Overexpression of Toll-Like Receptors 2, 3, 4, and 8 Is Correlated to the Vascular Atherosclerotic Process in the Hyperlipidemic Rabbit Model: The Effect of Statin Treatment.

BACKGROUND: Atherosclerosis is the major cause of cardiovascular disease; hypercholesterolemia is a major risk factor. We hypothesized that specific TLR members (TLR2, TLR3, TLR4, TLR8) may play a role in atherosclerosis progression and its accompanying inflammatory response. We determined the association of atherosclerotic lesions and TLR mRNA expression in different aortic sites. We also assessed the effects of fluvastatin (Flu) treatment on TLR expression and plaque characteristics. METHODS: Male rabbits, fed with an atherogenic diet for a duration of 3 months, were screened for advanced atherosclerotic lesions in the aorta. Additional animals received normal diet or normal diet plus Flu for 1 additional month. TLR mRNA expression in various thoracic and abdominal aortic segments was assessed, together with atherosclerotic changes. RESULTS: After high lipid diet, the atherosclerotic burden increased more in the abdominal than in the thoracic aorta; TLR2, 3, 4, and 8 also increased significantly. Flu decreased atherosclerotic plaque, calcium deposition, lipid cores, intraplaque hemorrhage, erythrocyte membranes, endothelial cells, and macrophage infiltration, while increasing smooth muscle cells in plaques of both aortic segments; it also lowered TLR2, 3, 4, and 8 expression in all aortic segments to a stronger degree than resumption of normal diet. There was a strong association between blood and tissue parameters during experimental period and finally a strong correlation found between these parameters with mRNA of TLR2, 3, 4, and 8 in various stages. CONCLUSION: For the first time TLR2, 3, 4, and 8 mRNA expression is prospectively explored after hypercholesterolemic diet in the rabbit model. TLR2, 3, 4, and 8 mRNA expression is strongly upregulated and correlates with the progression of atherosclerosis in the aorta. Flu significantly inhibited this progress and reduced inflammation via TLR downregulation which was strongly associated with regression of plaque morphology and atherosclerosis promoting factors.

The effect of increasing operator experience on procedure-related characteristics in patients undergoing carotid artery stenting.

Objectives To evaluate the efficacy and safety of carotid artery stenting for the treatment of severe carotid artery disease in our department and to investigate the effect of increasing operator experience on perioperative and procedure-related characteristics. Methods From January 2007 to February 2015 200 patients underwent 207 endovascular procedures for carotid artery stenosis. Of all, 113 arteries (56.5%) were symptomatic. Significant changes across time were calculated with the use of Change Point analysis using bootstrap and mean squared error estimates. Results The technical success was 98.6% (204/207 cases). Thirty-day neurological events included stroke in four patients (2%) and transient ischemic attack in two (1%). None of the patients died during the first 30 days. The most significant change of radiation duration occurred after the 33rd patient with a decrease from 25.31 min to 12.31 min, while for the total operative time that change occurred between the 31st and 33rd patient where mean operation time decreased from 88.89 min to 49.22 min. The most significant change of contrast media used occurred at the 40th patient with a decrease from 91.58 ml to 62 ml. During a mean follow-up period of 42 ± 20.02 months none of the patients experienced any cerebrovascular event. There was one case of significant recurrent stenosis, which was successfully treated by endovascular means. Conclusions Endovascular treatment of carotid artery stenosis performed in a single center with the use of a cerebral protection device seems to consist a safe therapeutic choice with acceptable results, within the referenced benchmarks proposed in the latest guidelines. Certain perioperative parameters such as the amount of contrast media used, the fluoroscopy and operation time, seem to decline overtime indicating increasing operator's experience. A number of performed cases above 40 was related to the significant decrease of those parameters and may represent the learning curve of the procedure.

Standard endovascular treatment of abdominal aortic aneurysms in patients with very short proximal necks using the Endurant stent graft.

