Current Trends and Evidence on Post-Thoracic Endovascular Aortic Repair Aorto-Pulmonary and -Bronchial Fistula: A Narrative Review

Background: Aorto-bronchial or aorto-pulmonary fistulas (ABPF) are a rare but life-threatening complication following thoracic endovascular aortic repair (TEVAR). This narrative review aims to provide an overview of the current trends and available evidence on ABPF following TEVAR, evaluating risk factors, diagnostic approaches, and possible preventive and therapeutic strategies. Methods: Relevant publications on post-TEVAR ABPF were selected through a literature search on PubMed. Studies providing data on post-TEVAR ABPF concerning pathogenesis, clinical presentation, diagnostic tools, surgical approaches, and outcomes were included. Results: The literature search obtained 169 articles. After selection, 37 studies, published between 2000 and 2024, remained for analysis. The primary symptom of ABPF is typically hemoptysis, which may be recurrent or persistent. The diagnostic pathway for ABPF encompasses medical history, clinical evaluation, blood tests, sputum and blood cultures. Computed tomography angiogra

Peripheral Artery Disease: Underappreciated Impact and Residual Cardiovascular Risk Despite Revascularization

This Commentary highlights the under-recognized prevalence and heavy burden of peripheral artery disease (PAD) and its important role as a harbinger of complications of atherosclerotic cardiovascular disease. Although increasing in prevalence globally, PAD is being further accelerated with diabetes, and patients with advanced PAD are at high risk for chronic limb-threatening ischemia. The need for (repeated) revascularization and amputation places a heavy social burden on patients and family, and a heavy financial burden on the health care system, exceeding the cost of coronary artery and cerebrovascular diseases. Clinical trial research in PAD will be enhanced by widely agreed-upon definitions of major adverse cardiovascular events and major adverse limb events. Antithrombotic and lipid-lowering therapies are recommended but underutilized, while the optimal peri-interventional antithrombotic regimen is still under debate. Additional antiinflammatory treatment is currently an unaddressed strategy in the management of patients with PAD, and there is a strong case for the evaluation of widely available antiinflammatory agents such as colchicine

Cell Therapy for Chronic Limb-Threatening Ischemia: Current Evidence and Future Directions

Cell-based therapies have gained interest as a potential treatment method in cardiovascular disease in the past two decades, peripheral artery disease amongst others. Initial pre-clinical and small pilot clinical studies showed promising effects of cell therapy in peripheral artery disease and chronic limb-threatening ischemia in particular. However, these promising results were not corroborated in larger high quality blinded randomized trials. This has led to a shift of the field towards more sophisticated cell products, especially mesenchymal stromal cells. Mesenchymal stromal cells have some important benefits, making these cells ideal for regenerative medicine, e.g., potential for allogeneic application, loss of disease-mediated cell dysfunction, reduced production costs, off-the-shelf availability. Future high quality and large clinical studies have to prove the efficacy of mesenchymal stromal cells in the treatment of peripheral artery disease. Stem Cells Translational Medicine 2018;7:842–846

Differences in Symptom Presentation in Women and Men with Confirmed Lower Limb Peripheral Artery Disease: A Systematic Review and Meta-Analysis

