectively included. The presence of calcifications in the visceral aorta, the celiac trunk, the superior mesenteric artery, and the renal arteries was assessed on computed tomography scan images at the arterial phase. The calcification volumes were measured using the software Aquarius iNtuition Edition®. RESULTS: The all-cause mortality was 55 out of 86 patients (63.9%) for a median follow-up of 3.5 days (1-243). The survival rate of patients with calcification in the superior mesenteric artery was significantly lower than that of those without calcification (22% vs. 55.6%, P = 0.019). Patients who died had significantly a higher frequency of calcifications in the superior mesenteric artery, the visceral aorta, the celiac trunk, and the renal arteries. CONCLUSIONS: The presence of vascular calcifications in the superior mesenteric artery is associated with increased mortality in patients diagnosed with acute mesenteric ischemia. Further studies are required to identify the mechanisms underlying this association.

Computed Tomography-Aortography Versus Color-Duplex Ultrasound for Surveillance of Endovascular Abdominal Aortic Aneurysm Repair: A Prospective Multicenter Diagnostic-Accuracy Study (the ESSEA Trial).

Background Color-duplex ultrasonography (DUS) could be an alternative to computed tomography-aortography (CTA) in the lifelong surveillance of patients after endovascular aneurysm repair (EVAR), but there is currently no level 1 evidence. The aim of this study was to assess the diagnostic accuracy of DUS as an alternative to CTA for the follow-up of post-EVAR patients. Methods Between December 16, 2010, and June 12, 2015, we conducted a prospective, blinded, diagnostic-accuracy study, in 15 French university hospitals where EVAR was commonly performed. Participants were followed up using both DUS and CTA in a mutually blinded setup until the end of the study or until any major aneurysm-related morphological abnormality requiring reintervention or an amendment to the follow-up policy was revealed by CTA. Database was locked on October 2, 2017. Our main outcome measures were sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios of DUS against reference standard CTA. CIs are binomial 95% CI. Results This study recruited prospectively 659 post-EVAR patients of whom 539 (82%) were eligible for further analysis. Following the baseline inclusion visit, 940 additional follow-up visits were performed in the 539 patients. Major aneurysm-related morphological abnormalities were revealed by CTA in 103 patients (17.2/100 person-years [95% CI, 13.9-20.5]). DUS accurately identified 40 patients where a major aneurysm-related morphological abnormality was present (sensitivity, 39% [95% CI, 29-48]) and 403 of 436 patients with negative CTA (specificity, 92% [95% CI, 90-95]). The negative predictive value and positive predictive value of DUS were 92% (95% CI, 90-95) and 39% (95% CI, 27-50), respectively. The positive likelihood ratio was 4.87 (95% CI, 2.9-9.6). DUS sensitivity reached 73% (95% CI, 51-96) in patients requiring an effective reintervention. Conclusions DUS had an overall low sensitivity in the follow-up of patients after EVAR, but its performance improved meaningfully when the subset of patients requiring effective reinterventions was considered. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01230203.

Artificial intelligence in abdominal aortic aneurysm.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening disease, and the only curative treatment relies on open or endovascular repair. The decision to treat relies on the evaluation of the risk of AAA growth and rupture, which can be difficult to assess in practice. Artificial intelligence (AI) has revealed new insights into the management of cardiovascular diseases, but its application in AAA has so far been poorly described. The aim of this review was to summarize the current knowledge on the potential applications of AI in patients with AAA. METHODS: A comprehensive literature review was performed. The MEDLINE database was searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search strategy used a combination of keywords and included studies using AI in patients with AAA published between May 2019 and January 2000. Two authors independently screened titles and abstracts and performed data extraction. The search of published literature identified 34 studies with distinct methodologies, aims, and study designs. RESULTS: AI was used in patients with AAA to improve image segmentation and for quantitative analysis and characterization of AAA morphology, geometry, and fluid dynamics. AI allowed computation of large data sets to identify patterns that may be predictive of AAA growth and rupture. Several predictive and prognostic programs were also developed to assess patients' postoperative outcomes, including mortality and complications after endovascular aneurysm repair. CONCLUSIONS: AI represents a useful tool in the interpretation and analysis of AAA imaging by enabling automatic quantitative measurements and morphologic characterization. It could be used to help surgeons in preoperative planning. AI-driven data management may lead to the development of computational programs for the prediction of AAA evolution and risk of rupture as well as postoperative outcomes. AI could also be used to better evaluate the indications and types of surgical treatment and to plan the postoperative follow-up. AI represents an attractive tool for decision-making and may facilitate development of personalized therapeutic approaches for patients with AAA.

