Collecting biological tissue samples in a biobank grants a unique opportunity to validate diagnostic and therapeutic strategies for translational and clinical research. In the present work, we provide our long-standing experience in establishing and maintaining a biobank of vascular tissue samples, including the evaluation of tissue quality, especially in formalin-fixed paraffin-embedded specimens (FFPE). Our Munich Vascular Biobank includes, thus far, vascular biomaterial from patients with high-grade carotid artery stenosis (n = 1567), peripheral arterial disease (n = 703), and abdominal aortic aneurysm (n = 481) from our Department of Vascular and Endovascular Surgery (January 2004–December 2018). Vascular tissue samples are continuously processed and characterized to assess tissue morphology, histological quality, cellular composition, inflammation, calcification, neovascularization, and the content of elastin and collagen fibers. Atherosclerotic plaques are further classified in accordance with the American Heart Association (AHA), and plaque stability is determined. In order to assess the quality of RNA from FFPE tissue samples over time (2009–2018), RNA integrity number (RIN) and the extent of RNA fragmentation were evaluated. Expression analysis was performed with two housekeeping genes—glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB)—using TaqMan-based quantitative reverse-transcription polymerase chain reaction (qRT)-PCR. FFPE biospecimens demonstrated unaltered RNA stability over time for up to 10 years. Furthermore, we provide a protocol for processing tissue samples in our Munich Vascular Biobank. In this work, we demonstrate that biobanking is an important tool not only for scientific research but also for clinical usage and personalized medicine.
Abdominal aortic aneurysm (AAA) is a disease with high morbidity and mortality, especially when ruptured. The rationale of this study was to evaluate the repurposing of lenvatinib, a multi–tyrosine kinase inhibitor, in limiting experimental AAA growth targeting vascular smooth muscle cells (VSMCs) and angiogenesis. We applied systemic and local lenvatinib treatment to elastase-induced murine aortic aneurysms, and RNA profiling identified myosin heavy chain 11 ( Myh11 ) as the most deregulated transcript. Daily oral treatment substantially reduced aneurysm formation in 2 independent mouse models. In addition, a large animal aneurysm model in hypercholesterolemic low-density lipoprotein receptor–knockout (
LDLR
–/– ) Yucatan minipigs was applied to endovascularly deliver lenvatinib via drug-eluting balloons (DEBs). Here, a single local endovascular delivery blocked AAA progression successfully compared with a DEB-delivered control treatment. Reduced VSMC proliferation and a restored contractile phenotype were observed in animal tissues (murine and porcine), as well as AAA patient-derived cells. Apart from increasing MYH11 levels, lenvatinib reduced downstream ERK signaling. Hence, lenvatinib is a promising therapy to limit aortic aneurysm expansion upon local endovascular delivery. The tyrosine kinase inhibitor was able to positively affect pathways of key relevance to human AAA disease, even in a potentially new local delivery using DEBs.
Background: Peripheral arterial disease (PAD) and acute limb ischemia (ALI) pose an increasing strain on health care systems. The objective of this study was to describe the German health care landscape and to assess hospital utilization with respect to PAD and ALI. Methods: Secondary data analysis of diagnosis-related group statistics data (2009–2018) provided by the German Federal Statistical Office. Inclusion of cases encoded by the International Classification of Diseases (ICD-10) codes for PAD and arterial embolism or thrombosis. Construction of line diagrams and choropleth maps to assess temporal trends and regional distributions. Results: A total of 2,589,511 cases (median age 72 years, 63% male) were included, of which 2,110,925 underwent surgical or interventional therapy. Overall amputation rate was 17%, with the highest rates of minor (28%) and major amputations (15%) in patients with tissue loss. In-hospital mortality (overall 4.1%) increased in accordance to Fontaine stages and was the highest in patients suffering arterial embolism or thrombosis (10%). Between 2009 and 2018, the annual number of PAD cases with tissue loss (Fontaine stage IV) increased from 97,092 to 111,268, whereby associated hospital utilization decreased from 2.2 million to 2.0 million hospital days. Hospital incidence and hospital utilization showed a clustering with the highest numbers in eastern Germany, while major amputation rate and mortality were highest in northern parts of Germany. Conclusions: Increased use of endovascular techniques was observed, while hospital utilization to treat PAD with tissue loss has decreased. This is despite an increased hospital incidence. Addressing socioeconomic inequalities and a more homogeneous distribution of dedicated vascular units might be advantageous in reducing the burden of disease associated with PAD and ALI.
