Publications by authors named "Mauro Gargiulo"

129 Publications

Position Paper on Young Vascular Surgeons Training of the Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS): State of the Art and Perspectives.

Ann Vasc Surg 2021 Aug 25. Epub 2021 Aug 25.

Department of Vascular and Endovascular Surgery, Klinikum Nuremberg, Paracelsus Medical University Nuremberg, Nuremberg, Germany.

The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded in 2018, with the aim to promote cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic peripheral artery was selected as the very first topic to be investigated by the federation. In this second paper, different experiences from delegates of participating countries were shared to define common strategies to harmonize, standardize, and optimize education and training in the Vascular Surgery specialty.
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http://dx.doi.org/10.1016/j.avsg.2021.08.002DOI Listing
August 2021

Adventitial Microcirculation Is a Major Target of SARS-CoV-2-Mediated Vascular Inflammation.

Biomolecules 2021 07 20;11(7). Epub 2021 Jul 20.

Pathology Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

We report the case of a 77-year-old woman affected by coronavirus disease-19 (COVID-19) who developed an occlusive arterial disease of the lower limb requiring a left leg amputation. We studied the mechanisms of vascular damage by SARS-CoV-2 by means of a comprehensive multi-technique in situ analysis on the diseased popliteal arterial district, including immunohistochemistry (IHC), transmission electron microscopy (TEM) and miRNA analysis. At histological analyses, we observed a lymphocytic inflammatory infiltrate, oedema and endothelialitis of adventitial vasa vasorum while the media was normal and the intima had only minor changes. The vasa vasorum expressed the ACE2 receptor and factor VIII; compared with the controls, VEGFR2 staining was reduced. TEM analyses showed endothelial injury and numerous Weibel-Palade bodies in the cytoplasm. No coronavirus particle was seen. IL-6 protein and mRNA, together with miR-155-5p and miRs-27a-5p, which can target IL-6, were significantly increased compared with that in the controls. Our case report suggests an involvement of adventitial artery microcirculation by inflammation in the course of COVID-19. Without evident signs of current infection by SARS-CoV-2, endothelial cells show a spectrum of structural and functional alterations that can fuel the cardiovascular complications observed in people infected with SARS-CoV-2.
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http://dx.doi.org/10.3390/biom11071063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301851PMC
July 2021

MicroRNA profiles of human peripheral arteries and abdominal aorta in normal conditions: MicroRNAs-27a-5p, -139-5p and -155-5p emerge and in atheroma too.

Mech Ageing Dev 2021 Sep 28;198:111547. Epub 2021 Jul 28.

DIMES-Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Subcellular Nephro-Vascular Diagnostic Program, Pathology Unit, IRCCS, Policlinico S. Orsola Hospital, Bologna, Italy.

Atherosclerosis may starts early in life and each artery has peculiar characteristics likely affecting atherogenesis. The primary objective of the work was to underpin the microRNA (miR)-profiling differences in human normal femoral, abdominal aortic, and carotid arteries. The secondary aim was to investigate if those identified miRs, differently expressed in normal conditions, may also have a role in atherosclerotic arteries at adult ages. MiR-profiles were performed on normal tissues, revealing that aorta and carotid arteries are more similar than femoral arteries. MiRs emerging from profiling comparisons, i.e., miR-155-5p, -27a-5p, and -139-5p, were subjected to validation by RT-qPCR in normal arteries and also in pathological/atheroma counterparts, considering all the available 20 artery specimens. The three miRs were confirmed to be differentially expressed in normal femoral vs aorta/carotid arteries. Differential expression of those miRs was also observed in atherosclerotic arteries, together with some miR-target proteins, such as vimentin, CD44, E-cadherin and an additional marker SLUG. The different expression of miRs and targets/markers suggests that aorta/carotid and femoral arteries differently activate molecular drivers of pathological condition, thus conditioning the morphology of atheroma in adult life and likely suggesting the future use of artery-specific treatment to counteract atherosclerosis.
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http://dx.doi.org/10.1016/j.mad.2021.111547DOI Listing
September 2021

Outcomes of radiocephalic arteriovenous fistula in octogenarians.

J Vasc Access 2021 Jul 28:11297298211015498. Epub 2021 Jul 28.

Vascular Surgery Unit, IRCCS University Hospital, Policlinico S. Orsola-Malpighi, Bologna, Italy.

Background: Current guidelines recommend radiocephalic arteriovenous fistula (RCAVF) as a first choice access for hemodialysis, without specific indication for octogenarians .This study was undertaken to assess the efficacy of RCAVF in octogenarians compared with younger patients.

Material And Methods: All patients treated by RCAVF from January 2013 to December 2017 were included in a prospective database for a retrospective analysis. Patient demographics, comorbidities, and dialytic treatment data were collected prospectively and compared in patients <80 year-old and ⩾80 years-old. Clinical surveillance was performed during each dialysis session. The main endpoints were primary (PP) and assisted patency (AP).

Results: Within the study period, a total of 294 RCAVF were analyzed: 245 (83.3%) RCAVF were performed in <80 year-old and 49 (16.7%) ⩾80 years old. The overall PP and AP at 2-year was 69% ± 2% and 73% ± 3%, respectively. Patients ⩾ 80 years-old had a significantly reduced 2-year PP, AP of RCAVF compared with the younger patients: 50% ± 8% and 62% ± 7% versus 73% ± 3% and 75% ± 3%,  = 0.01 and  = 0.03, respectively.The analysis for possible risk factors for reduction of PP in patients ⩾80 years identified in the central venous catheter(CVC) a predictor of earlier RCAVF failure: HR 3.03(95% CI 1.29-7.13),  = 0.01.Kaplan-Meier curve confirms the reduction of PP in ⩾80 years old patients at 2-year follow-up with previous CVC compared patients without history of CVC: 59% ± 10% versus 24% ± 11%,  = 0.01. A comparison between the two groups was made in order to evaluate the impact of previous history of CVC .In absence of a history of CVC use older patients had a similar 2-year PP compared with younger patients: 59% ± 10% versus 72% ± 4%,  = 0.46. Otherwise, the history of a previous CVC reduced significantly the 2-year PP in ⩾80 years old patients compared the younger: 24% ± 12% versus 75% ± 5%,  = 0.0001.

Conclusions: Despite lower overall primary and primary assisted patency, RCAVF are associated with satisfactory results also in octogenarians if performed in absence of history of CVC. Under these circumstances RCAVF can be considered a first choice treatment.
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http://dx.doi.org/10.1177/11297298211015498DOI Listing
July 2021

Tissue Ki67 proliferative index expression and pathological changes in hemodialysis arteriovenous fistulae: Preliminary single-center results.

J Vasc Access 2021 Jul 24:11297298211015495. Epub 2021 Jul 24.

