HIV-1 matrix protein p17 promotes lymphangiogenesis and activates the endothelin-1/endothelin B receptor axis.

OBJECTIVE: AIDS-related lymphomas are high grade and aggressively metastatic with poor prognosis. Lymphangiogenesis is essential in supporting proliferation and survival of lymphoma, as well as tumor dissemination. Data suggest that aberrant lymphangiogenesis relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. HIV-1 matrix protein p17 was found to accumulate and persist in lymph nodes of patients even under highly active antiretroviral therapy. Because p17 was recently found to exert a potent proangiogenic activity by interacting with chemokine (C-X-C motif) receptors 1 and 2, we tested the prolymphangiogenic activity of the viral protein. APPROACH AND RESULTS: Human primary lymph node-derived lymphatic endothelial cells were used to perform capillary-like structure formation, wound healing, spheroids, and Western blot assays after stimulation with or without p17. Here, we show that p17 promotes lymphangiogenesis by binding to chemokine (C-X-C motif) receptor-1 and chemokine (C-X-C motif) receptor-2 expressed on lymph node-derived lymphatic endothelial cells and activating the Akt/extracellular signal-regulated kinase signaling pathway. In particular, it was found to induce capillary-like structure formation, sprout formation from spheroids, and increase lymph node-derived lymphatic endothelial cells motility. The p17 lymphangiogenic activity was, in part, sustained by activation of the endothelin-1/endothelin receptor B axis. A Matrigel plug assay showed that p17 was able to promote the outgrowth of lymphatic vessels in vivo, demonstrating that p17 directly regulates lymphatic vessel formation. CONCLUSIONS: Our results suggest that p17 may generate a prolymphangiogenic microenvironment and plays a role in predisposing the lymph node to lymphoma growth and metastasis. This finding offers new opportunities to identify treatment strategies in combating AIDS-related lymphomas.

Three-year follow-up analysis of automated microfoam preparation system for great saphenous vein incompetence and varicose veins sclerotherapy treatment.

BACKGROUND: To describe the treatment of patients with great saphenous vein (GSV) incompetence and varicose veins (VVs), utilizing an Automated Microfoam Preparation System (AMPS, Varixio®, VB Devices, Barcelona, Spain). METHODS: Adults between January and June 2021 were included. The AMPS system was used for foam preparation. Sclerotherapy treatment followed international recommendations. The primary endpoint was GSV closure rate after 36 months. RESULTS: 164 patients were enrolled. During the 7-day follow-up period, all GSVs showed complete closure, which was maintained at the 1-year mark. No major complications were reported. A cumulative complete GSV recanalization rate of 6.1% and a partial recanalization rate of 26.8% after 36 months were noted. Some patients (9.7%) required additional treatment. A higher BMI was associated with complete recanalization. CONCLUSION: The AMPS offers an easy-to-use and standardized procedure, potentially enhancing treatment outcomes if compared with manual preparation. Caution is advised when treating obese patients.

Association between human parainfluenza virus type 1 and smoking history in patients with an abdominal aortic aneurysm.

Several studies have suggested that infectious agents may induce the development of abdominal aortic aneurysms and/or accelerate their progression. The aim of this study was to evaluate the presence of the respiratory-transmitted viruses such as influenza A and B and parainfluenza type 1 genomes in bioptic fragments of abdominal aortic aneurysms. Furthermore, the association between viral infection and traditional risk factors for aneurysms was investigated employing multivariate logistic regression models. The genome of parainfluenza 1 was detected in 11 out of 57 patients with abdominal aortic aneurysm, influenza A only in one, whereas none of the specimens analyzed resulted positive for influenza B. After adjustment of age, gender, and clinical diagnosis, being current smokers was associated independently with parainfluenza 1 detection in aneurysms. The identification of parainfluenza 1 in aortic aneurysm biopsies supports previous observations of a possible role of viruses in the lesion development. Smoking, by interfering with the respiratory tract's ability to defend itself and predisposing to upper and lower respiratory tract infections may accelerate the onset and progression of abdominal aortic aneurysms.

Lymph node-derived lymphatic endothelial cells express functional costimulatory molecules and impair dendritic cell-induced allogenic T-cell proliferation.

