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Objective To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. Summary background data The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. Methods Patients underwent transcatheter aortic arch repair with a single branch, two stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the two stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid - carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through one year. Survival analysis used the Kaplan-Meier method. Results Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5(17.8%) had combined or other pathologies. At one month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all non-disabling) and combined mortality/stroke rate was 10.7%. One year mortality was 10.7%, without device or aneurysm related death. Two patients (7.1%) reported stroke or transient ischemic attack at one year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were three patients (10.7%) that had device related unplanned reinterventions through one year. Conclusions The NEXUS Aortic Arch Stent Graft System, a novel single branch, two stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent one year safety and performance.

Abdominal aortic aneurysm (AAA) is a common cardiovascular disease with a strong correlation to smoking, although underlying mechanisms have been minimally explored. Electronic cigarettes (e-cigs) have gained recent broad popularity and can deliver nicotine at comparable levels to tobacco cigarettes, but effects on AAA development are unknown.We evaluated the impact of daily e-cig vaping with nicotine on AAA using two complementary murine models and found that exposure enhanced aneurysm development in both models and genders. E-cigs induced changes in key mediators of AAA development including cytokine chitinase-3-like protein 1 (CHI3L1/Chil1) and its targeting microRNA-24 (miR-24). We show that nicotine triggers inflammatory signaling and reactive oxygen species while modulating miR-24 and CHI3L1/Chil1 in vitro, and that Chil1 is crucial to e-cig-augmented aneurysm formation using a knockout model.In conclusion our work shows increased aneurysm formation along with augmented vascular inflammation in response to e-cig exposure with nicotine. Further we identify Chil1 as a key mediator in this context. Our data raise concerns regarding the potentially harmful long-term effects of e-cig nicotine vaping.Smoking is one of the most hazardous modifiable risk factors, with clear links to abdominal aortic aneurysm. E-cig vaping has displayed explosive growth in popularity. Intended for smoking cessation, it has been taken up by millions with no such clinical need, delivering nicotine addiction to new generations. The presumption that vaping is safer than tobacco overlooks the potential cardiovascular risks of nicotine. This study shows for the first time that inhaled e-cig nicotine vapor augments experimental AAA and aortic inflammation, suggests a mechanistic role for the cytokine Chil1/CHI3L1 and its regulator microRNA-24, and raises red flags regarding longitudinal e-cig safety.

Zusammenfassung Hintergrund Postoperative Wundinfektionen sind nach wie vor ein hoch relevantes Thema. In den vergangenen Jahrzehnten konnte jedoch ein stetiger Rückgang der Inzidenzen erreicht werden, was insbesondere auf konkrete präventive Ansätze zurückzuführen ist. Ziel der Arbeit Zusammenfassung aktueller epidemiologischer Zahlen, Risikostratifizierungsansätze und präventiver Maßnahmen für postoperative Wundinfektionen. Material und Methode Eine ausführliche Literaturrecherche medizinischer Datenbanken (MEDLINE, EMBASE, Cochrane) sowie der offiziellen Surveillance-Institutionen Robert Koch-Institut (RKI), European Centre for Disease Prevention and Control (ECDC), Centers for Disease Control and Prevention (CDC) wurde durchgeführt und im Sinne eines narrativen Reviews zusammengefasst. Fokussiert wurden die Themen Epidemiologie, Risikoassessment sowie präventive prozedurale und strukturelle Maßnahmen. Ergebnisse Epidemiologisch rangieren postoperative Wundinfektionen in den Top 3 der nosokomialen Infektionen und zeigen eine stark variierende Inzidenz zwischen 3 und 31 % in gefäßchirurgischen Eingriffen. Risikoscores, z. B. Surgical Site Infection Risk Score (SSIRS), Wounds-at-risk (W.A.R.), werden zunehmend entwickelt, um Maßnahmen gezielter einzusetzen, benötigen jedoch noch weitere Validierung. Während ein breites Feld valider und evidenzbasierter Empfehlungen besteht, ist der endgültige präventive Nutzen mancher Maßnahmen (z. B. antimikrobielle Wundspülung vor Hautverschluss) bisher noch unsicher. Andere Maßnahmen, wie die Verwendung von Inzisionsmanagementsystemen, haben mittlerweile eine solide Evidenzbasis und tragen insbesondere in Risikogruppen dazu bei, Infektionen vorzubeugen. Schlussfolgerungen Adäquate Identifikation von Risikogruppen und gezielte Anwendung präventiver Maßnahmen können den bisherigen positiven Trend bei Wundinfektionen weiter ausbauen. Hierzu müssen insbesondere Werkzeuge zur Risikoabschätzung und spezifische präventive Maßnahmen weiterführend rigoros validiert werden.

Abdominal aortic aneurysm (AAA) is a common disease and highly lethal if untreated. The progressive dilatation of the abdominal aorta is accompanied by degradation and remodeling of the vessel wall due to chronic inflammation. Pannexins represent anion-selective channels and play a crucial role in non-vesicular ATP release to amplify paracrine signaling in cells. Thus, pannexins are involved in many (patho-) physiological processes. Recently, Panx1 channels were identified to be significantly involved in abdominal aortic aneurysm formation through endothelial derived Panx1 regulated inflammation and aortic remodeling. In platelets, Panx1 becomes activated following activation of glycoprotein (GP) VI. Since platelets play a role in cardiovascular diseases including abdominal aortic aneurysm, we analyzed the contribution of platelet Panx1 in the progression of abdominal aortic aneurysm. We detected enhanced Panx1 plasma levels in abdominal aortic aneurysm patients. In experimental abdominal aortic aneurysm using the pancreatic porcine elastase (PPE) mouse model, a major contribution of platelet Panx1 channels in platelet activation, pro-coagulant activity of platelets and platelet-mediated inflammation has been detected. In detail, platelets are important for the migration of neutrophils into the aortic wall induced by direct cell interaction and by activation of endothelial cells. Decreased platelet activation and inflammation did not affect ECM remodeling or wall thickness in platelet-specific Panx1 knock-out mice following PPE surgery. Thus, aortic diameter expansion at different time points after elastase infusion of the aortic wall was unaltered in platelet-specific Panx1 deficient mice suggesting that the modulation of inflammation alone does not affect abdominal aortic aneurysm formation and progression. In conclusion, our data strongly supports the role of platelets in inflammatory responses in abdominal aortic aneurysm via Panx1 channels and adds important knowledge about the significance of platelets in abdominal aortic aneurysm pathology important for the establishment of an anti-platelet therapy for abdominal aortic aneurysm patients.

