Mills valvulotome reduces distal vein injuries and improves follow-up freedom from restenosis in patients undergoing infrainguinal in-situ saphenous vein bypass.

BACKGROUND: In this study, the early and mid-term outcomes of the use of the Mills valvulotome in patients with chronic limb-threatening ischemia (CLTI) undergoing infrainguinal in-situ saphenous vein bypass were investigated. METHODS: From January 2018 until December 2019, 153 consecutive CLTI patients from 7 centers have been treated with infrainguinal in-situ saphenous vein bypass. In all patients the devalvulation of the great saphenous vein (GSV) was obtained with the use of the HYDRO LeMaitre® valvulotome (LeMaitre Vascular, Burlington, MA, USA). Eighty-six patients (56.2%) received the additional treatment of the LeMills valvulotome (LeMaitre Vascular) to disrupt the distal valves of the GSV (Group MV), whilst in the remaining 67 patients (43.8%) this adjunctive device was not used (Group no-MV). Initial outcome measures including intraoperative vein injuries were assessed and compared. At 2-year follow-up, estimated outcomes of primary patency, primary assisted patency, secondary patency, freedom from distal vein restenosis, and limb salvage were analyzed using Kaplan-Meier curves and compared between groups using the log-rank test. RESULTS: Intraoperatively, the overall rate of vein injuries related to the devalvulation was 5.2% (8 cases) with four cases in both groups (4/86, 4.6%, Group MV vs. 4/67, 6%, Group no-MV; P=0.49). Overall, 4 lesions occurred in the distal portion of the GSV and were all reported in Group no-MV (0/86, 0%, Group MV vs. 4/67, 6%, Group no-MV; P=0.03). Median duration of follow-up was 12 months (IQR: 6-24). At 2-year follow-up there were no differences between the two groups in terms of primary patency (69.9% Group MV vs. 79.8% Group no-MV, P=0.08), primary assisted patency (85.4% Group MV vs. 90.5% Group no-MV, P=0.37), secondary patency (94.2% Group MV vs. 92.1% Group no-MV, P=0.61), and limb salvage (97.4% Group MV vs. 98.2% Group no-MV, P=0.74). Patients in Group MV had a higher rate of freedom from distal vein restenosis (92.2% Group MV vs. 76% Group no-MV, P=0.03). CONCLUSIONS: Adjunctive use of the Mills valvulotome (LeMaitre Vascular) reduces intraoperative distal vein injuries and improves the 2-year freedom from distal vein restenosis in patients undergoing infrainguinal in-situ saphenous vein bypass.

Eagle Syndrome and Internal Carotid Artery Dissection: Description of Five Cases Treated in Two Italian Institutions and Review of the Literature.

Eagle syndrome is a rare pattern of symptoms (0.16% of the general population) due to the conflict with adjacent anatomical structures by an elongated styloid process or a calcified stylohyoid ligament; 2 variants of this condition have been described in the literature, classical and vascular. The classical form is caused by compression of the glossopharyngeal nerve and the surrounding structures from an abnormal stylohyoid apparatus, causing odynophagia and neck pain and is usually treated by an otorhinolaryngologist. The vascular form, determined by the conflict between the osteoligamentous malformation and the extracranial carotid artery, can cause neurological symptoms due to the compression of the vessel or in some cases the dissection of the carotid artery itself. However, an elongated styloid process occurs in about 4% of the general population, and the most recent literature shows that the vascular form of Eagle syndrome could be an underestimated cause of carotid artery dissection (CAD) and should be considered in the differential diagnosis of this condition. In addition to the literature many different treatment options for this condition are reported, either medical and/or surgical, but an ideal approach has not yet been fully identified. We report 5 cases of internal CAD due to the vascular variant of Eagle syndrome treated in 2 different Italian institutions (Department of Vascular and Endovascular Surgery, Galliera Hospital, Genoa and Department of Vascular Surgery, Santi Filippo e Nicola Hospital, Avezzano, L'Aquila) and a careful and analytical review of the available literature on this topic.

High dose rosuvastatin increases ABCA1 transporter in human atherosclerotic plaques in a cholesterol-independent fashion.