Co-culture of human fibroblasts, smooth muscle and endothelial cells promotes osteopontin induction in hypoxia.

Arteriovenous fistulas (AVFs) are the preferred vascular access for haemodialysis of patients suffering from end-stage renal disease, a worldwide public health problem. However, they are prone to a high rate of failure due to neointimal hyperplasia and stenosis. This study aimed to determine if osteopontin (OPN) was induced in hypoxia and if OPN could be responsible for driving AVF failure. Identification of new factors that participate in remodelling of AVFs is a challenge. Three cell lines representing the cells of the three layers of the walls of arteries and veins, fibroblasts, smooth muscle cells and endothelial cells, were tested in mono- and co-culture in vitro for OPN expression and secretion in normoxia compared to hypoxia after silencing the hypoxia-inducible factors (HIF-1α, HIF-2α and HIF-1/2α) with siRNA or after treatment with an inhibitor of NF-kB. None of the cells in mono-culture showed OPN induction in hypoxia, whereas cells in co-culture secreted OPN in hypoxia. The changes in oxygenation that occur during AVF maturation up-regulate secretion of OPN through cell-cell interactions between the different cell layers that form AVF, and in turn, these promote endothelial cell proliferation and could participate in neointimal hyperplasia.

Nuclear receptors in abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAA) pose a considerable health burden and at present are only managed surgically since there is no proven pharmacotherapy that will retard their expansion or reduce the incidence of fatal rupture. This pathology shares several pathophysiological mechanisms with atherosclerosis, such as macrophage infiltration, inflammation, and degradation of extracellular matrix. Therefore, therapeutic targets proven effective in the treatment of atherosclerosis could also be considered for treatment of AAA. Different members of the nuclear receptor (NR) superfamily have been extensively studied as potential targets in the treatment of cardiovascular disease (CVD) and therefore might also be suited for AAA treatment. In this context, this review summarizes the role of different NRs in CVD, mostly atherosclerosis, and discusses in detail the current knowledge of their implications in AAA. From this overview it becomes apparent that NRs that were attributed a beneficial or adverse role in CVD have similar roles in AAA. Together, this overview provides compelling evidence to consider several NRs as attractive targets for future treatment of AAA.

Relationship between metformin and abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a life-threatening disease and pharmacologic agents to treat the disease remain lacking for clinical practice. Epidemiologic studies have highlighted a negative association between the use of antidiabetic drugs, including metformin, and AAA. Metformin is well-known for its blood glucose-lowering effect, but its action on both metabolism and inflammatory response has led to propose it as a potential therapeutic target in several cardiovascular diseases. In this review, we summarize the current knowledge on the link between metformin and AAA. Based on the known effects of the drug on the aortic wall, translational applications and clinical trials investigating the interest of metformin in the management of patients with AAA are discussed.

Comparison of Cryopreserved Arterial Allografts Versus Heparin-bonded Vascular Grafts in Infragenicular Bypass for Chronic Limb Threatening Ischemia.

BACKGROUND: The purpose of this study was to compare cryopreserved arterial allograft (CAA) to heparin-bonded prosthesis (HBP) in infragenicular bypasses for patients with chronic limb-threatening ischemia (CLTI). METHODS: This retrospective study took place in 2 university hospitals and included 41 consecutive patients treated for CLTI. In the absence of a suitable saphenous vein, an infragenicular bypass was performed using either CAA (24 cases) or HBP (17 cases). Kaplan-Meyer analysis compared primary and secondary patency and amputation-free survival rates. Binomial logistic regression analyzed risk factors for major amputation and thrombosis. RESULTS: The mean followup was 18.5 months (±14.3) in the CAA group, 17.6 (±6.1) in the HBP group. In the CAA group, primary and secondary patency rates at 12 months were 52% (±10.6) and 61% (±10.3), compared to 88% (±7.8) and 94% (±5.7) in the HBP group, respectively. The difference in patency rates was not statistically different (P = 0.27 and P = 0.28, respectively). The statistically significant factors of graft thrombosis were, a stage 4 from the WIfI classification (Wound Ischemia foot Infection) with a 6 times higher risk (P = 0.04), and a distal anastomosis on a leg artery with a 9 times higher risk of thrombosis (P = 0.03). Amputation-free survival rates at 18 months were similar between the groups (CCA: 75% (±9) versus HBP: 94% (±6), P = 0.11). Patients classified as WIfI stage 4 had 13 times higher odds to undergo major amputation than patients with WIfI stage 2 or 3 (95% CI, 1.16-160.93; P = 0.04). The intervention was longer in the CCA group of 74 min (278 min ± 86) compared to the HBP group (203 min ± 69). This difference was statistically significant (95% CI, 17.86-132.98), t(35) = 2.671, P = 0.01. CONCLUSIONS: CCA is not superior to HBP in infragenicular bypasses for CLTI, and may not be worth the extra cost and the longer operative duration.