Department of Specialty, Diagnostic and Experimental Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Background: Arteriovenous fistula (AVF) for hemodialysis integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes. Aim of this study is to determine the role of Ki67, a well-established proliferative marker, related to AVF, and its relationship with time-dependent histological morphologic changes.

Materials And Methods: All patients were enrolled in 1 year and stratified in two groups: (A) pre-dialysis patients submitted to first AVF and (B) patients submitted to revision of AVF. Morphological changes: neo-angiogenesis (NAG), myointimal thickening (MIT), inflammatory infiltrate (IT), and aneurysmatic fistula degeneration (AD). The time of AVF creation was recorded. A biopsy of native vein in Group A and of arterialized vein in Group B was submitted to histological and immunohistochemical (IHC) analysis. IHC for Ki67 was automatically performed in all specimens. Ki67 immunoreactivity was assessed as the mean number of positive cells on several high-power fields, counted in the hot spots.

Results: A total of 138 patients were enrolled, 69 (50.0%) Group A and 69 (50.0%) Group B. No NAG or MIT were found in Group A. Seven (10.1%) Group A veins showed a mild MIT. Analyzing the Group B, a moderate-to-severe MIT was present in 35 (50.7%), IT in 19 (27.5%), NAG in 37 (53.6%); AD was present in 10 (14.5%). All AVF of Group B with the exception of one (1.4%) showed a positivity for Ki67, with a mean of 12.31 ± 13.79 positive cells/hot spot (range 0-65). Ki67-immunoreactive cells had a subendothelial localization in 23 (33.3%) cases, a myointimal localization in SMC in 35 (50.7%) cases. The number of positive cells was significantly correlated with subendothelial localization of Ki67 ( = 0.001) and with NA ( = 0.001).

Conclusions: Native veins do not contain cycling cells. In contrast, vascular cell proliferation starts immediately after AVF creation and persists independently of the time the fistula is set up. The amount of proliferating cells is significantly associated with MIT and subendothelial localization of Ki67-immunoreactive cells, thus suggesting a role of Ki-67 index in predicting AVF failure.
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http://dx.doi.org/10.1177/11297298211015495DOI Listing
July 2021

Intracranial Hemorrhage After Endovascular Repair of Thoracoabdominal Aortic Aneurysm.

J Endovasc Ther 2021 Jun 30:15266028211028226. Epub 2021 Jun 30.

University of Bologna, Hospital of Bologna Sant'Orsola-Malpighi Polyclinic IRCCS, Bologna, Emilia-Romagna, Italy.

Background: Intracranial hemorrhage (ICH) is a rare but devastating complication of thoracoabdominal aortic aneurysm (TAAA) repair with fenestrated/branched endograft (f/bEVAR). The cerebrospinal fluid drainage (CSFD) is considered one of the leading causes; however, other possible concomitant factors have not been individualized yet. The aim of the present work was to evaluate the pattern of ICH events after f/bEVAR for TAAA and to identify possible associated factors.

Materials And Methods: All f/bEVAR procedures for TAAA performed in a single academic center from 2012 to 2020 were evaluated. ICH was assessed by cerebral computed tomography if neurological symptoms arose. Pre-, intra-, and postoperative characteristics were analyzed in order to identify possible factors associated.

Results: A total of 135 f/bEVAR were performed for 72 (53%) type I, II, III and 63 (47%) type IV TAAA; 74 (55%) were staged procedures, 101 (73%) required CSFD, and 24 (18%) were performed urgently. The overall 30-day mortality was 8% (5% in elective cases); spinal-cord ischemia occurred in 11(8%) and ICH in 8 (6%) patients. All ICH occurred in patients with CSFD. ICH occurred intraoperatively in 1 case, inter-stage in 4 and after F/BEVAR completion in 3, after a median of 6 days the completion stage. Three (38%) of 8 patients with ICH died at 30 days and ICH was associated with 30-day mortality: odds ratio (OR) 13.2, 95% confidence interval (CI): 2.3-76, p=0.01. The analysis of the perioperative characteristics identified platelet reduction >60% (OR 11, 95% CI 1.6-77, p=0.03), chronic kidney disease (16% vs 0%, p=0.002), and total volume of liquor drained >50 mL (OR 8.1, 95% CI 1.1-69, p=0.03) as associated with ICH.

Conclusions: Current findings may suggest that ICH is a potential lethal complication of the endovascular treatment for TAAAs and it mainly occurs in patients with CSFD. High-volume liquor drainage, platelet reduction, and chronic kidney disease seems increase significantly the risk of ICH and should be considered during the perioperative period and for further studies.
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http://dx.doi.org/10.1177/15266028211028226DOI Listing
June 2021

Reinterventions after fenestrated and branched endografting for degenerative aortic aneurysms.

J Vasc Surg 2021 Jun 2. Epub 2021 Jun 2.

Division of Vascular Surgery, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Sant'Orsola-Malpighi, Bologna, Italy.

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 < .001) and had had TAAAs (TAAAs, 34 of 41 [83%]; J/P-AAAs, 7 of 41 [17%]; P < .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 < .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.
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http://dx.doi.org/10.1016/j.jvs.2021.05.027DOI Listing
June 2021

[Endovascular repair of an aortic aneurysm by a custom-made three-inner branched endograft].

G Ital Cardiol (Rome) 2021 03;22(3 Suppl 1):46S-50S

U.O. Chirurgia Vascolare.

We report the case of a total endovascular repair of an aortic arch aneurysm by a custom-made endograft with three inner branches for supra-aortic trunks in a high-risk patient unfit for open surgery. An 82-year-old female at high risk for open repair was treated for an asymptomatic aortic arch aneurysm (97 mm in diameter) by a custom-made three-inner branched endograft. Two anterograde branches were planned for the innominate trunk and the left carotid artery while a retrograde branch with a preloaded catheter was planned for the left subclavian artery. The procedure was successfully completed and postoperative course was uneventful. Computed tomography angiography demonstrated aneurysm exclusion, patency of the three supra-aortic branches and absence of cerebral ischemic lesion at 30 and 90 days. A custom-made endovascular device with three inner branches is a safe and effective option to guarantee a total endovascular repair of aortic arch aneurysm in high-risk patients in the presence of anatomical feasibility.
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http://dx.doi.org/10.1714/3578.35635DOI Listing
March 2021

Tailored Sac Embolization During EVAR for Preventing Persistent Type II Endoleak.

Ann Vasc Surg 2021 Apr 3. Epub 2021 Apr 3.

Vascular Surgery, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy.

Background: Persistent type II endoleaks (ELIIp) occur in 8-23% of patients submitted to endovascular aneurysm repair (EVAR) and may lead to aneurysm progression and rupture. Intraoperative embolization of the abdominal aortic aneurysm (AAA) sac is effective to prevent their occurrence, however a method to achieve complete sac thrombosis has not been standardized yet. Aim of our study was to identify factors associated with prevention of ELIIp after intraoperative embolization, in order to optimize technical details.

