Biochemical and immunomorphological evaluation of hepatocyte growth factor and c-Met pathway in patients with critical limb ischemia.

OBJECTIVES: Hepatocyte growth factor (HGF), the c-Met receptor, and hypoxia-inducible factor (HIF) are crucial for regenerative processes including ischemic wound healing. The aims of the present study are (a) to analyze the tissue c-Met and HIF-1\u3b1 expression in skin from patients with critical limb ischemia (CLI); (b) to compare the serum HGF levels of CLI and control subjects. METHODS: This is a prospective, controlled, single-center study. Thirty-seven patients were enrolled. A skin sample adjacent to the ischemic lesion was taken from 20 patients with CLI; skin samples were taken from the surgical wounds of 17 patients surgically treated for abdominal aortic aneurysm as healthy controls. Serum samples were taken in all cases. Samples were formalin fixed, paraffin embedded, and routinely processed. Tissue inflammation was histologically assessed. Immunohistochemistry was performed with antibodies against total c-Met receptor, activated Met (p-Met), and HIF-1\u3b1. RT-polymerase chain reaction was used to quantify HIF-1\u3b1 mRNA. The enzyme-linked immunosorbent assay was performed to evaluate serum HGF levels. RESULTS: With immunohistochemistry, while total c-Met was unchanged, different patterns of p-Met positivity were observed between CLI and control cases (p < .001). In particular, CLI skin showed a total negativity or membrane positivity for p-Met (19/20 cases), while control skin mainly showed cytoplasmic positivity in the epidermal basal layer (16/17 cases). HIF-1\u3b1 was diffusely lost in CLI, but HIF-1\u3b1 mRNA was threefold higher than in controls. Finally, mean serum HGF levels were 590.5 pg/mL and 2380.0 pg/mL in CLI and control groups respectively (p < .001). CONCLUSIONS: In CLI patients a significant decrease in serum HGF levels, concomitant with a loss of skin HIF-1\u3b1 stabilization and a lack of c-Met phosphorylation were seen, probably driving a decrease in wound-healing functions. The next hypothesis is that HGF application might reactivate the c-Met receptor, stabilizing the normal wound healing process

Biochemical and immunomorphological evaluation of hepatocyte growth factor and c-Met pathway in patients with critical limb ischemia.

none7noOBJECTIVES: Hepatocyte growth factor (HGF), the c-Met receptor, and hypoxia-inducible factor (HIF) are crucial for regenerative processes including ischemic wound healing. The aims of the present study are (a) to analyze the tissue c-Met and HIF-1α expression in skin from patients with critical limb ischemia (CLI); (b) to compare the serum HGF levels of CLI and control subjects. METHODS: This is a prospective, controlled, single-center study. Thirty-seven patients were enrolled. A skin sample adjacent to the ischemic lesion was taken from 20 patients with CLI; skin samples were taken from the surgical wounds of 17 patients surgically treated for abdominal aortic aneurysm as healthy controls. Serum samples were taken in all cases. Samples were formalin fixed, paraffin embedded, and routinely processed. Tissue inflammation was histologically assessed. Immunohistochemistry was performed with antibodies against total c-Met receptor, activated Met (p-Met), and HIF-1α. RT-polymerase chain reaction was used to quantify HIF-1α mRNA. The enzyme-linked immunosorbent assay was performed to evaluate serum HGF levels. RESULTS: With immunohistochemistry, while total c-Met was unchanged, different patterns of p-Met positivity were observed between CLI and control cases (p < .001). In particular, CLI skin showed a total negativity or membrane positivity for p-Met (19/20 cases), while control skin mainly showed cytoplasmic positivity in the epidermal basal layer (16/17 cases). HIF-1α was diffusely lost in CLI, but HIF-1α mRNA was threefold higher than in controls. Finally, mean serum HGF levels were 590.5 pg/mL and 2380.0 pg/mL in CLI and control groups respectively (p < .001). CONCLUSIONS: In CLI patients a significant decrease in serum HGF levels, concomitant with a loss of skin HIF-1α stabilization and a lack of c-Met phosphorylation were seen, probably driving a decrease in wound-healing functions. The next hypothesis is that HGF application might reactivate the c-Met receptor, stabilizing the normal wound healing process.mixedVasuri F; Fittipaldi S; Abualhin M; Degiovanni A; Gargiulo M; Stella A; Pasquinelli G.Vasuri F; Fittipaldi S; Abualhin M; Degiovanni A; Gargiulo M; Stella A; Pasquinelli G

