Search

Summary: Background: Multi-morbidity poses a substantial challenge for health care in an aging population. Recent studies did not provide evidence for general side effects of anti-cancer therapy regarding the growth rate of coincident abdominal aortic aneurysms, although it was suggested that specific therapeutic substances might accelerate growth. Aneurysm pathology, however, differs with respect to localization. Hence, we present the first ever analysis on the association of cancer and cancer therapy with growth alteration of aneurysms of the ascending aorta (AscAA). Patients and methods: A retrospective single-center identification of AscAA+cancer patients was performed in the institutional picture archiving and communication system (PACS). Included were all patients with ≥2 CT angiograms over ≥6 months and additional malignancy. Clinical data and aneurysm diameters were retrieved and analyzed for an association of cancer (stratified by tumor entity) or cancer therapy (stratified by several classes of chemotherapeutic agents and radiation therapy) with annual growth rate, respectively. Statistics included t-test, Wilcoxon test, and a linear regression model accounting for initial AscAA diameter and type of treatment. Results: From 2003 to 2021, 151 patients (median age 70 years; 85% male) with AscAA and coincident 163 malignancies were identified. Prostate (37%) and hematologic cancer (17%) were most frequent. One-hundred-eleven patients (74%) received chemotherapy and 75 patients (50%) had radiation. After exclusion of six patients with an initial AscAA diameter >55 mm, the average annual AscAA growth rate was 0.18±0.64 mm/year, with only 12 patients experiencing a growth rate >1mm/year. Neither tumor entity nor radiation or chemotherapy – alone or in combination – were significantly associated with an alteration of the annual AscAA growth rate. Likewise, a subanalysis for singular chemotherapeutic agents did not reveal a specific association with AscAA growth alteration. Conclusions: Growth rates of AscAA are low in this cohort with coincident malignancy. Cancer and/or chemotherapy or radiation are not associated with an alteration of the annual growth rate. Additional control examinations seem unnecessary.

Abdominal aortic aneurysms (AAA) are the most frequent aortic dilation, with considerable morbidity and mortality. Inflammatory (infl) and IgG4-positive AAAs represent specific subtypes of unclear incidence and clinical significance. Here, histologic and serologic analyses with retrospective clinical data acquisition are investigated via detailed histology, including morphologic (HE, EvG: inflammatory subtype, angiogenesis, and fibrosis) and immunhistochemic analyses (IgG and IgG4). In addition, complement factors C3/C4 and immunoglobulins IgG, IgG2, IgG4 and IgE were measured in serum samples and clinical data uses patients’ metrics, as well as through semi-automated morphometric analysis (diameter, volume, angulation and vessel tortuosity). A total of 101 eligible patients showed five (5%) IgG4 positive (all scored 1) and seven (7%) inflammatory AAAs. An increased degree of inflammation was seen in IgG4 positive and inflAAA, respectively. However, serologic analysis revealed no increased levels of IgG or IgG4. The operative procedure time was not different for those cases and the short-term clinical outcomes were equal for the entire AAA cohort. Overall, the incidence of inflammatory and IgG4-positive AAA samples seems very low based on histologic and serum analyses. Both entities must be considered distinct disease phenotypes. Short-term operative outcomes were not different for both sub-cohorts.

Long non-coding RNAs (lncRNAs) orchestrate various biological processes and regulate the development of cardiovascular diseases. Their potential therapeutic benefit to tackle disease progression has recently been extensively explored. Our study investigates the role of lncRNA Nudix Hydrolase 6 (NUDT6)and its antisense target Fibroblast Growth Factor 2 (FGF2)in two vascular pathologies: abdominal aortic aneurysms (AAA) and carotid artery disease. Using tissue samples from both diseases, we detected a substantial increase ofNUDT6, whereasFGF2was downregulated. TargetingNudt6 in vivowith antisense oligonucleotides in three murine and one porcine animal models of carotid artery disease and AAA limited disease progression. Restoration of FGF2 uponNudt6knockdown improved vessel wall morphology and fibrous cap stability. Overexpression ofNUDT6 in vitroimpaired smooth muscle cell (SMC) migration, while limiting their proliferation and augmenting apoptosis. By employing RNA pulldown followed by mass spectrometry as well as RNA immunoprecipitation, we identified Cysteine and Glycine Rich Protein 1 (CSRP1) as another directNUDT6interaction partner, regulating cell motility and SMC differentiation. Overall, the present study identifiesNUDT6as a well-conserved antisense transcript ofFGF2. NUDT6silencing triggers SMC survival and migration and could serve as a novel RNA-based therapeutic strategy in vascular diseases.

