Contribution of vascular mesenchymal cells to abdominal aortic aneurysm pathogenesis

Introduzione. Un’infiltrazione infiammatoria e un’eccessiva proteolisi della matrice extracellulare(ECM), mediata da metallo-proteinasi(MMPs), sono alterazioni dell’aneurisma dell’addominale(AAA). Le cellule staminali mesenchimali(MSC) sono state isolate dalla parete vascolare e rappresentano potenziali candidati target per la medicina rigenerativa in virtù di differenziazione mesodermica e immuno-modulatoria. Scopo dello studio è stato valutare la presenza di un potenziale ruolo delle MSCs nello sviluppo di AAA. Metodi. Sono stati prelevati segmenti di parete aortica aneurismatica da AAA sottoposti a trattamento chirurgico open e segmenti di tessuti aortici da donatori sani. È stata effettuata valutazione istologica della parete di AAA. Le MSCs sono state isolate dal tessuto di AAA(AAA-MSC) e caratterizzate. Le AAA-MSCs sono poi state testate per caratteristiche di immuno-modulazione mediante co-colture di cellule mononucleate attivate(PBMC)da sangue periferico e di MSCs da donatore sano. Risultati. Le cellule AAA-MSCs hanno mostrato proprietà feno/genotipiche mesenchimali: forma fibroblastica, presenza di antigeni MSC e geni staminali. Le MMP-9 sono risultate significativamente aumentate in AAA-MSCs rispetto MSCs. Le AAA-MSCs hanno dimostrato una debole attività immunosoppressiva. I livelli di MMP-9 sono modulate a livello trascrizione attraverso 'azione paracrina di MSCs sane. Conclusioni. L’AAA non ha influenzato il fenotipo delle MSC, ma ne ha alterato la funzione, aumentando l’attività di MMP-9 e mostrando un’inefficace attività di immuno-modulazione. Questi dati suggeriscono che le MSCs della nicchia vascolare contribuiscono alla formazione diAAA. Lo studio dei processi per ripristinare l’immunomodulazione delle MSsC potrebbe essere utile per trovare un approccio medico per il monitoraggio/progressionee degli AAA.Background. inflammatory infiltrate and excessive extracellular matrix proteolysis (ECM), by Metalloproteinasis (MMPs), are typical characteristics of abdominal aortic aneurysm (AAA). Mesenchymal Stromal Cells (MSCs) have been detected in the vascular wall and represent attractive target for regenerative medicine, due to the mesodermal lineage differentiation and immunomodulatory activity. Previous papers underlined an impaired MSC behaviour under pathological conditions. Aim of the study was to define the potential role of vascular MSCs to AAA development. Methods. Aortic tissues were collected from patients with AAA and healthy donors. The analysis was organized in three steps: 1) histology of AAA wall; 2) detection of MSCs and evaluation of MMP-9 expression in AAA; 3) MSC isolation from AAA and characterization for mesenchymal/stemness markers, MMP-2, MMP-9, TIMP-1, TIMP-2 and EMMPRIN. AAA-MSCs were tested for immunomodulation, when cultured with activated peripheral blood mononuclear cells (PBMCs). Co-culture of both healthy and AAA MSCs was performed and afterwards MMP-2/9 mRNA levels were analyzed. Results. AAA-MSCs showed mesenchymal features: fibroblastic aspect, MSC antigens, stemness genes. MMP-9 mRNA, protein and enzymatic activity were increased in AAA-MSCs. Moreover, AAA-MSCs showed a weak immunosuppressive activity, as shown by PBMC ongoing along cell cycle. MMP-9 was shown to be modulated at the transcriptional level through the contact as well as the paracrine action of healthy MSCs. Discussion. Vascular injury did not affect the MSC phenotype, but altered their function, as increased MMP-9 expression and ineffective immunomodulation. These data suggest that vascular MSCs can contribute to aortic disease. The study of key processes to restore MSC immunomodulation could be relevant to find a pharmacological approach for the aneurysm progressio

The Outcome of Technical Intraoperative Complications Occurring in Standard Aortic Endovascular Repair