Lymphatic endothelial cells (LECs) interact with different immune cells, including T cells within lymph nodes (LNs). However, direct interactions of LECs with immune cells have yet to be investigated. In vitro studies were performed to characterize primary cultures of human LECs derived from LNs in their capacity of interacting with T cells. The results show that LECs express HLA molecules and functional costimulatory molecules needed for T-cell activation. A direct binding of LECs and T cells was detected in cell cultures connected with a clustering of costimulatory molecules on the contact phase. LECs were also able to take up and process antigens. However, major histocompatibility complex class II(+) LECs fail to induce allogeneic T-cell proliferation. Interestingly, supernatants of IFN-γ activated LECs impair proliferation of T cells cocultured with allogeneic dendritic cells, suggesting an inhibitory role of LECs. Indoleamine 2,3 dioxygenase was identified as one inhibitory molecule, which may be responsible for the impaired CD4(+) T-cell proliferation. Our observations suggest a regulatory function for activated LECs on CD4(+) T cells, which may play a role in vivo in the maintenance of the critical balance between tolerance and recall responses.

Sequential multiple visceral arteries dissections without aortic involvement.

Isolated dissection of visceral arteries without associated aortic pathology is very rare. Risk factors, etiology, and natural history of this pathology continue to be unclear, and the guidelines for clinical management remain to be defined. We present a case not described previously, with sequential dissections of the celiac trunk, superior mesenteric artery, and renal arteries without aortic involvement. The patient presented with severe back thoracic and abdominal pain and without evidence of peritonitis. An abdominal angio-CT scan showed dissection of the superior mesenteric artery (SMA), with partial thrombosis of the false lumen and subsequent stenosis of around 60%. Conservative treatment with anticoagulants seemed to be appropriate in the beginning, because the patient became asymptomatic spontaneously within a few hours and angio-CT showed dissection but no ischemic lesions. On day 10 after onset, however, he again indicated severe back thoracic and abdominal pain. Emergent CT was performed. The prior SMA dissection appeared to be worse due to increased size of the false lumen, followed by SMA stenosis (about 75‒80%). In addition, dissection of the celiac artery and both renal arteries could be seen. The patient underwent angiography and stenting of the main trunk of the SMA, with good clinical and radiologic outcome. Double oral antiplatelet therapy was then introduced. An angio-MRI scan 6 months later showed stability of the multiple dissections.

A drastic complex atheromatous aorta. A case report.

Aortic atherosclerosis is the most common disease of the aorta. More than 50% of the plaques thicker than 4 mm are located along the descending aorta. The complex morphology of the plaque, such as ulceration or the presence of thrombi, is associated with increased embolic risk. The increasing use of transesophageal echocardiogram has enhanced the recognition of aortic atheromas. We describe a case of a male patient with complex atherosclerotic disease involving the coronary vessels and descending aortic tract with some embolic complications.

Ultrasound assessment is linked to histological vein wall thickness in chronic venous disease.

OBJECTIVES: Few studies compared both ultrasound and histological approaches for the same series of patients with chronic venous disease (CVD). We aimed to assess the diagnostic performances of duplex ultrasound assessment (US) of Vein Wall Thickness (VWT) among patients with CVD. METHODS: 38 adults with primary varicose veins having undergone Great Saphenous Vein thermal ablation with phlebectomy, and agreeing to biopsy of the Posterior Accessory Great Saphenous Vein (PASV) were consecutively included in a two-center prospective study. VWT assessment of the PASV was performed using both US, and microscope examination. High values for microscope-assessed VWT were defined at > 0.5 mm. RESULTS: The mean age was 53.0 ± 13.1 years, 71% were women. Maximization of US performances was obtained with a threshold of 0.6 mm: Sensitivity (Se) = 92.9%, Specificity (Sp) = 91.7%, positive (86.7%) and negative predictive value (NPV) (95.7%), positive (11.1) and negative likelihood ratio (NLR) (0.07). CONCLUSIONS: US assessment of VWT could be a non-invasive tool for diagnosis and follow-up in CVD, and an interesting in vivo parameter complementing diameter and reflux measures, with a view to optimizing treatment. It could help to determine i) the energy level necessary in case of endovenous laser ablation, and ii) the sclerosing agent concentration in case of chemical ablation.

Predictors and outcomes of acute kidney injury after thoracic aortic endograft repair.

