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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.

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.

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

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.

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.

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.

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.

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.

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.

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?

Spinal cord ischemia (SCI) is a clinical complication following aortic repair that significantly impairs the quality and expectancy of life. Despite some strategies, like cerebrospinal fluid drainage, the occurrence of neurological symptoms, such as paraplegia and paraparesis, remains unpredictable. Beside the major blood supply through conduit arteries, a huge collateral network protects the central nervous system from ischemia—the paraspinous and the intraspinal compartment. The intraspinal arcades maintain perfusion pressure following a sudden inflow interruption, whereas the paraspinal system first needs to undergo arteriogenesis to ensure sufficient blood supply after an acute ischemic insult. The so-called steal phenomenon can even worsen the postoperative situation by causing the hypoperfusion of the spine when, shortly after thoracoabdominal aortic aneurysm (TAAA) surgery, muscles connected with the network divert blood and cause additional stress. Vessels are a conglomeration of different cell types involved in adapting to stress, like endothelial cells, smooth muscle cells, and pericytes. This adaption to stress is subdivided in three phases—initiation, growth, and the maturation phase. In fields of endovascular aortic aneurysm repair, pre-operative selective segmental artery occlusion may enable the development of a sufficient collateral network by stimulating collateral vessel growth, which, again, may prevent spinal cord ischemia. Among others, the major signaling pathways include the phosphoinositide 3 kinase (PI3K) pathway/the antiapoptotic kinase (AKT) pathway/the endothelial nitric oxide synthase (eNOS) pathway, the Erk1, the delta-like ligand (DII), the jagged (Jag)/NOTCH pathway, and the midkine regulatory cytokine signaling pathways.

Aim: Arterial stiffness is a significant risk factor for many cardiovascular diseases, including abdominal aortic aneurysms (AAA). Nicotine, the major active ingredient of e-cigarettes and tobacco smoke, induces acute vasomotor effects that may temporarily increase arterial stiffness. Here, we investigated the effects of long-term nicotine exposure on structural aortic stiffness. Methods: Mice (C57BL/6) were infused with nicotine for 40 days (20 mg/kg/day). Arterial stiffness of the thoracic (TS) and abdominal (AS) aortic segments was analyzed using ultrasound (PWV, pulse wave velocity) and ex vivo pressure myograph measurements. For mechanistic studies, aortic matrix-metalloproteinase (MMP) expression and activity as well as medial elastin architecture were analyzed. Results: Global aortic stiffness increased with nicotine. In particular, local stiffening of the abdominal segment occurred after 10 days, while thoracic aortic stiffness was only increased after 40 days, resulting in aortic stiffness segmentation. Mechanistically, nicotine exposure enhanced expression of MMP-2/-9 and elastolytic activity in both aortic segments. Elastin degradation occurred in both segments; however, basal elastin levels were higher in the thoracic aorta. Finally, MMP-inhibition significantly reduced nicotine-induced MMP activity, elastin destruction, and aortic stiffening. Conclusion: Chronic nicotine exposure induces aortic MMP expression and structural aortic damage (elastin fragmentation), irreversibly increasing aortic stiffness. This process predominantly affects the abdominal aortic segment, presumably due in part to a lower basal elastin content. This novel phenomenon may help to explain the role of nicotine as a major risk factor for AAA formation and has health implications for ECIGs and other modes of nicotine delivery.