BACKGROUND: To report technical and clinical 30-day results following treatment with the Zenith Alpha™ abdominal stent graft from the ZEnith alPHa for aneurYsm Repair Registry (ZEPHYR).METHODS: Multicenter, nonrandomized, single arm, core laboratory-controlled, prospective registry collecting data on the Zenith Alpha Abdominal Endovascular Graft being used in subjects with abdominal aortic aneurysms (AAA) from sites in Germany, Belgium, and The Netherlands between December 2016 and December 2019. Inclusion criteria were non-ruptured AAAs with a maximum diameter ≥50 mm or enlargement >5 mm over 6 months with an AAA neck length ≥10 mm (site reported). Primary outcome measure was treatment success at 30 days. Treatment success was defined as a combined endpoint consisting of technical and clinical success. Technical success was defined as successful stent graft delivery and deployment as well as successful removal of the delivery system. Clinical success at 30 days was defined as freedom from type I and III endoleak, aneurysm rupture, conversion to open surgery and stent graft occlusion.RESULTS: Three hundred forty-seven subjects were included from 14 sites with a median age of 73.0 years (IQR 68.0-79.0). Thirty-four patients were female (9.8%). The median AAA diameter was 58.3 mm (IQR 55.0-63.5). The median proximal neck diameter was 23.6 mm (IQR 22.0-25.2) with a median proximal neck length of 24.4 mm (IQR 15.0-34.8) and a median infrarenal neck angulation of 24.5° (IQR 15.0-35.0). The right and left common iliac diameter were 16.1 mm (IQR 14.1-19.4) and 16.2 mm (IQR 14.1-19.1), respectively. The treatment success rate at 30 days was 94.8% (N = 329). Technical success was achieved in 333 patients (96.0%). The clinical success rate at 30 days was 98.8% (N = 343). Three patients had limb occlusions at 30 day follow up (0.9%). One patient had a type Ib endoleak (0.3%). Seventy percent of vascular access approaches were percutaneous. The reintervention rate was 1.7% (N = 6) within 30 days. Indications for reinterventions were a false aneurysm at puncture site (N = 1), limb complications (N = 2), stentgraft-associated renal artery occlusions (N = 2), and an external iliac artery thrombosis (N = 1).CONCLUSIONS: Endovascular aneurysm repair using the Zenith Alpha Abdominal Endovascular Graft is effective in the short term. Long term results will be reported in the future.

Abdominal aortic aneurysm (AAA) is a common disease and highly lethal if untreated. The progressive dilatation of the abdominal aorta is accompanied by degradation and remodeling of the vessel wall due to chronic inflammation. Pannexins represent anion-selective channels and play a crucial role in non-vesicular ATP release to amplify paracrine signaling in cells. Thus, pannexins are involved in many (patho-) physiological processes. Recently, Panx1 channels were identified to be significantly involved in AAA formation through endothelial derived Panx1 regulated inflammation and aortic remodeling. In platelets, Panx1 becomes activated following activation of glycoprotein (GP)VI. Since platelets play a role in cardiovascular diseases including AAA, we analyzed the contribution of platelet Panx1 in the progression of AAA. We detected enhanced Panx1 plasma levels in AAA patients. In experimental AAA using the pancreatic porcine elastase (PPE) mouse model, a major contribution of platelet Panx1 channels in platelet activation, pro-coagulant activity of platelets and platelet-mediated inflammation has been detected. In detail, platelets are important for the migration of neutrophils into the aortic wall induced by direct cell interaction and by activation of endothelial cells. Decreased platelet activation and inflammation did not affect ECM remodeling or wall thickness in platelet-specific Panx1 knock-out mice following PPE surgery. Thus, aortic diameter expansion at different time points after elastase infusion of the aortic wall was unaltered in platelet-specific Panx1 deficient mice suggesting that the modulation of inflammation alone does not affect AAA formation and progression. In conclusion, our data strongly supports the role of platelets in inflammatory responses in AAA via Panx1 channels and adds important knowledge about the significance of platelets in AAA pathology important for the establishment of an anti-platelet therapy for AAA patients.

Gefasrekonstruktionen in der onkologischen Chirurgie sind komplex und erfordern eine hohe gefaschirurgische Expertise. Zur Wahl des Gefasersatzes stehen autologe, xenogene und alloplastische Materialien zur Verfugung. Diese Ubersichtsarbeit soll auf Basis aktueller wissenschaftlicher Referenzen und eigener operativer und klinischer Erfahrungen Rekonstruktionsmoglichkeiten der Arterien und Venen in der onkologischen Chirurgie darstellen. Analyse der aktuellen wissenschaftlichen Literatur uber Gefasersatz in der onkologischen Chirurgie. Die Wahl des Gefasersatzmaterials ist von der Lokalisation, dem Durchmesser und der Tumorinfiltration des beteiligten Gefases abhangig. Prinzipiell ist der autologe Gefasersatz anzustreben, jedoch bieten alloplastische Materialien bei groseren Gefasen den Vorteil einer unmittelbaren Verfugbarkeit, ohne zusatzliches Zugangstrauma. Fur den Ersatz groslumiger Gefase werden Gefasprothesen aus Polyester (Dacron) oder Polytetrafluorethylen (PTFE) verwendet. Im potenziell kontaminierten Operationsfeld konnen infektresistente, silberbeschichtete Prothesen verwendet werden. Bei alloplastischem Ersatz der V. cava inferior wird die ringverstarkte PTFE-Gefasprothese bevorzugt. Ausgepragte Wundinfektionen sowie Graftthrombosen nach Extremitatengefasersatz konnen zur Arrosionsblutung und Majoramputation fuhren. Zum Gefasersatz in der onkologischen Chirurgie stehen verschiedene gefasrekonstruktive Techniken und Materialien zur Verfugung. Faktoren, die die Wahl des Gefasersatzes fur die Rekonstruktion beeinflussen, sind Lange und Kaliber des zu rekonstruierenden Gefases und die Verfugbarkeit eines geeigneten (venosen) Ersatzmaterials.

Neben den klassischen operativen Techniken haben Gefaschirurgen im letzten Jahrhundert auch endovaskulare Verfahren in ihr Portfolio aufgenommen. Diese Techniken alleine oder in Kombinationen sind Alltag in der Gefasmedizin. Ziel ist es, fur jeden Patienten ein masgeschneidertes Verfahren zur Heilung seiner Gefaspathologie anbieten zu konnen. Eine Moglichkeit, den Status quo aber auch die Zukunft in der Gefaschirurgie einzuordnen, bietet die Einteilung in bekannte Aufgabengebiete der Gefasmedizin: septische Gefaschirurgie, Hybrideingriffe, periphere Gefaschirurgie und Aortenchirurgie. Die offene Gefaschirurgie wird evolutionar in Kombination mit endovaskularen Verfahren im Sinne von Hybridverfahren voranschreiten. Innovative, insbesondere biologische Gefasersatzmaterialien werden sowohl in der allgemeinen als auch in der endovaskularen Gefaschirurgie helfen, Patienten schonender und besser versorgen zu konnen.

Spinal strokes may be associated with tremendous spinal cord injury. Erythropoietin (EPO) improves the neurological outcome of animals after spinal cord ischemia (SCI) and its effects on ischemia-induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are considered possible molecular mechanisms. Furthermore, sphingosin-1-phosphate (S1P) is suggested to correlate with SCI. In this study, the effect of recombinant human EPO (rhEPO) and carbamylated EPO (cEPO-Fc) on the outcome of mice after SCI and a prognostic value of S1P were investigated. SCI was induced in 12-month-old male mice by thoracic aortal cross-clamping after administration of rhEPO, cEPO-Fc, or a control. The locomotory behavior of mice was evaluated by the Basso mouse scale and S1P serum levels were measured by liquid chromatography-tandem mass spectrometry. The spinal cord was examined histologically and the expressions of key UPR proteins (ATF6, PERK, and IRE1a, caspase-12) were analyzed utilizing immunohistochemistry and real-time quantitative polymerase chain reaction. RhEPO and cEPO-Fc significantly improved outcomes after SCI. The expression of caspase-12 significantly increased in the control group within the first 24 h of reperfusion. Animals with better locomotory behavior had significantly higher serum levels of S1P. Our data indicate that rhEPO and cEPO-Fc have protective effects on the clinical outcome and neuronal tissue of mice after SCI and that the ER is involved in the molecular mechanisms. Moreover, serum S1P may predict the severity of impairment after SCI.

