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Introduction Aim of our study is to evaluate the outcomes of mini-laparotomy, suprarenal cross-clamping, and enhanced recovery after elective open surgical repair for juxta-renal abdominal aortic aneurysms (JAAA) in a tertiary referral center. Methods Data of all consecutive patients with abdominal aortic aneurysms (AAA) electively treated with left sub-costal mini-laparotomy requiring infrarenal or suprarenal cross-clamping between 2013 and 2018 were retrospectively collected. Patients were divided into two groups: infra-renal cross-clamping (group A) and JAAA requiring supra-renal cross-clamping (group B). Early and mid-term mortality, postoperative renal dysfunction according to RIFLE criteria and factors affecting postoperative outcome were analysed. Results Four hundred one patients, 356 (88.8%) men, mean age 70.8 yrs, underwent open surgical repair (OSR), 343 (85.5%) AAA in group A, 58 (14.5%) JAAA in group B. Mean diameter of the aneurysms was 54 ± 11.4 mm vs. 52 ± 9 mm and mean time of intervention 154.9 ± 56.3 min vs. 180.1 ± 65.7 min respectively. Total clamp time was 72.27 ± 31.4 vs. 75 ± 33.1 and suprarenal clamp time in group B 27.82 ± 14.1 min. Mean hospital length of stay was 5.1 ± 2.8 vs. 5.37 ± 3.4 days respectively. At 30 days, 3 (0.9%) patients died in group A and no one in group B; at 24 months 7 (2%) deaths in group A and 4 (6.9%) in group B. Preoperative, postoperative and discharge serum creatinine mean value, in group B, were 1.07 ± 0.32, 1.31 ± 0.36 and 1.83 ± 1.24 respectively. Based on RIFLE criteria for renal function, we observed Risk in 14.2% and Injury in 12.7% of patients after suprarenal cross clamping. Conclusions Our results show that mini-invasive open repair for JAAA with a suprarenal cross-clamping can be performed with acceptable morbidity and mortality rates similar to traditional surgical approach without significant modifications of renal functions.

Background: Identifying sex-related differences/variables associated with 30-day/1-year mortality in patients with chronic limb-threatening ischemia (CLTI). Methods: Multicenter/retrospective/observational study. Database sent to all-the-Italian vascular surgeries to collect all-the¬-patients operated for CLTI in 2019. Acute lower-limb ischemia and neuropathic-diabetic foot not included. Follow-up: 1-year. Data on demographics/comorbidities, treatments/outcome, and 30-day/1-year mortality investigated. Results: Information on 2399 cases (69.8% men) from 36/143 (25.2%) centers. Median (IQR) age: 73 (66-80) and 79 (71-85) yrs for men/women, respectively (p75 (HR3.63, p=.003) associated with 30-day mortality. Age >75 (HR2.14, p

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study conducted through cross-sectional survey. Each received a 13-point questionnaire, investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs 2019 (9161 patients): post-EVAR surveillance, treatment for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased [1484 (16.2%) vs 1014 (14.3%), p=0.0009; 1401 (15.29%) vs 959 (13.52%), p=0.0006; and 1558 (17.01%) vs 934 (13.17%), p

Coronavirus-19 disease (COVID-19) affects more people than previous coronavirus infections, namely Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) and has a higher mortality. Higher incidence and mortality can probably be explained by COVID -19 causative agent greater affinity (about 10-20 times) for angiotensin-converting enzyme-2 (ACE-2) receptor compared to other coronaviruses. Here, we first summarize clinical manifestations, then present symptoms of COVID-19 and the pathophysiological mechanisms underlying specific organ/system disease. Endothelial cells activated by a hyperinflammatory state induced by viral infection may promote localized inflammation, increase reactive oxidative species (ROS) production and alter dynamic interplay between the procoagulant and fibrinolytic factors in the vascular system, leading to thrombotic disease not only in the pulmonary circulation but also in peripheral veins and arteries. In this context, the worse clinical outcome observed in COVID-19 patients with diabetes may be in part related to the increased ADAM17 activity and its unbalanced interplay with ACE2. Therefore, strategies aimed to inhibit ADAM17 activity may be explored to develop new effective therapeutic approaches.

