Protein S on the surface of plasma lipoproteins: a potential mechanism for protein S delivery to the atherosclerotic plaques?

The anticoagulant protein S (PS) binds phospholipids with very high affinity, but PS interaction with lipoproteins and lipidrich atherosclerotic plaques remains still poorly defined. We investigated PS in plasma lipoproteins and in atherosclerotic plaques from ten patients undergoing endarterectomy. PS was detected by Western blotting after exposure of the necrotic core to liposomes and was found to maintain its ability to bind phosphatidylserine micelles. The amounts of PS bound to low/very low-density lipoproteins in patient' plasmas were higher and more variable than those detected in healthy subjects. A direct correlation between bound PS and low-density lipoproteins (LDL), plasma levels was found only in patients (r=0.921, p<0.001), thereby leading to hypothesize that the PS-phospholipids binding may increase by oxidative processes of LDL in atherosclerotic patients. The presence of the PS into the necrotic core of atherosclerotic plaques and on the surface of lipoproteins, particularly the atherogenic LDL, suggests a LDL-based delivery of PS to the atherosclerotic plaques and emphasizes the deep link between plasma lipids and coagulation in cardiovascular diseases

IDENTIFICAZIONE DI BIOMARCATORI EMATICI COINVOLTI NEL RIMODELLAMENTO DELLA PARETE AORTICA DOPO TRATTAMENTO DI ANEURISMI DELL’AORTA ADDOMINALE