OBJECTIVE: To evaluate the differences in symptoms between men and women that present with lower limb peripheral artery disease (PAD). DATA SOURCES: Systematic review and meta-analysis using PubMed, EMBASE, and the Cochrane Library. REVIEW METHODS: A systematic search of the literature to identify studies that examined PAD and its symptoms using PubMed, EMBASE, and the Cochrane Library, which were screened in duplicate by two reviewers. Information on study design, source of data, population characteristics, and outcomes of interest was extracted and used the Newcastle-Ottawa Scale and Cochrane risk of bias tool. Quality of evidence was rated using the GRADE methodology. Estimates of relative effects were pooled to generate pooled odds ratios (OR) and their 95% confidence interval (CI) using a random effects model. RESULTS: Thirteen cross sectional studies, six cohorts, one case control, and one randomised clinical trial, reporting on 1 929 966 patients with confirmed PAD (established by clinical history, clinical examination, and/or ankle brachial index, or further tests) were included. Women presented less often with intermittent claudication than men (25.9% vs. 30.2%) OR 0.78 (95% CI 0.72 - 0.84, very low quality of evidence), while rest pain and atypical leg symptoms were more prevalent in women (12.8% vs. 9.2%) OR 1.40 (95% CI 1.22 - 1.60, very low quality of evidence) and (22.8% vs. 19.8%) OR 1.18 (95% CI 0.96 - 1.45, very low quality of evidence), respectively. CONCLUSION: Women with PAD more often present with rest pain, while their prevalence of intermittent claudication is lower. They also tend to present more often with atypical leg symptoms. This study underlines that PAD symptom presentation differs between the sexes. Therefore, clinicians and researchers should not consider men and women as a single population and report their data separately

The effect of chronic kidney disease on tissue formation of in situ tissue-engineered vascular grafts

Vascular in situ tissue engineering encompasses a single-step approach with a wide adaptive potential and true off-the-shelf availability for vascular grafts. However, a synchronized balance between breakdown of the scaffold material and neo-tissue formation is essential. Chronic kidney disease (CKD) may influence this balance, lowering the usability of these grafts for vascular access in end-stage CKD patients on dialysis. We aimed to investigate the effects of CKD on in vivo scaffold breakdown and tissue formation in grafts made of electrospun, modular, supramolecular polycarbonate with ureido-pyrimidinone moieties (PC-UPy). We implanted PC-UPy aortic interposition grafts (n = 40) in a rat 5/6th nephrectomy model that mimics systemic conditions in human CKD patients. We studied patency, mechanical stability, extracellular matrix (ECM) components, total cellularity, vascular tissue formation, and vascular calcification in CKD and healthy rats at 2, 4, 8, and 12 weeks post-implantation. Our study shows successful in vivo application of a slow-degrading small-diameter vascular graft that supports adequate in situ vascular tissue formation. Despite systemic inflammation associated with CKD, no influence of CKD on patency (Sham: 95% vs CKD: 100%), mechanical stability, ECM formation (Sirius red +, Sham 16.5% vs CKD 25.0%-p:0.83), tissue composition, and immune cell infiltration was found. We did find a limited increase in vascular calcification at 12 weeks (Sham 0.08% vs CKD 0.80%-p:0.02) in grafts implanted in CKD animals. However, this was not associated with increased stiffness in the explants. Our findings suggest that disease-specific graft design may not be necessary for use in CKD patients on dialysis. </p

Long Term Survival and Limb Salvage in Patients With Non-Revascularisable Chronic Limb Threatening Ischaemia

OBJECTIVE: The aim of this study was to provide long term survival and limb salvage rates for patients with non-revascularisable (NR) chronic limb threatening ischaemia (CLTI). METHODS: This was a retrospective review of prospectively collected data, derived from a randomised controlled trial (JUVENTAS) investigating the use of a regenerative cell therapy. Survival and limb salvage of the index limb in CLTI patients without viable options for revascularisation at inclusion were analysed retrospectively. The primary outcome was amputation free survival, a composite of survival and limb salvage, at five years after inclusion in the original trial. RESULTS: In 150 patients with NR-CLTI, amputation free survival was 43% five years after inclusion. This outcome was driven by an equal rate of all cause mortality (35%) and amputation (33%). Amputation occurred predominantly in the first year. Furthermore, 33% of those with amputation subsequently died within the investigated period, with a median interval of 291 days. CONCLUSION: Five years after the initial need for revascularisation, about half of the CLTI patients who were deemed non-revascularisable survived with salvage of the index limb. Although the prospects for these high risk patients are still poor, under optimal medical care, amputation free survival seems comparable with that of revascularisable CLTI patients, while the major amputation rate within one year, especially among NR-CLTI patients with ischaemic tissue loss, is very high