Background: The aim of this study was to evaluate how the high sensitivity C-reactive protein (hs-CRP) values influence the risk of carotid plaque instability in association with other cardiovascular risk factors. Methods: One hundred and fifty-six carotid plaques from both symptomatic and asymptomatic patients requiring surgical carotid endarterectomy were retrospectively collected. According to the modified American Heart Association, atherosclerosis plaques have been histologically distinguished into unstable and stable. The following anamnestic and hematochemical data were also considered: age, gender, hypertension, diabetes mellitus, smoking habit, therapy, low-density lipoprotein (LDL)-C, kidney failure and hs-CRP. Results: The results of our study clearly show that high levels of hs-CRP significantly increase the carotid plaque instability in dyslipidemic patients. Specifically, a 67% increase of the risk of carotid plaque instability was observed in patients with high LDL-C. Therefore, the highest risk was observed in male dyslipidemic patients 2333 (95% CI 0.73–7.48) and in aged female patients 2713 (95% CI 0.14–53.27). Discussion: These data strongly suggest a biological relationship between the hs-CRP values and the alteration of lipidic metabolism mostly in male patients affected by carotid atherosclerosis. The measurement of hs-CRP might be useful as a potential screening tool in the prevention of atheroscletotic disease.

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown ( n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 ± 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32–0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions.

Limb graft occlusion (LGO) is the third reason for hospital readmission after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm. We reviewed the clinical features, incidence, anatomical and devices related predictive factors for LGO after EVAR, and compared them with our experience.EVAR between 2010-2017 were included. Patients with LGO (LGO group) were matched for age and type of endograft with the rest of the entire cohort without LGO (control group). Clinical, anatomical, operative, outcome, and follow-up data were collected.Two hundred seventy-six EVAR, (30 aorto-uniliac), 276 patients. The incidence of LGO was 2.5% (seven limbs, seven patients) at 27±24.6 days. Symptomatic patients were successfully treated. No mortality, limb loss, critical limb ischemia or residual claudication due to LGO was observed. Fifty patients resulted from the matching. Among the predictive factors of LGO between the two groups, significant differences were observed in graft limb oversizing ≥15% (57.1% vs. 8%, P=0.005), or kinking (42.9% vs. 2%, P=0.01), and diameter of the aortic bifurcation20 mm (71.4% vs. 20%, P=0.01). Logistic regression analysis showed that these three variables increased the risk of LGO (P=0.003, P=0.006, and P=0.01, respectively).The strongest predictive factors of LGO issued from our review were: extension in the external iliac artery, or small diameter; tortuous, angled, and calcific iliac axis; excessive oversizing of the limb graft, or kinking; use of old generation devices; EVAR performed outside the instructions for use. Limb graft oversizing15%, or kinking, and aortic bifurcation20 mm appear to be independent predictive factors of LGO.

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RATIONALE: Endovascular treatment of renal artery aneurysms has offered a viable alternative with a high success rate and low procedure-related morbidity and mortality. PATIENT CONCERNS: A 60-year-old man, having a right renal artery aneurysm involving the main vessel with two arteries (supplying the inferior and superior lobes of the kidney) originating from the aneurysm sac as well. INTERVENTIONS: A 6 × 28 mm covered stent was inflated in vitro and a side hole was made with a femoral needle in the polytetrafluoroethylene (PTFE) layer, through which a wire was placed in an outside/inside direction in to be inserted in the inferior pole branch. The other wire was inserted inside the main lumen of the stent (to be inserted in the main artery) and the latter, carefully re-crimped on the balloon. This way, the authors guaranteed continuous access to both arteries during aneurysm exclusion and if needed, a second stent could be advanced at the level of the bifurcation to preserve side branch patency. CONCLUSION: Perforating the PTFE of the stent before its introduction into the vessel and keeping a wire into the side branch could be a good strategy to protect any vessel arising from aneurysmal sac that needs to be excluded.