Chronic ischemia of the lower extremities is an everyday problem in vascular surgery clinics. In Germany, approximately 3% of all hospitalizations are due to peripheral artery disease (PAD), with critical limb ischemia (CLI) in particular showing a rapid increase. The consequences of chronic undersupply range from reduced walking distance to loss of limbs. At the beginning there are stress factors, such as hyperlipidemia (LDL), free radicals, arterial hypertension, infections or subclinical inflammation that interfere with endothelial homeostasis and cause endothelial dysfunction with increased permeability. Cells of the immune system are attracted and migrate into the vascular wall, where they lead to the degradation of matrix components and destabilization of the plaque. By changing the phenotype of smooth muscle cells and macrophages towards osteoclast-like cells, bone-like hardening of the vessel wall takes place. Above a vessel wall thickness of approximately 100 µm, hypoxia-induced factor (HIF-1α) is intensified by the lack of oxygen, which leads to an increase in growth factors, such as vascular endothelial growth factor (VEGF). This promotes angiogenesis, but it is not sufficient to compensate for a stenosed artery. Arteriogenesis refers to the growth of existing collateral vessels. The driving forces are the pressure gradient before and after the stenosis and the shear forces acting on the vessel walls. In the case of progressive stenosis, the compensatory capacities can be overtaxed and a manifest hypoxia in the tissue with regression of the obtained vascular structures and tissue atrophy occurs.Die chronisch arterielle Ischämie der unteren Extremitäten stellt ein alltägliches Problem in gefäßchirurgischen Kliniken dar. In Deutschland sind etwa 3 % aller Hospitalisierungen auf eine periphere arterielle Verschlusskrankheit (PAVK) zurückzuführen, wobei vor allem die kritischen Ischämien stark zunehmen. Die Folgen der chronischen Ischämie reichen von eingeschränkter Gehstrecke bis hin zum Verlust der Extremität. Am Anfang stehen Stressfaktoren wie Hyperlipidämie (LDL), freie Radikale, arterielle Hypertonie, Infektionen oder subklinische Entzündungen, die die Endothelhomöostase stören. Es kommt zu einer Dysfunktion des Endothels mit erhöhter Durchlässigkeit. Zellen des Immunsystems werden angelockt und wandern in die Gefäßwand ein, wo sie zum Abbau von Matrixkomponenten und zur Destabilisierung des Plaques führen. Durch Änderung des Phänotyps von glatten Muskelzellen und Makrophagen entstehen osteoklastenähnliche Zellen, die zu Verhärtungen in der Gefäßwand führen. Ab einer Gefäßwandstärke von etwa 100 μm wird durch den Sauerstoffmangel Hypoxie induzierter Faktor (HIF-1α) verstärkt exprimiert, was zu einem Anstieg an Wachstumsfaktoren wie VEGF („vascular endothelial growth factor“) führt. Dadurch wird die Angiogenese als Kapillarenbildner gefördert, reicht aber nicht aus, um eine stenosierte Arterie zu kompensieren. Arteriogenese bezeichnet das Wachstum von bereits vorhandenen Kollateralgefäßen. Die treibenden Kräfte sind der Druckgradient vor und hinter der Stenose sowie die Scherkräfte, die auf die Gefäßwände einwirken. Bei voranschreitender Stenosierung können die Kompensationsfähigkeiten überfordert werden und es kommt zu einer manifesten Hypoxie im Gewebe mit Rückbildung der gewonnenen Gefäßstrukturen/Kollateralkreisläufen und Gewebsatrophie.

Objective Hypogastric artery aneurysms (HAAs) are rare but life-threatening in cases of rupture. Open or endovascular techniques traditionally aimed at occluding the hypogastric artery (HA) have considerable risk of pelvic ischemia. Iliac branch devices (IBDs) are indicated for aortoiliac aneurysms; however, they have also been used lately for HAAs. Currently, there are no reports about patient outcomes focusing on HAA therapy using IBDs. We retrospectively analyzed early and midterm outcomes using IBDs for HAAs. Methods Patients who received IBDs for HAAs at our department from January 1, 2012, through March 1, 2018, were included. Exclusion criteria were as follows: no HA involvement, emergency procedures, and HA stent grafting without IBD. Perioperative and follow-up data were collected from medical records. Results There were 18 IBDs (only IBD, n = 4; IBD + endovascular aneurysm repair [EVAR], n = 7; IBD ± EVAR + side branch occlusion, n = 7) implanted into 14 male patients (76 ± 4 [70-83] years). There were no intraoperative complications, and the technical success rate was 100%. After 19 ± 11 (2-39) months of follow-up, two hybrid (external iliac artery occlusion, n = 1; EVAR graft kinking, n = 1) and four endovascular reinterventions due to two type IB (side branch coiling + stent graft extension) and two type IIIB (stent grafting) endoleaks were required. One IBD-related type II endoleak revealed constant aneurysm diameters during follow-up. One small type IB endoleak was self-limited. Estimated freedom from reintervention was 31% ± 23% at 2.7 years. The clinical success and patency rate was 100%. The IBD-related mortality was 0%. Conclusions The IBD for HAA shows good early and midterm results. Adequate sealing of HA landing zones and side branch occlusion are technically challenging but crucial to prevent type IB and type II endoleaks.