Background: Vascular surgery of the inguinal area can be complicated by persistent lymphatic fistulas. Rapid and effective treatment is essential to prevent infection, sepsis, bleeding, and possible leg amputation. Current data on irradiation of lymphatic fistulas lacks recommendation on the appropriate individual and total dose, the time of irradiation, and the target volume. Presumably, a dose of 0.3-0.5 to 1-12 Gy should be sufficient for the purpose. Currently, radiotherapy is a “can” recommendation, with a level 4 low evidence and a grade C recommendation, according to the DEGRO S2 guidelines. As part of a pilot study, we analyzed the impact and limitations of low-dose radiation therapy in the treatment of inguinal lymphatic fistulas.Patients and Methods: As part of an internal quality control project, patients with lymphatic fistulas irradiated in the groin area after vascular surgery for arterial occlusive disease (AOD) III-IV, repair of pseudo aneurysm or lymph node dissection due to melanoma were selected, and an exploratory analysis on retrospectively collected data performed.Results: Twelve patients (10 males and 2 females) aged 62.83 + 12.14 years underwent open vascular reconstruction for stage II (n= 2), III (n=1), and IV (n=7) arterial occlusive disease (AOD), lymph node dissection for melanoma (n=1) or repair of a pseudoaneurysm (n=1). Surgical vascular access was obtained through the groin and was associated with a persistent lymphatic fistula, secreting more than 50 ml/day. Patients were irradiated five times a week up to a maximum of 10 fractions for the duration of the radiation period. Fraction of 0.4 Gy were applied in the first 7 cases, while 5 patients were treated with a de-escalating dose of 0.3 Gy. There was a resolution of the lymphatic fistula in every patient without higher grade complications.Conclusion: Low-dose irradiation of the groin is a treatment option for persistent lymphatic fistula after inguinal vascular surgery.

Journal of endovascular therapy 28(6), 914-926 (2021). doi:10.1177/15266028211030536, Published by Sage, Thousand Oaks, Calif.

Purpose: Laser-fenestrated thoracic endovascular aortic repair (LfTEVAR) in the aortic arch with covering of the left subclavian artery (LSA) orifice is challenging. To optimize fenestration, the so-called squid-capture technique has been introduced. We present here a modification to the technique that may help improve time-efficiency and safety. Technique:: During the originally proposed squid-capture maneuver, the stent-graft is deployed in a preset snare wire loop, which is used to pull the stent graft toward the penetration device during in-situ fenestration. In preparation, the guidewire needs to be passed through the loop inside the aortic arch, which can be difficult and may predispose for embolic events. We propose here the creation of a “guidewire-through-snare-loop” configuration outside the body, which can then be reliably transferred into the aortic arch. The modified technique was successfully applied in a patient undergoing LfTEVAR for penetrating aortic ulcers. Conclusion: The proposed modification may help facilitate the squid-capture technique for LfTEVAR while saving time and resources. Given that LfTEVAR is becoming more frequently used, it is important to ensure technical success and safety of the procedure.

Background: Tight junction (TJ) disruption and dysfunction are involved in the progression of arteriosclerosis. miR-501-3p regulates endothelial TJ protein-1, resulting in TJ disruption. Because exosomal microRNAs can travel to distant tissues and influence cell behavior, patients with elevated miR-501-3p may experience accelerated vascular disease progression secondary to miR-501-3p-induced reductions in TJ. This study investigated whether plasma exosome miR-501-3p levels are associated with vascular stiffness, an indicator for arteriosclerotic changes. Methods and Results: Fifty-one subjects (mean [±SD] age 70±8 years, 37% male) enrolled in a medical checkup program were recruited to the study. Brachial-ankle arterial pulse wave velocity (baPWV) and plasma exosome miR-501-3p expression were measured. Patients were divided into 2 groups depending on whether their miR-501-3p ∆Ct values were above (“High”; n=24) or below (“Low”; n=27) the cut-off levels determined by receiver operating characteristic (ROC) curve analysis. Median (interquartile range) baPWV levels were significantly higher in the miR-501-3p High than Low group (1,664 [1,496–1,859] vs. 1,450 [1,353–1,686] cm/s, respectively; P

Background The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent. Methods Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA –DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease. Results The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males. Conclusion The existence of certain HLA haplotypes is associated with more severe disease.

Background Vaccination against SARS-CoV-2 has been the main tool to contain the pandemic. The rush development of the 3 vaccines and their expedited approval have led to inoculation of millions of patients around the world, leading to a containment of the disease. Despite continuous viral mutations and the identification of weaker variants, the severity of the infections has been mild, with many patients being either asymptomatic or recovering at home. Currently the focus has shifted from the host of organ damage related to the infection to potential side effects of the vaccine. Myocarditis has been reported as one of the potential side effects from the mRNA vaccine, affecting young healthy individuals. Up to September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© were registered in young adults by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©). Patients and methods Eight patients between 13 and 56 years of age, vaccinated with either BNT162b2 or mRNA-1273 mRNA vaccine between January and August 2021 developed cardiac side effects shortly after either their first or second dose of the vaccine. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after the onset of symptoms, with further investigations in severe cases. Symptoms were defined as dyspnea, chest pain and cardiac arrhythmia as determined by electrocardiography. Results Eight patients (5 males and 3 females) developed cardiac symptoms compatible with myocarditis, according to the CDC criteria, shortly after SARS-CoV-2 mRNA vaccination. Three patients (2 males, 1 female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within 7 days from the symptom onset. Conclusions Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.

Purpose: To report the outcomes of bypass grafting (BG) vs endovascular therapy (EVT) in patients with non-dialysis-dependent chronic kidney disease (CKD) and chronic limb-threatening ischemia (CLTI). Materials and Methods: The CRITISCH Registry is a prospective, national, interdisciplinary, multicenter registry evaluating the current practice of all available treatment options in 1200 consecutive CLTI patients. For the purposes of this analysis, only the 337 patients with non-dialysis-dependent CKD treated by either BG (n=86; median 78 years, 48 men) or EVT (n=251; median age 80 years, 135 men) were analyzed. The primary composite outcome was amputation-free survival (AFS); secondary outcomes were overall survival (OS) and amputation-free time (AFT). All outcomes were evaluated in Cox proportional hazards models; the results are reported as the hazard ratio (HR) and 95% confidence interval (CI). Results: The Cox regression analysis revealed a significantly greater hazard of amputation or death after BG (HR 1.78, 95% CI 1.05 to 3.03, p=0.028). The models for AFT and overall survival also suggested a higher hazard for BG, but the differences were not significant (AFT: HR 1.66, 95% CI 0.78 to 3.53, p=0.188; OS: HR 1.41, 95% CI 0.80 to 2.47, p=0.348). The absence of runoff vessels (HR 1.73, 95% CI 1.15 to 2.60, p=0.008) was associated with a decreased AFS. The likelihood of amputation was higher in male patients (HR 2.21, 95% CI 1.10 to 4.45, p=0.027) and was associated with a lack of runoff vessels (HR 1.95, 95% CI 0.96 to 3.95, p=0.065) and myocardial infarction (HR 3.74, 95% CI 1.23 to 11.35, p=0.020). Death was more likely in patients without runoff vessels (HR 1.76, 95% CI 1.11 to 2.80, p=0.016) and those with a higher risk score (HR 1.73, 95% CI 1.03 to 2.91, p=0.038). Conclusion: This analysis suggested that BG was associated with poorer AFS than EVT in patients with non-dialysis-dependent CKD and CLTI. Male sex, previous myocardial infarction, and the absence of runoff vessels were additionally identified as predictors of poorer outcomes.