Inflammation plays a role in the development and progression of type 2 diabetes macroangiopathy. Interleukin 33 (IL-33) drives production of Th2-associated cytokines. The soluble form of suppression of tumorigenicity 2 (sST2) acting as a decoy receptor blocks IL-33 and tones down Th2 inflammatory response. We investigated the role of sST2 as a predictor of CV and all-cause mortality in a cohort of patients affected by established atherosclerotic disease. 399 patients with atherosclerotic disease from the Tor Vergata Atherosclerosis Registry performed follow-up every year by phone interview. The primary endpoint was cardiovascular death and the secondary endpoint was death for any other disease. sST2 plasma levels were significantly increased from normal glucose-tolerant patients to patients with history of type 2 diabetes (p

The aims of this study were to determine the effect of failed prior endovascular treatment (EV) on early and midterm outcomes of subsequent lower extremity open surgical (OS) bypass.Patients undergoing infrainguinal bypass for critical limb ischemia (CLI) from January 2008 to December 2011 were retrospectively reviewed. The results after first-line bypass and bypass after failure of EV treatment were compared. A total of 213 patients (65.25% men; average age, 73.30 years) underwent bypass. OS patients were then divided into 2 groups: group 1 consisted of 138 patients who underwent primary OS for CLI without prior EV (control group) and group 2 consisted of 75 patients who had OS after a failed attempt at elective EV for peripheral vascular disease. Of the 213 bypass performed, 34% had a prior infrainguinal failed EV. The primary study end points were early and 1-year major amputations and graft occlusion. The secondary outcomes included early and 1-year mortality and the level of distal revascularization.Secondary patency and limb salvage rates were significantly better in group 1 up to 1 year (99% vs. 86%; P0.001 at 1 month and 95% vs. 76%, P0.05 at 12 months, respectively).Previous failed EV should be predictive of poor outcome in patients undergoing distal OS for CLI.

Background The long-term results of carotid artery stenting (CAS) for post-carotid endarterectomy (CEA) restenosis are disappointing (4-year patency rates: ∼75%). Since 1988, our group has offered carotid bypass (CB) as an alternative to redo CEA and later also to CAS in this setting. The aim of this retrospective study was to investigate early and late outcomes associated with CB in this population. Methods Data were collected from patients treated with CB in the year 2000–2012 for significant/symptomatic post-CEA restenosis (or intra-stent restenosis [ISR] after CAS for post-CEA restenosis). All patients had good life expectancy. CB was performed under loco-regional anesthesia. With the aid of sequential vessel clamping, the graft (great saphenous vein [GSV] or polytetrafluoroethylene) was anastomosed with the common carotid artery (side-to-end) and the distal internal carotid artery (end-to-side). Patients were followed with clinical and duplex scan assessments at 1, 3, and 6 months and yearly thereafter. Results The study population comprised 21 patients (mean age 67.3 years; 17 men). CB was performed for post-CEA restenosis (or ISR after CAS for post-CEA restenosis, n = 3) 51.2 months (mean) after the previous operation. GSV grafts were used in half of the cases ( n = 11; 52.4%); temporary shunting was used in 4 (19%) patients. Intraoperative complications (none fatal) occurred in 4 (19%) patients (3 transient peripheral nerve injuries, 1 cervical hematoma). During follow-up (mean 64.8 months), there were no neurologic complications or restenoses. Overall mortality was 33.3% (6 deaths from acute myocardial infarctions, 1 from a ruptured abdominal aortic aneurysm). Conclusions For post-CEA restenosis (or ISR after CAS for post-CEA restenosis), CB offers superior long-term patency rates than CAS (or redo angioplasty) and an acceptable risk of cranial nerve damage.