To describe a case of intraoperative thrombotic occlusion of the left hypogastric artery (HA) during endovascular treatment for acute Leriche syndrome and a feasible technique for HA embolectomy and prevention of pelvic ischemia. After bilateral transfemoral vascular access Fogarty thrombectomy of the infrarenal aorta and bilateral common and external iliac arteries was performed. Then, an intraoperative angiography revealed new thrombotic occlusion of the left HA. Ipsilateral transfemoral approach was impeded by a strong angulation between HA and iliac artery. Therefore, a right-transfemoral approach was used for crossover Fogarty thrombectomy. The thrombus was mobilized into the left common iliac artery and could easily be removed by left-transfemoral embolectomy. No complications occurred. Crossover thrombectomy is a feasible technique for endovascular treatment of acute thrombotic occlusion of HAs. Occlusion of HA should be treated whenever possible.

Background Subclavian carotid transposition (SCT) is a safe, effective, and durable treatment in atherosclerotic disease of the proximal subclavian artery. We report about our experience in SCT in a retrospective study with a long-term outcome in 126 cases and discuss our results with the current literature. Methods From January 1995 to December 2013, we treated 126 patients (51 men, 75 women; mean age, 60.9 years; range, 25–80 years) for proximal subclavian atherosclerotic lesions. Preoperative angiography revealed 58 stenoses (46.0%) and 68 occlusions (54.0%). We performed 126 SCTs. The following parameters were documented through a retrospective chart review: demographic data, occlusion site, preoperative symptoms, cardiovascular risk profile, coexisting cerebrovascular disease, and postoperative outcome. Continuous variables are summarized as mean. Categoric variables are expressed as frequency and percentage. Survival and patency rates were estimated using Kaplan–Meier analysis. Results Four immediate occlusions and 1 hemodynamic relevant stenosis (4.0%) occurred postoperatively. Thrombectomy was successful in 2 and a carotid axillary bypass was performed in 3 cases. Three strokes occurred, one during concomitant carotid endarterectomy. The 30-day mortality was 0%. Follow-up data were obtained on 106 of 126 patients (84.0%). The mean follow-up period was 53.8 months (range, 3–159 months). Twenty-three (18.3%) late deaths occurred. Estimated survival was 121.48 ± 6.86 months (range, 3–112 months). Ninety-five percent reported continuous resolution of symptoms. Primary patency rate was 96.0% and secondary patency rate was 100% at 30 days. The long-term patency rate was 96.3% at a mean follow-up of 53.8 months. Conclusions SCT is safe, effective, and durable in the long term. SCT is a standard procedure for occlusion and stenosis. Vessel occlusions, ineffective angioplasty, and preparation for thoracic stent grafting make SCT an important procedure in the surgeon's repertoire.

Acute ischemia of an extremity occurs in several stages, a lack of oxygen being the primary contributor of the event. Although underlying patho-mechanisms are similar, it is important to determine whether it is an acute or chronic event. Healthy tissue does not contain enlarged collaterals, which are formed in chronically malperfused tissue and can maintain a minimum supply despite occlusion. The underlying processes for enhanced collateral blood flow are sprouting vessels from pre-existing vessels (via angiogenesis) and a lumen extension of arterioles (via arteriogenesis). While disturbed flow patterns with associated local low shear stress upregulate angiogenesis promoting genes, elevated shear stress may trigger arteriogenesis due to increased blood volume. In case of an acute ischemia, especially during the reperfusion phase, fluid transfer occurs into the tissue while the vascular bed is simultaneously reduced and no longer reacts to vaso-relaxing factors such as nitric oxide. This process results in an exacerbative cycle, in which increased peripheral resistance leads to an additional lack of oxygen. This whole process is accompanied by an inundation of inflammatory cells, which amplify the inflammatory response by cytokine release. However, an extremity is an individual-specific composition of different tissues, so these processes may vary dramatically between patients. The image is more uniform when broken down to the single cell stage. Because each cell is dependent on energy produced from aerobic respiration, an event of acute hypoxia can be a life-threatening situation. Aerobic processes responsible for yielding adenosine triphosphate (ATP), such as the electron transport chain and oxidative phosphorylation in the mitochondria, suffer first, thus disrupting the integrity of cellular respiration. One consequence of this is irreparable damage of the cell membrane due to an imbalance of electrolytes. The eventual increase in net fluid influx associated with a decrease in intracellular pH is considered an end-stage event. Due to the lack of ATP, individual cell organelles can no longer sustain their activity, thus initiating the cascade pathways of apoptosis via the release of cytokines such as the BCL2 associated X protein (BAX). As ischemia may lead to direct necrosis, inflammatory processes are further aggravated. In the case of reperfusion, the flow of nascent oxygen will cause additional damage to the cell, further initiating apoptosis in additional surrounding cells. In particular, free oxygen radicals are formed, causing severe damage to cell membranes and desoxyribonucleic acid (DNA). However, the increased tissue stress caused by this process may be transient, as radical scavengers may attenuate the damage. Taking the above into final consideration, it is clearly elucidated that acute ischemia and subsequent reperfusion is a process that leads to acute tissue damage combined with end-organ loss of function, a condition that is difficult to counteract.