Background Technical intraoperative complications (TICs) may occur during standard endovascular repair (EVAR) with possible effects on the outcome. This study evaluates the early and midterm effects of TICs on EVARs. Methods All EVARs (from 2012 to 2016) were analyzed to identify all TICs: (1) endoluminal defects (stenosis, dissection, rupture, compression of native arteries, or endograft); (2) type I-III endoleaks; (3) unplanned artery coverage; and (4) surgical access complications. Follow-up was performed by Doppler ultrasound/ontrast enhanced ultrasound/computed tomography scan at yearly intervals. The outcome was compared with that of uneventful cases (UCs) through Fisher's exact test and Kaplan-Maier curve. Results TICs occurred in 68 (18%) of 377 patients undergoing EVAR. Thirty-two endoluminal defects were relined endovascularly; 24 type I-III endoleaks were treated with cuff deployment/forced ballooning (23) and surgical conversion (1); 3 of 8 unplanned artery coverages were revascularized (2 renal and 1 hypogastric); 5 hypogastric coverages had an unsuccessful correction; and 4 access artery injuries were repaired. Although fluoroscopy time and contrast usage were significantly higher in the TIC group than those in the UC group (309 cases), 30-day outcome was similar for death (1.4% TIC vs 0% UC, P = 0.18), reintervention (0% TIC vs 0.3% UC, P = 1), type I-III endoleak (0% TIC vs 0.9% UC, P = 1), steno-occlusions (0% TIC vs 0.3% UC, P = 1), buttock claudication, and renal failure (0% in both groups). At 24 months, TIC and UC groups had similar survival (91.7 ± 8% vs 96.2 ± 2.1%, P = 0.5), freedom from reintervention (81.4 ± 9.9% vs 96 ± 2.2%, P = 0.49), overall complication rate (13.4 ± 7.6% vs 11.4 ± 3.5%, P = 0.49), type I-III endoleak (11.2 ± 7.5% vs 7 ± 2.9%, P = 0.8), buttock claudication (0% vs 2 ± 2% P = 0.6), and hemodialysis (0% in both). Midterm iliac leg occlusion was significantly higher in the TIC group (26.9 ± 12.3% vs 3 ± 2.1%, P = 0.01). Conclusion TICs may affect several aspects during EVAR, leading to the necessity of adjunctive maneuvers, which have no impact on early outcome but may cause an increased rate of midterm iliac leg occlusion

Fate of target visceral vessels in fenestrated and branched complex endovascular aortic repair

Objective: To assess branch vessel outcomes after endovascular repair of complex aortic aneurysms analyzing possible factors influencing early and long-term results.Methods: The Italian Multicentre Fenestrated and Branched registry enrolled 596 consecutive patients treated with fenestrated and branched endografts for complex aortic disease from January 2008 to December 2019 by four Italian academic centers. The primary end points of the study were technical success (defined as target visceral vessel [TVV] patency and absence of bridging device-related endoleak at final intraoperative control), and freedom from TVV instability (defined as the combined results of type IC/IIIC endoleaks and patency loss) during follow-up. Secondary end points were overall survival and TVV-related reinterventions.Results: We excluded 591 patients (3 patients with a surgical debranching and 2 patients who died before completion from the study cohort) were treated for a total of 1991 visceral vessels targeted by either a directional branch or a fenestration. The overall technical success rate was 98.4%. Failure was related to the use of an off-the-shelf (OTS) device (custom-made device vs OTS, HR, 0.220; P = .007) and a preoperative TVV stenosis of >50% (HR, 12.460; P < .001). The mean follow-up time was 25.1 months (interquartile range, 3-39 months). The overall estimated survival rates were 87%, 77.4%, and 67.8% at 1, 3, and 5 years, respectively (standard error [SE], 0.015, 0.022, and 0.032). During follow-up, TVV branch instability was observed in 91 vessels (5%): 48 type IC/IIIC endoleaks (2.6%) and 43 stenoses-thromboses (2.4%). The extent of aneurysm disease (thoracoabdominal aortic aneurysm [TAAA] types I-III vs TAAA type IV/juxtarenal aortic aneurysm/pararenal aortic aneurysm) was the only independent predictor for developing a TVV-related type IC/IIIC endoleak (HR, 3.899; 95% confidence interval [CI]:, 1.924-7.900; P < .001). Risk of patency loss was independently associated with branch configuration (HR, 8.883; P < .001; 95% CI, 3.750-21.043) and renal arteries (HR, 2.848; P = .030; 95% CI, 1.108-7.319). Estimated rates at 1, 3, and 5 years of freedom from TVV instability and freedom from TVV-related reinter-vention were 96.6%, 93.8%, and 90% (SE, 0.005, 0.007, and 0.014) and 97.4%, 95.0%, and 91.6% (SE, 0.004, 0.007, and 0.013), respectively.Conclusions: Intraoperative failure to bridge a TVV was associated with a preoperative TVV stenosis of >50% and the use of OTS devices. Midterm outcomes were satisfying, with an estimated 5-year freedom from TVV instability and reintervention of 90.0% and 91.6%, respectively. During follow-up, the larger extent of aneurysm disease was associated with an increased risk of TVV-related endoleaks, whereas a branch configuration and renal arteries were more prone to patency loss