Thromboangiitis obliterans or Buerger's disease is a rare non-atherosclerotic segmental inflammatory vasculitis that most commonly involves small and medium-sized arteries, veins and nerves of the extremities, and generally affects young tobacco smokers. A 53-year-old man was found to have critical ischaemia of his left lower limb with foot gangrene. He underwent extremely distal surgical revascularisation using a great saphenous vein bypass graft. The choice of a very distal artery as run-off vessel promoted a faster wound healing and pain relief, with improvement in quality of life.

Background— Aging is a major risk factor for the development of atherosclerosis and coronary artery disease. Through a microarray approach, we have identified a microRNA ( miR-217 ) that is progressively expressed in endothelial cells with aging. miR-217 regulates the expression of silent information regulator 1 (SirT1), a major regulator of longevity and metabolic disorders that is progressively reduced in multiple tissues during aging. Methods and Results— miR-217 inhibits SirT1 expression through a miR-217 –binding site within the 3′-UTR of SirT1. In young human umbilical vein endothelial cells, human aortic endothelial cells, and human coronary artery endothelial cells, miR-217 induces a premature senescence-like phenotype and leads to an impairment in angiogenesis via inhibition of SirT1 and modulation of FoxO1 (forkhead box O1) and endothelial nitric oxide synthase acetylation. Conversely, inhibition of miR-217 in old endothelial cells ultimately reduces senescence and increases angiogenic activity via an increase in SirT1. miR-217 is expressed in human atherosclerotic lesions and is negatively correlated with SirT1 expression and with FoxO1 acetylation status. Conclusions— Our data pinpoint miR-217 as an endogenous inhibitor of SirT1, which promotes endothelial senescence and is potentially amenable to therapeutic manipulation for prevention of endothelial dysfunction in metabolic disorders.

Cell death & disease 5, e1029, 1-9 (2014). doi:10.1038/cddis.2013.556, Published by Nature Publishing Group, London [u.a.]

Purpose:Long-term survival and late vascular complications in patients who survived repair of ruptured abdominal aortic aneurysms (RAAA) is not well known. The current study compared late outcome after repair of RAAA with those observed in patients who survived elective repair of abdominal aortic aneurysms (AAA). Methods:The records of 116 patients, 102 men and 14 women (mean age: 72.5 (8.3 years), who survived repair of RAAA (group I) between 1980 to 1989 were reviewed. Late vascular complications and survival were compared with an equal number of survivors of elective AAA repair matched for sex, age, surgeon, and date of operation (group II). Survival was also compared with the age and sex-matched white population of west-north central United States. Results:Late vascular complications occurred in 17% (20/116) of patients in group I and in 8% (9/116) in group II. Paraanastomotic aneurysms occurred more frequently in group I than in group II (17 vs. 8,p = 0.004). At follow-up, 32 patients (28%) were alive in group I (median survival: 9.4 years) and 53 patients (46%) were alive in group II (median survival: 8.7 years). Cumulative survival rates after successful RAAA repair at 1, 5, and 10 years were 86%, 64%, and 33%, respectively. These were significantly lower than survival rates at the same intervals after elective repair (97%, 74%, and 43%, respectively, p = 0.02) or survival of the general population (95%, 75%, and 52%, respectively,p < 0.001). Coronary artery disease was the most frequent cause of late death in both groups. Vascular and graft-related complications caused death in 3% (3/116) in group I and 1% (1/116) in group II. Cox proportional hazards modeling identified age p = 0.0001), cerebrovascular disease p = 0.009), and number of days on mechanical ventilation p = 0.01) to be independent prognostic determinants of late survival in group I. Conclusions:Late vascular complications after repair of RAAA were higher and late survival rates lower than after elective repair. These data support elective repair of AAA. As two-thirds of the patients discharged after repair of RAAA are alive at 5 years, aggressive management of RAAA remains justified. (J Vasc Surg 1998;27:813-20.)