OBJECTIVE: This study evaluated and compared the midterm results of endovascular aortic aneurysm repair with the Endurant (Medtronic Inc, Santa Rosa, Calif) stent graft system in off-label use in patients with short (<10 mm) proximal aortic necks and in patients treated according to device-specific instructions for use. METHODS: This was a case-control (2:1) single-center retrospective analysis of prospectively collected data performed between September 2008 and December 2012. Analysis identified 19 elective patients with short (<10 mm) proximal necks and mild angulations (≤45°) treated with the Endurant stent graft and 38 patients matched for age, sex, and aneurysm diameter with proximal aortic necks ≥10 mm in length who met the instructions for use. End points included technical and clinical success and freedom from any secondary intervention, any type of endoleak, and aneurysm-related death. RESULTS: The short-neck group was a mean ± standard deviation age of 71.7 ± 8.9 years, 84% were men, and their mean infrarenal aortic neck length was 6.1 ± 1.2 mm. Mean suprarenal and infrarenal angles were 110° ± 10.4° and 170° ± 15.4°, respectively. Aortic neck diameters were similar between the groups (26.6 ± 3.8 vs 25.7 ± 3.7 mm; P = .36). Primary technical success was achieved in all cases. Off-label patients were more likely to require additional proximal cuff deployment to successfully obtain a seal (21% vs 3%; P = .04). The two patient groups were similar in rates of perioperative mortality, morbidity, and complications. Mean follow-up of 24 ± 12 months revealed no differences in clinical success, freedom from reintervention, and aneurysm-related death. No type I endoleaks were observed in either group during the follow-up period. CONCLUSIONS: The Endurant stent graft system applied off-label in patients with very short aneurysm necks (<10 mm) with mild angulation showed acceptable treatment results. These midterm results might suggest its use in carefully selected patients with very short neck anatomy. Long-term data are needed to verify the observed durability of the Endurant stent graft.

Endovascular Treatment of Chronic Total Occlusions of the Iliac Arteries: Early and Midterm Results.

BACKGROUND: To examine the effects of endovascular therapy on the treatment of chronic total occlusions (CTOs) of the iliac arteries. METHODS: We analyzed a cohort of 48 patients (56 limbs) who were treated by endovascular means for iliac artery CTOs during a period of 4 years in 2 vascular surgery centers in Greece. The data were collected retrospectively and were statistically analyzed to report on technical success, morbidity, mortality, primary and secondary patency, and limb salvage through different patient and/or lesion stratifications. RESULTS: Recanalization was accomplished without assisting devices, and primary stenting was always performed. The technical success of the endovascular treatment reached 91%. Patients experienced 4.2% major morbidity and 2.1% mortality rate. Mean ankle-brachial pressure index increased from 0.43 ± 0.12 preoperatively to 0.89 ± 0.11 postoperatively. A median improvement by 3 Rutherford clinical categories was recorded at the first-month follow-up. The estimated limb salvage rate for patients suffering from critical limb ischemia (CLI) was 90.9% at 36 months. Kaplan-Meier analysis estimation for overall primary and secondary patency rate of the treated lesions was 91.4% and 95.3%, respectively at 36 months. There were no statistically significant differences in primary and secondary patency rate between patients in different clinical stages (CLI versus intermittent claudication), as well as between CTO lesions of different Trans-Atlantic Inter-Society Consensus (TASC) categories (TASC B versus TASC C versus TASC D). There was not statistical significant difference between the technical success of TASC B, C, and D lesion groups. CONCLUSIONS: The endovascular treatment of iliac CTOs seems to be safe and feasible. The technical success of the procedure could be high, whereas primary and secondary patency rates seem to be optimal, with remarkable limb salvage rate and overall clinical improvement. A potential shift to an endovascular-first approach for such lesions might be currently justified.

Use of the vascu-guard bovine pericardium patch for arteriotomy closure in carotid endarterectomy. Early and long-term results.