Methods: Patients at high risk for ELIIp, who underwent EVAR with AAA - sac coil embolization were prospectively collected into a dedicated database from January 2012 to March 2015. The endoluminal residual sac volume (ERV), not occupied by the endograft [ERV= AAA total volume (TV) - (AAA-thrombus volume (THV) + endograft volume (EgV)] was calculated on preoperative computed tomography and the concentration of coils implanted (CCoil= n coils implanted/ERV) for each patient was evaluated. AAA volumetric evaluation was conducted by dedicated vessels analysis software (3Mensio). ELIIp presence was evaluated by contrast-enhanced ultrasound at 6 and 12-month. Patients with ELIIp at 12 months (Group 1) were clustered and compared to patients without ELIIp (Group 2), in order to evaluate the incidence of ELIIp in patients undergone to preventive AAA-sac embolization, and identify the predictors of ELIIp prevention. Morphological potential risk factors for ELIIp such as TV, THV, VR% and EgV were also considered in all patients. Statistical correlation was assessed by Fisher Exact Test.

Results: Among 326 patients undergone to standard EVAR, 61 (19% - M: 96.7%, median age: 72 [IQR: 8] years, median AAA diameter: 57 [IQR: 7] mm) were considered at high risk for ELIIp and were submitted to coil embolization. The median AAA total volume (TV) and median ERV were 156 (IQR: 59) cc and 46 (IQR: 26) cc, respectively. The median number and concentration of coils (IMWCE-38-16-45 Cook M-Ray) positioned in AAA-sac were 5 (IQR: 1) coils and 0.17 coil/cm (range 0.02-1.20). Among this high-risk population, the incidence of ELIIp was 29.5% and 23% at 6 and 12-month, respectively. Fourteen patients (23%) were clustered in Group1 and 47 (77%) in Group 2. Both groups were homogeneous for clinical characteristics and preoperative morphological risk factors. There were no differences in the preoperative median TV, AAA-thrombus volume (THV), %VR, EgV and number of implanted coils between Group1 and Group2. Patients in Group1 had a significantly higher ERV (59 [IQR: 13] cm vs. 42 [IQR: 27] cm, P = 0.002) and lower CCoil (0.09 [IQR: 0.03] vs. 0.18 [IQR: 0.21], P = 0.006) than patients of Group2. ELIIp was significantly related to the presence of ERV > 49 cm (86 % vs. 42 %, Group1 and Group2 respectively, P = 0.006) and CCoil < 0.17coil/ cm (100% vs. 68%, Group1 e Group2 respectively, P = 0.014).

Conclusion: According with our results, Coil concentration and endoluminal residual volume can affect the efficacy of the AAA - sac embolization in the prevention of ELIIp, moreover CCoil ≥0.17coil/ cm maight be considered to determine the tailored number of coils.
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http://dx.doi.org/10.1016/j.avsg.2021.01.118DOI Listing
April 2021

Involvement of miR-30a-5p and miR-30d in Endothelial to Mesenchymal Transition and Early Osteogenic Commitment under Inflammatory Stress in HUVEC.

Biomolecules 2021 02 5;11(2). Epub 2021 Feb 5.

Laboratory of Clinical Pathology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), St. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.

The endothelial to mesenchymal transition (End-MT) can be associated with vascular calcification, by providing mesengenic progenitors. In this study, we investigated a link between End-MT and the osteogenic process and explored the involvement of miR-30a-5p and miR-30d as potential regulators of these processes. End-MT was induced in Human Umbilical Vein Endothelial Cells (HUVEC) through transforming growth factor-β1 (TGF-β1), TGFβ-3 and tumor necrosis factor-α (TNF-α), for 24 h and 6 days. End-MT mediators, mesenchymal and osteo/chondrogenic markers were analyzed through Real-Time PCR, immunofluorescence, flow cytometry and Western Blot. miR-30a-5p and miR-30d over-expression was carried out in HUVEC to explore their effects on End-MT and osteogenic differentiation. HUVEC at 24 h and 6 days gained mesenchymal morphology markers, including matrix metalloproteinase 9 (MMP-9), SLUG, VIMENTIN and α-smooth muscle actin (α-SMA), and a significant migratory potential, notably with TNF-α. After 6 days, the osteo/chondrogenic markers runt-related transcription factor 2 (RUNX-2) and SRY box transcription factor 9 (SOX-9) were upregulated. At this time point, miR-30a-5p and miR-30d decreased. Over-expression of miR-30a-5p and miR-30d affected End-MT mediators and the osteogenic potency in HUVEC, by reducing SLUG, VIMENTIN and RUNX-2. Our data suggest that End-MT represents a key link between inflammation and vascular calcification. Further, miR-30a-5p and miR-30d can regulate both the End-MT and the osteogenic processes, prompting future studies for exploring their potential use as therapeutic targets or biomarkers in vascular diseases.
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http://dx.doi.org/10.3390/biom11020226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915105PMC
February 2021

Carotid Endarterectomy is often not Possible after an Unheralded Stroke: Unheralded Stroke in Carotid Artery Stenosis.

J Stroke Cerebrovasc Dis 2021 Mar 8;30(3):105594. Epub 2021 Jan 8.

Division of Vascular Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

Objectives: The ongoing literature recommends carotid endarterectomy (CEA) primarily for patients with neurological symptoms, however CEA can be precluded by the onset of a severe stroke or a total carotid occlusion. The present study aims to evaluate the effect of unheralded strokes in patients with a previously asymptomatic carotid stenosis (ACS) possibly considered for CEA.

Materials And Methods: From 2009 to 2019, patients with an unheralded stroke from an ACS were considered. By neurological examination, patients were divided in unfit-for-CEA (uCEA) - either for the severity of the stroke (according to modified Rankin-Scale - mRS) or the onset of a total carotid occlusion - and patients submitted to CEA. Predictors for uCEA and stroke severity were evaluated.

Results: Over a total of 532 patients with symptomatic carotid stenosis, 277 (52%) with unheralded stroke were included in the study. One hundred and one (36%) were considered uCEA: 64(23%) due to their neurological conditions (mRS:5) and 37 (13%) because of the onset of carotid occlusion. One hundred seventy-six (64%) patients underwent CEA. The preoperative medical therapy was similar in uCEA vs CEA patients. Age≥80 years and female sex were independently associated with uCEA (OR:5.9, 95%CI:3.1-11.4, P<.01; OR:3.9, 95%CI:2.0-7.6, P<.01. respectively). Patients submitted to CEA had mRS: 0-2 in 102(37%) cases and mRS:3-4 in 74 (27%). The contralateral carotid occlusion (CCO) was independently associated with mRS:3-4 (OR:8.4, 95%CI 1.8-79, P=.01). Postoperative stroke rate after CEA was 2.9% (4/167); patients with preoperative mRS:3-4 had a higher risk for postoperative stroke compared to those with mRS:0-2 (5.9% vs. 0%. P=.02).