SummaryTo evaluate whether atherosclerosis may be associated with altered leucocyte rheology, we assessed leucocyte count (by Coulter counter), aggregation (by means of the leukergy test) and expression of adhesion molecules integrin LFA-1 and CD 44 (by means of immunofluorescence staining and flow cytometry) in 9 patients with carotid plus lower limb artery atherosclerosis (group A), 14 patients with carotid atherosclerosis only (group B) and 23 controls without atherosclerosis (group C). The level of LFA-1 (calculated as mean fluorescence channels - MFCs) on neutrophils, lymphocytes and monocytes was significantly higher (p

AIM: The aim of the study was to investigate the possible role of individual predisposition in the pathogenesis of carotid restenosis. METHODS:Over 1700 patients have undergone carotid endarterectomy (CEA) in our institute over the past 15 years. We retrospectively reviewed the charts of those who also had contralateral carotid stenting (CAS) for primary atherosclerotic stenosis and recorded the rates of post-CEA and post-CAS restenosis ≥50%. RESULTS: In the 29 cases analyzed (21 men/8 women), CEA was performed with conventional technique and direct suturing in most cases. Mean ages at the time of CEA and CAS were 69.2±6.6 and 73±6.7 yrs, respectively, and risk profiles at the 2 time points were similar: hypertension (96.5%), dyslipidemia (55.2%), smoking (51.7%), diabetes (31%), coronary artery disease (48.3%), chronic obstructive pulmonary disease (37.9%), and chronic renal failure (13.8%). Antiplatelet therapy protocols were identical for the two procedures. During follow-up (mean: 67.25±51.6 months after CEA, 24.6±16.9 months after CAS), Duplex scans revealed restenosis in 12 patients (9 arteries treated with CEA, 6 managed with CAS). In three patients, restenosis was bilateral. Restenosis-free survival rates at five years were 85% after CEA and 66% after CAS (P=NS). CONCLUSION: In this selected group of patients, CEA and CAS were associated with a similar incidence of restenosis. Only 25% of the patients who developed restenosis did so after both procedures. These preliminary findings indicate that individual predisposition does not play a crucial role in the pathogenesis of restenosis. To confirm this conclusion, an analysis of a much larger, multicenter cohort is essential.

Objective Undiagnosed diabetes (DM2), especially in individuals that have experienced a major atherosclerotic vascular event, could increase the risk of a second major cardiovascular (CV) event. The aim of this study was to evaluate the impact of type 2 diabetes (DM2), diagnosed after a major cardiovascular event, on subsequent CV disease in high risk individuals. Methods 411 subjects without known DM2 and with a history of a prior major CV event were followed for a second major CV event (fatal and nonfatal MI, fatal and nonfatal stroke or any arterial revascularization procedure). At baseline, each individual underwent a physical, biochemical examination, an OGTT and dosed A1c. In addition, patients were classified as having monovascular or polyvascular disease. The average follow-up duration was 31 months. Results The incidence of second CV events was 10.70 per 100 person-years (114 events/1066 person-years). The diagnosis of occult DM2 was not associated with major CV events, either using A1c values ≥6.5%, fasting glucose ≥126 mg/dL or 2 h post-load glucose ≥200 mg/dL. Polyvascular disease was the only significant predictor of a second major CV event (HR 2.60, 95% CI 1.72–3.95) after adjustment for age, BMI, smoking status, systolic blood pressure, high-density and low-density lipoprotein cholesterol and high sensitivity C-reactive protein. Conclusion DM2 that was newly diagnosed after established vascular atherosclerotic disease did not increase the risk of new major CV events. In our population only the polyvascular disease was able to identify the subjects at high risk for a second major cardiovascular event.