Objective We assessed outcomes of open surgical venous thrombectomy with temporary arteriovenous fistula, and the procedure’s effect on health-related quality of life. Method We retrospectively analyzed 48 (26 at long-term) patient medical records. Mortality rates, patency, and risk of post-thrombotic syndrome were analyzed using Kaplan–Meier estimation. The association between risk factors/coagulation disorders and patency/post-thrombotic syndrome along with patient health-related quality of life at long-term was analyzed employing various statistical methods. Results Patient one-year survival rate was 93 ± 4% and primary one-year patency rate was 89 ± 5% (secondary one-year patency rate 97 ± 3%). Freedom from post-thrombotic syndrome after eight years was 80 ± 12% (post-thrombotic syndrome rate 20 ± 12%). Health-related quality of life was impaired vs. normative data in the physical and social subscales, and in the mental component score ( p Conclusions Open surgical venous thrombectomy appears safe compared with literature-reported outcomes in similar patients using alternative approaches. Iliofemoral deep vein thrombosis impairs physical, social, and mental health-related quality of life.

An analysis was conducted of intermediate outcomes and possible influencing factors in patients with end-stage renal disease (ESRD) and critical limb ischemia after lower limb revascularization compared with patients with regular renal function (non-ESRD).Data collection was performed by inquiry of the German multicenter registry of First-Line Treatments in Patients with Critical Limb Ischemia (CRITISCH); 102 ESRD patients and 674 non-ESRD patients were included. Four different therapy modalities were analysed: bypass surgery, endovascular therapy (EVT), femoral artery endarterectomy, and no vascular intervention (conservative treatment or primary major amputation). Predefined end points were amputation-free survival (AFS), death, major amputation, and reintervention. Cox regression models were built to analyze independent risk factors for outcome parameters.ESRD patients showed inferior results at 2 years in the rate of AFS (ESRD, 35.4%; non-ESRD, 67.2%; P .001). Similarly, death rate (ESRD, 55.0%; non-ESRD, 20.7%; P .001) and major amputation rate (ESRD, 24.5%; non-ESRD, 15.8%; P = .029) were significantly elevated for ESRD patients. The choice of therapeutic approach in ESRD did not influence the incidence of the investigated end points (death or major amputation: EVT, 56.9% vs bypass, 76.9% [P = .225]; death: EVT, 46.2% vs bypass, 61.5% [P = .372]; amputation: EVT, 15.4% vs bypass, 15.4% [P = 1.000]; reintervention: EVT, 32.3% vs bypass, 15.4% [P = .324]). Cox regression analysis indicated that dialysis patients carry a twofold increased hazard of death or major amputation (hazard ratio, 2.27; 95% confidence interval, 1.67-3.10; P .001), and open surgical treatment (all patients combined) was associated with reduced risk of death compared with EVT (hazard ratio, 0.58; 95% confidence interval, 0.37-0.91; P = .017). Comorbidities were not found to have a noticeable impact on AFS, survival, reintervention, or major amputation.Two-year AFS, overall survival, and freedom from major amputation were decreased in ESRD patients compared with non-ESRD patients with critical limb ischemia. Cardiovascular comorbidities were without significant impact on outcome parameters, whereas choice of treatment modality within the ESRD group did not influence AFS. Decision-making in ESRD as to choice of therapeutic approach in dialysis patients should notably account for the individual's lesion characteristics and vascular disease; surgical revascularization and EVT may be used as complementary options.