BACKGROUND: This study analyzed the incidence and the predictive factors of postoperative acute kidney injury (AKI) after thoracic endovascular aortic repair (TEVAR) and evaluated the effect of AKI on postoperative survival. METHODS: Between November 2000 and April 2011, all consecutive patients undergoing TEVAR of the descending thoracic or thoracoabdominal aorta were enrolled at four teaching hospitals. Estimated glomerular filtration rate (eGFR) was evaluated during the entire hospitalization. AKI was defined by the RIFLE (Risk, Injury, Failure, Loss of function, End-stage renal disease) consensus criteria. RESULTS: The study included 171 patients (80% men) who were a mean age of 69±14 years (range, 18-87 years). AKI occurred in 24 patients (14%). Independent predictors of postoperative AKI were preoperative depressed eGFR, thoracoabdominal extent, and postoperative transfusion. Patients with AKI experienced major postoperative complications (P=.001), longer hospitalization (P=.008), and higher hospital mortality (29% vs 4%; P<.001). Kaplan-Meier analysis showed a survival of 82%, 51%, and 51% at 1, 3, and 5 years for patients who developed AKI, which was significantly worse than the 99%, 89%, and 80% for patients who did not experience AKI (P=.001). CONCLUSIONS: Preoperative poor renal function, blood transfusions, and the thoracoabdominal extent of the aortic disease were the most important predictors for AKI.

Prospective randomized comparison of open versus laparoscopic management of splenic artery aneurysms: a 10-year study.

BACKGROUND: The literature does not support the choice between open and laparoscopic management of splenic artery aneurysms (SAA). METHODS: We designed a prospective, randomized comparison between open and laparoscopic surgery for SAA. Primary end points were types of surgical procedures performed and clinical outcomes. Analysis was developed on an intention-to-treat basis. RESULTS: Fourteen patients were allocated to laparotomy (group A) and 15 to laparoscopy (group B). Groups displayed similar patient- and aneurysm-related characteristics. The conversion rate to open surgery was 13.3 %. The type of surgical procedure performed on the splenic artery was similar in the two groups: aneurysmectomy with splenic artery ligature or direct anastomosis was performed in 51 % and 21 % of patients in group A and in 60 % and 20 % in group B, respectively. The splenectomy rate was similar (14 % vs. 20 %). Postoperative splenic infarction was observed in one case in each group. Laparoscopy was associated with shorter procedures (p = 0.0003) and lower morbidity (25 % vs. 64 %, p = 0.045). Major morbidity requiring interventional procedures and blood transfusion was observed only in group A. Laparoscopy was associated with quicker resumption of oral diet (p < 0.001), earlier drain removal (p = 0.046), and shorter hospital stay (p < 0.01). During a mean follow-up of 50 months, two patients in group A required hospital readmission. In group B, two patients developed a late thrombosis of arterial anastomoses. CONCLUSIONS: Our study demonstrates that laparoscopy permits multiple technical options, does not increase the splenectomy rate, and reduces postoperative complications. It confirms the supposed clinical benefits of laparoscopy when ablative procedures are required but laparoscopic anastomoses show poor long-term results.

Preoperative cardiac evaluation and perioperative cardiac therapy in patients undergoing open surgery for abdominal aortic aneurysms: effects on cardiovascular outcome.

BACKGROUND: Cardiovascular complications, such as death, myocardial infarction, or heart failure, are the leading causes of morbidity and mortality in adult patients undergoing major noncardiac surgery. OBJECTIVE: To evaluate the effects of an accurate preoperative cardiac evaluation, together with optimized perioperative drug therapy, in reducing cardiovascular events in patients undergoing open aortic surgery for abdominal aneurysm. METHODS: Between January 2000 and December 2008, we considered all consecutive patients undergoing elective abdominal aortic open surgery at the Vascular Surgery Unit of the University of Study-Spedali Civili (Italy). Since January 2003, we have used an intensive cardiac preoperative evaluation: patients with at least one cardiac risk factor received a preoperative cardiac evaluation; all non-invasive and invasive tests were performed preoperatively when indicated by the consultant cardiologist, that also optimized the pharmacological perioperative therapy. The outcome of the 418 patients undergoing surgery between 2003 and 2008 was compared with those of the 204 patients in the previous triennium 2000 to 2002, when only patients with positive history for cardiac disease received a standard preoperative cardiological clinical or instrumental evaluation. RESULTS: Patients enrolled in the 2003 to 2008 interval were slightly older and with a higher prevalence of comorbidities compared with those observed in the previous triennium; furthermore, the number of noninvasive tests performed before surgery increased significantly. Nevertheless, the number of major cardiac perioperative complications decreased over time: particularly, in-hospital mortality rate was 0.9% in the latter period, compared with 3.4% in the years 2000 to 2002. Also, the long-term mortality was significantly reduced in patients operated on between 2003 and 2008 compared with those operated on in the previous triennium. CONCLUSION: These data suggest a significant benefit of an intensive cardiac preoperative evaluation in reducing the incidence of perioperative and postoperative cardiac morbidity and mortality.