The purpose of this study was to assess the associations between malignancy, therapeutic regimens, and aorto-iliac aneurysm (i.e., abdominal aortic aneurysm [AAA]) growth rates.A retrospective single centre analysis identified patients with an AAA plus cancer. Patients who had two or more computed tomography angiograms over six months or more and additional malignancy were included. Clinical data and aneurysm diameters were analysed. AAA growth under cancer therapy (chemotherapy or radiation) was compared with a non-cancer AAA control cohort and to meta-analysis data. Statistics included t tests and a linear regression model with correction for initial aortic diameter and type of treatment.From 2003 to 2020, 217 patients (median age 70 years; 92% male) with 246 aneurysms (58.8% AAA) and 238 malignancies were identified. Prostate (26.7%) and lung (15.7%) cancer were most frequently seen. One hundred and fifty-seven patients (72.3%) received chemotherapy, 105 patients (48.4%) radiation, and 79 (36.4%) both. Annual AAA growth (mean ± standard deviation) was not statistically significantly different for cancer and non-cancer patients (2.0 ± 2.3 vs. 2.8 ± 2.1 mm/year; p = .20). However, subgroup analyses revealed that radiation was associated with a statistically significantly reduced mean aneurysm growth rate compared with cancer patients without radiation (1.1 ± 1.3 vs. 1.6 ± 2.1 mm/year; p = .046) and to the non-cancer control cohort (1.7 ± 1.9 vs. 2.8 ± 2.1 mm/year; p = .007). Administration of antimetabolites resulted in statistically significantly increased AAA growth (+ 0.9 mm/year; p = .011), while topoisomerase inhibitors (- 0.8 mm/year; p = .17) and anti-androgens (- 0.5 mm/year; p = .27) showed a possible trend for reduced growth. Similar observations were noted for iliac aneurysms (n = 85). Additionally, the effects persisted for chemotherapy combinations (2.6 ± 1.4 substances/patient).Patients with cancer and concomitant aortic aneurysms may require intensified monitoring when undergoing specific therapies, such as antimetabolite treatment, as they may experience an increased aneurysm growth rate. Radiation may be associated with reduced aneurysm growth.

Introduction Visceral artery aneurysms (VAA) are a rare entity of arterial aneurysms with the imminent threat of rupture. The impact of cancer and chemotherapy on the growth of VAAs is unknown. Patients and methods A retrospective dual center cohort study of patients with concomitant VAA and different types of cancer was conducted and the impact of various chemotherapeutic agents on VAA growth was studied by sequential CT analysis. For comparison, a non-cancer all comer cohort with VAAs and no cancer was studied to compare different growth rates. The primary endpoint was aneurysm progress or regression >1.75 mm. Chi-Square Test, Fisher's-Exact-Test and Mann-Whitney test was used for statistical comparison. Results In the 17-year-period from January 2003 to March 2020, 59 patients with 30 splenic artery aneurysms, 14 celiac trunk aneurysms, 11 renal artery aneurysms and 4 other VAA and additional malignancy were identified. 20% of patients suffered from prostate cancer, the rest were heterogeneous. The most prevalent chemotherapies were alkylating agents (23%), antimetabolites (14%) and mitose inhibitors (10%). 8 patients had relevant growth of their VAA and one patient showed diameter regression (average growth rate 0.1±0.5mm/year). 29 patients with 14 splenic, 11 RAAs (seven right) and 4 celiac trunk aneurysms were available in the non-cancer comparison cohort (average growth rate 0.5±0.9mm/year, p=0.058). However, the growth rate of patients receiving operative treatment for relevant VAA growth was significantly higher (p=0.004). Conclusion VAAs grow rarely, and rather slow. Cancer and/or chemotherapy do not significantly influence the annual growth rate. Additional control examinations seem unnecessary.