INTRODUZIONE L'Aneurisma dell'Aorta Addominale (AAA) è una malattia degenerativa che determina dilatazione del vaso. L'intervento chirurgico (RP) o l'intervento endovascolare (EVAR) sono i trattamenti per prevenire la rottura dell'AAA. La patogenesi dell'AAA coinvolge la degradazione della matrice extracellulare che indebolisce la parete dell'aorta e l'infiltrazione infiammatoria nelle pareti dei vasi accelera la progressione dell'aneurisma. I micro-RNA (miRNA) sono costituiti da unità di 21-23 nucleotidi che possono legarsi all'RNA messaggero (mRNA), regolando l'espressione di determinati geni. Alcuni autori hanno osservato che attraverso questo sistema di regolazione dell'espressione genica, si verifica un cluster di geni upregolati o downregolati nei pazienti con AAA. Inoltre è stato evidenziato che gli esosomi dei pazienti con AAA contengano miRNA che codificano proteine che contribuiscono allo sviluppo dell'aneurisma. Il trasporto di miRNA attraverso gli esosomi regola l'espressione di multipli geni bersaglio nelle cellule riceventi. Il profilo di espressione dei miRNA esosomiali circolanti può identificare nuovi marcatori per valutare la progressione e la gravità della malattia nei pazienti operati. L'obiettivo dello studio è investigare le variazioni quantitative e qualitative dei miRNA dopo il trattamento chirurgico o endovascolare degli AAA. Questa indagine ipotizza il loro potenziale coinvolgimento come predittori e bersagli terapeutici per prevenire la progressione della patologia aneurismatica. MATERIALI E METODI Studio prospettico osservazionale condotto in pazienti affetti da AAA, presso la Chirurgia Vascolare dell’Azienda Ospedaliero-Universitaria di Ferrara, ricoverati tra maggio e settembre 2023. Sono stati arruolati pazienti con AAA asintomatico, escludendo quelli con aneurismi sintomatici o rotti. I pazienti sono stati sottoposti a trattamento chirurgico open (RP) o a trattamento endovascolare (EVAR) in elezione. E’ stata eseguita una ricerca della presenza e quantificazione di esosomi e microRNA mediante tecniche di biologia molecolare presenti a livello ematico sia prima che dopo l'intervento chirurgico a 3 mesi. RISULTATI Dei 22 pazienti totali, 10 pazienti sono stati sottoposti a EVAR e 12 pazienti sono stati sottoposti a correzione chirurgica open. Non sono state rilevate differenze significative per quanto riguarda età e comorbidità fra i due gruppi esaminati. Dall’analisi delle dimensioni degli esosomi circolanti isolati da sangue raccolti nei due tempi, è stato dimostrato che la distribuzione è omogenea confermando una dimensione media tra gli 80 e i 120 nm. Gli esosomi sono stati analizzati per il loro contenuto in miRNA. I dati hanno evidenziato una grandissima variabilità sia tra campioni dello stesso gruppo che tra campioni diversi. Si è proceduto ad effettuare una analisi raggruppandoli per macro aree di funzione evidenziando come le principali aree in cui i miRNA vanno ad agire sono il rimodellamento (33%), l’infiammazione (34%) e i processi di invecchiamento cellulare (21%). Non si è rilevata una variazione dei miRNA preoperatori e quelli post operatori a 3 mesi dall’intervento chirurgico. CONCLUSIONI La regolazione dei miRNA potrebbe rappresentare un'efficace strategia per prevenire lo sviluppo e la progressione della patologia aneurismatica. Sono necessari ulteriori studi per comprendere i meccanismi coinvolti e sviluppare strategie terapeutiche mirate che possano tradursi in benefici clinici significativi. Probabilmente il secondo tempo di prelievo scelto è ancora troppo a ridosso dell’intervento, quindi i processi di rigenerazione tissutale sono ancora nel pieno della fase infiammatoria. Pertanto dovremmo valutare l'espressione di specifici miRNA post operatori in un periodo di tempo più esteso per comprendere il significato nella modulazione dei processi di rimodellamento vascolare.INTRODUCTION: Abdominal Aortic Aneurysm (AAA) is a degenerative arterial disease. Currently, both surgical (RP) and endovascular interventions (EVAR) are the treatment of choice to prevent AAA rupture. The pathogenesis of AAA starts with the degradation of the extracellular matrix, this process weakens the aortic wall, while the inflammatory infiltration in vessel’s wall accelerates the aneurysm progression. MicroRNAs (miRNA) are composed of 21-23 nucleotide units that can specifically bind to messenger RNA (mRNA), regulating the expression of specific genes. Some authors have observed that, through this gene expression regulation system, a cluster genes are upregulated or downregulated in AAA patients. Some authors have also noted that exosomes, isolated from AAA patients, contain miRNAs that encode proteins which enhance aneurysm development. The circulating exosomal miRNA profile could represent a new marker of disease progression in patients operated for AAA. This study aims to investigate quantitative and qualitative variations of miRNA after surgical or endovascular treatment of AAA. This investigation hypothesizes the potential role of miRNA as predictors of aneurysmal progression or possible therapeutic targets to prevent aneurysmal pathology and enlargement. MATERIALS AND METHODS: This prospective, observational study considers patients affected by asymptomatic abdominal aortic aneurysm (AAA) admitted at the Vascular Surgery department of the University Hospital of Ferrara, between May and September 2023. All symptomatic or ruptured aneurysms were excluded. All patients enrolled underwent either elective open surgical or endovascular treatment (EVAR). The presence of exosomes and microRNA were investigated using molecular biology techniques in blood samples, collected the day before and three months after surgery. RESULTS: 10 patients underwent abdominal aortic aneurysm exclusion with aortic endoprosthesis. 12 patients underwent open surgical correction of abdominal aorta. No significant differences were detected in terms of age and comorbidities between the two examined groups. The analysis of circulating exosomes, isolated from blood collected at both time points, revealed homogeneous distribution of exosome’s diameter with an average size between 80 and 120 nm. Exosomes were analyzed for their miRNA content: a significant variability within patients operated for AAA was detected. Analyzing the subgroups of miRNA isolated, we found that the major functional areas where miRNA were involved were: remodeling (33%), inflammation (34%), and cellular aging processes (21%). No variations were observed between preoperative and postoperative miRNA at 3 months. CONCLUSIONS: miRNA regulation could represent an effective strategy to prevent the development and progression of aneurysmal pathology. However, the absence of mi-RNA variations between pre- and post-operative blood samples may signify that tissue regeneration processes are still in the midst of the inflammatory phase; a wider period between blood sample collection could be necessary to highlight their significance in vascular remodeling modulation. Further studies are needed to understand their mechanisms of action and to develop targeted therapeutic strategies to prevent AAA development or progression