Conclusions: An unheralded stroke in patients with ACS leads to a severe neurological damage in more than half of cases, either precluding CEA (36%) or increasing the risk of postoperative complications (27%). Female sex, age≥80 and CCO are independent predictors of these occurrences and should be considered in ACS patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105594DOI Listing
March 2021

Proximal Aortic Coverage and Clinical Results of the Endovascular Repair of Juxta-/Para-renal and Type IV Thoracoabdominal Aneurysm with Custom-made Fenestrated Endografts.

Ann Vasc Surg 2021 May 4;73:397-406. Epub 2021 Jan 4.

Vascular Surgery, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Background: Juxta-renal (JAAA)/para-renal (PAAA) and type IV-thoracoabdominal (TAAA) aneurysms can be repaired by custom-made fenestrated endografts (CM-FEVAR). Differently from open repair, a relatively long segment of healthy proximal aorta needs to be covered to achieve a durable sealing, and this may be considered a disadvantage of the endovascular approach. We aimed to quantify the additional proximal aortic coverage in JAAAs, PAAAs, and type-IV TAAAs treated with CM-FEVAR and to evaluate its impact on early/follow-up clinical outcomes.

Methods: Between 2006 and 2018, preoperative, intraoperative, and postoperative data of JAAAs, PAAAs, and type-IV TAAAs submitted to CM-FEVAR were collected. The length of proximal healthy aortic coverage was evaluated on the preoperative endograft planning as the distance between the top of the CM-FEVAR endograft and the hypothetical level of aortic cross-clamping in case of open repair (type-IV TAAA-above the celiac trunk; PAAA-above the superior mesenteric artery; JAAA-above the lowest renal artery). Spinal cord ischemia (SCI), bowel ischemia (BI), renal function worsening (RFW) (estimated glomerular filtration rate reduction > 25% of the baseline level - RFW), and mortality were assessed at 30-day. Survival, target visceral vessel (TVV) patency, and freedom from reinterventions (FFRs) were assessed during follow-up by Kaplan-Meier analysis R2.

Results: One hundred forty-seven cases were submitted to CM-FEVAR, for 72 (49%) JAAAs, 46 (31%) PAAAs, and 29 (20%) type IV-TAAAs, with 1(4-3%), 2 (28-19%), 3 (48-33%), and 4 (67-45%) fenestrations. JAAAs required a fenestration + bridging stent graft for the superior mesenteric artery and celiac trunk, in 46(64%) and 24(33%) cases, respectively. Nineteen (41%) PAAAs required a fenestration + bridging stent graft for the celiac trunk. The mean proximal additional aortic coverage was 48 ± 2 mm with no differences among JAAAs (52 ± 1 mm), PAAAs (42 ± 2 mm), and type IV-TAAAs (50 ± 2 mm) (P.09). Technical success, defined as correct endograft deployment, with TVV patency, absence of type I-III endoleaks, iliac leg stenosis/occlusions, open surgical conversion, and 24-hour mortality, was achieved in 98% of cases. Failures occurred for 1 type-III endoleak (type-IV TAAA) and 2 renal artery losses (PAAA and type IV-TAAA). The only case of SCI (0.7%) occurred in a type-IV TAAA where the proximal healthy aortic coverage was 80 mm. One BI was caused by acute thrombosis of the bridging stent graft for the superior mesenteric artery at 24 hours in 1 type IV-TAAA (0.7%). Thirty-five patients (24%) suffered postoperative RFW and required hemodialysis in 1 (0.7%) JAAA with severe preoperative chronic renal failure. There was no difference of proximal additional aortic coverage between patients with (49 ± 29 mm) and without (48 ± 23 mm) RFW (P.2). The 30-day mortality was 1.4%. The mean follow-up was 37 ± 2 months with no cases of aneurysm-related late mortality. Survival was 94%, 89%, and 75% at 1, 2, and 5 years, respectively. TVV patency was 97%, 97%, and 93% at 1, 2, and 5 years, respectively. FFR was 98%, 95%, and 87% at 1, 2, and 5 years, respectively.

Conclusions: Custom-made FEVAR requires a mean proximal additional aortic coverage of 48 ± 2 mm above the level of hypothetical aortic cross-clamping in case of open repair. This aspect should be considered for CM-FEVAR indication in JAAAs, PAAAs, and type-IV TAAAs; nevertheless, it does not appear to be associated with negative early and follow-up clinical sequelae.
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http://dx.doi.org/10.1016/j.avsg.2020.12.008DOI Listing
May 2021

Impact of cerebral ischemic lesions on the outcome of carotid endarterectomy.

Ann Transl Med 2020 Oct;8(19):1264

Vascular Surgery, Department of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna, Italy.

Patients with carotid artery stenosis (CAS) are commonly defined as asymptomatic or symptomatic according with their neurological conditions, however, emerging evidences suggest stratifying patients according also with the presence of cerebral ischemic lesions (CIL). In asymptomatic patients, the presence of CIL increases the risk of future neurologic event from 1% to 4% per year, leading to a stronger indication to carotid revascularization. In symptomatic patients, the presence of CIL does not seem to influence the outcome of the carotid revascularization if the volume of the lesion is small (<4,000 mm); the benefit of the revascularization is also more significant if performed within 2 weeks from the index event. However, high volume (>4,000 mm) CIL are associated in some experiences with a higher risk of carotid revascularization suggesting to delay the carotid revascularization for at least 4 weeks. As a matter of fact, the evaluation of CIL dimensions and characteristics in patients with CAS gives to the physician involved in the treatment a valuable adjunctive tool in the choice of the ideal treatment.
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http://dx.doi.org/10.21037/atm-20-1098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607094PMC
October 2020

Revascularization of occluded renal artery stent grafts after complex endovascular aortic repair and its impact on renal function.

J Vasc Surg 2021 May 19;73(5):1566-1572. Epub 2020 Oct 19.

Department of Vascular Surgery, University Hospital, LMU Munich, Munich, Germany.

Background: Acute occlusion of renal bridging stent grafts after fenestrated/branched endovascular aortic repair (F/B-EVAR) is an acknowledged complication with high morbidity that often results in chronic dialysis dependence. The feasibility and effect of timely or late (≥6 hours of ischemia) renal artery revascularization has not been adequately reported.

Methods: We performed a retrospective, multicenter study across 11 tertiary institutions of all consecutive patients who had undergone revascularization of renal artery stent graft occlusions after complex EVAR. The end points were technical success, association between ischemia time and renal function salvage, interventional complications, mortality, and mid-term outcomes.