Human cytomegalovirus productively infects lymphatic endothelial cells and induces a secretome that promotes angiogenesis and lymphangiogenesis through interleukin-6 and granulocyte-macrophage colony-stimulating factor.

Endothelial cells (ECs) are a site of human cytomegalovirus (HCMV) productive replication, haematogenous dissemination and persistence, and are assumed to play a critical role in the development of HCMV-associated vascular diseases. Although early reports have shown the presence of HCMV antigens and DNA in lymphoid tissues, the ability of HCMV to infect lymphatic ECs (LECs) has remained unaddressed due to the lack of a suitable in vitro system. This study provided evidence that a clinical isolate of HCMV (retaining its natural endotheliotropism) was able to productively infect purified lymph node-derived LECs and that it dysregulated the expression of several LEC genes involved in the inflammatory response to viral infection. Qualitative and quantitative analysis of virus-free supernatants from HCMV-infected LEC cultures revealed virus-induced secretion of several cytokines, chemokines and growth factors, many of which are involved in the regulation of EC physiological properties. Indeed, functional assays demonstrated that the secretome produced by HCMV-infected LECs stimulated angiogenesis in both LECs and blood ECs, and that neutralization of either interleukin (IL)-6 or granulocyte-macrophage colony-stimulating factor (GM-CSF) in the secretome caused the loss of its angiogenic properties. The involvement of IL-6 and GM-CSF in the HCMV-mediated angiogenesis was further supported by the finding that the recombinant cytokines reproduced the angiogenic effects of the HCMV secretome. These findings suggest that HCMV induces haemangiogenesis and lymphangiogenesis through an indirect mechanism that relies on the stimulation of IL-6 and GM-CSF secretion from infected cells.

Upper limb artery segmental occlusions due to chronic use of ergotamine combined with itraconazole, treated by thrombolysis.

BACKGROUND: The ergotamine tartrate associated with certain categories of drugs can lead to critical ischemia of the extremities. Discontinuation of taking ergotamine is usually sufficient for the total regression of ischemia, but in some cases it could be necessary thrombolytic and anticoagulant therapy to avoid amputation. CASE REPORT: A woman of 62 years presented with a severe pain left forearm appeared 10 days ago, with a worsening trend. The same symptoms appeared after 5 days also in the right forearm. Physical examination showed the right arm slightly hypothermic, with radial reduced pulse in presence of reduced sensitivity. The left arm was frankly hypothermic, pulse less on radial and with an ulnar humeral reduced pulse, associated to a decreased sensitivity and motility.Clinical history shows a chronic headache for which the patient took a daily basis for years Cafergot suppository (equivalent to 3.2 mg of ergotamine).From about ten days had begun therapy with itraconazole for vaginal candidiasis. The Color-Doppler ultrasound shown arterial thrombosis of the upper limbs (humeral and radial bilateral), with minimal residual flow to the right and no signal on the humeral and radial left artery. RESULTS: Angiography revealed progressive reduction in size of the axillary artery and right humeral artery stenosis with right segmental occlusions and multiple hypertrophic collateral circulations at the elbow joint. At the level of the right forearm was recognizable only the radial artery, decreased in size. Does not recognize the ulnar, interosseous artery was thin. To the left showed progressive reduction in size of the distal subclavian and humeral artery, determined by multiple segmental steno-occlusion with collateral vessels serving only a thin hypotrophic interosseous artery.Arteriographic findings were compatible with systemic drug-induced disease. The immediate implementation of thrombolysis, continued for 26 hours, with heparin in continuous intravenous infusion and subsequent anticoagulant therapy allowed the gradual disappearance of the symptoms with the reappearance of peripheral pulses. CONCLUSION: Angiography showed regression of vasospasm and the resumption of flow in distal vessels. The patient had regained sensitivity and motility in the upper limbs and bilaterally radial and ulnar were present.