OBJECTIVES Endovascular aortic arch stent grafting with branched devices has shown initial promising results. The aim of this prospective, multicentre study was to evaluate 3-year outcomes of aortic arch stent grafting with NEXUS® Aortic Arch Stent Graft System (Nexus), a single-branch, bi-modular, off-the-shelf aortic arch stent graft system in high-risk patients. METHODS Patients treated with Nexus, either under the feasibility clinical study or as compassionate use procedures in 5 centres, were included in this study. The primary end point was overall survival. The secondary end points included the incidence of procedure-related unplanned intervention, stroke, paraplegia and endoleak. Clinical and radiologic follow-up was performed at each study site at 30 days, 6 months and on a yearly basis thereafter up to 3 years postoperatively. RESULTS We analysed data from a total of 28 patients. The overall median follow-up was 1132 (interquartile range: 809–1537). There were no device or procedure-related deaths between 1 and 3 years. Overall survival at 1 and 3 years was 89% and 71%, respectively. The cumulative incidence of unplanned reintervention at 1 and 3 years was 11% and 29%, respectively. There were no reports of stroke, paraplegia, aneurysm rupture, myocardial infarction or new aortic valve insufficiency. In this study’s 1–3 year follow-up period, 1 type Ib (4%), 1 type II (4%) and 2 type III (8%; between Nexus’ distal end and Thoracic endovascular aortic repair (TEVAR) extensions) endoleak were detected. CONCLUSIONS Endovascular aortic arch exclusion with the single-branch, off-the-shelf Nexus system provides promising clinical and radiologic results at 3-year follow-up in a high-risk patient cohort.

A posterior circulation infarction is caused by a vertebral artery (VA) lesion (stenosis or occlusion). The purpose of this study is to assess early and long-term outcomes after open surgery for a VA lesion at the origin.In a retrospective study conducted from January 1, 2000 through March 31, 2020 in a single center, patients were treated with vertebral artery to carotid artery transposition (VCT).A total of 28 patients, with a mean age of 65.29 ± 9.81 years (range 45-84), were screened, including 22 patients with VA stenosis and 6 patients with VA occlusion. The complication rate was 21.4% (n = 6), including Horner syndrome (n = 2), lymphocele (n = 1), respiratory failure (n = 1), embolism of a subclavian artery stenosis (n = 1), and vocal cord paralysis (n = 1). The 30-day mortality rate was 0%. Primary patency was 100%. Overall, improvement in symptoms was 85.7% (n = 24) after surgery and 96.4% after 30 days. In the long-term results, primary patency was 100%, and the cumulative patency rate after 60 months was 85.7%, with 1 occlusion of the VA. Cumulative survival rates were 94%, 87%, 69%, and 59% after 12, 24, 60, and 72 months (n = 5). One of the 3 patients died after 60 months because of VA occlusion and posterior circulation infarction.VCT is a safe, effective, and durable procedure. It provides good stroke protection, symptomatic relief, and perioperative risk at acceptable levels, in experienced hands.

Objective: Thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) aims to induce false lumen (FL) thrombosis by sealing intimal tears between the true (TL) and the FL, and blocking the inflow into the FL. Incomplete thrombosis of the FL is correlated with poor clinical outcome. We hypothesize that the number of major and minor branches arising from the FL affects FL patency and may negatively influence TEVAR induced FL thrombosis.Methods: Computed tomography (CT)-scans from 89 patients diagnosed with TBAD [best medical treatment (BMT) n = 52, TEVAR n = 37] from two high-volume vascular surgery centers were analyzed retrospectively. Analysis included evaluation of the FL patency status, the number, location and size of intimal tears, and the presence of minor and major side branches originating from the FL. Multiple regression analysis was conducted to evaluate obtained parameters as predictors for FL thrombosis status.Results: In univariate analysis, the strongest correlation for FL patency was found for the number of major (R = 0.79) and minor (R = 0.86) side branches originating from the FL. When applying a multiple linear regression model, the number of major (normalized beta 0.37; P < 0.001) and minor (normalized beta 0.41; P < 0.01) side branches arising from the FL were valid predictors for the axial length of the patent and non-patent FL, and additionally determined the length of the patent FL at 12-month follow-up in patients that underwent TEVAR.Conclusions: Our data suggest that the number of minor side branches that originate from the FL in TBAD is an important determinant of FL patency, to a greater degree than previously assumed.

Die Therapieoptionen der peripheren arteriellen Verschlusskrankheit (pAVK) bestehen, abhangig vom Fontaine-Stadium, aus konservativen und revaskularisierenden Verfahren. Ziele der konservativen Therapie sind stadienabhangig die Verhinderung des Krankheitsprogresses, die Steigerung der Gehleistung, die Schmerzreduktion, die Ulkusabheilung und der Beinerhalt. Eine ausreichende Evidenz und Leitlinienempfehlungen existieren in allen Stadien fur den Nikotinverzicht, die medikamentose Einstellung von Blutdruck und -zucker, die Statintherapie sowie fur die Thrombozytenaggregationshemmung, das strukturierte Gehtraining und die Cilostazol- oder Naftidrofurylmedikation ab Stadium IIa. Alternative Verfahren wie die Alprostadilinfusion, die computertomographiegesteuerte lumbale Sympathikolyse, die epidurale Ruckenmarkstimulation, die intermittierende pneumatische Kompression oder die hyperbare Sauerstofftherapie besitzen keine ausreichende Evidenz und sollten nur nach Ausschopfen der Standardtherapie eingesetzt werden.

Objective: Thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) aims to induce false lumen (FL) thrombosis by sealing intimal tears between the true (TL) and the FL, and blocking the inflow into the FL. Incomplete thrombosis of the FL is correlated with poor clinical outcome. We hypothesize that the number of major and minor branches arising from the FL affects FL patency and may negatively influence TEVAR induced FL thrombosis. Methods: Computed tomography (CT)-scans from 89 patients diagnosed with TBAD [best medical treatment (BMT) n = 52, TEVAR n = 37] from two high-volume vascular surgery centers were analyzed retrospectively. Analysis included evaluation of the FL patency status, the number, location and size of intimal tears, and the presence of minor and major side branches originating from the FL. Multiple regression analysis was conducted to evaluate obtained parameters as predictors for FL thrombosis status. Results: In univariate analysis, the strongest correlation for FL patency was found for the number of major (R = 0.79) and minor (R = 0.86) side branches originating from the FL. When applying a multiple linear regression model, the number of major (normalized beta 0.37; P < 0.001) and minor (normalized beta 0.41; P < 0.01) side branches arising from the FL were valid predictors for the axial length of the patent and non-patent FL, and additionally determined the length of the patent FL at 12-month follow-up in patients that underwent TEVAR. Conclusions: Our data suggest that the number of minor side branches that originate from the FL in TBAD is an important determinant of FL patency, to a greater degree than previously assumed.