Background Median arcuate ligament syndrome is a rare condition with abdominal symptoms. Accepted treatment options are open release of median arcuate ligament, laparoscopic release of edian arcuate ligament, robot-assisted release of median arcuate ligament and open vascular treatment. Here we aimed to evaluate the central priority of open vascular therapy in the treatment of median arcuate ligament syndrome. Methods We conducted a monocentric retrospective study between January 1996 and June 2016. Thirty-one patients with median arcuate ligament syndrome underwent open vascular surgery, including division of median arcuate ligament in 17 cases, and vascular reconstruction of the celiac artery in 14 cases. Results In a 20-year period, 31 patients (n = 26 women, n = 5 men) were treated with division of median arcuate ligament (n = 17) or vascular reconstruction in combination with division of median arcuate ligament (n = 14). The mean age of patients was 44.8 ± 15.13 years. The complication rate was 16.1% (n = 5). Revisions were performed in 4 cases. The 30-day mortality rate was 0%. The mean in-hospital stay was 10.7 days. Follow-up data were obtained for 30 patients. The mean follow-up period was 52.2 months (range 2–149 months). Patients were grouped into a decompression group (n = 17) and revascularisation group (n = 13). The estimated Freedom From Symptoms rates were 93.3, 77.8, and 69.1% for the decompression group and 100, 83.3, and 83.3% for the revascularisation group after 12, 24 and 60 months respectively. We found no significant difference in the Freedom From Re-Intervention CA rates of the decompression (100% at 12, 24 and 60 months post-surgery) and revascularisation (100% at 12 months, and 91.7% at 24 and 60 months post-surgery) groups during follow-up (p = 0.26). Conclusions Open vascular treatment of median arcuate ligament syndrome is a safe, low mortality-risk procedure, with low morbidity rate. Treatment choice depends on the clinical and morphological situation of each patient.

Ischemic stroke may occur in patients in whom vascular imaging shows the ipsilateral internal carotid artery (ICA) to be occluded. In younger patients this is often due to carotid artery dissection, while in older people this most likely results from cardiac embolism or thrombosis secondary to high-grade stenosis at the carotid bifurcation. Interventional techniques aim at recanalization of the carotid artery for early restoration of cerebral blood flow and secondary prevention of future strokes. In chronic ICA occlusion the ischemic infarct may be related to hemodynamic compromise. In this situation, extracranial-intracranial bypass surgery was introduced, but its role remains still unclear. Ischemic stroke may also occur in patients with a chronic occlusion of the contralateral ICA. This situation demands the usual stroke treatment, but surgical and neuroradiological interventions face a higher risk than unilateral vascular pathology. Medical treatment supports stroke prevention in carotid artery occlusion.

Objective Inferior vena cava thrombosis is rare, but patients are at high risk for development of a post-thrombotic syndrome (PTS) in the long term. Surgical approaches include indirect transfemoral venous thrombectomy (iTFVT) and direct open venous thrombectomy (dOVT). This study reports patient outcomes after iTFVT and dOVT for inferior vena cava thrombosis covering a 25-year follow-up period. Methods The study period was from January 1, 1982, to December 31, 2013. Data were retrieved from archived medical records, and patients were invited for a detailed phlebologic follow-up examination (DPFE). Health-related quality of life was assessed with the 36-Item Short Form Health Survey questionnaire. Patient survival, patency rates, and freedom from PTS were calculated using Kaplan-Meier estimation with log-rank testing. The χ2 test with Yates continuity correction and logistic regression analysis were applied to identify associations between risk factors or coagulation disorders, mortality, and PTS. Results Complete medical records were available for 152 patients. Patients' 5-year survival was 91% ± 3%, and 5-year primary and secondary patency rates were 80% ± 3% and 94% ± 2%. Freedom from PTS after 25 years was 84% ± 6%. No differences for patient survival, patency rates, or freedom from PTS were identified between iTFVT, dOVT, and a combination of both procedures. Antithrombin III deficiency was the most common coagulation disorder, and patients' physical function and social function were impaired compared with those found in German normative data (P Conclusions Open surgical venous thrombectomy is safe and delivers satisfying short- and long-term outcomes compared with endovascular approaches. It remains valuable for patients who are not eligible for other interventional therapies.