IL-6 Promotes compensatory liver regeneration in cirrhotic rat after partial hepatectomy.

Major hepatic resection in cirrhotic patients is associated with impaired liver regeneration and failure, leading to high peri-operative mortality. In this work, the causes of defective regeneration in cirrhotic liver and the utility of IL-6 treatment were investigated in an experimental model combining cirrhosis and partial hepatectomy in the rat. Relative to normal controls, decompensated cirrhotic animals showed decreased survival, while compensated cirrhotic animals showed similar survival but reduced hepatic DNA synthesis and newly regenerated liver mass amount. Defective liver regeneration was associated with a decrease in STAT3 and NF-kB activation, consistent with an increased accumulation of their respective inhibitors PIAS3 and IkBalpha, and with a decreased induction of Bcl-xL. Treatment with recombinant IL-6 enhanced survival of decompensated cirrhotic animals, while it did not affect survival of compensated cirrhotic animals but sustained liver regeneration, by restoring STAT3 and NF-kB activation and Bcl-xL induction to the levels found in normal controls. The pro-growth effects exerted by IL-6 treatment in cirrhotic liver were attained also at low, pharmacologically acceptable doses. In conclusion, our results suggest that IL-6 treatment may be therapeutic in major resection of cirrhotic liver.

Late open conversion after endovascular repair of abdominal aneurysm failure: Better and easier option than complex endovascular treatment.

AIM: Conversion to open repair becomes the last option in case of endovascular repair of abdominal aneurysm failure, when radiological interventional procedures are unfeasible. While early conversion to open repair generally derives from technical errors, aetiopathogenesis and results of late conversion to open repair often remain unclear. METHODS: We report data from our Institute's experience on late conversion to open repair. Twenty-two late conversion to open repairs out of 435 consecutive patients treated during a 18 years period, plus two endovascular repair of abdominal aneurysms performed in other centres, are analysed. The indication for conversion to open repair was aneurysm enlargement because of type I, type III, type II endoleak and endotension. Even if seven cases (23%) had shown an initial aneurysmal shrinkage, in a later phase, the sac began to enlarge again. In 12 patients, conversion to open repair was the last chance after unsuccessful secondary endovascular procedures. RESULTS: Three cases (12.5%) were treated in emergency. Aortic cross-clamping was only infrarenal in 10 cases, only or temporarily suprarenal in 14 and temporarily supraceliac in 9 cases, for 19 total and 5 partial endograft excisions. Two patients died for Multiple Organ Failure (MOF), on 42nd (endovascular repair of abdominal aneurysm infection) and 66th postoperative day. No other conversion to open repair-related deaths or major complications were revealed by follow-up post-conversion to open repair (mean: 68 months ranging from 24 to 180 months). CONCLUSION: Late conversion to open repair is often an unpredictable event. It represents a technical challenge: specifically, the most critical point is the proximal aortic clamping that often temporarily excludes the renal circulation. In our series, conversion to open repair can be performed with a low rate of complications. In response to an endovascular repair of abdominal aneurysm failure, before applying complex procedures of endovascular treatment, conversion to open repair should be taken into account.

Interleukin-6 sustains hepatic regeneration in cirrhotic rat.

BACKGROUND/AIMS: In the liver IL-6 displays growth-inducing and pro-survival activities. We studied the pro-proliferative and protective mechanisms of IL-6 treatment in a model of liver cirrhosis in wild type rat, investigating the theoretical basis for a potential pharmacologic role of IL-6 in cirrhosis. METHODOLOGY: We analyzed IL-6 receptors levels in cirrhotic liver. We also studied the activation of signaling pathways downstream IL-6 receptors by analyzing the DNA-binding activity of transcription factors STAT3, AP-1, HNF-1 and NF-kappaB and the phosphorylation status of AKT and eNOS. We also analyzed hepato-cell proliferation, by determining BrdU incorporation into DNA, and liver mass expansion. RESULTS: We show that liver cells from cirrhotic animals have increased expression of the IL-6 receptor alpha/gp80. In addition, we show that in cirrhosis the main molecular pathways downstream the receptors are intact and that IL-6 activates STAT3, AP-1 and NF-kappaB transcription factors, induces AKT and eNOS phosphorylation and increases hepato-cell proliferation and liver mass expansion in a dose-dependent manner. CONCLUSIONS: Our data demonstrate that the theoretical basis exists for the therapeutic employment of IL-6 in liver cirrhosis.