Selective shunting during carotid endarterectomy (CEA) is advocated to reduce shunt-related stroke. Cerebral monitoring is essential for temporary carotid shunting. Many techniques are available for cerebral monitoring; however, none is superior to monitoring the patient's neurological status (awake testing) while performing the procedure under local anesthesia (LA). Cerebral oximetry (CO) has previously been used to show the adequacy of cerebral circulation in patients undergoing CEA. This investigation was designed to compare the performance of the INVOS-4100 cerebral oximeter and the neurologic functions, by means of detecting cerebral ischemia induced by carotid cross-clamping, in patients undergoing CEA under LA, namely cervical plexus block.Patients scheduled for CEA under LA were included. Patients converted to general anesthesia (GA) or other types of operations other than CEA were excluded from this study. We enrolled 100 consecutive patients from January 2009 to December 2010. Bilateral regional cerebrovascular oxygen saturation (rSO(2)) was monitored in all patients, in addition to the awake testing. Changes in rSO(2) following carotid artery clamping were recorded. A drop greater than 20% was considered as an indicator of cerebral ischemia that might predict the need for carotid shunting. Patients were only shunted based on the awake testing.Of the 100 patients undergoing CEA under LA, 9 showed a significant drop in rSO(2) (range: 22.6-32.8%, mean: 26.4%): only three of them required shunting, while the remaining 6 had no changes in consciousness after internal carotid artery (ICA) cross-clamping and it was not necessary to place a shunt (false positive). Compared to the preclamping values, a significant decrease in rSO(2) was found on the hemisphere of the operated side, while no significant change was observed contralaterally. Ninety-one patients had no significant changes of CO values: in 89 of them there was no consciousness deterioration, so we didn't place a shunt (true negative), but 2 patients showing a non-significant post-clamping decline in CO saturation (1.5% and 18.2%) required shunting based on the awake testing (2 false negative). In the current study, the median drop in rSO(2) was 19% (range: 1.5-26.4%) in the 5 patients that required shunting. This represents a sensitivity of 60% and a specificity of 25% for CO in comparison to the awake testing.The results of this study suggest that the usefulness of CO in predicting cerebral ischemia is modest. Cerebral monitoring with INVOS-4100 has a high negative predictive value, but the positive predictive value is low.

Objective The role of inflammatory adipokines has clear mechanistic effects in the promotion of both DM2 and cardiovascular diseases (CVDs), but it is unknown to what extent atherosclerosis-related inflammation might promote defects of glucose metabolism. The purpose of this study was to test the hypothesis that in subjects with atherosclerotic vascular disease and no previous medical record of type 2 diabetes mellitus (DM2), the diagnosis of occult impaired glucose regulation (IGR) is related to the severity of atherosclerosis, measured as the single or combined presence of an history of coronary artery disease (CAD), carotid atherosclerosis (Car-ATS) and peripheral artery disease (PAD). Methods In a population of 551 subjects (440 men and 111 women) with a previous history of atherosclerosis, we investigated the presence of IGR (including both impaired glucose tolerance and DM2). To test the correlation between conventional and non-conventional risk factors for cardiovascular disease and diabetes we used logistic and regression analysis models. Results IGR was more prevalent in patients with a documented vascular disease in two or three vessel districts compared with patients with only one symptomatic district ( p =0.016). Among classic risk factors we found that waist circumference was correlated neither to IGR nor to symptomatic vascular disease extension. By contrast, adiponectin level was independently associated to vascular and glucose regulation status ( p =0.012 and p Conclusion In subjects affected by atherosclerotic vascular diseases, the presence of impaired glucose regulation is associated to the number of vascular districts affected and to a reduced adiponectin level.