The Common Femoral Artery Bifurcation Lesions: Clinical Outcome of Simple Versus Complex Stenting Techniques - An Analysis Based on the TECCO Trial.

BACKGROUND: Common femoral artery (CFA) stenting appears as a promising alternative treatment to the open surgery for de novo CFA stenosis. The stenting of lesions just located at the CFA is simple, whereas stenting of CFA bifurcation lesions is more complex, and outcomes are still matter of debate. The aim of this study was to describe and to compare clinical outcomes of techniques used to treat simple over complex lesions for the stenting of CFA lesions. MATERIALS/METHODS: From the French randomized controlled trial, TECCO, a total of 54 patients underwent stenting intervention and were enrolled in this study. Patients were excluded if they had CFA thrombosis, restenosis, and nonatheromatous lesions. Patients were classified by simple and complex lesions based on the type of lesion. The primary end point was the primary sustained clinical improvement. RESULTS: Eighteen patients were included in the simple lesion group, and 36 patients, in the complex lesion group. Baseline characteristics of patients were comparable between the 2 groups. The technical success was 100% in the simple lesion group and 91.7% in the complex lesion group. There was no significant difference between the 2 groups, regarding the primary sustained clinical improvement. The primary patency rates at 24 months for simple and complex lesion groups were 86.3% and 79%, respectively (P = 0.66). Freedom from target lesion revascularization was of 93.3% and 82% in the simple and complex lesion group, respectively (P = 0.34). CONCLUSIONS: The stenting technique for CFA bifurcation lesions is a safe and effective technique. More trials with a large number of patients are needed to define the optimal stenting technique.

Evaluation of the Impact of Sarcopenia in Patients with Acute Mesenteric Ischemia.

BACKGROUND: Sarcopenia has been identified as a prognostic factor in several diseases. The aim of this study was to investigate the impact of sarcopenia in patients with acute mesenteric ischemia. METHODS: Consecutive patients admitted for acute mesenteric ischemia were retrospectively included at the University Hospital of Nice. Sarcopenia was assessed by the measurement of total psoas area normalized for height (TPA/H) on CT-scan and was defined as a TPA/H inferior to the lowest sex-specific quartile. The management of the patients and the 30-day outcomes were compared between sarcopenic and nonsarcopenic patients. Correlations between the TPA/H and biological characteristics were investigated. RESULTS: Among the 80 patients included, the lowest quartile of TPA/H that defined sarcopenia was 406.1 mm2/m2 for men and 307 mm2/m2 for women. The rate of revascularization or the need of intestinal resection did not significantly differ between sarcopenic and nonsarcopenic patients (10.5% vs. 26.2%, P = 0.214 and 26.3% vs. 47.5%, P = 0.118 respectively). The 30-day mortality did not significantly differ between the two groups (63.2% vs. 47.5%, P = 0.297). The TPA/H was significantly negatively correlated with the neutrophil, thrombocyte, and monocyte counts (r = -0.283; -0.288, -0.225, P < 0.05) and positively correlated with the hemoglobin concentration and the glomerular filtration rate (r = 0.368; 0.261, P < 0.05). CONCLUSIONS: Further studies on longer follow-up period would be of interest to fully understand the prognostic value of sarcopenia in patients with acute mesenteric ischemia.

Platelet to lymphocyte ratio as a predictive factor of 30-day mortality in patients with acute mesenteric ischemia.

INTRODUCTION: Acute mesenteric ischemia is associated with high rates of mortality. The aim of this study was to investigate the prognostic value of the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on 30-day outcomes in patients with acute mesenteric ischemia. MATERIAL AND METHODS: Consecutive patients who were admitted for an acute mesenteric ischemia were retrospectively included. The full white blood count at the time of admission to the hospital was recorded. The population was divided into 4 subgroups according to the quartiles of the NLR and the PLR. The 30-day outcomes including the mortality and the complications were compared among the subgroups. RESULTS: In total, 106 patients were included. A surgical treatment including revascularization and/or digestive resection was performed for 56 patients (52.8%). The 30-day all-cause mortality was 72 patients (67.9%). Patients with higher PLR value (PLR >429.3) had significantly higher rate of mortality compared to the other groups (80.8% vs 46.2%, 66.7% and 77.8%, p = 0.03). No significant difference on 30-day outcome was observed among the subgroups divided according to the NLR. CONCLUSION: The PLR, but not the NLR, is a predictive factor of 30-day mortality in patients with acute mesenteric ischemia.