BACKGROUND: To report the early and long-term results of Vascu-Guard bovine pericardium (BP) for patch angioplasty in carotid endarterectomy (CEA). METHODS: We retrospectively analyzed the data of 256 CEAs with BP patch closure performed in 238 patients during the past 12 years in our department. Patch-related complications (restenosis, infection, and aneurysm formation) and early and late (12 to 144 months follow-up) clinical outcomes were recorded and statistically analyzed. RESULTS: Thirty-day postoperative stroke rate was 1.2% (3/256) with zero mortality. Major complications occurred in 3.5% (9 of 256) of the procedures and cranial nerve injury in 4.3% (11 of 256). At 12 years, cumulative estimates of freedom from any stroke, stroke-free survival, and freedom from restenosis were 88.4% (standard error [SE]: 3.3%), 60% (SE: 7.8%), and 98.3% (SE: 0.8%), respectively. No patient experienced patch infection or aneurysm formation. CONCLUSIONS: This series shows the efficacy, safety, and durability of CEA with BP patch closure, in both the short and long term. BP combines the advantages of vein and synthetic patches, representing a suitable option when performing CEA.

Endovascular treatment for isolated acute abdominal aortic dissection.

BACKGROUND: Isolated acute abdominal aortic dissection (IAAAD) is considered an unusual clinical entity and is traditionally treated by open surgical repair. We report our single-center experience during the last 9 years, evaluating the outcomes after endovascular repair in this patient population. METHODS: All patients with a diagnosis of IAAAD treated in our institute were included in this retrospective review. Between January 2004 and December 2012, 38 patients suffering from an acute aortic dissection were referred regionally for intervention to our department: 24 (63.2%) with a thoracic aortic dissection type B and 14 patients (36.8%, all male; median age, 65 years) with an IAAAD. Demographics, perioperative, procedure-specific, and follow-up data were prospectively aggregated in an electronic database. RESULTS: Patients suffering from IAAAD presented with acute abdominal pain (n = 13) and acute lumbar pain (n = 1). Insufferable pain and enlargement of the aorta were the main indications for treatment. Mean (± standard deviation) maximal abdominal aortic diameter at presentation was 3.5 ± 0.94 cm (range, 2.6-5.1 cm). None of these patients had a concomitant thoracic aortic dissection. All patients were treated by endovascular means, with a primary technical success rate of 100%. Two patients (14%) died perioperatively from cardiac causes. Median hospital stay was 4.5 days (range, 3-16 days). During a mean follow-up period of 37.41 ± 23.56 months (range, 8-82 months; median, 32.5 months), two patients experienced primary treatment failure needing reintervention that led to a successful outcome. The cumulative free-from-reintervention rate was estimated 90.9% at 58 months (standard error, 8.7%). A full aortic remodeling without any events was noted in all other patients during the follow-up period. CONCLUSIONS: Based on our series, IAAAD may represent a not so rare clinical entity as generally thought, suggesting that it may be underdiagnosed. Endovascular treatment of IAAAD appears to be a feasible and efficient therapeutic approach and might be considered as the first-line treatment in all patients with suitable anatomy.

Analysis of effects of fixation type on renal function after endovascular aneurysm repair.

PURPOSE: To report a prospective nonrandomized study comparing the effects of suprarenal (SR) vs. infrarenal (IR) stent-graft fixation on renal function in patients undergoing endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). METHODS: Patients with AAA undergoing elective EVAR between June 2008 and June 2010 were eligible for the comparative study of fixation method on renal function. Patients with impaired renal function [estimated creatinine clearance (eCrCl) <30 mL/min] or a history of renal impairment were not eligible. Renal function was assessed by measuring serum creatinine (SCr) and total proteins and microalbumin in the urine preoperatively, on postoperative day 1, and at 1, 6, and 12 months. The eCrCl was calculated using the Cockcroft-Gault formula. A standard preoperative hydration protocol was followed in all patients, and stent-graft choice was at the operator's discretion. Of 116 patients undergoing elective EVAR in the study period, 16 were ineligible, leaving 100 patients (95 men; median age 74 years) enrolled in the study (49 SR and 51 IR). RESULTS: There was no statistically significant difference between the groups in the prevalence of any risk factor, the baseline SCr and eCrCl values, contrast usage, or procedure duration. At the postoperative measurement, there was no significant deterioration of renal function in either group, although total urinary proteins increased significantly in both groups (IR p=0.01, SR p<0.001). At the 12-month follow-up, patients in the IR group had no significant alteration in any marker vs. baseline, while patients in the SR group had significant alterations in SCr (p=0.001), eCrCl (p<0.001), and microalbumin (p=0.04) in urine. The number of patients with a >20% decrease in eCrCl was not significantly different between the groups. No patient had an adverse renal event. CONCLUSION: Deterioration in renal function was observed 12 months after EVAR in patients receiving a stent-graft with suprarenal fixation, even though this did not seem to increase the likelihood of postoperative renal impairment. Furthermore, suprarenal fixation may be responsible for progressively significant proteinuria. Further studies are needed to determine the long-term impact of suprarenal fixation on renal function and investigate the potential risk of progressive renal disease in relation to type of fixation.