Secondary prevention in patients with critical limb ischemia (CLI) is crucial for the reduction of cardiovascular morbidity and mortality. Nonetheless, current recommendations are extrapolated from other high-risk populations because of the lack of CLI-dedicated trials. The aim of this explorative study was to evaluate the association of statin therapy with the outcomes of CLI patients.The First-Line Treatments in Patients With Critical Limb Ischemia (CRITISCH) registry is a prospective multicenter registry analyzing the effectiveness of all available treatment strategies in 1200 CLI patients. For the purposes of this analysis, patients were divided into two groups based on statin administration. Treatment crossovers and nonadherent patients were excluded from analysis. The primary composite end point of this study was the amputation-free survival (AFS). Major adverse cardiovascular and cerebral events (MACCEs), time to death, and time to major amputation were also analyzed.Statin therapy was applied in 445 individuals (37%), 371 (31%) patients received no statins, and 384 subjects were excluded from analysis (treatment crossovers). Patients receiving statins were more likely to be younger (P .001) and to have a history of coronary heart disease (P .001) or previous intervention at index limb (P .001). Patients receiving statin therapy had a lower hazard regarding AFS (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.34-0.63; P .001) and death (HR, 0.40; 95% CI, 0.24-0.66; P .001) as well as lower odds of MACCE (odds ratio, 0.41; 95% CI, 0.23-0.69; P = .001). However, statin therapy was not associated with reduced amputation rates (HR, 1.02; 95% CI, 0.67-1.56; P = .922). Statin effect on AFS was consistent among diabetics (HR, 0.47; 95% CI, 0.31-0.70; P .001), patients with chronic kidney disease (HR, 0.53; 95% CI, 0.32-0.87; P = .012), and patients older than 75 years (HR, 0.40; 95% CI, 0.26-0.60; P .001). Statin administration was also associated with an improved AFS in patients with antiplatelet medication (HR, 0.64; 95% CI, 0.41-0.99; P = .049) and without antiplatelet medication (HR, 0.26; 95% CI, 0.12-0.57; P = .001) and after both endovascular therapy (HR, 0.51; 95% CI, 0.34-0.76; P = .001) and bypass revascularization (HR, 0.38; 95% CI, 0.21-0.68; P = .001).Statin therapy in CLI patients is associated with an increased AFS and lower rates of mortality and MACCEs without improving, however, the salvage rates of the affected limb.

To test the hypothesis that a carbamylated EPO-FC fusion protein (cEPO-FC) or recombinant human erythropoietin (rhEPO) would protect against kidney ischemia/reperfusion (I/R) injury in pigs with atherosclerosis.Anesthetized and mechanically ventilated animals received cEPO-FC (50 μg kg(-1)), rhEPO (5,000 IU kg(-1)), or vehicle (n = 9 per group) prior to 120 min of aortic occlusion and over 4 h of reperfusion. During aortic occlusion, mean arterial pressure (MAP) was maintained at 80-120 % of baseline values by esmolol, nitroglycerin, and ATP. During reperfusion, noradrenaline was titrated to keep MAP at pre-ischemic levels. Blood creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels, creatinine clearance, fractional Na(+) excretion, and HE and PAS staining were used to assess kidney function and histological damage. Plasma interleukin-6, tumor necrosis factor-α, nitrate + nitrite and 8-isoprostane levels were measured to assess systemic inflammation, and nitrosative and oxidative stress.I/R caused acute kidney injury with reduced creatinine clearance, increased fractional Na(+) excretion and NGAL levels, moderate to severe glomerular and tubular damage and apoptosis, systemic inflammation and oxidative and nitrosative stress, but there were no differences between the treatment groups. Pre-ischemia nitrate + nitrite and 8-isoprostanes levels were lower and higher, respectively, than in healthy animals of a previous study, and immune histochemistry showed higher endothelial nitric oxide synthase and lower EPO receptor expression in pre-ischemia kidney biopsies than in biopsies from healthy animals.In swine with atherosclerosis, rhEPO and cEPO-FC failed to attenuate prolonged ischemia-induced kidney injury within an 8-h reperfusion period, possibly due to reduced EPO receptor expression resulting from pre-existing oxidative stress and/or reduced NO release.