Risk factors for immediate results and long-term survival following elective open surgery for AAA. Statistical analysis of 1111 consecutively-treated patients.

AIM OF THE STUDY: Perioperative and 10 years follow-up risk factors for 1111 consecutive open AAA repairs were statistically analyzed (X2-test and Log-rank test methods for univariate analysis, and logistic regression model and Cox proportional-hazard model for multivariate analysis). Overall operative mortality rate was 2.7%, and significant risk factors were: 1) univariate analysis: Age (>70 years 3.9% vs 1.5% <70 years); CAD (4.3% vs 1.9% without CAD); PAD (4.7% vs 2.0%); III-IV ASA classes (3.8% vs 0% in I-II ASA classes); 2) multivariate analysis: only ASA classes. RESULTS: Long-term survival (42.3 +/- 32.6 months) was 93% and 88% at 3 and 5 years respectively, with 0.2% graft-related deaths, and significant risk factors were 1) univariate analysis: Age (92% and 84% at 3 and 5 years in patients aged >70 vs 94% and 91% <70 years); ASA classes (91% and 87% at 3 and 5 years in ASA III-IV vs 98% and 92% in ASA I-II); CAD (92% and dell'85% vs 94% and 90% without CAD); COPD (90% and 80% vs 95% and 92% without COPD); CRF (90% and 82%, vs 94% and 89% without CRF); suprarenal aortic cross-clamping for pararenal aneurysms (91% and 77% in pararenal AAA, vs 94 % and 90% in infrarenal AAA; 2) multivariate analysis: Age; ASA classes; pararenal aneurysms. There was a close relation between number (0-5) of risk factors in each patient and early and late complications. These data are very satisfactory overall, and even in high risk patients who are routinely considered for EVAR.

Appearance and rapid evolution of thoraco-abdominal intramural hematoma after TEVAR.

Some studies consider the different physical properties of the stent graft when compared with the blood vessel on the basis of vascular lesions that may require further intervention. We present a case in which a patient developed an intramural hematoma at the distal landing of previous thoracic endovascular aortic repair (TEVAR) that required the relining with a flared prosthesis. During follow-up, we observed the appearance of more caudal hematoma. We decided to observe this lesion with close radiological controls. In order to prevent serious complication after the induction of TEVAR, accurate planning of the procedure is very important to study the impact of the prosthesis implanted in the cardiovascular system. In particular, oversize, radial forces and length of coverage have been taken into account. The adherence to follow-up is very important to precociously detect the lesions to avoid the onset of complication.

Role of different vascular approaches on transcatheter aortic valve implantation outcome: a single-center study.

OBJECTIVE: To compare different vascular approaches on clinical outcome of patients undergoing transcatheter aortic valve implantation (TAVI) with self-expandable bioprosthesis. METHODS: We included all the patients undergoing CoreValve implantation at our institute between September 2007 and March 2014. They were divided into four groups based on the vascular approach: percutaneous transfemoral (pTF), cut-down transfemoral (cTF), transaxillary (TAx) and transaortic (TAo). Clinical outcomes were evaluated according to Valve Academic Research Consortium-2 recommendations. RESULTS: Out of 322 consecutive patients, 170 (53%) underwent pTF, 76 (23%) cTF, 32 (10%) TAx and 44 (14%) TAo approach. Although the TAx and TAo patients had a higher risk profile, they had a similar outcome compared with the pTF and cTF groups; in particular, there were no differences regarding cardiovascular and all-cause mortality at 30 days, 1 and 2 years, as well as stroke, myocardial infarction, bleeding, major vascular complications, permanent pacemaker implantation and acute kidney injury rates. The observed device success rate was higher in the TAo than in the other approaches (88.6 versus 65.9, 68.7 and 76.3% in the pTF, cTF and TAx groups, respectively; P = 0.019). No differences occurred regarding 30-day early safety and 1-year clinical efficacy across the four groups. Fluoroscopy time, amount of contrast medium used and minor vascular complications were significantly higher in pTF patients, as well as in-hospital stay in the TAo group. Atrial fibrillation and prosthetic valve regurgitation, but not the vascular approach, were independent predictors of all-cause mortality. CONCLUSION: A more invasive vascular approach, for CoreValve implantation, even in higher risk patients, does not affect early-term, mid-term and long-term outcomes.