Summary: Background: To determine the adherence to supervised exercise training and underlying reasons for non-adherence amongst patients with inpatient treatment of symptomatic lower extremity peripheral arterial disease (PAD). Patients: This was a prospective questionnaire-based survey study of all consecutively treated inpatients with treatment for either intermittent claudication or chronic limb-threatening ischaemia (CLTI) surveyed at sixteen participating centres in Germany. Results: A total of 235 patients (median age 70 years) were included, thereof 29.4% females and 34.6% with CLTI. The median time from first PAD diagnosis was 4 years (IQR: 1–8). Only 11.4% have previously participated in any walking exercise programme before the index treatment, thereby 10.0% in the IC subgroup and 12.0% with CLTI. Amongst all patients, 35.6% responded they were appropriately informed about the necessity and benefits of walking exercise programmes by their hospital physicians (25.8% by general practitioners), and 65.3% agreed that adherence to supervised exercise may improve their pain-free walking distance. A total of 24.5% responded they had access to necessary information concerning local walking exercise programmes. Amongst 127 free text comments on the reasons for non-adherence to supervised exercise training, 64% of the comments contained lack of information or consent on such measures. Conclusions: Less than 12% of the patients enrolled in the current study have ever participated in a walking exercise programme during their life course. Although all practice guidelines contain corresponding class I recommendations, especially for patients suffering from IC, most patients responded that they were not appropriately informed about the necessity of exercise training along with the fact that 65% agreed that exercise may increase the pain-free walking distance. Taken all together, these results emphasise that we miss an important opportunity in the patient-physician communication. Efforts should be made to improve acceptance and application of structured walking-exercise for patients with PAD.

Summary: Background: Abdominal aortic aneurysm (AAA) rupture is still associated with a mortality rate of 80–90%. Imaging techniques or molecular fingerprinting for patient-specific risk stratification to identify pending rupture are still lacking. The chemokine (C-X-C motif) receptor (CXCR4) activation by CXCL12 ligand has been identified as a marker of inflammation and atherosclerosis, associated with AAA. Both are highly expressed in the aortic aneurysm wall. However, it is still unclear whether different expression levels of CXCR4 and CXCL12 can distinguish ruptured AAAs (rAAA) from intact AAAs (iAAA). Patients and methods: Abdominal aortic tissue samples (rAAA: n=29; iAAA: n=54) were excised during open aortic repair. Corresponding serum samples from these patients (n=9 from rAAAs; n=47 from iAAA) were drawn pre-surgery. Healthy aortic tissue samples (n=8) obtained from adult kidney donors during transplantation and serum samples from healthy adult volunteers were used as controls (n=5 each). Results: CXCR4 was mainly expressed in the media of the aneurysmatic tissue. Focal positive staining was also observed in areas of inflammatory infiltrates within the adventitia. In tissue lysates, no significant differences between iAAA, rAAA, and healthy controls were observed upon ELISA analysis. In serum samples, the level of CXCR4 was significantly increased in rAAA by 4-fold compared to healthy controls ( p=0.011) and 3.0-fold for rAAA compared to iAAA ( p

ZusammenfassungDer offen-chirurgische thorakale und thorakoabdominelle Aortenersatz (open repair, OR) bei Aneurysmen oder Dissektionen hat in der aktuellen Versorgungsrealität im Vergleich zur endovaskulären Versorgung mit einfachen und speziellen Stentprothesen (fenestrated/branched [thoracic] endovascular aortic repair, f/b[T]EVAR) eine deutlich untergeordnete Rolle. Zudem besteht die Notwendigkeit einer hohen technischen Expertise und eines umfangreichen operativen Settings, um ein OR sicher anbieten zu können.Zu Reduktion der spezifischen Komplikationen, wie z. B. perioperative Mortalität, permanente Dialysepflichtigkeit, spinale Ischämie, Schlaganfall oder Mesenterialischämie, ist ein hohes Maß an intraoperativer Protektion, z. B. mittels Liquordrainage, Point-of-Care-Gerinnungstherapie, distaler oder selektiver Aortenperfusion im Sinne eines temporären Linksherzbypasses und sequenziellem Clamping der Aorta erforderlich. Trotz der Dominanz der endovaskulären Therapie ist diese Expertise aber weiterhin nötig, um spezifische Indikationen, wie beispielsweise junges Patientenalter oder Bindegewebserkrankungen bzw. Protheseninfektionen, sicher versorgen zu können. Zusätzlich ist nicht jedes Aneurysma oder jede Dissektion anatomisch langfristig sicher mit einer endovaskulären Behandlung zu therapieren.Die aktuelle Evidenzlage sieht einen geringen, meist nicht statistisch signifikanten Vorteil von TEVAR und f/bEVAR versus OR bei den wichtigsten kurz- und mittelfristigen Ergebnisparametern, bei deutlich geringerer Invasivität und verkürzter Krankenhausliegedauer. Im langfristigen Verlauf sind die Ergebnisse bezüglich Gesamtüberleben und Re-Interventionsraten bzw. sekundärer Komplikationen bei OR deutlich besser.Der offene thorakoabdominelle Aortenersatz ist also nach wie vor mehr als ein exklusives Hobby, sondern vielmehr eine absolute Notwendigkeit im Gesamtspektrum der aortalen Chirurgie, dessen Bedeutung in den nächsten Jahren mutmaßlich wieder zunimmt.