BACKGROUND: ATP-binding cassette A1 (ABCA1) and G1 (ABCG1) mediate cholesterol efflux from lipid-laden macrophages, thus promoting anti-atherosclerotic outcomes. The mechanism(s) linking treatment with statins and ABCA1/ABCG1 in human atherosclerosis are not fully understood and require further investigation. Therefore, we studied whether short-term treatment with low- or high-dose rosuvastatin may affect ABCA1 and ABCG1 expression in human atherosclerotic plaques. METHODS: Seventy patients with severe stenosis of the internal carotid artery were randomized to receive low (10 mg/day) or high (40 mg/day) dose rosuvastatin for 12 weeks before elective endarterectomy. As controls, we analyzed a reference group of 10 plaques from subjects with hypercholesterolemia but not receiving statin treatment and an additional set of 11 plaques collected from normocholesterolemic patients. On atherosclerotic plaques, ABCA1 and ABCG1 expression was evaluated at RNA level by qPCR and at protein level by immunoblotting and immunohistochemistry. RESULTS: Both rosuvastatin doses were associated with lower plaque ABCA1 mRNA levels and with a trend toward reduction for ABCG1. However, ABCA1 protein was paradoxically higher in patients treated with high-dose rosuvastatin and was associated with lower levels of miR-33b-5p, a microRNA known as a regulator of ABCA1. Multivariate analyses showed that the effect is cholesterol-independent. Finally, no effects were found for ABCG1 protein. CONCLUSIONS: High-dose rosuvastatin increases macrophage ABCA1 protein levels in human atherosclerotic plaque despite mRNA reduction in a mechanism unrelated to plasma cholesterol reduction and potentially involving miR-33b-5p. This pathway may reflect an additional feature contributing to the anti-atherosclerotic effect for high-dose rosuvastatin. TRIAL REGISTRATION: ISRCTN16590640.

Safety and effectiveness of a new valvulotome: insights from the LIMBSAVE registry.

BACKGROUND: In the endovascular era peripheral bypass surgery still plays a key role. In situ saphenous vein bypass is a standardized technique. The main limitation of this procedure is the vein diameter. A new hydrophylic valvulotome (HYDRO LeMaitre® Valvulotome; LeMaitre Vascular, Burlington, MA, USA) allows even to disrupt the valves in smaller veins. The aim of this study was to analyze the intraprocedural and technical successes of this new valvulotome. METHODS: In January 2018 in Italy a national, multicenter, observational, prospective registry based on the examination of treatment of critical limb ischemia with infragenicular bypass adopting in situ saphenous vein technique (LIMBSAVE registry) started the enrollment. Until December 2018 216 patients have been enrolled in the registry. All data concerning the procedures were prospectively collected in a dedicated database. The information included demographics, preoperative risk factors, clinical and diagnostic preoperative assessments, intraoperative features, and discharge outcomes, including the safety and effectiveness of the valvulotome during the surgical procedure. RESULTS: Patients were predominantly male (160, 74.1%) with a mean age of 74.1 years (range 49-95). The mean diameter of the great saphenous vein was 3.7 mm (range 1.7-10) in the proximal part of the thigh, 3.4 mm (range 1.6-7) in the distal part of the thigh, and 3.1 mm in the proximal part of the leg (range 1.6-5). The technical success was obtained in all cases (the bypass pulsed after the utilization of the valvulotome). The valvulotome was able to reach the proximal anastomosis in all cases. The mean number of utilizations was 2.6 (range 1-5). No vein perforation has been detected. In 6 cases (2.8%) a vein adventitial damage occurred. In one case with uncontrolled bleeding (0.5%) the substitution of the deleted vein segment was necessary. CONCLUSIONS: Preliminary intraprocedural outcomes of LIMBSAVE registry showed that HYDRO LeMaitre® Valvulotome was safe and effective in disrupting the valves and obtaining the pulsatility of the saphenous vein. The rate of complications related to the utilization of the valvulotome was low. Further examinations are needed to evaluate the long-term outcomes of the bypass in terms of patency, reinterventions, and limb salvage.

Ten-year outcome analysis of the Italian Excluder Registry with the Gore Excluder endograft for infrarenal abdominal aortic aneurysms.