OBJECTIVE Atherosclerosis is accelerated in subjects with type 2 diabetes by unknown mechanisms. We identified tissue inhibitor of metalloproteinase 3 (TIMP3), the endogenous inhibitor of A disintegrin and metalloprotease domain 17 (ADAM17) and other matrix metalloproteinases (MMPs), as a gene modifier for insulin resistance and vascular inflammation in mice. We tested its association with atherosclerosis in subjects with type 2 diabetes and identified Sirtuin 1 (SirT1) as a major regulator of TIMP3 expression. RESEARCH DESIGN AND METHODS We investigated ADAM10, ADAM17, MMP9, TIMP1, TIMP2, TIMP3, and TIMP4 expression levels in human carotid atherosclerotic plaques (n = 60) from subjects with and without diabetes. Human vascular smooth muscle cells exposed to several metabolic stimuli were used to identify regulators of TIMP3 expression. SirT1 small interference RNA, cDNA, and TIMP3 promoter gene reporter were used to study SirT1-dependent regulation of TIMP3. RESULTS Here, we show that in human carotid atherosclerotic plaques, TIMP3 was significantly reduced in subjects with type 2 diabetes, leading to ADAM17 and MMP9 overactivity. Reduced expression of TIMP3 was associated in vivo with SirT1 levels. In smooth muscle cells, inhibition of SirT1 activity and levels reduced TIMP3 expression, whereas SirT1 overexpression increased TIMP3 promoter activity. CONCLUSIONS In atherosclerotic plaques from subjects with type 2 diabetes, the deregulation of ADAM17 and MMP9 activities is related to inadequate expression of TIMP3 via SirT1. Studies in vascular cells confirmed the role of SirT1 in tuning TIMP3 expression.

To the editor: We and others have found that either genetic insulin resistance or hyperinsulinemia may dampen insulin ability to activate the PI3-kinase/Akt pathway, leading to perturbation of endothelial nitric oxide synthase (eNOS) activation.1,2 However, little is known about insulin effects on transcription of antiatherogenic and proatherogenic genes in insulin resistant conditions. Therefore, we used a genetic model of vascular insulin resistance, primary human umbilical vein endothelial cells (HUVECs) naturally carrying the G972R Insulin Receptor Substrate-1 (IRS-1) variant,2 to investigate the effect of both genetic insulin resistance and hyperinsulinemia on transcription of atherosclerosis related genes. G972R IRS-1 variant reduces IRS-1 activation of the PI3-K/Akt pathway,3 and it has been associated to coronary artery disease and obesity.3,4 HUVECs carrying the wild-type (WT) or G972R IRS-1 variant were obtained as previously described.3 For the experiments, 3rd through 5th passage HUVEC-WT and 972 were incubated in serum free EGM-2 medium for 16 hours in the presence or absence of insulin 5×10−7 mol/L, to obtain a full effect of insulin on nitric oxide production.5 Total RNA was extracted from the HUVECs with Trizol reagent according to the manufacturer’s protocol. To profile gene expression pattern we made use of U133A Affymetrix DNA microarray containing a total number of 22283 probe sets corresponding to about 15 000 genes, using previously described methods.6 Gene expression profiling was obtained by …

A review of the literature on the surgical treatment of abdominal aortic aneurysms (AAAs) reveals that aortofemoral bypass (AFB) is used frequently in some centers. The latter series are characterized by higher rates of graft-related complications than in those in which AFB is used less frequently. The aim of our study was to evaluate the relative frequency and outcome of different types of bypass grafts in the surgical treatment of AAAs with iliac involvement, in our center and in others.Between 1994 and 2004, 190 AAA patients with involvement of the iliac axes underwent elective repair in our department. Surgery was performed via median transperitoneal access.The AAAs extended to the common iliac artery (CIA) in 90.5% of patients. The remaining 9.5% extended to the external iliac artery (EIA). Aorto bi-iliac grafts were used in 159 cases, straight tube grafts in 13, aorto EIA grafts in 15, and AFBs in 3. Overall 30-day morbidity and mortality rates were 12.1% and 2.6%, respectively. At follow-up (mean: 5.6 years), one distal limb infection of an AFB and 4 CIA/EIA aneurysmal enlargements occurred and were repaired accordingly. Secondary patency and 5-year cumulative survival rate were 100% and 80%, respectively.In this series of AAAs extending to the iliac axes, AFB was used selectively (1.6%), even when the AAA extended to the EIA. This allowed us to maintain direct vascularization of the hypogastric arteries and eliminate the risk of complications associated with inguinal access. We feel, therefore, that for the repair of aortoiliac aneurysms, AFB is rarely indicated.