Venous thoracic outlet syndrome: Single center five years experience

BACKGROUND: Patients with thoracic outlet syndrome. can present neurogenic, venous, and/o arterialsymptoms due to compression of the neurovascular structures by the scalene muscle, first rib, or fibrous bands. METHODS: Twenty-six patients underwent decompressive surgery of the thoracic outlet via the supraclavicular approach. The indication for operation was compression of the subclavian artery in 7 instances (5 females and 2 males, aged 44±9), axillo-subclavian venous thrombosis in 6 instances (5 females and 1 male, aged 22±4), and brachial plexus irritation in 13 instances (9 females and 4 males, aged 35±6). Operation consisted of resection of the anterior scalene and medial aspect of the middle scalene muscles and brachial plexus neurolysis for neurogenic indication, with first rib resection reserved for vascular complications. RESULTS: Clinical evaluation including a history and physical examination followed by catheter-based venography to confirm or exclude the diagnosis and allowing for immediate treatment using thrombolysis. After thrombolysis, to prevent early recurrent thrombosis, patients should be maintained with systemic anticoagulation and surgery should be performed earlier in patients with severe residual SCV stenosis. CONCLUSIONS: Early diagnosis and thrombolytic therapy followed by operative first-rib resection produces the most favorable long-term outcome for the patients

Silent Contained Rupture of an Inflammatory IgG4-Related Abdominal Aortic Aneurysm

This report describes a case of a 66-year-old male patient with accidental diagnosis of chronic contained rupture of an aortic aneurysm. Surgery was performed through a median laparotomy. A thick periaortic tissue with fibrosis and lymphnodes covered the AAA. Immunohistochemical examination of the aneurismatic aortic wall revealed intense positivity for inflammatory markers and a large number of immunoglobulin G4 (IgG4) positive cells. The postoperative course was uneventful and patient was discharged in the fifth postoperative day. Patient was then followed periodically at the outpatient rheumatologic clinic. No adverse events occurred during 3 and 6 months follow up. Conclusion: Identification of IgG4-inflammatory aneurysms as an expression of the IgG4-related systemic disease is essential both for clinical follow up and surgical and pharmacological treatment considering the possibility of aneurysm rupture and the involvement of other organs

Prevention of post-thrombotic syndrome: Role of fibrinolysis in proximal deep vein thrombosis

BACKGROUND: Deep vein thrombosis (DVT) of the lower limbs is a relatively common clinical condition, with an incidence estimated at 1-2 cases per 1000 inhabitants per year. Post-thrombotic syndrome (PTS) is a chronic complication which particularly affects patients with proximal DVT (ilio-femoral); it significantly impacts upon patients' quality of life and it also has major health-economic implications. METHODS: We report our experience with ultrasound accelerated thrombolysis EKOS system in treatment of patients affected by proximal DVT. RESULTS: In our experience, we treated three cases of proximal DVT adopting ultrasound accelerated thrombolysis with EKOS system. Technical success rate was 100% in absence of embolic or hemorrhagic complications. The mean follow-up was 18 months: there were no thrombotic recurrences and none of the three patients had clinical signs of PTS. Loco-regional thrombolysis applied in selected cases of proximal DVT, unlike traditional therapy with oral anticoagulants, is able to ensure a rapid resolution of the thrombotic process, thus limiting valvular damage, that underlies the development of PTS. In recent years new techniques like mechanical, pharmaco-mechanical and ultrasound enhanced thrombolysis were developed. They allow a further reduction in both duration of treatment and drugs dose used, compared to pharmacological thrombolysis alone and also lead to an overall costs' reduction. CONCLUSIONS: In conclusion, from both a review of the literature and our own experience, pharmacological thrombolysis has proven to be a safe and effective technique in the treatment of proximal DVT, in order to prevent the development of PTS; nevertheless, it appears appropriate that those techniques are reserved to highly selected patients and practiced in centers with adequate experience and resources

Endovascular Revascularisation versus Open Surgery with Prosthetic Bypass for Femoro-Popliteal Lesions in Patients with Peripheral Arterial Disease