OBJECTIVE: The objective of this study was to report the 10-year outcomes of the multicenter Italian Excluder Registry for elective endovascular aneurysm repair (EVAR). METHODS: A retrospective analysis of all patients who underwent elective EVAR using the Gore Excluder (W. L. Gore & Associates, Flagstaff, Ariz) endograft (EG) at four Italian centers between 1998 and 2006 was carried out. Follow-up consisted of duplex ultrasound scan and computed tomography performed at 1 month, 6 months, and 12 months and yearly thereafter. Long-term outcomes were evaluated according to a life-table analysis. RESULTS: The Excluder EG was used in 461 patients (425 men; mean age, 72.9 ± 9.2 years) with abdominal aortic aneurysm (mean diameter, 52.2 ± 11.9 mm) who underwent elective EVAR. The 10-year cumulative survival was 62.5% ± 3.5% (95% confidence interval [CI], 55.5%-69.1%). During the follow-up, 14 (3.03%) patients were lost to follow-up. Estimated freedom from EG-related complication was 90.5% ± 1.5% (95% CI, 87.4%-92.9%) at 5 years, 89.2% ± 1.6% (95% CI, 85.6%-91.9%) at 7 years, and 88.4% ± 1.8% (95% CI, 84.4%-91.5%) at 10 years. Freedom from reintervention at 5, 7, and 10 years was 87.7% ± 1.8% (95% CI, 83.7%-90.8%), 82.4% ± 2.4% (95% CI, 77.2%-86.6%), and 80.6% ± 2.6% (95% CI, 75.5%-84.9%), respectively. On multivariable analysis, we did not find independent predictors of a higher rate of reintervention. There were 127 (27.5%) endoleaks detected during the follow-up. Only one type I endoleak was identified beyond 5-year follow-up. Cumulative freedom from endoleak rate was significantly different between the two different follow-up intervals (0-5 years, 2.6%; 6-10 years, 0.8%; P < .001). Estimated freedom from aorta-related mortality was 97.2% ± 0.8% (95% CI, 49.7%-99.9%) at 10 years. CONCLUSIONS: The Italian Excluder Registry outcomes confirmed sustained EVAR effectiveness at 10-year follow-up using the Gore Excluder EG. Freedom from EG-related complications, endoleaks, and reinterventions was satisfactory and remained acceptable beyond 5 years of follow-up, supporting a reasonable long-term durability of this device.

A multicenter comparison between autologous saphenous vein and heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft in the treatment of critical limb ischemia in diabetics.

OBJECTIVES: The aim of this study was to evaluate early and follow-up results of below-knee bypasses performed using a bioactive heparin-treated expanded polytetrafluoroethylene (ePTFE) graft in diabetic patients with critical limb ischemia (CLI) in a multicenter retrospective registry involving seven Italian vascular centers and to compare them with those obtained in patients operated on with autologous saphenous vein (ASV) in the same centers in the same period of time. METHODS: Over an 8-year period, ending in 2009, a heparin-bonded prosthetic graft (Propaten Gore-Tex; W. L. Gore & Associates Inc, Flagstaff, Ariz) was implanted in 180 diabetic patients undergoing below-knee revascularization for CLI in seven Italian hospitals (group 1). In the same period in these seven centers, 133 below-knee bypasses with ipsilateral ASV in diabetics with CLI were performed (group 2). Data concerning these interventions were retrospectively collected in a multicenter registry with a dedicated database. Early (<30 days) results were analyzed in terms of graft patency, major amputation rates, and mortality. Follow-up results were analyzed in terms of primary and secondary graft patency, limb salvage, and survival. RESULTS: The interventions consisted of below-knee bypasses in 132 cases in group 1 (73%) and in 45 cases in group 2 (33%; P < .001); 48 patients in group 1 (27%) and 88 patients in group 2 (67%; P < .001) had distal tibial anastomosis. Patients in group 1 had more frequently adjunctive procedures performed at distal anastomotic sites to improve run-off status. Postoperative and long-term medical treatment consisted of single antiplatelet therapy in 93 cases (52%) in group 1 and in 64 cases (48%, P = ns) in group 2, of double antiplatelet therapy in 18 cases (10%) in group 1 and in four cases (3%; P = .05) in group 2 and of oral anticoagulants in 69 patients in group 1 (38%) and in 65 (49%; P = .02) in group 2. Mean duration of follow-up was 28.3 ± 21.4 months; 308 patients (98%) had at least one postoperative clinical and ultrasonographic examination and 228 (72%) reached at least a 1-year follow-up. Estimated 48-month survival rates were 76.6% in group 1 and 72.7% in group 2 (P = > .9, log-rank 0.08). Primary patency rate at 48 months was significantly better in group 2 (63.5%) than in group 1 (46.3%; P = .03, log-rank 4.1). Assisted primary patency rates at 48 months were 47.3% (SE 0.05) in group 1 and 69% (SE 0.05) in group 2 (P = .01, log-rank 6.3). The rates of secondary patency at 48 months were 57.5% in group 1 and 69.6% in group 2 (P = .1, log-rank 2.3); the corresponding values in terms of limb salvage and amputation free-survival rates were 75.4% and 82.4% (P = .3, log-rank 1), and 59.9% and 64.4% (P = .3, log-rank 0.9), respectively. CONCLUSIONS: Data from this large, retrospective registry confirmed that the indexed heparin-bonded ePTFE graft provides satisfactory early and midterm results in diabetic patients undergoing surgical treatment of CLI. While autologous saphenous vein maintains its superiority in terms of primary patency, secondary patency rates are not statistically different, even in the presence of a trend for improved secondary patency with vein graft; and also limb salvage rates are comparable.