Popliteal artery aneurysm (PAA) is a rare disease with a prevalence of 0.1% to 1%. Within previous years, endovascular repair (ER) of PAAs has been performed more frequently despite the lack of high-level evidence compared with open surgical repair (OSR). In 2014, the POPART registry was initiated to validate the current treatment options for PAA repair.POPART is a multinational multicenter registry of the peri- and postoperative outcomes of ER and OSR for PAAs. Data sets were recorded using the online survey tool SurveyMonkey (available at: https://www.surveymonkey.com/). Regular monitoring and plausibility checks of the data sets are performed to ensure reliability. The aim of the present study was to report the findings from the POPART registry, which includes data from 41 centers.From June 2014 to August 2019, 794 cases had been recorded in the POPART registry. OSR had been performed in 662 patients and ER in 106 patients; 23 patients had been treated conservatively. Of the 106 patients in the primary ER group, 4 had required conversion to OSR. The ER patients were significantly older (ER, median, 71 years; OSR, median, 67 years; P .05). No other significant differences were present in the demographic data, comorbidities, or aneurysm morphology between the two groups. Of the 662 patients in the OSR group, 50.3% were symptomatic compared with 29.2% of the 106 patients in the ER group (P .05). Emergency treatment because of acute ischemia, critical ischemia, or rupture was necessary for 149 patients (22.5%) in the OSR group and 11 patients (10.3%) in the ER group. The most frequent postoperative complications were impaired wound healing (OSR, n = 47 [7.1%]; ER, n = 3 [2.8%]; P.05) and major bleeding (OSR, n = 26 [3.9%]; ER, n = 3 [2.8%]; P.05). The in-hospital length of stay was significantly longer for the OSR group than for the ER group (median, 10 days; range, 3-65 days; vs median, 7 days; range, 1-73 days). The overall patency for the OSR and ER groups after 12 and 24 months was 83.2% and 44.7% (P .005) and 74.2% and 29.1% (P .005), respectively. The outcomes with a prosthetic graft vs an autologous vein were significantly poorer in the OSR group (primary patency, 71.4% vs 88.1% at 12 months).To evaluate new treatment techniques such as ER for PAAs, real-world data are of essential importance. The present analysis of the first results for the POPART registry shows good perioperative results for endovascular treatment of PAA in asymptomatic patients with good outflow vessels. The perioperative complication rate is low and the postoperative hospital stay is shorter than after OSR. However, the patency rates after 12 and 24 months are low in the ER group compared to patients treated with open repair. More follow-up data is required for further interpretation; the completion of the data sets in the registry is ongoing.

An amendment to this paper has been published and can be accessed via the original article.

Background: An aberrant right subclavian artery (ARSA) is in most cases an asymptomatic aortic arch anomaly. However, dysphagia, aneurysm formation (ARSAA), associated Kommerell diverticulum, or cerebellar/arm malperfusion may require invasive therapy. Large-scale clinical trials do not exist in current literature. We report our patient's outcome of a single-center experience and delineate indications for treatment and surgical techniques. Methods: A single-center retrospective study was conducted between January 1, 2012 through March 1, 2018. Symptomatic or asymptomatic patients with ARSAA who received invasive treatment at the Department for Vascular and Endovascular Surgery, University Hospital Dusseldorf, Germany were included. Results Eight patients (4 men, 63 ± 14 (39–78) years) were treated with single-stage (n = 4) or multistage (n = 4) procedures. Treatment for ARSAA (n = 4) included ARSA revascularization (subclavian-carotid transposition (SCT) = 3; carotid-subclavian bypass (CSB) = 1), aortic arch debranching (left SCT = 2, bilateral aorto-carotid bypass + left CSB = 1, right-to-left CSB + left-carotid-to-bypass transposition = 1), and thoracic endovascular aortic repair (TEVAR; n = 4). Other strategies included SCT for dysphagia (n = 2) or subclavian steal syndrome (n = 1) and balloon angioplasty for arm claudication (n = 1). Complications involved vascular access (n = 2) and each one partial common carotid artery overstenting without stroke during TEVAR and Horner syndrome after SCT. Mean follow-up was 23 ± 26 (9–67) months. After 7 months, 1 patient required vertebral artery coiling due to type II endoleak with ARSAA progression. Overall mortality was 0%. Technical and clinical success rates were 100%. Conclusions: Surgical concepts for ARSA aim on preventing aneurysm rupture and alleviate dysphagia or ischemic symptoms. To generate satisfying patient outcomes, individualized therapy planning in specialized centers is vital.

To evaluate short term outcomes related to the use of the Zenith TX2 Dissection Endovascular Graft (ZDEG) and the Zenith Dissection Bare stent (ZDES) for the treatment of Stanford type B aortic dissections.This retrospective multicenter case cohort study collated data from 10 European institutions for patients with both complicated and uncomplicated type B aortic dissection treated with ZDEG and ZDES between 2011 and 2018. The primary end point was mortality at 30 and 90 days. Secondary end points included complications related to TEVAR, such as, type Ia endoleak, stroke, paraparesis, paraplegia, and retrograde type A dissection (RTAD). Statistical analysis was carried out using the t test, or one-way analysis of variance and the χWe treated 120 patients (87 male; mean age, 62.7 ± 12.2years) either in the acute 76 (63.3%), subacute 16 (13.3%), or chronic 28 (23.3%) phase. Seven patients (5.8%) died within 30 days after the index procedure and two (1.7%) between 30 and 90 days. There was one instance of postoperative RTAD in a patient treated for rupture. Stroke and paraplegia occurred in three (2.5%) and five (4.2%), patients, respectively. Eight patients (6.7%) had a type Ia endoleak in the perioperative period. There were no instances of paraplegia, no permanent dialysis, and no requirement for adjunctive superior mesenteric or celiac artery stenting in the 33 patients (27.5%) who were treated by concurrent placement of ZDES distal to the ZDEG. The length and distal oversizing of ZDEG components used was less in this group.The present series demonstrates a low (1%) RTAD rate and favorable morbidity and mortality. The lower rate of paraplegia, dialysis, and visceral artery stenting in the cohort that had adjunctive use of ZDES is compelling and merits further assessment.

Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors.

IntroductionOxidized regenerated cellulose-based (ORC – TABOTAMP), oxidized non-regenerated cellulose-based (ONRC – RESORBA CELL), and gelatin-based (GELA – GELITA TUFT-IT) hemostats are commonly used in surgery. However, their impact on the wound healing process remains largely unexplored. We here assess time-dependent effects of exposure to these hemostats on fibroblast-related wound healing processes.Material and methodsHemostats were applied to fibroblast cell cultures for 5–10 (short-), 30 and 60 min (intermediate-) and 24 h (long-term). Representative images of the hemostat degradation process were obtained, and the pH value was measured. Cell viability, apoptosis and migration were analyzed after the above exposure times at 3, 6 and 24 h follow-up. Protein levels for tumor necrosis factor α (TNF-α) and transforming-growth factor β (TGF-β) were assessed.ResultsORC and ONRC reduced pH values during degradation, while GELA proved to be pH-neutral. Hemostat structural integrity was prolonged for GELA (vs. ORC and ONRC). TGF-β and TNF-α levels were reduced for ORC and ONRC (vs. GELA and control) (p < 0.05). Further, exposure of ORC and ONRC for longer than 5-10 min reduced cell viability vs. GELA and control at 3 h post-exposure (p < 0.05). Similarly, cell migration was impaired with ORC and ONRC exposure longer than 60 min at 24 h follow-up (p < 0.05).ConclusionsShort-term exposure to ORC and ONRC impairs relevant wound healing-related processes in fibroblasts, and alters protein levels of key mediating cytokines. GELA does not show similar effects. We conclude that GELA may be preferred over ORC and ONRC over short-, intermediate- and long-term exposures. Future validation of the clinical relevance is warranted.

Journal of Clinical Medicine 11(5), 1282 (2022). doi:10.3390/jcm11051282, Published by MDPI, Basel

Type B aortic dissection is a relatively rare clinical picture that involves many fields of medicine and requires a multidisciplinary approach. In this report, the disciplines involved constitute the most important aspects of the new S2k guidelines for the diagnosis and treatment of type B aortic dissection. More specifically, the definition and epidemiology, the clinical and technical diagnostic methods, in addition to the imaging methods, are presented, and recommendations for the individual topics based on scientific studies and expert opinion are given. In the guidelines, the various procedures related to the main conservative and surgical treatment regimes in the acute, subacute, and chronic phases of the condition are dealt with.