Aim: Complex atherosclerotic femoro-popliteal lesions have traditionally been treated with bypass surgery. A prosthetic graft is used to save the vein graft for more distal revascularisations or when a vein graft is unavailable. The endovascular approach has gained popularity and is offered as a first-line strategy for complex lesions. This study aimed to evaluate whether endovascular procedures can be used as a first-line treatment strategy for complex native femoro-popliteal lesions over open surgery with prosthetic bypass in patients with peripheral arterial disease (PAD). Methods: This single-centre retrospective observational study was conducted between 2013 and 2021; it included patients with symptomatic PAD who required limb revascularisation at the femoro-popliteal segment and who had complex lesions. The primary endpoints analysed were technical success, primary patency, freedom from clinically driven target lesion revascularisation (cdTLR), freedom from major adverse limb and cardiovascular events (MALE and MACE, respectively), freedom from limb loss, and survival. The secondary endpoints were length of in-hospital stay, and duration and costs of the procedure. Results: We identified 185 limbs among 174 suitable candidates for comparison, wherein 105 were treated with an endovascular procedure and 80 with a femoro-popliteal prosthetic bypass. Most patients in both groups presented with chronic limb-threatening ischaemia, and >90% of them had an American Society of Anesthesiologists (ASA) physical status classification of >3. The endovascular group had more octogenarians (p = 0.02) and patients with coronary disease (p = 0.004). The median follow-up was 30 months. The technical failure rate for endovascular procedures was 4.7%, versus 0% in the open group (p = 0.047). Freedom from MACE was similar in both groups. The endovascular group showed superior primary patency (p p p p = 0.0018) at 24 and 48 months. Further analysis performed for the open above-the-knee sub-group showed that the aforementioned endpoints were similar between the groups at 12 months and were better in the endovascular group at 24 and 48 months. Procedural time and in-hospital stay were longer in the open group than in the endovascular group (p p Conclusions: Endovascular procedures are safe for treating complex femoro-popliteal lesions in patients at a high risk for surgery and show better outcomes at 24 months than prosthetic bypasses do. The latter may be considered as an alternative should endovascular treatment fail

Management of iatrogenic subclavian artery rupture: two case reports

Bleeding of the branches of a subclavian artery can be a life-threatening condition. Subclavian artery bleeding can lead to tracheal obstruction, hemothorax, respiratory failure, hemorrhagic shock, and death if not diagnosed early and treated promptly. Injury to the subclavian artery occurs in multiple different manners including blunt, penetrating, or iatrogenic trauma. Here we reported two cases of injury of the branches of the right subclavian artery (RSA); one following a central venous catheterization and the other following a thoracic drainage tube placement. Herein we describe two endovascular treatment options used in the management of rupture of a subclavian artery. The proximal tract of the subclavian artery and its main branches is also considered a 'border territory' between interventional vascular radiology and interventional neuroradiology because it gives rise to branches both cervical and to the upper limbs

Primary drug-coated balloon versus drug-eluting stent for native atherosclerotic femoropopliteal lesions: A systematic review and meta-analysis

Objective: In this systematic review and meta-analysis, we aimed to compare drug-coated balloon (DCB) to drug-eluting stent (DES) angioplasty as a primary option in patients with femoropopliteal lesions in terms of primary patency and freedom from clinically driven target lesion revascularization (cdTLR) and major adverse limb events (MALE). Methods: A comprehensive literature search was performed using the PubMed and Embase databases. All studies written in English language and reporting data presenting a comparison between patients receiving primary percutaneous balloon angioplasty using the DCB versus primary percutaneous stenting with DES for native femoropopliteal lesions were included in this meta-analysis. Results: There were 984 patients with 1078 femoropopliteal lesions, of which procedures with DCB and DES were performed in 514 and 564 lesions, respectively. Overall, majority patients were men with a mean age of 70.9 years; and there were no significant differences between the two groups regarding the cardiovascular comorbidities. With regards to the procedural strategy, there was significant heterogeneity in the DCB group. This included adjunctive procedures such as atherectomy besides the angioplasty of the target vessel, which was reported in one study as a part of 32.1% of the procedures in the DCB group. Provisional bare metal stents (pBMS) for residual stenosis and dissection were used in four studies with a percentage varying from 14.8-25.3%. Overall, at 1 year, all outcomes were similar for all the endpoints; however, where adjunctive procedures were performed (atherectomy + pBMS) in the DCB group, the outcomes were better (primary patency p.001, freedom cdTLR p.001, freedom form MALE p.002). In studies where no adjunctive procedures were performed in the DCB group, the results favored the DES group for the primary patency (p.026) and freedom from cdTLR (p.044). Conclusions: DES seems to be superior in terms of cdTLR and primary patency at 1 year when compared to the procedures performed solely with DCB. For DCB to achieve optimal results, further adjunctive procedures such as pBMS and atherectomy are needed. More studies are needed to confirm the superiority of the primary stenting with DES at the femoropopliteal segment