Latest results of In.Pact SFA Trial encourage the use of drug coating balloon in the endovascular treatment of superficial femoral artery lesions

Restenosis remains a major drawback of the endovascular treatment of femoro-popliteal arterial steno-obstructive disease. Although the use of the stent, in particular the drug eluting stent with paclitaxel, has modified the incidence of this late complication, in clinical practice the indication for femoro-popliteal stenting is limited to post-angioplasty flowlimiting dissection, recoil and wall thrombosis. As the current concept for the prevention of restenosis after angioplasty include the use of antiproliferative drug leaving nothing inside the artery, the drug eluting balloon seem to be a promising tool to decrease the risk of this complications. The results of In.Pact SFA Trial presented at the Charing Cross Meeting in London in April 2014 are in line with this hypothesis. The purpose of this article is to report the rationale of paclitaxelcoated balloon in the prevention of restenosis, the most recent trials/registry investigating the clinical effectiveness of paclitaxel-coated balloon for treatment superficial femoral artery obstructive disease and the results of the In.Pact SFA trial

The impact of new technologies in endovascular repair of thoraco-abdominal aortic aneurysm

BACKGROUND: Thoraco-abdominal aortic aneurysms (TAAAs) are considered a challenging clinical scenarios. Despite modern intra/perioperative adjuncts, T A A A open repair has not negligible mortality and morbidity rates also in high volume centres. New technologies with the endovascular approach can reduce the complication rate of TAAA treatment. A i m of present work is to evaluate the outcome of endovascular treatment of TAAA in a single centre. METHODS: A retrospective evaluation of the endovascular T A A A treatment in a single center from 2010 to 2017 was performed. The technical success, mortality, morbidity and visceral vessels patency were evaluated at 30-day and during the follow-up. RESULTS: In the study period, an overall of 80 TAAAs (urgent and elective cases) were treated in our centre by FB-EVAR . Five cases were ruptured TAAAs (6.3%). Custom made and off the shelf device were used in 57 (71.2%) and 23 (28.8%) cases for an overall of 289 target visceral vessels (3.6/patient). Technical Success was 92.5%. The postoperative target visceral vessels patency rate was 97.0%. Spinal cord ischemia was 6%. The 30-day mortality was 3.8%. A t a mean follow-up was 18.5- SD 15.0 months the overall survival was 96%, 83%, and 70% at 6, 12 and 24 months. CONCLUSIONS: The total endovascular TAAA repair is technical demanding, time-consuming, and requires a dedicated and advanced knowl¬ edge in the endovascular materials, technologies and a dedicated team for planning. However the results are promising and associated with low mortality and morbidity

Reinterventions after fenestrated and branched endografting for degenerative aortic aneurysms