Die Typ-B-Aortendissektion ist ein relativ seltenes Krankheitsbild, welches in sehr vielen Bereichen der Medizin vorkommt und einen interdisziplinaren Behandlungsansatz erfordert. Die beteiligten Disziplinen stellen in diesem Beitrag die wesentlichen Aspekte der neuen S2k-Leitlinie zur Diagnostik und Therapie der Aortendissektion Typ B dar. Im Einzelnen werden die Definition und Epidemiologie, die klinische und instrumentelle Diagnostik sowie die bildgebenden Verfahren dargestellt und zu den einzelnen Themen aufgrund von wissenschaftlichen Studien und Expertenmeinung Empfehlungen gegeben. In der Leitlinie wird auserdem auf die unterschiedlichen Vorgehensweisen in Bezug auf primar konservative und operative Therapieregime in der akuten, subakuten und chronischen Phase der Erkrankung eingegangen.

Red blood cells (RBCs) influence rheology, and release ADP, ATP, and nitric oxide, suggesting a role for RBCs in hemostasis and thrombosis. Here, we provide evidence for a significant contribution of RBCs to thrombus formation. Anemic mice showed enhanced occlusion times upon injury of the carotid artery. A small population of RBCs was located to platelet thrombi and enhanced platelet activation by a direct cell contact via the FasL/FasR (CD95) pathway known to induce apoptosis. Activation of platelets in the presence of RBCs led to platelet FasL exposure that activated FasR on RBCs responsible for externalization of phosphatidylserine (PS) on the RBC membrane. Inhibition or genetic deletion of either FasL or FasR resulted in reduced PS exposure of RBCs and platelets, decreased thrombin generation, and reduced thrombus formation in vitro and protection against arterial thrombosis in vivo. Direct cell contacts between platelets and RBCs via FasL/FasR were shown after ligation of the inferior vena cava (IVC) and in surgical specimens of patients after thrombectomy. In a flow restriction model of the IVC, reduced thrombus formation was observed in FasL–/– mice. Taken together, our data reveal a significant contribution of RBCs to thrombosis by the FasL/FasR pathway.

Die chronisch arterielle Ischamie der unteren Extremitaten stellt ein alltagliches Problem in gefaschirurgischen Kliniken dar. In Deutschland sind etwa 3 % aller Hospitalisierungen auf eine periphere arterielle Verschlusskrankheit (PAVK) zuruckzufuhren, wobei vor allem die kritischen Ischamien stark zunehmen. Die Folgen der chronischen Ischamie reichen von eingeschrankter Gehstrecke bis hin zum Verlust der Extremitat. Am Anfang stehen Stressfaktoren wie Hyperlipidamie (LDL), freie Radikale, arterielle Hypertonie, Infektionen oder subklinische Entzundungen, die die Endothelhomoostase storen. Es kommt zu einer Dysfunktion des Endothels mit erhohter Durchlassigkeit. Zellen des Immunsystems werden angelockt und wandern in die Gefaswand ein, wo sie zum Abbau von Matrixkomponenten und zur Destabilisierung des Plaques fuhren. Durch Anderung des Phanotyps von glatten Muskelzellen und Makrophagen entstehen osteoklastenahnliche Zellen, die zu Verhartungen in der Gefaswand fuhren. Ab einer Gefaswandstarke von etwa 100 μm wird durch den Sauerstoffmangel Hypoxie induzierter Faktor (HIF-1α) verstarkt exprimiert, was zu einem Anstieg an Wachstumsfaktoren wie VEGF („vascular endothelial growth factor“) fuhrt. Dadurch wird die Angiogenese als Kapillarenbildner gefordert, reicht aber nicht aus, um eine stenosierte Arterie zu kompensieren. Arteriogenese bezeichnet das Wachstum von bereits vorhandenen Kollateralgefasen. Die treibenden Krafte sind der Druckgradient vor und hinter der Stenose sowie die Scherkrafte, die auf die Gefaswande einwirken. Bei voranschreitender Stenosierung konnen die Kompensationsfahigkeiten uberfordert werden und es kommt zu einer manifesten Hypoxie im Gewebe mit Ruckbildung der gewonnenen Gefasstrukturen/Kollateralkreislaufen und Gewebsatrophie.

Strukturiertes Gehtraining (SGT) zur Verbesserung arterieller Kollateralkreislaufe ist ein wichtiger Baustein in der Therapie und Sekundarprophylaxe der peripheren arteriellen Verschlusskrankheit (PAVK). Trainingsangebote sind deutschlandweit nicht ausreichend. Wir prasentieren die Organisation und Ergebnisse unseres SGT. Die Klinik fur Gefas- und Endovaskularchirurgie des Universitatsklinikums Dusseldorf bietet seit 2014 Patienten mit einer PAVK im Fontaine-Stadium II, einem ankulobrachialen Index (ABI) von ≤0,9 in Ruhe und/oder einem ABI-Abfall von ≥15 % nach Belastung ein SGT an. In Einstiegs‑/Folgeuntersuchungen (0/3/6/12 Monate) werden schmerzfreie/maximale Gehstrecken sowie der ABI vor/nach Belastung erhoben. Verlaufsergebnisse existieren von 37 Patienten (weiblich = 12, Durchschnittsalter = 66 ± 10 Jahre) im Stadium IIa/b (n = 4/33) bzw. 57 Beinen. Nach acht Monaten stieg die schmerzfreie/maximale Gehstrecke, als Zeichen der Bildung von Kollateralkreislaufen, um 63 ± 88 m (75 ± 106 %)/113 ± 212 m (44 ± 78 %) mit uneingeschrankter Gehstrecke bei funf Patienten an. Der ABI hingegen korreliert als Charakteristikum fur Leitungsgefase physiologischerweise nur schwach mit dem Kollateralisierungsgrad und stieg in Ruhe um 0,04 ± 0,13 (11 ± 27 %) und bei zwei Beinen auf >0,9 an. Der Abfall des Belastungs-ABI ging um 2 % zuruck. Drei Beine zeigten keinen pathologischen Belastungs-ABI. 14 Patienten beendeten das Training fruhzeitig. 75 % der Patienten fuhrten das SGT nach der 12-Monats-Kontrolle fort. Unser SGT erzeugt hinsichtlich der schmerzfreien/maximalen Gehstrecken gute Ergebnisse. Der Angebotsmangel erfordert einen bundesweiten Aufbau ahnlicher Trainingsprogramme.

Der akute arterielle Gefasverschluss einer Extremitat (AGE) fuhrt zur akuten Extremitatenischamie (AEI) und gefahrdet sowohl das Leben eines Patienten als auch die betroffene Gliedmase selbst. Ein Verschluss stellt eine haufige Ursache fur eine Extremitatenamputation dar. Daher ist der AGE ein vaskularer Notfall, der einer raschen Revaskularisation innerhalb von Stunden bedarf. Die Ursachen sind kardiale Embolien, lokale Thrombosen, postrekonstruktive thrombotische Gefasverschlusse, embolisierende Aneurysmen, Aortendissektionen und Gefasverletzungen. Das 30-Tage-Major-Amputationsrisiko betragt 10–30 % und die 30-Tage-Mortalitat 15–30 %. Die Auspragung des Krankheitsbilds ist abhangig von der peripheren Restperfusion. Die Einteilung nach Rutherford und die 6 P nach Pratt beschreiben die Klinik. Man unterscheidet eine komplette Ischamie mit voller Auspragung der Symptomatik von einer inkompletten Form mit Erhalt der Sensibilitat und Motorik. Nach erfolgreicher Revaskularisation kann es als Folgeereignis zu einem Reperfusions- oder Kompartmentsyndrom kommen. Der AGE mit AEI ist ein multifaktorielles Geschehen und fuhrt unbehandelt zum Multiorganversagen. Bei komplexer Vorgeschichte ist eine unverzugliche CTA fur die Therapieplanung hilfreich. Mittel der Wahl zur Diagnostik sind die Duplexsonographie und Angiographie. Als Therapieoptionen stehen die offen chirurgische Therapie, die endovaskulare Therapie und eine Kombination aus beidem (Hybridverfahren) zur Verfugung.