Midterm results from a multicenter registry on the treatment of infrainguinal critical limb ischemia using a heparin-bonded ePTFE graft.

OBJECTIVES: To report midterm results of infrainguinal bypasses performed with a heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft in patients presenting with critical limb ischemia. METHODS: Over a 7-year period ending in 2008, 425 patients presenting with critical limb ischemia underwent infrainguinal revascularization using a heparin-bonded ePTFE graft in seven Italian vascular centers. Preoperative, intraoperative, and follow-up data were collected in a multicenter registry. Patients were predominantly male (79%) with a mean age of 73.5 years. Mean preoperative ankle brachial index (ABI) was 0.35 and 192 of the patients (45%) were diabetic. Intervention consisted of a femoral to below-knee bypass in 324 patients (76%), whereas the remaining 101 patients had a femoral to above-knee bypass. In patients with below-knee bypass, distal target vessels were the popliteal artery in 238 cases, the tibioperoneal trunk in 38 cases, and a tibial vessel in the remaining 48 cases (anterior tibial artery in 20 cases, posterior tibial artery in 23 cases, and peroneal artery in 5). Follow-up consisted of clinical and duplex scanning examinations within 3 months from the intervention and yearly thereafter. Early (<30 day) results were analyzed in terms of deaths, graft thromboses, and amputations with univariate and multivariate (stepwise logistic regression) analysis. Follow-up results were evaluated in terms of primary and secondary graft patency, limb salvage, and survival rate with univariate and multivariate (Cox regression) analysis. RESULTS: Thirteen perioperative deaths occurred (3.1%). Thirty-day primary graft patency was 92.5% and limb salvage was 95.8%. Follow-up was available in 98% of patients with a median duration of 25.5 months (SD, 17.6; range, 1-72). Cumulative estimated 36-month primary and secondary patency, limb salvage, and survival rates were 61%, 70%, 83%, and 83%, respectively. At univariate analysis, the factors associated with poorer limb salvage rates during follow-up were the presence of ischemic ulcers or gangrene (log-rank, 8.4; P = .004; 95% confidence interval [CI] 1.2-3.5; odds ratio [OR], 2.1), the presence of only one patent tibial vessel (log-rank, 41.3; P < .001; 95% CI, 3.1-10.8, OR, 5.8), redo surgery (log-rank, 12.4; P < .001; 95% CI, 1.4-4; OR, 2.4) and the postoperative treatment with antiplatelet therapy in comparison to oral anticoagulants (log-rank, 5.1; P = .02; 95% CI, 1.0-3.4; OR, 1.8). At multivariate analysis redo surgery (P = .02; 95% CI, 1.1-3.1; OR, 1.8), poor runoff score (P < .001; 95% CI, 2.5-9.1; OR, 4.7) and preoperative clinical status (P = .02; 95% CI, 1.1-3.1; OR, 1.8) were independently associated with decreased limb salvage rates. CONCLUSION: The use of a heparin-bonded ePTFE graft provides good early and midterm results, with low rates of late amputations. Primary and secondary patency made this graft an excellent alternative to autologous saphenous vein when it is absent, unsuitable, or of poor quality.