Objective: Fenestrated/branched endovascular abdominal aortic aneurysm repair (F/B-EVAR) is widely accepted technique to treat juxta/pararenal abdominal aortic aneurysms (J/P-AAAs) and thoracoabdominal aortic aneurysms (TAAAs) for patients at high-surgical risk. However, the follow-up results should be carefully evaluated, especially in terms of the reintervention rate. The aim of the present study was, therefore, to evaluate the early and mid-term reinterventions after FB-EVAR for J/P-AAAs and TAAAs and their effects on follow-up survival. Methods: From 2006 to 2019, all consecutive patients who had undergone F/B-EVAR for J/P-AAAs or TAAAs were prospectively enrolled. Cases requiring reinterventions were retrospectively analyzed. Patients with aortic dissection were excluded from the present analysis. Reinterventions were classified as follows: access related, aortoiliac related, or target visceral vessel (TVV) related. Freedom from reintervention and survival were assessed using the Kaplan-Meier method, and univariate and multivariate analyses were used to determine the risk factors. Results: Overall, 221 F/B-EVAR procedures were performed for 111 J/P-AAAs (50.3%) and 110 TAAAs (49.7%) in an elective (182; 82%) or urgent (39; 18%) setting. The median follow-up was 27 months (interquartile range, 13 months). Overall, 41 patients had undergone 52 reinterventions (single, 30 [14%]; multiple, 11 [5%]; access related, 17 [33%]; aortoiliac related, 6 [12%]; TVV related, 29 [55%]). Of the 52 reinterventions, 32 (62%) and 20 (38%) had occurred within and after 30 days, respectively. Eight reinterventions (15%) had been were performed in an urgent setting. Endovascular and open reinterventions were performed in 32 (62%) and 20 (38%) cases, respectively. Open reinterventions were frequently access related (access, 16; no access, 4; P ≤ .001). Technical success was 95% (39 patients); failures consisted of one splenic artery rupture and one renal artery loss. Patients undergoing reintervention had more frequently undergone a primary urgent F/B-EVAR (urgent, 12 of 39 [31%]; elective, 29 of 182 [16%]; P &lt; .001) and had had TAAAs (TAAAs, 34 of 41 [83%]; J/P-AAAs, 7 of 41 [17%]; P &lt; .001). The patients with TAAAs had had a greater incidence of TVV-related reintervention (TAAAs, 26 of 28 [93%]; J/P-AAAs, 2 of 28 [7%]; P &lt; .001) and multiple reinterventions (TAAAs, 9 of 11 [82%]; J/P-AAAs, 2 of 11 [18%]; P = .03) compared with those with J/P-AAAs. Survival at 3 years was 75%. Freedom from reintervention was 81% at 3 years. Patients who had undergone reinterventions had lower 3-year survival (reintervention, 61%; no reintervention, 77%; P = .02). Preoperative chronic renal failure (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.1-3.6; P = .02), TAAAs (HR, 2.3; 95% CI, 1.1-4.8; P = .03), and urgent primary F/B-EVAR procedures (HR, 2.5; 95% CI, 1.2-4.9; P = .01) were independent predictors of late mortality. Conclusions: Reinterventions after F/B-EVAR are not uncommon and were related to TVVs in only one half of cases. Most of them can be performed in an elective setting using endovascular techniques. The technical success rate was excellent. Reinterventions were more frequent after TAAAs and urgent F/B-EVAR procedures and had a significant effect on overall survival in these situations

Anatomical Predictors of Flared Limb Complications in Endovascular Aneurysm Repair