Inflammatory abdominal aortic aneurysms (IAAAs) are rare clinical entities with an exaggerated inflammatory component. The aim of this study is to report outcomes of a single-center 10-year experience in open surgical management of IAAA and to compare the results with noninflammatory, atherosclerotic abdominal aortic aneurysms (non-IAAAs).We retrospectively reviewed the medical records of 18 patients with IAAA selected out of patients with AAA who underwent open surgery in the Department of Vascular and Endovascular Surgery at the University Hospital Dusseldorf from January 2006 to December 2015. These patients were matched with controls, selected from a prospectively retained database of patients with AAA undergoing open surgery during the study period. A 1:2 case-control match regarding age, gender, and year of treatment was performed. We analyzed both groups for preoperative parameters, intraoperative findings, and early postoperative outcomes.The 2 groups showed considerable similarities with no significant differences in the clinical features. Both groups outlined comparable aneurysm size (62 vs. 56 mm); however, the mean preoperative C-reactive protein was found to be significantly elevated in the study group (mean value: 2.6 vs. 0.9 mg/dL, P 0.05). Most patients were operated using a standard transperitoneal median laparotomy approach; only 1 patient of each group was operated using a left retroperitoneal approach. There was no significant difference in operation time (190 vs. 194 min) and 30-day mortality 0%. The in-hospital mortality was 11% in the study group and 0% in the control group. We found a significant higher complication rate in the study group 10 (56%) vs. 12 (33%). The major complications were also more frequent in the study group 4 (22%) vs. 6 (16.7%). IAAA showed a statistically significant longer length of intensive care unit and hospital stay when compared with non-IAAA (7 and 20 days vs. 2 and 14 days, P 0.05). IAAAs outlined a significantly greater transfusion requirement for erythrocytes and fresh frozen plasma than non-IAAA.Open surgical treatment of IAAA guarantees a regression of the inflammatory process in most patients, which was detected through ultrasound in follow-up examination, although the approach to the surgical site is highly demanding. IAAA exhibits clear gender predominance and is associated with significantly higher transfusion requirement, early morbidity, and length of stay.

PLoS one 12(2), e0170644 (2017). doi:10.1371/journal.pone.0170644, Published by PLoS, Lawrence, Kan.

Objective Renal artery (RA) aneurysm (RAA) is a rare and complex disease. Treatment options for a RAA include endovascular surgery and open surgery with ex vivo repair or in situ reconstruction. This study evaluated the long-term outcome after vascular reconstruction of RAAs using the tailoring technique. Tailoring or aneurysmorrhaphy means a partial resection of the aneurysm with direct suture of the remaining arterial wall. Methods A single-center retrospective study was conducted between January 1990 and December 2015. The tailoring technique was used to surgically repair 88 RAAs in 80 patients (52 women) with a mean age of 52.9 years. Patients' demographic data, vascular therapy, and renal function during follow-up were retrospectively evaluated. Results The localization of the RAA was at the right kidney in 58 patients. The mean size of the aneurysm was 21.4 ± 9.7 mm (range, 8-67 mm). Hypertension was diagnosed in 56 patients, and 23 were asymptomatic. One RAA was ruptured. The overall morbidity rate was 16.3%, including bleeding (n = 4), RA stenosis (n = 3), RA occlusion (n = 4), RA dissection (n = 1), and myocardial infarction (n = 1). One patient died of myocardial infarction for a 30-day mortality rate of 1.3%. The 30-day primary patency rate was 90.0%. The 30-day secondary patency rate was 95.0%. Follow-up data were obtained from 71 patients who underwent tailoring in 78 RAAs. The mean follow-up period was 60.7 months (range 2-229 months). In 76.4% of patients with RAA and hypertension, RAA reconstruction contributed to the cure or improvement of hypertension. The long-term patency after RAA reconstruction was demonstrated in a Kaplan-Meier curve, with cumulative patency rates of 98.7%, 97.4%, 94.8%, and 92.3% after 18, 24, 36, and 48 months, respectively. Estimated survival rates were 98.8%, 97.5%, and 96.3% after 12, 48, and 60 months, with an estimated mean time of 216.5 ± 7.2 months. Conclusions The tailoring technique is a safe and effective procedure with good long-term outcomes. RAA reconstruction contributed to the cure or improvement of renovascular hypertension.