Results: From 2009 to 2019, 38 patients with 46 target vessels (TVs; eight bilateral occlusions) were treated for renal artery occlusions after complex EVAR (mean age, 63.5 ± 10 years; 63.2% male). Six patients had a solitary kidney (15.8%). Of the 38 patients, 16 (42.1%) had undergone FEVAR and 22 (57.9%) had undergone BEVAR. The technical success rate was 95.7% (44 of 46 TVs). The recanalization technique used was sole aspiration thrombectomy in 5.3%, aspiration thrombectomy and stent graft relining in 52.6%, and sole stent graft relining in 36.8%. The median renal ischemia time was 27.5 hours (range, 4-720 hours; interquartile range, 4-36 hours). Most patients (94.4%) had been treated after ≥6 hours of renal ischemia time, and 55.6% had been treated after 24 hours. In 14 patients (36.8%), renal function had improved after intervention (mean glomerular filtration rate improvement, 14.2 ± 9 mL/min/1.73 m). However, 24 patients (63.2%) showed no improvement. Improvement of renal function did not correlate with the length of renal ischemia time. Of the 14 patients with bilateral renal artery occlusion or a solitary kidney, 9 experienced partial recovery of renal function and no longer required hemodialysis. In-hospital mortality was 2.6%. The cause of renal stent graft occlusion could not be identified in 50% of the TVs (23 of 46). However, in 19 (41.3%), significant stenosis or a kink of the renal stent graft was found. The median follow-up was 11 months (interquartile range, 0-28 months). The estimated 1-year patient survival and patency rate of the renal stent grafts was 97.4% and 83.8%, respectively.

Conclusions: Revascularization of occluded renal bridging stent grafts after F/B-EVAR is a safe and feasible technique and can lead to significant improvement of renal function, even after long ischemia times (>24 hours) of the renal parenchyma or bilateral occlusion, as long as residual perfusion of the renal parenchyma has been preserved. Also, the long-term patency rates justify aggressive management of renal artery occlusion after F/B-EVAR.
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http://dx.doi.org/10.1016/j.jvs.2020.09.036DOI Listing
May 2021

Current status on aortic endografts.

J Cardiovasc Surg (Torino) 2020 Oct 23;61(5):544-554. Epub 2020 Sep 23.

Unit of Vascular Surgery, Department of Experimental Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Polyclinic, University of Bologna, Bologna, Italy -

Endovascular treatment has become widespread to treat aneurysmal disease, especially located in the aorta. The modern era of abdominal aortic aneurysm repair started between 1986 and 1991, and in the last 30 years, Endovascular Treatment for abdominal aortic aneurysms evolved both due to the development of new materials and devices and the increasing appeal and effectiveness of the endovascular therapy itself. Vascular surgeons are using nowadays different solutions of Endovascular Treatment to treat all the expressions of aortic pathology (aneurysms, dissections and trauma) both in the acute and elective setting. Despite its use in every location of the aorta (the ascending aorta, the aortic arch, the thoracic aorta, thoraco-abdominal aorta, pararenal, iuxtarenal and infrarenal aortic aneurysms and iliac aneurysms), its safety and efficiency, endovascular treatment for aortic aneurysms presents some drawbacks: despite a lower short-term morbi-mortality, reinterventions and long-term patency are higher compared to open repair. In this review, we detail the most used types of endografts according to location, their performances and durability for each device. We conclude by discussing options to overcome ET limitations. Therefore, an obvious question arises: what we need in the future? What can the technological progress gives to physicians to further improve this new way of treating aorta?
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http://dx.doi.org/10.23736/S0021-9509.20.11614-8DOI Listing
October 2020

Predictors and Consequences of Silent Brain Infarction in Patients with Asymptomatic Carotid Stenosis.

J Stroke Cerebrovasc Dis 2020 Oct 14;29(10):105108. Epub 2020 Jul 14.

Vascular Surgery, University of Bologna "Alma Mater Studiorum", Policlinico S. Orsola Malpighi, 40138 Bologna. Electronic address:

Aim: Silent brain infarction (SBI) is associated with an increased risk of stroke in patients with asymptomatic carotid stenosis (ACS), and is therefore one of the criteria for performing carotid endarterectomy (CEA). Despite an extensive literature, this issue is still a matter of debate. Aim of the present work was to evaluate incidence and predictors of SBI in patients undergoing CEA for ACS, and to investigate its possible impact on CEA outcome.

Methods: All patients submitted to CEA in a single academic center from 2005 to 2019 were prospectively inserted into a specific database. The presence of SBI was evaluated by preoperative computed tomography (CT), considering exclusively infarctions in the carotid territories from an athero-embolic source. Preoperative characteristics were investigated as possible risk factor for SBI at the uni- and multivariate analysis. The impact of SBI on stroke occurrence after CEA was also evaluated.

Results: In the designated period, over a total of 1288 ACS considered and submitted to CEA, 105 (8.2%) were associated with SBI. Male sex, hypertension, dyslipidaemia, smoking, contralateral carotid occlusion and severity of carotid stenosis were associated with SBI at the univariate analysis; preoperative statin therapy showed to be a protective factor. At the multivariate analysis, contralateral carotid occlusion and severity of stenosis were independently associated with SBI (OR: 3.16, 95%CI 1.62-6.18, P=.001; OR: 1.04, 95%CI 1.01-1.07, P=.004, respectively), with statin therapy confirmed as a protective factor (OR: 0.60, 95%CI: 0.40-0.92, P=.002). Overall post-CEA stroke rate was 0.9%, with a higher post-operative risk independently predicted by the presence of SBI (OR:4.23, 95%CI: 1.40-12.73, P=.01).

Conclusion: SBI is present in 8% of patients with ACS, and is significantly associated with contralateral carotid occlusion and severity of the carotid stenosis. Statin therapy reduces the occurrence of this phenomenon. The presence of SBI should be carefully considered in indication to CEA since it significantly increases the surgical risk.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105108DOI Listing
October 2020

Kissing Stent Technique for TASC C-D Lesions of Common Iliac Arteries: Clinical and Anatomical Predictors of Outcome.

Ann Vasc Surg 2021 Feb 2;71:288-297. Epub 2020 Sep 2.

Vascular Surgery, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Background: The endovascular treatment of peripheral artery obstructive disease in Trans-Atlantic Inter-Society (TASC) C and D lesions involving the aortic bifurcation is a matter of debate. The aim of this study is to evaluate the technical and clinical success of kissing stenting in this context and to analyze predictors of outcome.

Methods: All patients treated for aortoiliac TASC C and D lesions with kissing stenting (from 2012 to 2017) in a 6-year period were retrospectively analyzed. Preoperative anatomical features were evaluated by reviewing computed tomography angiography images to identify severe iliac calcifications (SICs) versus not SIC (NSICs). Primary end points were as follows: technical success (TS), procedural success, primary patency (PP), and clinical success (CS). Secondary end points were as follows: secondary patency, assisted patency, survival, mid-term procedure-related complications, and risk factors that affected TS and mid-term results.