IntroductionOrgans-on-chips represent novelin vitromodels that have the capacity to emulate aspects of human physiology and pathophysiology by incorporating features like tissue-multicellularity and exposure to organ-relevant physical environment. We developed anartery-on-a-chipwith the objective to recapitulate the structure of the arterial wall composed of intimal and medial layers and the relevant hemodynamic forces that affect luminal cells.ResultsBy comparingarteries-on-chipsexposed either toin vivo-like shear stress values or kept in static conditions, we identified a panel of novel genes modulated by shear stress. We next measured the expression pattern of shear stress-modulated genes in areas of the vascular tree affected by atherosclerotic plaques and aortic aneurysms, where disease development and progression are induced by alterations of shear stress. We obtained biopsies from patients affected by carotid artery disease (CAD), comprising the atherosclerotic plaque (diseased artery) and the adjacent region (non-diseased artery). From patients with abdominal aortic aneurysms (AAA), we obtained the aneurysmal portion (diseased aorta) and non-dilated adjacent segment (non-diseased aorta). Genes modulated by shear stress followed the same expression pattern in non-diseased segments of human vessels and were expressed by endothelial and smooth muscle cells as evidenced by immunofluorescence analysis and single cell RNA sequencing. Using mice and porcine models of vascular CAD and AAA, we confirmed that shear stress mediated targets are important in discriminating diseased and non-diseased vessel portionsin vivo. Furthermore, we showed that ourartery-on-a-chipcan serve as a platform for drug-testing. We were able to reproduce the effects of a therapeutic agent previously used in AAA animal models inartery-on-a-chipsystems and extend our understanding of its therapeutic effect through a multicellular structure.ConclusionsOur novelin vitromodel is capable of mimicking important physiological aspects of human arteries, such as the response to shear stress, and can further shed light on the mechanism of action of potential therapeutics before they enter the clinical stage.TeaserTheartery-on-a-chipis a novelin vitroplatform that enables the mimicry of human arteries and can be used to gain insights into the development and therapeutic targeting of vascular diseases.

Hinsichtlich der Anzahl an Publikationen, grundlagenwissenschaftlichen Projekten und klinischen Studien bleibt die deutsche Gefaschirurgie im internationalen Vergleich innerhalb des Fachs sowie im nationalen Vergleich mit anderen chirurgischen Fachern zuruck. Ziel dieses Beitrags ist es, die zentrale Rolle des vascular surgeon scientist fur die akademische Gefaschirurgie, insbesondere als Bindeglied zwischen (Grundlagen‑)Forschung und Patientenversorgung herauszustellen. Ferner sollen Anstose zur sinnvollen Umsetzung eines Cinician-scientist-Programms in der Gefaschirurgie gegeben werden. Es erfolgte eine selektive Literaturrecherche. Auserdem wurde das Modell des vascular surgeon scientist durch Beitrage von Co-Autoren unterschiedlicher gefaschirurgischer Ausbildungsstande aus verschiedenen Blickwinkeln beleuchtet. Dem vascular surgeon scientist kommt eine entscheidende Rolle in der modernen Gefaschirurgie zu. Er vollzieht die Translation von der (Grundlagen‑)Forschung uber die Patientenversorgung bis hin zur Weiterentwicklung medizinischer „devices“ und ist somit Triebfeder des gefaschirurgischen Fortschritts. Die zentrale Stellung verlangt ausgepragte Fahigkeiten und die Vereinigung beruflicher und personlicher Bedurfnisse. Intensivierung der gefaschirurgischen Lehre, Mentoring und strukturierte Programme konnten zentrale Punkte zur Vertiefung eines Vascular-surgeon-scientist-Konzepts sein und so zur Starkung der akademischen Gefaschirurgie in Deutschland beitragen.

Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs). This study has addressed the notion that NET components might serve as AAA biomarkers or novel targets of AAA therapy. Thus, parameters of neutrophil activation and NET formation were measured in plasma. Their diagnostic marker value was explored in 41 AAA patients and 38 healthy controls. The NET parameter citrullinated histone H3 (citH3) was then validated in 63 AAA patients and 63 controls matched for cardiovascular disease. The prognostic marker potential was investigated in 54 observation periods of AAA growth over 6 months. NETs were further assessed in conditioned medium and sections of aortic tissue. CitH3 was found to be increased in blood (median 362 vs 304 ng/mL, P = 0.004) and aortic tissue (50 vs 1.5 ng/mg, P0.001) of AAA patients compared to healthy controls and accumulated in the intraluminal thrombus (629 ng/mg). The diagnostic potential of citH3 ranged at 0.705 area under the ROC curve (AUROC) and was validated with the independent sample set. Furthermore, plasma citH3 predicted AAA growth over the next 6 months (AUROC: 0.707, P = 0.015) and dropped significantly after surgical aneurysm repair. In an angiotensin II - based mouse model of experimental AAA, an inhibitor of histone citrullination was applied to block NET formation and AAA progression. Of note, further growth of an established aneurysm was prevented in mice treated with the NET inhibitor (P = 0.040). In conclusion, histone citrullination represents a promising AAA biomarker and potential therapeutic target to control disease progression.

Since pharmaceutical treatment options are lacking in the clinical management of abdominal aortic aneurysm (AAA), animal models, in particular mouse models, are applied to advance the understanding of the disease pathogenesis and to identify potential therapeutic targets. Testing novel drug candidates to block AAA growth in these models generally requires repeated drug administration during the time course of the experiment. Here, we describe a compiled protocol for AAA induction, insertion of an intravenous catheter to facilitate prolonged therapy, and serial AAA monitoring by 3D ultrasound. Aneurysms are induced in apolipoprotein E (ApoE) deficient mice by angiotensin II release over 28 days from osmotic mini-pumps implanted subcutaneously into the mouse back. Subsequently, the surgical procedure for external jugular vein catheterization is conducted to allow for daily intravenous drug treatment or repeated blood sampling via a subcutaneous vascular access button. Despite the two dorsal implants, the monitoring of AAA development is readily facilitated by sequential semi-automated 3D ultrasound analysis, which yields comprehensive information on the expansion of aortic diameter and volume and on aneurysm morphology, as illustrated by experimental examples.

Infizierte Kunststoffprothesen zählen zu den gravierendsten Komplikationen in der Gefäßchirurgie. Das OP-Team des Klinikums rechts der Isar schildert, wie eine infizierte Aortenprothese durch eine handgenähte Perikardprothese ersetzt wird.

Zusammenfassung Hintergrund Mausmodelle zur Erforschung der Pathogenese von Aortenerkrankungen sind seit Jahren in der vaskulären Forschung etabliert. Aufgrund der komplexen multifaktoriellen Prozesse der Entstehung von Aortenaneurysmen, die bis heute noch nicht vollständig verstanden sind, wurden verschiedene Mausmodelle entwickelt. Der vorliegende Artikel stellt eine Übersicht der verfügbaren Modelle sowie der Vor- und Nachteile des jeweiligen Modells vor dem Hintergrund spezifischer Fragestellungen dar. Methodik Es erfolgte eine selektive Literaturrecherche zum Thema. Ergebnisse Die verfügbaren Mausmodelle lassen sich in drei Kategorien einteilen: genetisch induzierte, chemisch-topisch induzierte und medikamentös-systemisch induzierte Modelle. Die einzelnen Mausmodelle bieten jeweils spezifische Vor- und Nachteile, sodass die Auswahl des Modelles anhand der zugrunde liegenden Fragestellung erfolgen muss. Idealerweise werden mehrere Modelle kombiniert, um auszuschließen, dass den Ergebnissen modellspezifische Effekte zugrunde liegen. Medikamentös-systemisch induzierte Modelle mittels Angiotensin II und chemisch-topisch induzierte Modelle mittels Kalziumchlorid oder Elastase stellen dabei aufgrund ihrer Flexibilität die am häufigsten verwendeten Mausmodelle dar. Sie erlauben die Untersuchung einer Vielzahl verschiedener Einflussfaktoren oder medikamentöser Therapieansätze. Schlussfolgerung Mausmodelle liefern grundlegende Erkenntnisse zur bislang noch unzureichend verstandenen komplexen und multifaktoriellen Pathophysiologie der Entstehung und Progression von Aortenaneurysmen. Tiermodellbasierte Forschungsansätze stellen dabei eine ideale Grundlage für translationale Forschungsprojekte dar, welche prospektiv für die Entwicklung konservativer medikamentöser Therapieansätze für Aortenaneurysmen wesentliche Erkenntnisse beitragen können.