Introduction Increased susceptibility to infections in MDS is due to neutropenia as well as functional impairment of neutrophils. We investigated whether neutrophil dysfunction includes diminished formation of neutrophil extracellular traps (NETs). The latter are networks of extracellular fibers, primarily composed of DNA, which bind pathogens. This component of the immune system's first line of defense was first described in 2004 by Zychlinsky and coworkers. Formation of NETS is triggered by reactive oxygen species (ROS), which in neutrophils are mainly produced by NADPH-oxidase and myeloperoxidase (MPO). Methods Fluorescence microscopy was used to show NET formation in patients with MDS (n=12) (1 MDS del(5q), 1 MDS-RS-SLD, 1 MDS-RS-MLD, 5 MDS-MLD, 2 MDS-EB-1, 2 MDS-EB-2) in comparison to an age-adjusted normal control group (n=15). Neutrophils were isolated from peripheral blood by density gradient centifugation, sedimented on cover slips in 24-well plates, and incubated with phorbol-12-myristate-13-acetate (PMA) for 30 and 180 minutes to stimulate NET formation. Neutrophil elastase was detected by primary anti-NE (Abcam) plus secondary goat anti-rabbit Alexa 488 (FITC), histones by primary anti-histone (Millipore) plus secondary goat anti-mouse Alexa 568 (PE), and cell nuclei by DNA staining with DAPI. Fluorescent images were loaded into Image J/FIJI Software (https://imagej.nih.gov/ij/) for automatic cell detection and assessment of the proportion of cells undergoing NET formation, detectable by positive histone staining. Flow cytometry was used to further characterize NET formation and demonstrate the production of ROS by NADPH-oxidase and MPO. Intracellular MPO staining was positive for 96.7% and 99.1% of neutrophils in controls and MDS patients, respectively. Reactive oxygen species (ROS) were detected using dihydro-rhodamin 123 (DHR) for hydrogen peroxide, hydroethidine (HE) for superoxide anion, and 3`-(p-aminophenyl) fluorescein (APF) and 3`-(hydroxyphenyl) fluorescein (HPF) for hypochloride (HOCl). In order to block certain components of cellular ROS production, the following inhibitors were used: 4-aminobenzoic hydrazide (ABAH) to block MPO; 4-dimethylamino-antipyrine (AP) to block MPO and quench ROS; and diphenylen-iodonium chloride (DPI) to inhibit NADPH oxidase and mitochondrial respiratory complex I. Flow cytometry data were analysed using CellQuest Software (Becton Dickinson) and FCS Express Reader (De Novo Software). Results By fluorescence microscopy, marked morphological abnormalities of NET formation were observed. PMA-stimulated neutrophils of patients with MDS generated significantly fewer NETs than neutrophils from controls (increase from 17% to 67% vs. increase from 17% to 85% of cells, respectively) (p=0.02), see Fig. 1. MDS neutrophils showed significantly less cellular swelling after stimulation with PMA (p=0.04). Histone staining showed a more condensed chromatin in MDS neutrophils prior to stimulation (smaller mean fluorescence intensity (MFI) for PE; p=0.05). Upon stimulation with PMA, the decrease in MFI of DAPI, indicating chromatin decondensation, was significantly less in MDS neutrophils than controls (delta MFI 3467 vs. 4687, p=0.03). In addition, assessment of neutrophil elastase showed that its release from cytoplasmic granules (decreasing MFI for FITC) was diminished in patients with MDS (p=0.00002). On flow cytometry, forward scatter confirmed a significant difference in cell swelling after PMA stimulation (p=0.02). Sideward scatter showed a smaller decrease in granularity after stimulation with H2O2 (p=0.002). The morphological abnormalities did not seem to be attributable to diminished ROS production since measurement of PMA-stimulated ROS production using HE, and assessing oxidative burst activity using DHR did not reveal significant differences. However, H202-stimulated production of HOCl by MPO was lower in MDS patients, albeit only when MPO activity was simultaneously impeded by inhibitors (ABAH and AP). Inhibition of MPO activity was more easily achieved in patients with MDS (p=0.01), corroborating the notion of a partial MPO defect in MDS. Conclusions Our results indicate that NET formation is significantly impaired in MDS neutrophils. Although we found abnormalities of MPO-dependent generation of HOCl, impaired ROS production may not be the only cause of deficient NETosis in MDS. Figure Disclosures Gattermann: Novartis: Honoraria, Research Funding.

Die perioperative Komplikationsrate bei Patienten nach gefaschirurgischen Rekonstruktionen wird in erster Linie durch das Ausmas des operativen Eingriffes und die Begleiterkrankungen bestimmt. Meist handelt es sich hier um Patienten im 7. oder 8. Lebensjahrzehnt mit den fur diese Alters- und Patientengruppe typischen Risikofaktoren, wie arterieller Hypertonus, Diabetes mellitus, Hyperlipidamie, Adipositas, Nikotinabusus, etc. (Garcia 2006). Aus gefaschirurgischer Sicht bedeutet dies, den pathophysiologischen Folgezustanden vor, wahrend und nach der Therapie gefaschirurgischer Krankheitszustande Rechnung zu tragen.

Purpose. To report the effectiveness of left renal artery (LRA) occlusion using Amplatzer Vascular Plug (AVP) II as treatment for a high-flow renal arteriovenous fistula (RAVF) with multiple renal vein aneurysms (RVA) to prevent aneurysm rupture and cardiac decompensation. Case Report. A 59-year-old female suffering from a post-traumatic RAVF presented with tachycardia and increased cardiac output (CO). Doppler ultrasonography and computed tomography (CT) scan revealed a high-flow RAVF with multiple RVAs and unilateral critically reduced kidney function. Appreciating recent interventional therapeutic advances, the patient was treated with endovascular placement of AVP II into the left renal artery (LRA) resulting in complete occlusion of the RAVF to effectively reduce the risk of RVA rupture and cardiac decompensation. No anti-platelet medication was administrated after the occlusion of the LRA. The patient’s physical capacity improved since right heart volume strain was normalized, and CO was reduced. Conclusion. Transbrachial AVP II occlusion of the LRA is effective to occlude high-flow RAVFs to prevent risk of life-threatening RVA rupture. Additional follow-up is warranted to verify long-term effectiveness of this approach.