Results: In a 6-year period, 51 patients fulfilled the inclusion criteria. TS was achieved in 49 (96.1%) cases. Thirty-one patients (60.8%) received a dual antiplatelet therapy (DAPT) for at least 1 month after the procedure. 30-day CS was 94.1%. Median follow-up was 45.7 months (IQR: 24.5, 8-86 range). The CS was 92.6% at 3 years, with a PP of 86.8% and a secondary patency of 93.2% at 3 years. Six (13.2%) iliac axis occluded during the first follow-up year. NSIC was statistically and independently associated with a lower PP (73% vs. 96%, P = 0.03); DAPT was statistically and independently associated with higher PP than single antiplatelet therapy (96% vs. 75%, P = 0.03); these results were confirmed by Cox regression analysis (HR: 0.14, 95%, IC: 0.01-0.89, P = 0.05 for DAPT analysis; HR: 6.8, 95%, IC: 1.21-59, P = 0.05 for NSIC analysis).

Conclusions: Endovascular treatment for TASC C-D is an effective technique. Postoperative stent occlusion is higher in patients with no DAPT and it usually occurs during the first postoperative year. Preoperative NSIC lesions are associated with reduced PP at 3 years of follow-up.
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http://dx.doi.org/10.1016/j.avsg.2020.07.058DOI Listing
February 2021

Fenestrated and Branched Thoraco-abdominal Endografting after Previous Open Abdominal Aortic Repair.

Eur J Vasc Endovasc Surg 2020 Dec 24;60(6):843-852. Epub 2020 Aug 24.

Vascular Surgery, University of Bologna, DIMES, Policlinico S. Orsola, Bologna, Italy.

Objective: Proximal para-anastomotic aneurysms, or aneurysmal degeneration of the native aorta above a previous open abdominal aortic repair (Pr-AAAs), are challenging scenarios. The aim of this study was to report the early and mid term outcomes of endovascular repair of Pr-AAAs by fenestrated and branched endovascular aneurysm repair (FB-EVAR).

Methods: From 2006 to 2017, pre-operative, intra-operative, and post-operative data from patients undergoing FB-EVAR for Pr-AAAs at two European vascular surgery units were prospectively collected and retrospectively analysed. Early results were considered in terms of technical success (target visceral vessel cannulation and stenting, absence of type I - III endoleak, iliac limb occlusion and 24 h mortality); spinal cord ischaemia (SCI) and 30 day and in hospital mortality. Survival, target visceral vessel (TVV) patency, and freedom from re-interventions were also considered at the mid term follow up.

Results: Five hundred and forty-four patients underwent FB-EVAR to treat juxta/pararenal or thoraco-abdominal aneurysms. Of these patients, 108 (19.8%) cases were Pr-AAAs (94% male; mean ± standard deviation [SD] age 71 ± 4 years; American Society of Anesthesiologists' grade 3-4 in 74% and 26%, respectively). The previous open aortic repair (OR) was performed 10 ± 2 years before FB-EVAR. It was a tubular aorto-aortic repair in 63 (58.3%) cases, a bifurcated aortobi-iliac repair in 37 (34.2%) cases, and an aortobifemoral bypass repair in eight (7.4%) cases. A previous thoracic endovascular aneurysm repair (TEVAR) had been performed in seven patients (6.5%). The aortic lesion at the time of FB-EVAR was, according to the Crawford classification, a type I - III in 69 (63.9%) or a type IV 39 (36.1%) thoraco-abdominal aneurysm. The mean ± SD aneurysm diameter was 64 ± 6 mm. Overall, 390 TVVs (3.6 ± 1 TVV/case) were revascularised by an endograft with fenestrations (n = 63 [58.3%]), with branches (n = 26 [24.1%]), or with both fenestrations and branches (n = 19 [17.6%]). Tubular, trimodular, or aorto-uni-iliac implants were planned in 68 (63.0%), 38 (35.2%), and two (1.8%) patients, respectively. Proximal TEVAR, carotid-subclavian bypass, and iliac branch devices were planned as adjunctive procedures in 41 (38.0%), five (4.6%), and three (2.8%) cases, respectively. Overall technical success was 93%, with technical failures including five TVV losses (coeliac trunk, n = 1; renal arteries, n = 4) and three deaths within 24 h. Post-operative SCI occurred in seven patients (6.5%), four of which (3.7%) were permanent. SCI was more frequent in category I - III TAAAs (p = .042) and in endografts incorporating both fenestrations and branches (p = .023). Cardiac, pulmonary, and renal complications (reduction in glomerular filtration rate of ≥30% compared with baseline) occurred in 9%, 10%, and 20%, respectively. Bowel ischaemia was seen in three (2.8%) patients. Thirty day mortality was 4% and was associated with pre-operative chronic renal failure (p = .034), post-operative cardiac morbidity (p = .041), and bowel ischaemia (p = .003). Overall in hospital mortality was 5.5% (n = 6). Mean ± SD follow up was 38 ± 18 months. Survival was 82%, 64%, and 54% at one, three, and five years, respectively, and target visceral vessel patency was 93%, 91%, and 91%, respectively. Permanent haemodialysis was needed in four patients (3.7%). There was no late aneurysm related mortality. Survival during follow up was statistically significantly affected by pre-operative chronic renal failure (p = .022), post-operative cardiac morbidity (p = .042), SCI (p = .044), and bowel ischaemia (p = .003). Freedom from re-intervention at one, three, and five years was 89%, 77%, and 74%, respectively.

Conclusion: Endovascular treatment of aneurysmal aortic degeneration above a previous open abdominal repair with FB-EVAR is safe and effective. If those promising results are confirmed at later follow up, FB-EVAR should be considered a prominent therapeutic option, especially in high risk patients.
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http://dx.doi.org/10.1016/j.ejvs.2020.07.071DOI Listing
December 2020

The Efficacy of a Protocol of Iliac Artery and Limb Treatment During EVAR in Minimising Early and Late Iliac Occlusion.

Eur J Vasc Endovasc Surg 2020 Nov 25;60(5):663-670. Epub 2020 Aug 25.

Vascular Surgery, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy.

Objective: Iliac limb occlusion (ILO) is a complication of endovascular aortic repair (EVAR) and requires re-intervention in most cases. Attention to any intra-operative defect of iliac limbs and arteries may prevent ILO. The study aimed to analyse the long term effect of an intra-operative protocol of iliac limb treatment during EVAR on ILO.