Experimentally modified Fontan circulation in an adolescent pig model without the use of cardiopulmonary bypass.

BACKGROUND: The feasibility and the hemodynamic outcome of Fontan circulation, without the use of cardiopulmonary bypass, were studied on a beating heart of an adolescent pig model, using a modified total cavopulmonary connection. MATERIAL/METHODS: Eight open-chest anesthetized pigs underwent a successful total cavopulmonary connection with the use of an appropriate Y-shaped Dacron-type conduit. Through a median sternotomy, the distal part of the superior vena cava was anastomosed end-to-end to one side of the conduit. The other side of the graft was anastomosed end-to-side to the main pulmonary artery. The conduit was tailored to an appropriate length and anastomosed end-to-end to the inferior vena cava. The hemodynamic status of the animals was recorded before and after the establishment of the total cavopulmonary connection. RESULTS: Forty-five minutes after completion of total cavopulmonary connection, and for a total of 1 hour, hemodynamic measurements showed a decrease in mean arterial and mean pulmonary artery pressures, heart rate and cardiac output. The inferior vena caval pressure and total pulmonary vascular resistance were increased. CONCLUSIONS: A total cavopulmonary connection, performed on a beating heart, without extracorporeal circulation or other means of temporary bypass, although it is technically demanding, is feasible.

ERp46 is reduced by high glucose and regulates insulin content in pancreatic beta-cells.

Our studies focus on ERp46, an endoplasmic reticulum (ER) component, and analyze its involvement in glucose toxicity and in insulin production. Differences in pancreatic beta-TC-6 cell proteome under conditions of low vs. high glucose were examined by proteomic approaches, including two-dimensional gel electrophoresis, image analysis, and mass spectrometry. Among differentially expressed proteins, ERp46, a novel endoplasmic reticulum component, was examined further. The expression of ERp46 in pancreatic sections was analyzed by immunocytochemistry, and high glucose-induced alterations of expression were evaluated in cultured beta-cells, in isolated pancreatic islets, and in the pancreas of db/db diabetic animals. Inhibition of ERp46 expression by siRNA was performed to study its role in insulin production, in secretion, and in ER stress. Proteomic analysis led to identification of 46 differentially expressed spots corresponding to 23 proteins. Since ERp46 is a novel protein with a possible crucial role in secretory cells, we further analyzed its role in beta-cell function. ERp46 expression is reduced in high glucose concentration in beta-TC-6 cells and in isolated murine islets. Further analysis revealed high expression of ERp46 in pancreatic islets compared with exocrine tissue. Interestingly, a marked decrease in ERp46 expression was found in the pancreatic islets of db/db mice. Most importantly, siRNA-mediated knockdown of ERp46 in cultured beta-cells led to a significant decrease in the insulin content; however, no alterations in insulin mRNA levels were observed under these conditions. In addition, reduced expression of ERp46 by siRNA increased the expression of CHOP and peIF2a, indicating development of ER stress. We conclude that ERp46 may be an important component in the phenomenon of "glucose toxicity" involved in insulin production at the posttranslational level.

Altered expression of calreticulin during the development of fibrosis.