Introduction: Popliteal artery aneurysm (PAA) is an individually highly fatal disease, causing ischemia and eventual major amputation, mainly in 50-70-year-old males. It is the most frequent peripheral artery aneurysm and correct treatment is challenging for clinicians, since both open and endovascular repair have only modest success rates, depending on the clinical presentation. In comparison to other aneurysm entities, little is known about its specific pathogenesis. Material and Methods: 26 Human PAA and popliteal artery samples were analyzed by immunohistochemistry, mRNA and miRNA expression analysis and targeted proteomics (OLink platform) to identify key features of the disease and crucial pathways involved. Additionally, a primary cell culture of PAA specimen was established for in-vitro vascular smooth muscle cell (VSMC) modulation. Results: VSMCs lose their contractile phenotype along with significant inflammatory and proteolytic changes in the vessel wall architecture. Extensive tissue remodeling with high cell turnover rates (as indicated by Ki67+ cells) compared to non-diseased popliteal artery is a unique feature in comparison to AAA. This correlates with highly abundant co-expression of the apolipoproteins E and CI with Ki67 in VSMCs in double immune-fluorescent stains. Stimulation of VSMCs with external APOE or APOCI alters proliferation rates and significantly changes a subset of contractile markers proteins upon gene expression analysis. These findings are emphasized by a specific case of a solely mechanically induced PAA in a young male. Conclusion: Pathogenesis of PAA shows similar histologic features than AAA, yet differs in key pathways involved. Increased cell turnover in the aneurysm neck area suggests evaluation of alternative treatment strategies, i.e., targeting key processes of pathogenesis such as angiogenesis and cell turnover.

[No abstract]

IntroductionAcute lower limb ischemia (ALI) is a limb- and potentially life-threatening condition which requires urgent evaluation and treatment. Contemporary data on optimal therapy and prognosis of ALI are lacking, while surgical, hybrid, and foremost endovascular techniques have rapidly evolved over the past decades. Available clinical guidelines are not based on high-level evidence and do not fully reflect day-do-day practice. Contemporary data on etiology, procedural strategies as well as patient outcomes in ALI are urgently needed to improve care and prevent limb loss. The current study was initiated by the European Vascular Research Collaborative (EVRC), established by young European vascular specialists, and aims to provide insight into contemporary treatment strategies in ALI and its clinical results within Europe. In this manuscript we report the rationale and a detailed study protocol.Material and MethodsThe proposed study is a prospective, international, multicenter, observational study on ALI (PROMOTE-ALI) (ClinicalTrials.gov - NCT05138679). Patients with ALI (Rutherford classification grade I -III) of one or both lower extremities will be included in the study. The primary endpoint of the study is amputation-free survival (AFS) at 30 d. Secondary endpoints are freedom from target limb reintervention, freedom from complications, clinical outcome of the index leg, and limb salvage and survival at 30 and 90 d after diagnosis of ALI.ConclusionsALI remains a challenging condition and due to the heterogeneous etiology, clinical presentation and treatment strategies, a large multicenter study on this topic is needed to gain contemporary data on clinical outcomes and prognosis, especially for modern endovascular techniques. PROMOTE-ALI is expected to provide these data and set a benchmark for future randomized controlled trials (RCTs).