Objective: This study aimed at assessing outcomes after carotid endarterectomy (CEA) in dependence of center policy with respect to imaging intraoperative completion study (ICSi) usage. Background: Although randomized controlled studies are missing, a beneficial effect was shown for ICSi techniques (ie, angiography and intraoperative duplex ultrasound) after CEA. Methods: This secondary data analysis is based on the German statutory quality assurance database. The research was funded by Germany’s Federal Joint Committee Innovation Fund (G-BA Innovationsfonds, 01VSF19016 ISAR-IQ). According to their ICSi policy, hospitals were categorized as routine ICSi (>90%), selective ICSi (10%–90%), or sporadic ICSi (<10%) centers. Primary study outcome was in-hospital stroke or death. Multivariable regression analyses were performed. Results: Between 2012 and 2016, a total of 119,800 patients underwent CEA. In-hospital stroke or death rates were lower in routine ICSi centers (1.7%) compared with selective (2.1%) and sporadic ICSi centers (2.0%). The multivariable regression analysis showed, that in routine ICSi centers, ICSi use was associated with lower rates of stroke or death (adjusted odds ratio: 0.64; 95% CI: 0.44–0.93). In selective ICSi centers, ICSi was not associated with the occurrence of either of the assessed outcomes. In sporadic ICSi centers, ICSi was associated with higher rates of stroke or death (adjusted odds ratio: 1.91; 95% CI: 1.26–2.91). Conclusions: Lowest in-hospital stroke or death rates are achieved in routine ICSi centers. Although ICSi is associated with a lower perioperative risk in routine ICSi centers, it might act as a surrogate marker for worse outcomes due to intraoperative irregularities in sporadic ICSi centers. Routine use of ICSi is advisable.
21 June 2024 in Journal of NeuroInterventional Surgery
Objective: To investigate associations between individual embolic protection device (EPD) use and respective center policy with periprocedural outcomes after carotid artery stenting (CAS). Methods: This analysis is based on the nationwide German statutory quality assurance database and was funded by Germany’s Federal Joint Committee Innovation Fund (G-BA Innovationsfonds, 01VSF19016 ISAR-IQ). According to their policy towards EPD use, hospitals were categorized as routine EPD (>90%), selective EPD (10–90%), or sporadic EPD (<10%) centers. Primary study outcome was in-hospital stroke or death. Univariate and multivariate regression analyses were performed. Results: Overall, 19 302 patients who had undergone CAS between 2013 and 2016 were included. The highest in-hospital stroke or death rate was found in sporadic EPD centers, followed by selective and routine EPD centers (3.1% vs 2.9% vs 1.8%; P<0.001). Across the whole cohort, EPD use was associated with a lower in-hospital stroke or death rate (OR=0.60; 95% CI 0.50 to 0.72). In the multivariate regression analysis, EPD use was independently associated with a lower in-hospital stroke rate (aOR=0.66; 95% CI 0.46 to 0.94). Regarding center policy, routine EPD centers showed a significantly lower in-hospital mortality compared with sporadic EPD centers (aOR=0.44; 95% CI 0.22 to 0.88). Conclusions: In a contemporary real-world cohort with low risk of selection bias, EPD use was associated with a lower in-hospital risk of stroke. A center policy of routine EPD use was associated with lower mortality. These data support routine use of EPD during CAS to enhance patient safety.