Tissue damage following injury leads to inflammation and fibrosis. To understand the molecular mechanisms and the proteins involved in the fibrotic process, we used the well-established unilateral ureteric obstruction rat model and we analyzed the alterations at early and late time intervals using a classical proteomic approach. Data analysis demonstrates a correlation between calreticulin up-regulation and progression of fibrosis. Calreticulin is involved in Ca++ homeostasis but has not been previously implicated in animal models of fibrosis. Proteomic analysis consistently revealed up-regulation of calreticulin in both early and late time intervals. These findings were further confirmed by biochemical and morphological approaches. Next, animal models of lung fibrosis (bleomycin-induced) and heart fibrosis (desmin-null) were examined. In the lung model, calreticulin expression was up-regulated from early time intervals, whereas in the heart model no change in the expression of calreticulin was observed. In addition, TGF-beta, a well known major contributing factor in several fibrotic processes, was found to up-regulate calreticulin in cultured human proximal tubule epithelial cells. The above observations suggest that calreticulin might be involved in fibrotic processes; however the mechanism(s) underlying its possible involvement are yet unresolved.

Initial Clinical Experience with the Endologix AFX Unibody Stent Graft System for Treating Patients with Abdominal Aortic Aneurysms: A Case Controlled Comparative Study.

PURPOSE: The newly designed unibody AFX endograft system for endovascular aortic aneurysm repair is the only graft with anatomical fixation to the aortic bifurcation in comparison to most other grafts that use the infrarenal neck as the main fixation point. The aim of this study was to assess the preliminary results of the AFX stent-graft system used with infrarenal aortic component and compare them with those obtained in patients treated with a well established endograft of the same material and pure infrarenal fixation as the Gore Excluder. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data from March 2014 to December 2014 identified 10 elective abdominal aortic aneurysm patients treated with the AFX endograft, in comparison to a matched group of 20 patients treated with the Excluder stent-graft. Endpoints included technical and clinical success, freedom from any secondary intervention, any type of endoleak and aneurysm related death. RESULTS: Primary technical success was achieved in all patients and no 30-day device related complications or deaths were occurred. The two groups were similar in terms of radiation burden, contrast media, duration of the procedure, post implantation syndrome and in-hospital stay. During a median follow-up period of 23 months (range, 18-26 months) there were no differences in clinical success, freedom from reintervention and aneurysm related death. No type I endoleak was observed in either group. Five of the 6 type II endoleaks (1 in the AFX and 4 in the Excluder group) spontaneously resolved, while in only one patient (Excluder) the endoleak remained without however any change in aneurysm sac diameter (log rank=0.34). CONCLUSION: The initial experience with the AFX stent graft system is promising, with successful aneurysm exclusion and good short-term results. Further and larger studies are needed to fully evaluate the sort as well as the long-term results.

Endovascular repair of blunt axillo-subclavian arterial injuries as the first line treatment.

AIM: To report and analyse our results regarding the endovascular management of blunt axillo-subclavian arterial injuries as the first line treatment. METHODS: During an eight-year period, seven patients (mean age 56.4±14.1 years, all males) with blunt traumatic axillo-subclavian arterial injuries were presented to the emergency department. All patients suffered also from concomitant other injuries and had a supraclavicular haematoma along with diminished or absent upper limb peripheral pulses, while computed tomography angiography set the diagnosis. RESULTS: The endovascular procedure was technically successful in all patients. No procedure-related complication was encountered during the in-hospital stay, while none of the patients died. The median hospital stay was 22 days (range 12-46). During a follow-up period spanning an average of 27 months (range 6-44 months) there was one stent-graft thrombosis at 12 months in an otherwise asymptomatic patient that required no further intervention. CONCLUSION: Endovascular technique seems to constitute a reliable approach for treating blunt axillo-subclavian arterial injuries in the emergent setting. Despite uncertainties in patient selection and optimal management algorithms, it seems that endovascular approach could be the first line treatment for such injuries. Accumulation of data on larger number of patients with longer follow-up is warranted to further define the value of this therapeutic modality in the trauma setting.

Management of an aorto-esophageal fistula, complicating a descending thoracic aortic aneurysm endovascularly repaired.