Journal of Clinical Medicine 11(3), (2022). doi:10.3390/jcm11030498 special issue: "Topical Collection "Peripheral Artery Disease: Epidemiology and Global Perspectives" / Editors: Dr. Christian-Alexander Behrendt, Collection Editor; Dr. Frederik Peters, Collection Editor; Dr. Ulrich Rother, Collection Editor", Published by MDPI, Basel

The classical approach of open repair (OR) for thoracic and thoracoabdominal aortic pathologies, including aneurysms and dissection, has been outnumbered by the use of fenestrated/branched (thoracic) endovascular aortic repair (f/b[T]EVAR) in recent years. Providing OR for complex cases in an aortic service requires a dedicated surgical setup and a huge body of expertise in this particular field.In order to reduce specific complications, such as perioperative mortality, kidney failure, spinal cord ischemia, stroke or bowel ischemia, it is necessary to apply cerebrospinal-spinal fluid drainage, point-of-care coagulation therapy, distal and retrograde aortic perfusion and sequential clamping. Despite the predominance of endovascular solutions, the specific OR expertise is still needed for specific indications, such as young patients, connective tissue disorder or aortic graft infections.Currently, the short and mid term results for f/b(T)EVAR outweigh those for OR, including the shorter hospital stay and less invasive procedures. However, OR provides better long-term results for overall mortality, re-intervention rates and secondary complications.In conclusion, in our opinion OR is a service that is still necessary for dedicated aortic centres, but will most likely become more frequent again in the years to come.Der offen-chirurgische thorakale und thorakoabdominelle Aortenersatz (open repair, OR) bei Aneurysmen oder Dissektionen hat in der aktuellen Versorgungsrealität im Vergleich zur endovaskulären Versorgung mit einfachen und speziellen Stentprothesen (fenestrated/branched [thoracic] endovascular aortic repair, f/b[T]EVAR) eine deutlich untergeordnete Rolle. Zudem besteht die Notwendigkeit einer hohen technischen Expertise und eines umfangreichen operativen Settings, um ein OR sicher anbieten zu können.Zu Reduktion der spezifischen Komplikationen, wie z. B. perioperative Mortalität, permanente Dialysepflichtigkeit, spinale Ischämie, Schlaganfall oder Mesenterialischämie, ist ein hohes Maß an intraoperativer Protektion, z. B. mittels Liquordrainage, Point-of-Care-Gerinnungstherapie, distaler oder selektiver Aortenperfusion im Sinne eines temporären Linksherzbypasses und sequenziellem Clamping der Aorta erforderlich. Trotz der Dominanz der endovaskulären Therapie ist diese Expertise aber weiterhin nötig, um spezifische Indikationen, wie beispielsweise junges Patientenalter oder Bindegewebserkrankungen bzw. Protheseninfektionen, sicher versorgen zu können. Zusätzlich ist nicht jedes Aneurysma oder jede Dissektion anatomisch langfristig sicher mit einer endovaskulären Behandlung zu therapieren.Die aktuelle Evidenzlage sieht einen geringen, meist nicht statistisch signifikanten Vorteil von TEVAR und f/bEVAR versus OR bei den wichtigsten kurz- und mittelfristigen Ergebnisparametern, bei deutlich geringerer Invasivität und verkürzter Krankenhausliegedauer. Im langfristigen Verlauf sind die Ergebnisse bezüglich Gesamtüberleben und Re-Interventionsraten bzw. sekundärer Komplikationen bei OR deutlich besser.Der offene thorakoabdominelle Aortenersatz ist also nach wie vor mehr als ein exklusives Hobby, sondern vielmehr eine absolute Notwendigkeit im Gesamtspektrum der aortalen Chirurgie, dessen Bedeutung in den nächsten Jahren mutmaßlich wieder zunimmt.

In many vascular centers an endovascular first policy for the treatment of abdominal aortic aneurysms (AAA) has resulted in endovascular aortic repair (EVAR) outnumbering open aortic repair (OAR). The declining routine in OAR raises the question whether this might influence procedural outcomes and diminish surgical expertise for current and future vascular surgeons. We aimed to analyze OAR outcomes, AAA morphology and procedural details over the past 15 years while an endovascular first approach was successively implemented.All patients operated for (i)ntact infra-/juxtarenal AAA between January 1, 2005 and December 31, 2019 were identified. Outcome parameters were length of stay (hospital/ICU), in-hospital mortality and medical/surgical complications. Operative details were clamping zone, access and graft configuration. AAA anatomy including neck and iliac parameters was analyzed with Endosize©. Logistic regression, uni- and multivariate analysis were applied.293 patients received elective OAR for iAAA. Baseline characteristics (age, sex, hypertension, smoking, occlusive disease, coronary disease, hyperlipidemia, diabetes, renal insufficiency and obesity) did not change over time. The number of OAR dropped significantly (-0.5 cases/year p = 0.02). The procedure time (2005-2007: 192.2 ± 87.5min to 2017-2019: 235.6 ± 88.2min; p = 0.0001) and the length of stay (2005-2007: 12.0 ± 7.9 to 2017-2019: 17.0 ± 23.1; p = 0.03) increased significantly, whereas the in-hospital mortality, length of ICU stay and complication rates didn't, nor did AAA anatomy. Upon multivariate analysis, annual number of OAR and any additional anastomosis significantly influenced procedure time, trainee involvement, for example, did not. Hospital length-of-stay depended on patient age (p = 0.002), complication rates (p0.0001) and procedure time (p = 0.006).Mortality and complication rates for OAR have remained low and constant. With the increase of EVAR, the absolute number of OARs has decreased significantly. However, the total procedure time has increased and depends significantly on the annual number of OARs in total and per surgeon. This might influence outcome parameters and should be implanted in future surgical education.