Fenestrated and Branched Endografts for Post-Dissection Thoraco-Abdominal Aneurysms: Results of a National Multicentre Study and Literature Review

Objective: Fenestrated and branched endografting (F/B-EVAR) has been proposed as an endovascular solution for chronic post-dissection thoraco-abdominal aneurysms (PD-TAAAs). The aim of this study was to analyse the experience of four high volume centres nationwide and the current available literature. Methods: Data on patients undergoing F/B-EVAR in four Italian academic centres between 2008 and 2019 were collected, and those from patients with PD-TAAAs were analysed retrospectively. Peri-operative morbidity and mortality were assessed as early outcomes. Survival, freedom from re-intervention (FFR), target visceral vessel (TVV) patency, and aortic remodelling were assessed as follow up outcomes. A MEDLINE search was performed for studies published from 2008 to 2020 reporting on F/B-EVAR in PD-TAAAs. Results: Among 351 patients who underwent F/B-EVAR for TAAAs, 37 (11%) had PD-TAAAs (Crawford's extent I–III: 35% – 95%). Overall, 135 TVVs (from true lumen 120; false lumen seven; both true and false lumen eight) were accommodated by fenestrations (96% – 71%) and branches (39% – 29%). Technical success (TS) was achieved in 34 (92%) cases with three failures due to endoleaks (Ia: 1; Ic: 1; III: 1). There were no 30 day deaths. No cases of permanent spinal cord ischaemia (SCI) were recorded and six (16%) patients suffered from transient deficits. Renal function worsening (eGFR < 30% than baseline) and pulmonary complications were reported in two (5%) and four (11%) cases, respectively. From the Kaplan–Meier analysis, three year survival, FFR, and TVV patency were 81%, 66%, and 97%, respectively. Radiological imaging was available for 30 (81%) patients at 12 months with complete false lumen thrombosis in 26 (87%). Two hundred and fifty-six patients were reported in seven published papers with TS, 30 day mortality, and SCI ranging from 99% to 100%, 0 to 6%, and 0 to 16%, respectively. The mean follow up ranged from 12 to 26 months, with estimated two year survival between 81% and 90% and a re-intervention rate between 19% and 53%. Conclusion: F/B-EVAR is effective to treat PD-TAAAs. A high re-intervention rate is necessary to complete the aneurysm exclusion and promote aortic remodelling successfully

Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM)

: The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended

Stent Graft Induced Thoracic Aortic Rupture After 10 Years

No abstract availabl

A “leaking” aorta

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Carotid disease. Clinical and morphological insights

Carotid endarterectomy (CEA) was successfully completed fore the first time in 1953 by DeBakey and, despite advanced in endovascular therapy and medical treatment, it remains on of the most frequently performed vascular surgical procedures worldwide. The ain of CEA is to prevent a potential stroke event, by reducing the risk of distal embolization from the plaque or the thrombosis of the norrowed lumen. In tihis sense CEA has been proven to be an effective intervention for stroke risk reduction

Carotid disease. Clinical and morphological insights

tHIS BOOK IS THE RESULT OF THE WORK OF MANY OF THE MOST RENOWNED EXPERTS IN THE FIELD, IN AN EFFORT TO SUMMARZE AND ASSESS THE CONTEMPORARY KNOWLEDGE ON THE PATHOLOGY