Purpose: To evaluate possible predictors of complications with flared iliac stent-graft limbs for ectatic common iliac arteries (CIAs) associated with abdominal aortic aneurysms treated with endovascular aneurysm repair (EVAR). Materials and Methods: A retrospective comparative analysis was conducted of 533 EVAR patients (mean age 75 years; 442 men) treated between 2012 and 2017 who had complications associated with the stent-graft limbs (n=1066). Complications, including type Ib endoleak, type IIIa endoleak, and limb occlusion, were compared between patients with nondilated (&lt;16 mm) CIAs treated with standard iliac limbs (SLs, n=808) vs patients with ectatic CIAs treated with flared limbs (FLs, n=258). Follow-up included a duplex scan at 3, 6, and 12 months and yearly thereafter; computed tomography angiography was performed in case of iliac complications. Risk factors for iliac complications in FLs were investigated using Cox regression and Kaplan-Meier analyses; results of the regression analysis are presented as the hazard ratio (HR) and 95% confidence interval (CI). Results: Overall, no iliac complications occurred at 30 days, but over a mean follow-up of 38±8 months, there were 10 (1%) events (4 limb occlusions, 6 type Ib endoleaks): 7 (3%) in FLs and 3 (0.4%) in SLs (p=0.20). Kaplan-Meier analysis found no differences at 5 years in SLs vs FLs for freedom from limb occlusion (99%±1% vs 98%±1%, respectively; p=0.30) or type Ib endoleak (96%±3% vs 97%±1%, respectively; p=0.44). Similarly, the overall 5-year iliac complication rates were similar in SLs vs FLs (96%±3% vs 95%±2%, p=0.21). Regression analysis found CIA length ≤30 mm (HR 4.7, 95% CI 1.02 to 21.6, p=0.04) and a diameter ≥20 mm (HR 7.8, 95% CI 1.05 to 64.8, p=0.03) to be independent predictors of iliac complications in FLs. Kaplan-Meier estimates of iliac complication–free survival in FLs were significantly worse when the CIA length was ≤30 mm (79%±9% vs 98%±1%, p=0.003) or the diameter was ≥20 mm (85%±7% vs 99%±1%, p=0.02). The combination of both risk factors produced significantly poorer iliac complication–free survival compared with cases in which there was one or no risk factor (67%±19% vs 96%±2% vs 99%±1%, respectively; p&lt;0.001). Conclusion: Iliac limb complications are infrequent in EVAR, regardless of the type of iliac limb chosen; however, CIAs ≤30 mm in length or ≥20 mm in diameter significantly increased the risk of late iliac complications in FLs. If both characteristics were present, this risk was further elevated

Renal Fenestration Closure Technique in fenestrated endovascular repair for para-renal aortic aneurysm

To describe an endovascular technique to close a renal artery fenestration during fenestrated endograft implant for a para-renal aneurysm (p-AAA) without interfering with other visceral vessels REPORT: A 76-year-old-male with p-AAA underwent repair by a four fenestrations custom-made endograft. At the intra-procedural angiography, the right renal artery was occluded. In order to avoid a high-flow endoleak from fenestration, we performed the following technique: a 9F-steerable sheath was used to advance a 7F-sheath through the fenestration into aneurism. A balloon-expandable covered-stent was deployed across the fenestration and then occluded by two vascular plugs. At the completion angiography there was not endoleak from the right renal fenestration and at 6-month p-AAA remained completely excluded

Cervical artery dissection: presentation and treatment

Cervical artery dissection (CeAD) is a rare condition whereby a tear occurs in the intimal layer of the artery wall. This condition can determine stroke, peripheral symptoms or can be asymptomatic. Vascular surgeons are often involved in the treatment of this pathology and the present paper aims to overview the actual knowledge on this topic. Clinical studies and randomized trials were screened and analyzed through PubMed to report the incidence, the clinical manifestations and the treatment options of CeAD. CeAD involving extracranial internal carotid artery is most frequently involved (80%) rather than vertebral artery (15%) or carotid artery in association with vertebral artery (5%). Internal carotid dissection occurs in all age group and it is responsible for 2.5% of all strokes, and 40% of stroke in patients older than 50 years. Carotid artery dissection typically begins with local symptoms, such as a sudden onset of unilateral and constant headache or an ipsilateral neck pain or a partial Horner’s syndrome, followed by retinal or cerebral ischemia. Stroke associated with CeAD are present in 50-60% of symptomatic cases, even if many of CeAD are asymptomatic and therefore the real incidence of stroke associated with CeAD is difficult to establish. The risk of recurrent stroke after carotid artery dissection is less than 3%. Anticoagulant or antiplatelet therapy are both associated with low-rate of symptoms recurrence (1-3%) at the follow-up. Surgical or endovascular therapy can be considered for patients with symptoms recurrence without benefit from medical therapy. CeAD is a possible cause of stroke, and it should be carefully investigated, particularly in young patients, in order to deliver an adequate therapeutic approach