Methods: Patients treated from 2012 to 2017 for abdominal aortic aneurysm (AAA) with standard EVAR were collected prospectively. Pre-operative computed tomography angiography anatomical characteristics were evaluated. The protocol for intra-operative iliac limb management was: a. pre-EVAR angioplasty of common/external iliac artery stenosis; b. precise contralateral iliac limb deployment at the same level of the flow divider; c. iliac limb kissing ballooning with high pressure non-compliant balloons; d. iliac limb stenting for residual tortuosity/kink and adjunctive external iliac stenting for residual stenosis/dissection after EVAR. ILO was evaluated at 30 days and at follow up, which was performed by duplex ultrasonography before discharge, at three, six, and 12 months and yearly thereafter. Kaplan-Meier and Cox linear regression were used.

Results: Four hundred and forty-two patients and 884 iliac limbs were included in the study. Severe iliac tortuosity and calcification were present in 15% (132/884) and 8% (70/884), respectively. External iliac angioplasty and stenting of iliac limb were performed in 2% (18/884) and 9.5% (84/884) of limbs. The thirty day mortality was 1.6%, with no ILO. At a mean follow up of 33 ± 12 months, ILO occurred in 7/884 (0.8%) limbs of six patients. Five ILO were treated by endovascular relining, two surgically: one by femorofemoral bypass and one by surgical explant. On univariable analysis, sac shrinkage was significantly associated with ILO (HR 1, 95% CI 0.8-2.5, p = .043).

Conclusion: A protocol of aggressive iliac limb treatment in EVAR leads to a very low rate of late ILO. The role of sac shrinkage in ILO should be investigated further.
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http://dx.doi.org/10.1016/j.ejvs.2020.07.066DOI Listing
November 2020

Sirolimus-eluting stents: opposite effects on the clonogenic cell potential on a long-term exposure.

Oncotarget 2020 Aug 4;11(31):2973-2981. Epub 2020 Aug 4.

Pathology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University, Bologna, Italy.

We evaluated the long-term effects of sirolimus on three different cell models, cultured in physiological conditions mimicking sirolimus-eluted stent, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival. Three cells lines (WPMY-1 myofibroblasts, HT-29 colorectal adenocarcinoma, and U2OS osteosarcoma) were selected and growth in 10 ml of Minimum Essential Medium for 5 weeks with serial dilutions of sirolimus. The number of colonies and the number of cells per colony were counted. As main result, the number of WPMY-1 surviving colonies increased in a dose-dependent manner when treated with sirolimus ( = 0.0011), while the number of U2OS colonies progressively decreased ( = 0.0011). The clonal capacity of HT-29 was not modified by the exposure to sirolimus ( = 0.6679). In conclusion sirolimus showed the well-known cytostatic effect, but with an effect on clonogenic potential different among the different cell types. In the practice, the plaque typology and composition may influence the response to sirolimus and thus the effectiveness of eluted stent.
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http://dx.doi.org/10.18632/oncotarget.27554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415404PMC
August 2020

"Flaring-Kissing Ballooning" of the Stentgrafts in Fenestrated Endograft Procedures to Ensure Target Visceral Vessels Patency.

Ann Vasc Surg 2021 Jan 12;70:567.e7-567.e11. Epub 2020 Aug 12.

Vascular Surgery, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Purpose: To describe a dedicated technique used in fenestrated endografting (FEVAR) for juxtarenal aneurysm (JAAA) to avoid intraoperative bridging stentgraft crushing in case of adjacent origin of left renal (LRA) and superior mesenteric (SMA) artery.

Case Report: A 78-year-old male, at high surgical risk, underwent FEVAR for JAAA. SMA and LRA fenestrations were adjacent, at 12:30 and 2:45 o'clock evaluation, respectively. The fenestrated endograft and the bridging stentgrafts for target visceral vessels (TVVs) were deployed without complications. The completion angiography and the cone-beam CT showed patency of TVVs, except for LRA, which showed crushing of its stentgraft. SMA and LRA were re-cannulated, and the renal stentgraft was dilated with a 4 × 40 mm balloon. Finally, "Flaring-Kissing ballooning" of SMA and LRA stentgrafts was performed using two 10 × 20 mm balloon under fluoroscopy rotational guidance, to ensure the patency of both arteries. The completion angiography and the postoperative CT-angiography showed the resolution of the crushing and the patency of TVVs. The postoperative course was uneventful; the patient was discharged home after 5 days. CT-angiography at 12 months showed patency of TVVs and no endoleaks.

Conclusions: The "Flaring-Kissing ballooning" of adjacent stentgrafts is a valid, safe and effective intra-procedural maneuver to preserve the patency of the TVVs.
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http://dx.doi.org/10.1016/j.avsg.2020.08.006DOI Listing
January 2021

New disappearance of complicated atheromatous plaques on rechallenge with PD-1/PD-L1 axis blockade in non-small cell lung cancer patient: follow up of an unexpected event.

Ther Adv Med Oncol 2020 24;12:1758835920913801. Epub 2020 Jul 24.

Medical Oncology, Policlinico S.Orsola-Malpighi, University of Bologna, Bologna, Italy.

Atherosclerosis is considered an irreversible process, with crucial contribution of inflammation and immune cells. Impact of cancer immunotherapy on a partly immune-driven disease, such as atherosclerosis, is poorly understood, but preclinical models suggest its worsening on programmed death/ligand-1 (PD-1/PD-L1) inhibitors. In a previously reported cohort of 11 patients with non-small cell lung cancer (NSCLC) treated with nivolumab and pre-existing complicated atheromatous plaques, 3 patients had a dramatic radiologic reduction of aortic plaques while on nivolumab; of these 3, 2 died receiving no further treatment. The remaining patient was an 83-year-old woman with history of arterial hypertension and hypothyroidism who was diagnosed with locally advanced squamous NSCLC. At relapse, complicated aortic atheromatous plaques were demonstrated on scans. The patient was then treated with nivolumab obtaining stable disease at radiological assessment, which also demonstrated almost complete vanishing of aortic plaques. After relapse and interval treatment with chemotherapy, she experienced new development of aortic atheromatous plaques. At further relapse she received atezolizumab, which yielded disease response and new reduction in aortic plaques, until nearly complete resolution. The observation of a repeated improvement of atheromatous plaques on treatment with PD-1/PD-L1 inhibitors favors the protective role of T cells on atheromatous plaques that is impaired by PD-L1 expression by plaque-associated macrophages. Validation by independent and prospective observation is needed.
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http://dx.doi.org/10.1177/1758835920913801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383634PMC
July 2020

The Italian Multicentre Registry of Fenestrated Anaconda™ Endografts for Complex Abdominal Aortic Aneurysms Repair.

Eur J Vasc Endovasc Surg 2020 Aug 21;60(2):181-191. Epub 2020 Jul 21.

Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Policlinico Sant'Orsola-Malpighi, Bologna, Italy.

Objective: The aim was to describe the outcomes of the Anaconda™ Fenestrated endograft Italian Registry for complex aortic aneurysms (AAAs), unsuitable for standard endovascular aneurysm repair (EVAR).