Background While numerous interventions effectively interfered with abdominal aortic aneurysm (AAA) formation/progression in preclinical models, none of the successes translated into clinical success. Hence, a systematic exploration of parallel and divergent processes in clinical AAA disease and its 2 primary models (the porcine pancreatic elastase and angiotensin‐II infusion [AngII] murine model) was performed to identify mechanisms relevant for aneurysm disease. Methods and Results This study combines Movat staining and pathway analysis for histological and genomic comparisons between clinical disease and its models. The impact of a notable genomic signal for metabolic reprogramming was tested in a rescue trial (AngII model) evaluating the impact of 1‐(4‐pyridinyl)‐3‐(2‐quinolinyl)‐2‐propen‐1‐one (PFK15)‐mediated interference with main glycolytic switch PFKFB3. Histological evaluation characterized the AngII model as a dissection model that is accompanied by adventitial fibrosis. The porcine pancreatic elastase model showed a transient inflammatory response and aortic dilatation, followed by stabilization and fibrosis. Normalization of the genomic responses at day 14 confirmed the self‐limiting nature of the porcine pancreatic elastase model. Clear parallel genomic responses with activated adaptive immune responses, and particularly strong signals for metabolic switching were observed in human AAA and the AngII model. Rescue intervention with the glycolysis inhibitor PFK15 in the AngII model showed that interference with the glycolytic switching quenches aneurysm formation. Conclusions Despite clear morphological contrasts, remarkable genomic parallels exist for clinical AAA disease and the AngII model. The metabolic response appears causatively involved in AAA progression and provides a novel therapeutic target. The clear transient genomic response classifies the porcine pancreatic elastase model as a disease initiation model.

Vascular graft infections (VGI) are severe complications in prosthetic vascular surgery with an incidence ranging from 1 to 6%. In these cases, synthetic grafts are commonly used in combination with antimicrobial agents. Expanded polytetrafluoroethylene (ePTFE) is in clinical use as a synthetic graft material and shows promising results by influencing bacterial adhesion. However, the literature on antibiotic-bound ePTFE grafts is scarce. Gentamicin is a frequently used antibiotic for local treatment of surgical site infections, but has not been evaluated as antimicrobial agent on ePTFE grafts. In this study, we examine the antimicrobial efficacy and biocompatibility of novel types of gentamicin-coated ePTFE grafts in vitro. ePTFE grafts coated with gentamicin salt formulations with covalently-bound palmitate were evaluated in two drug concentrations (GP1.75% and GP3.5%). To investigate effects from types of formulations, also suspensions of gentamicin in palmitate as well as polylactide were used at comparable levels (GS + PA and GS + R203). Antibacterial efficacies were estimated by employing a zone of inhibition, growth inhibition and bacterial adhesion assay againstStaphylococcus aureus(SA). Cytotoxicity was determined with murine fibroblasts according to the ISO standard 10993-5. Gentamicin-coated ePTFE grafts show low bacterial adherence and strong antibacterial properties in vitro against SA. Bactericidal inhibition lasted until day 11. Highest biocompatibility was achieved using gentamicin palmitate GP1.75% coated ePTFE grafts. ePTFE grafts with gentamicin-coating are effective in vitro against SA growth and adherence. Most promising results regarding antimicrobial properties and biocompatibility were shown with chemically bounded gentamicin palmitate GP1.75% coatings.