Aorto-esophageal fistula (AEF) is a rare but devastating complication of thoracic aorta endovascular repair (TEVAR). We report a case of a 64-year-old male who presented with chest pain and high CRP levels 10 months after TEVAR for a 9 cm diameter descending thoracic aortic aneurysm. The diagnosis of an AEF was confirmed and the patient was treated conservatively with broad spectrum antibiotics and total parental alimentation. After control of sepsis was achieved, esophagectomy with gastric tube reconstruction was performed and an omental pedicle was used to cover the aortic wall. No intervention to the aorta was made at that time due to the potentially infected mediastinum. The patient's recovery was uneventful and 2 years postoperatively he is in good condition and lives a normal life. Esophagectomy seems to be a mandatory stage of treatment in the setting of AEF. In cases where signs of graft infection are persistent, aortic surgery might be also necessary.

Safe and fast proximal aortic control using an aortic balloon through direct graft puncture for the explantation of an abdominal endograft with suprarenal fixation.

The late removal of an abdominal aortic endograft is technically challenging and can be associated with significant blood loss, especially when a graft with active suprarenal fixation is involved. The main issue in safe explantation of the endograft is control of the aorta above the proximal fixation site. We report an adjunctive technique for the safe and fast proximal control of the suprarenal aorta using an aortic balloon. The endograft is directly punctured and an aortic balloon is deployed and inflated above the fixation site in the supracoeliac aorta. The time for supracoeliac control in our 2 patients was <5 min. This simple technique offers a safe and fast aortic control during the removal of the endograft, especially when active suprarenal fixation is used, avoiding the risks from a technically demanding dissection in a potentially inflammatory region.

In endovascular aneurysm repair cases, when should you consider internal iliac artery embolization when extending a stent into the external iliac artery?

A best evidence topic was constructed according to a structured protocol. The question addressed was whether internal iliac artery (IIA) embolization is necessary for achieving the best clinical outcome in all patients when extension of the stent graft to the external iliac artery is required. Altogether more than 400 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. There is a significant gap in the current literature regarding the subset of patients that may benefit from an IIA embolization during endovascular aneurysm repair (EVAR) as indications have not been clearly defined. There are several situations concerning a small number of patients, that IIA embolization might be beneficial in preventing endoleak not only to the common iliac artery but also to the aortic aneurysmal sac. For the majority of patients requiring extension of the stent graft to the external iliac artery, the current evidence, even retrospective in nature and reporting on small numbers of patients, shows that IIA embolization seems to be associated with worse clinical outcome, mostly raising the risk for new-onset buttock claudication. It seems that not all patients require embolization, as IIA coverage solely by the stent graft was not associated with a significant higher rate of type II endoleak in either study. Furthermore, coil embolization in the largest study so far was associated with higher procedure and fluoroscopy time and amount of contrast media, facts that should not be neglected. However the above-mentioned results should be taken into account with caution, as all studies were retrospective and reported on small number of patients.

An uncommon, life-threatening, traumatic hematoma in the neck area.

It is well known that blunt neck trauma, when compared to a penetrating injury in the same anatomical area, is very rare. We report a case of an 81-year-old Caucasian woman with a blunt life-threatening neck trauma due to a bully goat. Although rare, direct evaluation should always be done in these cases because any misinterpretation may result in unfavorable outcomes. We have to highlight that close medical attention and prompt surgical treatment should be always considered in order to avoid dramatic consequences.

Biomechanical testing and material characterization for the rat large intestine: regional dependence of material parameters.

The function of the large bowel is to absorb water from the remaining indigestible food matter and subsequently pass useless waste material from the body, but there has been only a small amount of data in the literature on its biomechanical characteristics that would facilitate our understanding of its transport function. Our study aims to fill this gap by affording comprehensive inflation/extension data of intestinal segments from distinct areas, spanning a physiologically relevant deformation range (100-130% axial stretches and 0-15 mmHg lumen pressures). These data were characterized by the Fung-type exponential model in the thick-walled setting, showing reasonable agreement, i.e. root-mean-square error ~30%. Based on optimized material parameters, i.e. a(1)