Methods: Between 2012 and 2018 patients with a proximal neck unsuitable for standard EVAR, treated with the fenestrated Anaconda™ endograft, were prospectively enrolled in a dedicated database. Endpoints were peri-operative technical success (TS) and evaluation of type Ia/b or 3 endoleaks (T1/3 EL), target visceral vessel (TVV) occlusion, re-interventions, and AAA related mortality at 30 days, six months, and later follow up.

Results: One hundred twenty seven patients (74 ± 7 years, American Society Anesthesiology (ASA) II/III/IV: 12/85/30) were included in the study in 49 Italian Vascular Surgery Units (83 juxta/para-renal AAA, 13 type IV thoraco-abdominal AAA, 16 T1aEL post EVAR, and 15 short neck AAA). Configurations with one, two, three, and four fenestrations were used in 5, 56, 39, and 27 cases, respectively, for a total of 342 visceral vessels. One hundred and eight (85%) bifurcated and 19 (15%) tube endografts were implanted. In 35% (44/127) of cases the endograft was repositioned during the procedure, and 37% (128/342) of TVV were cannulated from brachial access. TS was 87% (111/127): five T1EL, six T3EL (between fenestration and vessel stent), and six loss of visceral vessels (one patient with a Type Ia EL had also a TVV loss) occurred. Thirty day mortality was 4% (5/127). Two of the five T1EL resolved spontaneously at 30 days. The overall median follow up was 21 ± 16 months; one T1EL (5%) occurred at six months and one T3EL (4%) at the three year follow up. Another two (3%) TVV occlusions occurred at six months and five (3%) at three years. The re-intervention rate at the 30 days, six months, and three year follow up was 5%, 7%, and 18 ± 5%, respectively.

Conclusion: The fenestrated Anaconda™ endograft is effective in the treatment of complex AAA. Some structure properties, such as the re-positionability and the possibility of cannulation from above, are specific characteristics helpful for the treatment of some complex anatomies.
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http://dx.doi.org/10.1016/j.ejvs.2020.04.032DOI Listing
August 2020

Is it Possible to Safely Maintain a Regular Vascular Practice During the COVID-19 Pandemic?

Eur J Vasc Endovasc Surg 2020 07 19;60(1):127-134. Epub 2020 May 19.

Vascular Surgery Metropolitan Unit, University of Bologna, DIMES, Policlinico S. Orsola and Ospedale Maggiore, Bologna, Italy.

Objective: This study aimed to evaluate the protocol adopted during the emergency phase of the COVID-19 pandemic to maintain elective activity in a vascular surgery unit while minimising the risk of contamination to both patients and physicians, and the impact of this activity on the intensive care (IC) resources.

Methods: The activity of a vascular surgery unit was analysed from 8 March to 8 April 2020. Surgical activity was maintained only for acute or elective procedures obeying priority criteria. The preventive screening protocol consisted of nasopharyngeal swabs (NPS) for all patients and physicians with symptoms and for unprotected contact infected cases, and serological physician evaluations every 15 days. Patients treated in the acute setting were considered theoretically infected and the necessary protective devices were used. The number of patients and the possible infection of physicians were evaluated. The number and type of interventions and the need for post-operative IC during this period were compared with those in the same periods in 2018 and 2019.

Results: One hundred and fifty-one interventions were performed, of which 34 (23%) were acute/emergency. The total number of interventions was similar to those performed in the same periods in 2019 and 2018: 150 (33, of which 22% acute/emergency) and 117 (29, 25% acute/emergency), respectively. IC was necessary after 6% (17% in 2019 and 20% in 2018) of elective operations and 33% (11) of acute/emergency interventions. None of the patients treated electively were diagnosed with COVID-19 infection during hospitalisation. Of the 34 patients treated in acute/emergency interventions, five (15%) were diagnosed with COVID-19 infection. It was necessary to screen 14 (47%) vascular surgeons with NPS after contact with infected colleagues, but none for unprotected contact with patients; all were found to be negative on NPS and serological evaluation.

Conclusion: A dedicated protocol allowed maintenance of regular elective vascular surgery activity during the emergency phase of the COVID-19 pandemic, with no contamination of patients or physicians and minimal need for IC resources.
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http://dx.doi.org/10.1016/j.ejvs.2020.05.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236703PMC
July 2020

The carotid plaque as paradigmatic case of site-specific acceleration of aging process: The microRNAs and the inflammaging contribution.

Ageing Res Rev 2020 08 28;61:101090. Epub 2020 May 28.

DIMES-Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Interdepartmental Center - Alma Mater Research Institute on Global Challenges and Climate Change - University of Bologna, Bologna, Italy. Electronic address:

Atherosclerosis is considered a chronic inflammatory disease of arteries associated with the aging process. Many risk factors have been identified and they are mainly related to life-styles, gene-environment interactions and socioeconomic status. Carotid and coronary artery diseases are the two major atherosclerotic conditions, being the primary cause of stroke and heart attack, respectively. Nevertheless, carotid plaque assumes particular aspects not only for the specific molecular mechanisms, but also for the types of atheroma which may be associated with a better or a worst prognosis. The identification of circulating blood biomarkers able to distinguish carotid plaque types (stable or vulnerable) is a crucial step for the improvement of adequate therapeutic approaches avoiding or delaying endarterectomy in the oldest old individuals (> 80 years), a population predicted to growth in the next years. The review highlights the most recent knowledge on carotid plaque molecular mechanisms, focusing on microRNAs (miRs), as a site-specific accelerated aging within the conceptual framework of Geroscience for new affordable therapies.
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http://dx.doi.org/10.1016/j.arr.2020.101090DOI Listing
August 2020

Commentary: Investigating and Predicting the Fate of Infrapopliteal Arterial Disease After Endovascular Treatment.

J Endovasc Ther 2020 08 29;27(4):581-583. Epub 2020 May 29.

Vascular Surgery, University of Bologna, Italy.

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http://dx.doi.org/10.1177/1526602820928087DOI Listing
August 2020

Commentary: How Old Is Too Old for EVAR?

J Endovasc Ther 2020 10 25;27(5):845-847. Epub 2020 May 25.

Unit of Vascular Surgery, Alma Mater Studiorum - University of Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy.

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http://dx.doi.org/10.1177/1526602820924659DOI Listing
October 2020

Unheralded Lower limb threatening ischemia in a COVID-19 patient.

Int J Infect Dis 2020 Jul 22;96:590-592. Epub 2020 May 22.

Vascular Surgery, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Acute thromboembolic events appear to be frequent in patients with SARS-CoV-2 infection. We report a case of an intubated patient, who developed a threatening lower limb ischemia. Intra-arterial fibrinolysis and intravenous heparin infusion did not lead to complete recanalization of the tibial arteries, which were successfully treated by surgical embolectomy.
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http://dx.doi.org/10.1016/j.ijid.2020.05.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242202PMC
July 2020
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