Objectives The most effective first-line treatment between endovascular therapy and bypass surgery for patients with critical limb ischemia (CLI) is still not well defined. The primary aim of the interim analysis of CRITISCH (Registry of First-Line Treatments in Patients With Critical Limb Ischemia) was to compare both treatment options in a prospective confirmatory manner. Background Only 1 randomized controlled trial between endovascular therapy and bypass surgery has been published yet. Several retrospective studies showed comparable outcomes between the 2 treatment strategies, but in the majority of them, current endovascular technologies have not been included. Methods Between January 2013 and September 2014, 1,200 CLI patients (Rutherford 4 to 6) from 27 vascular centers were enrolled. The selection of the first-line treatment was left completely to the discretion of the responsible physician. The primary composite endpoint was amputation-free survival (AFS), that is, time to major amputation and/or death from any cause. A pre-specified interim analysis aimed at showing noninferiority of the endovascular therapy versus bypass surgery as to the hazard ratio (HR) of AFS (noninferiority bound = 1.33; interim α = 0.0058). Time-to-event analyses of major amputation, death, and the composite endpoint of reintervention and/or above-ankle amputation were also conducted. Results Endovascular therapy was applied to 642 (54%) and bypass surgery to 284 (24%) patients. Median follow-up time was 12 months in both groups. One-year AFS was 75% and 72%, respectively. The noninferiority of endovascular therapy versus bypass surgery for AFS was confirmed (HR: 0.91; upper bound of 1-sided (1 − 0.0058) confidence interval [CI]: 1.29; p = 0.003). An impact of the treatment strategy on time until death (HR: 1.14; 95% CI: 0.80 to 1.63; p = 0.453), major amputation (HR: 0.86; 95% CI:0.56 to 1.30; p = 0.463), and reintervention and/or above-ankle amputation (HR: 0.89; 95% CI: 0.70 to 1.14; p = 0.348) was not observed. Conclusions The interim analysis confirmed that when physicians are free to individualize therapy to CLI patients, the endovascular-first approach achieved a noninferior AFS rate compared with bypass surgery. (Registry of First-Line Treatments in Patients With Critical Limb Ischemia [CRITISCH]; NCT01877252)

Background The risk of deep venous thrombosis is elevated during pregnancy and the puerperium. Therapy is usually limited to conservative measures as invasive thrombus removal is feared because of possible complications. However, leg- or life-threatening situations require fast thrombus removal, and the long-term rate of post-thrombotic syndrome (PTS) may be reduced by venous recanalization. Our center's experience may give support to surgical venous thrombectomy (VT). Methods Between 1996 and 2016, all women who received VT for pregnancy-related deep venous thrombosis in our department were included. Retrospective data were combined with a current follow-up. Results The study included 82 women with a mean age of 29 years (17-38 years). An additional arteriovenous fistula was performed in 79 and planned simultaneous cesarean section in 13 patients. Neither pulmonary emboli nor fetal complications occurred during surgery, and perioperative and postoperative mortality was 0%. Operative revision was required in 38% mainly for rethrombosis (24%) and bleeding (12%). One fetus died 2 months after VT of unrelated causes. After a mean of 83 months, complete venous recanalization was seen in 88%, venous valve sufficiency in 90%, and PTS in 31% without any ulcers. At 10 years, PTS incidence rose to reach 50% with limited statistical significance because of the number of patients reaching long-term follow-up. Conclusions Iliofemoral venous recanalization during pregnancy can be performed safely in a specialized center, with lower PTS rates than in historical controls.

Die Nierentransplantation (NTX) stellt die haufigste der Transplantationen solider Organe dar. Als Standard hat sich die heterotope Organimplantation in die Fossa iliaca etabliert. Eine Besonderheit ist, dass keine obere Altersbegrenzung sowohl fur Spenderorgane als auch Empfanger besteht. Arteriosklerotische Gefasveranderungen der Empfanger konnen insbesondere den Transplantatanschluss an die Beckengefase erschweren bzw. ohne entsprechende Korrektur verunmoglichen. Auch bei der Spenderniere kann es zu Problemen durch arteriosklerotische Gefase und Gefasanomalien kommen. Bei der Organentnahme verletzte Spendergefase erfordern die gefaschirurgische Expertise. Nach NTX auftretende aortoiliakale Gefasstenosen und Stenosen im Bereich der Transplantatarterie konnen mit geringer Ischamiegefahrdung der Transplantatniere endovaskular behandelt werden. Die Rekonstruktionsmethoden der modernen Gefaschirurgie erweitern die Organanschlussmoglichkeiten. Den sekundaren Transplantationserfolg im Langzeitverlauf sichern vaskulare Eingriffe.

Objectives This study sought to evaluate patient outcome within the Dusseldorf Extracorporeal Life Support (ECLS) Network, a suprainstitutional network for rapid-response remote ECLS and to define survival-based predictors. Background Mobile venoarterial extracorporeal membrane oxygenation (vaECMO) used for ECLS has become a treatment option for a patient population with an otherwise fatal prognosis. However, outcome data remain scarce and institutional standards required to manage these patients are still poorly defined. Methods This retrospective cohort study analyzes the outcome of 115 patients consecutively treated between July 2011 and October 2014 within the Dusseldorf ECLS Network due to refractory circulatory failure. Results Of the 115 patients (56 ± 15 years of age, vaECMO initiation under cardiopulmonary resuscitation [CPR] 77%, CPR duration 45 [range 5 to 90] min), 50 patients (44%) survived to primary discharge and 38 patients (33%) were alive after a median follow-up of 1.5 years (95% confidence interval [CI]: 1.2 to 1.7). Thirty-seven (97%) of the long-term survivors showed a favorable neurological outcome. Risk factors associated with mortality during vaECMO were CPR duration (hazard ratio [HR]: 1.006; 95% CI: 1.00 to 1.01) and ischemic stroke (HR: 2.63; 95% CI: 1.52 to 4.56). Risk factors associated with mortality after vaECMO weaning were renal failure (HR: 6.60; 95% CI: 2.72 to 16.01) and sepsis (HR: 3.6; 95% CI: 1.50 to 8.69). Visceral ischemia had a negative impact (HR: 0.30; 95% CI: 0.11 to 0.84) whereas assist device implantation promoted successful vaECMO weaning (HR: 2.95; 95% CI: 1.65 to 5.25). Further, 3 distinct risk groups with significant differences in survival could be identified, demonstrating that in patients with no or short CPR mortality was not conditioned by age, whereas in patients with prolonged CPR young age was associated with increased survival. Conclusions This study illustrates the implementation of a suprainstitutional ECLS Network. Further, our data suggest that mobile vaECMO is beneficial for a larger patient population than actually expected, especially regarding young patients presenting with prolonged CPR or patients regardless of age with no or short CPR.

Copyright ©2016 Simon F. This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Volume 1 : Issue 3 Article Ref. #: 1000NPOJ1e004 Kidney Ischemia and Reperfusion Injury – Field of Glory or Warterloo for Erythropoietin?

Die akute Extremitatenischamie (AEI) gefahrdet sowohl die betroffene Gliedmase als auch das Leben des Patienten und stellt eine haufige Ursache fur eine Extremitatenamputation dar. Deshalb ist die AEI ein vaskularer Notfall, der einer raschen Revaskularisation bedarf. Die Ursachen sind kardiale Embolien, lokale Thrombosen, postrekonstruktive thrombotische Gefasverschlusse, embolisierende Aneurysmen, Aortendissektionen und Gefasverletzungen. Das 30-Tage-Major-Amputationsrisiko betragt 10–30 % und die 30-Tage-Mortalitat 15–30 %. Die Auspragung des Krankheitsbilds ist abhangig von der peripheren Restperfusion. Die Einteilung nach Rutherford und die 6 Ps nach Pratt beschreiben die Klinik. Man unterscheidet eine komplette Ischamie mit voller Auspragung der Symptomatik und eine inkomplette Form mit Erhalt der Sensibilitat und Motorik. Als Folgeereignis kann es zu einem Reperfusions- oder einem Kompartmentsyndrom kommen. Bei komplexer Vorgeschichte ist eine CTA fur die Therapieplanung hilfreich. Mittel der Wahl zur Diagnostik ist die Duplexsonographie und Angiographie. Als Therapieoptionen stehen die offen chirurgische Therapie, die endovaskulare Therapie oder eine Kombination aus beidem (Hybridverfahren) zur Verfugung. Mittlerweile haben die endovaskulare und die offenchirurgische Methode einen vergleichbaren Stellenwert bei der Behandlung einer AEI.