Multidisciplinary day surgery unit: seven years' experience.

The autonomous multidisciplinary day surgery unit is the gold standard for day surgery procedures. The Authors report their experience with the Pescina Hospital autonomous multidisciplinary day surgery unit (Avezzano Heath Authority, University of L'Aquila). In total, 4140 patients were enrolled to the day surgery setting from 2001 to 2007. Age, gender and ASA of patients, type of disease, surgery, anaesthesia and the usual day surgery activity quality indices (cancellation and delays of operations, postoperative pain and nausea or vomiting, postoperative morbidity, discharge and early readmission) were evaluated. 4046 patients underwent day surgery (orthopaedic 29.8%, general surgery 26.2%, ophthalmology 21.6%, vascular surgery 19.8%, miscellaneous 2.6%). Rates of cancelled and delayed operations were 2.3% and 2.4%, respectively. Local anaesthesia was performed in 54.3% of operations. None of the patients reported postoperative nausea and vomiting. Severe postoperative pain was present in 10% of cases. 77% of patients was discharged within four hours of surgery, and the others within six hours. Four patients (0.11%) were readmitted early. The postoperative morbidity and mortality rates were 0.49% and 0%, respectively. None of the postoperative events correlated with gender, age, ASA, or type of surgery and anaesthesia. The multidisciplinary day surgery unit, with dedicated medical and nursing staff and suitable organisation such as ours is characterised by favourable surgery activity quality indices and good patient outcomes.

The receptor RAGE as a progression factor amplifying arachidonate-dependent inflammatory and proteolytic response in human atherosclerotic plaques: role of glycemic control.

BACKGROUND: RAGE (receptor for advanced glycation end products [AGEs]) plays a role in diabetic atherosclerosis. Recently, we have demonstrated enhanced expression of cyclooxygenase-2 and PGE synthase-1 (COX-2/mPGES-1) in human symptomatic plaques, and provided evidence that it is associated with metalloproteinase (MMP)-induced plaque rupture. However, the specific transmembrane signaling pathway(s) influencing plaque COX-2/mPGES-1 expression is unknown. The aim of this study was to characterize RAGE expression in human plaques and to correlate it with the inflammatory infiltration, COX-2/mPGES-1 and MMP expression, and with clinical evidence of diabetes. METHODS AND RESULTS: Plaques obtained from 60 patients undergoing carotid endarterectomy were divided into diabetic and nondiabetic according to clinical evidence of type 2 diabetes. Plaques were subjected to analysis of RAGE, NF-kappaB, COX-2/mPGES-1, MMP-2 and MMP-9, lipid and oxidized LDL (oxLDL) content, and collagen content by immunohistochemistry and Western blot, whereas zymography was used to detect MMP activity. Immunohistochemistry was used to identify CD68+ macrophages, CD3+ T-lymphocytes, smooth muscle cells (SMCs), and HLA-DR+ inflammatory cells. Diabetic plaques had more (P<0.0001) macrophages, T-lymphocytes, and HLA-DR+ cells, more (P<0.0001) immunoreactivity for RAGE, activated NF-kappaB, COX-2/mPGES-1, and MMPs, increased (P<0.0001) gelatinolytic activity, reduced (P<0.0001) collagen content, and increased (P<0.0001) lipid and oxLDL content. Interestingly, RAGE, COX-2/mPGES-1, and MMP expression was linearly correlated with plasma level of HbA1c. CONCLUSIONS: In conclusion, this study demonstrates in humans that RAGE overexpression is associated with enhanced inflammatory reaction and COX-2/mPGES-1 expression in diabetic plaque macrophages, and this effect may contribute to plaque destabilization by inducing culprit metalloproteinase expression.