Translational applications of glucose metabolism in abdominal aortic aneurysm.

Even though diabetes mellitus is a major risk for cardiovascular events and atherosclerosis-related diseases, it is negatively associated with abdominal aortic aneurysm. The understanding of the mechanisms underlying this negative association could bring new insights to identify prognostic and therapeutic targets. Here we summarize current knowledge of the relationship between glycemic parameters and clinical outcomes of patients with abdominal aortic aneurysm. Translational applications of glucose-targeted approaches as well as their potential interest for clinical practice are discussed in this context.

Differential micro-RNA expression in diabetic patients with abdominal aortic aneurysm.

OBJECTIVES: The potential implication of micro-RNAs (miRs) in the negative association between diabetes and abdominal aortic aneurysm (AAA) has so far never been addressed. The aim of this study was to compare miR expression between diabetic and non-diabetic patients with AAA. METHODS: Ten diabetic patients were prospectively included and compared to 10 age- and sex-matched non-diabetic patients with infrarenal AAA. A profiling analysis of 752 human miRs was performed from peripheral blood mononuclear cells (PBMCs) using miRCURY LNA Universal RT microRNA PCR (Exiqon- Qiagen®). miR that showed significant differential expression (P < 0.05) were selected and further analyzed in the entire cohort in sera, plasma and aneurysmal aortic tissues. RESULTS: Four miRs were significantly differentially expressed in PBMCs of diabetic patients compared to non-diabetics: 3 were upregulated (miR-144-3p, 20a-5p and 188-3p) and 1 downregulated (miR-548k). miR-144-3p and miR-548k were also increased in aneurysmal tissue and miR-20a-5p was increased in serum. The expression of miR-20a-5p in PBMCs was correlated with fructosamine concentration (r = 0.62, p = 0.006). CONCLUSIONS: Even if further studies are required to determine their direct role in AAA, these miRs could represent interesting new targets.

Transforming growth factor ß neutralization finely tunes macrophage phenotype in elastase-induced abdominal aortic aneurysm and is associated with an increase of arginase 1 expression in the aorta.

OBJECTIVE: Macrophages play a critical role in the initiation and progression of abdominal aortic aneurysm (AAA) and are classically distinguished into M1 "proinflammatory" and M2 "anti-inflammatory" macrophages. Topical application of elastase associated with transforming growth factor ß (TGF-ß) systemic neutralization reproduces the main pathologic features of human AAA, offering a new model to investigate their role. The aim of this study was to investigate whether macrophages contribute to the expression of canonical M1/M2 markers in the aorta in the AAA model induced by elastase and systemic blockade of TGF-ß and whether blocking of TGF-ß activity affects macrophage phenotype and the expression of the M2 marker arginase 1 (ARG1). METHODS: C57Bl/6J male mice (6-8 weeks old) were randomly assigned to three experimental groups: mice that had local application of heat-inactivated elastase or elastase and mice that had elastase application and received injection of anti-TGF-ß (elastase + anti-TGF-ß group). Monocyte-macrophage depletion was achieved in the elastase + anti-TGF-ß group using liposome clodronate. Macrophage phenotype was characterized by quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. Human infrarenal AAA tissues (n = 10) were obtained to analyze ARG1 expression. RESULTS: Analysis of gene expression in the infrarenal aortic wall revealed that after 14 days, no significant difference for the expression of CCL2, NOS2, and Ym1/2 was observed in the elastase group compared with the elastase + anti-TGF-ß group, whereas the expression of ARG1, interleukin (IL) 1ß, and IL-6 was significantly increased. Macrophage depletion in the elastase + anti-TGF-ß group led to a significant decrease of IL-1ß, IL-6, ARG1, and Ym1/2 gene expression. Immunofluorescent staining confirmed that TGF-ß neutralization significantly enhanced ARG1 protein expression in the aneurysmal tissue. Flow cytometry analysis revealed an increase of macrophages expressing ARG1 in the aorta of mice treated with elastase + anti-TGF-ß compared with the elastase group, and their proportion increased with aneurysmal dilation. In humans, ARG1 protein expression was increased in aneurysmal tissues compared with controls, and positive cells were mainly found in the adventitia. CONCLUSIONS: TGF-ß neutralization finely tunes macrophage phenotype in elastase-induced AAA and leads to an increase in ARG1 gene and protein expression in the aortic wall. Even if further studies are required to elucidate its role in AAA development, ARG1 could represent a new prognostic or therapeutic target in aneurysmal disease.