The delay phenomenon in the transverse rectus abdominis myocutaneous (TRAM) flap was studied by means of a laser-Doppler flowmeter and an echo color-flow Doppler device. Twenty-eight patients who underwent breast reconstruction with a TRAM flap in our hospitals were analyzed. Eighteen of them underwent selective delay 1 month before the major surgical procedure, and of them, 15 completed the reconstructive procedure. Ten patients were used as a control group and underwent TRAM flap breast reconstruction without selective delay. Cutaneous blood flow in the TRAM flaps was measured in 20 patients with a laser-Doppler flowmeter, and measurements were taken before, during, and after the surgical procedure, following a standardized protocol, as in Tuominen's original scheme. Variations in the cutaneous blood flow in the standard TRAM flap (10 patients) confirmed data obtained from the literature, i.e., an increase when elevating the cutaneous and subcutaneous parts of the flap and a decrease when ligating the deep inferior and superficial epigastric vessels. Compared with the standard TRAM flap, blood flow in the delayed flaps (10 patients) seemed to be more stable, without falling under the baseline. When elevating the cutaneous and subcutaneous parts of the flap (phase 3), blood flow values reached 120.2 percent (SEM 46.8 percent) on the random side and 131.6 percent (p < 0.009, SEM 9.58 percent, standard deviation 30.3 percent) on the axial side. During phase 4 (cutting the rectus muscles), blood flow values reached 115.0 percent (SEM 40.5 percent) on the random side and 102.8 percent (SEM 1.2 percent, standard deviation 3.8 percent, p < 0.049) on the axial side. In order to obtain further hemodynamic data, 10 patients who underwent selective vascular delay 1 month prior to breast reconstruction with a delayed TRAM flap in our hospitals were then studied by means of an echo color-flow Doppler device. Two of these patients also had been studied with the laser-Doppler flowmeter. Superior epigastric artery diameter (in millimeters) and resistivity (expressed as Pourcelot's index) were measured before and after selective delay of the deep and superficial inferior epigastric vessels, following a standardized protocol. Measurements were taken with 7.5- and 10-MHz linear probes at a point located after the origin of the costomarginal artery. In every patient an increase in the superior epigastric artery diameter and a decrease in the resistivity index were observed, and this was statistically significant. In the nonirradiated patients, the increase in the average diameter of the superior epigastric artery was 98.1 percent, and the average resistivity index decrease was 14.1 percent. In the irradiated patients, the increase in the average diameter of the superior epigastric artery was 35.5 percent, and the average resistivity index decrease was 29.8 percent. In conclusion, laser-Doppler flowmeter evaluations show that cutaneous blood flow in the delayed flap is more constant and undergoes fewer variations than that in the standard TRAM flap. In addition, echo color-flow Doppler indicates that the basis for the increase in the vascular territory of the superior epigastric artery caused by the delay maneuver is an increase in the superior epigastric artery diameter, always accompanied by a decrease in the resistivity index. Two different mechanisms seem to us to be related to these modifications in the blood circulation. In the nonirradiated patients, superior epigastric artery dilation prevails, whereas in the irradiated patients, a decrease in the resistivity index is the dominant mechanism of compensation. These hemodynamic findings well support the decrease in flap necrosis reported in our series (standard TRAM: 30 percent; delayed TRAM: 7.1 percent).