Objective The aim of this study was to investigate the 1-year safety and efficacy of a new iliac side-branched device (IBD) for revascularization of the hypogastric arteries. Methods Patients receiving the E-liac (Jotec GmbH, Hechingen, Germany) side-branched device at six German vascular centers either as a stand-alone procedure or in combination with abdominal aortic aneurysm exclusion were included in a prospectively created data bank. Collected data were analyzed for baseline characteristics, procedural events, and clinical follow-up; variables included endoleaks, reinterventions, and internal iliac artery (IIA) patency. Results Between January 2012 and January 2015, a total of 70 patients (69 men [98.6%]) with a median age of 74 years (range, 51-87 years) were consecutively treated; 66 patients had aneurysmatic disease of the iliac arteries, 2 patients had a para-anastomotic aneurysm after aortobi-iliac reconstruction, and another 2 patients had a type Ib endoleak after endovascular aneurysm repair. A total of 82 IIAs were revascularized, 12 bilaterally. Technical success was achieved in 100% (82/82) of the revascularized IIAs. All IBDs were patent at the end of the procedure. No instances of myocardial infarction, stroke, conversion to open repair, mesenteric or spinal cord infarction, or buttock necrosis were observed. There was one perioperative death (1.4%) in a 70-year-old patient with intraoperative gastrointestinal bleeding leading to multiple organ failure, which resulted in the patient's death on the fifth postoperative day. Within 30 days, one symptomatic occlusion of a treated common iliac artery (CIA) was observed. In two other patients, an asymptomatic kinking of the CIA segment of the IBD was revealed in the predischarge follow-up duplex ultrasound examination and corrected with relining. Median follow-up was 12 months (range, 6-16 months). One patient was lost during the follow-up period. Survival at 1 year was 98.5% with all IIAs remaining patent, whereas two CIA and two external iliac artery limb occlusions occurred. According to life-table analysis, the freedom from occlusion in a patient was 92% at 1 year, and freedom from type I endoleak was 87% at 1 year. Conclusions This first ever 1-year study reports the results with the new E-liac device and shows that it can be safely applied for the treatment of aortoiliac aneurysmatic disease with low reintervention rates and high patency rates. Long-term data are needed to confirm the durability of the device.

In rodents, inhaled H2S and injection of H2S donors protected against kidney ischemia/reperfusion (I/R) injury. During porcine aortic occlusion, the H2S donor Na2S (sulfide) reduced energy expenditure and decreased the noradrenaline requirements needed to maintain hemodynamic targets during early reperfusion. Therefore, we tested the hypothesis whether sulfide pretreatment may also ameliorate organ function in porcine aortic occlusion-induced kidney I/R injury. Anesthetized, ventilated, and instrumented pigs randomly received either sulfide or vehicle and underwent 90 min of kidney ischemia using intraaortic balloon-occlusion, and 8 h of reperfusion. During reperfusion, noradrenaline was titrated to maintain blood pressure at baseline levels. Sulfide attenuated the fall in creatinine clearance and the rise in creatinine blood levels, whereas renal blood flow and fractional Na+ excretion were comparable. Sulfide also lowered the blood IL-6, IL-1β, and nitrite + nitrate concentrations, which coincided with reduced kidney oxidative DNA base damage and iNOS expression, and attenuated glomerular histological injury as assessed by the incidence of glomerular tubularization. While expression of heme oxygenase 1 and cleaved caspase 3 did not differ, sulfide reduced the expression Bcl-xL and increased the activation of nuclear transcription factor κB. During porcine aortic occlusion-induced kidney I/R injury, sulfide pretreatment attenuated tissue injury and organ dysfunction as a result of reduced inflammation and oxidative and nitrosative stress. The higher nuclear transcription factor κB activation was probably due to the drop in temperature.

Over the last three decades, the development of systematic and protocol-based algorithms, and advances in available diagnostic tests have become the indispensable parts of practising medicine. Naturally, despite the implementation of meticulous protocols involving diagnostic tests or even trials of empirical therapies, the cause of one's symptoms may still not be obvious. We herein report a case of chronic back pain, which took about 5 years to get accurately diagnosed. The case challenges the diagnostic assumptions and sets ground of discussion for the diagnostic reasoning pitfalls and heuristic biases that mislead the caring physicians and cost years of low quality of life to our patient. This case serves as an example of how anchoring heuristics can interfere in the diagnostic process of a complex and rare entity when combined with a concurrent potentially life-threatening condition.

Tyrosine kinase inhibitors against the receptors of vascular endothelial growth factor (VEGFR), epidermal growth factor (EGFR) and the platelet derived growth factor (PDGFR) are increasingly used in the treatment of progressive cancers. However, the expression of these receptors especially in lung metastases has not been examined. Tissue specimen from 35 lung metastases of 33 patients with renal cell carcinoma (n=8), sarcoma (n=10), colorectal carcinoma (n=6), otolaryngologic carcinoma (OLC, n=4), testicular and endometrial cancer (n=1 each), malignant melanoma (n=1), adrenal cancer (n=2), malignant fibrous histiocytoma and malignant peripheral nerve sheath tumor (n=1 each) have been immunohistochemically tested for the expression of PDGFR alpha/beta, VEGFR and EGFR. None of the patients had been pretreated with angiogenic inhibitors prior to metastasectomy. PDGFRalpha was expressed in all metastases; 31% stained negative for PDGFRbeta, 86% negative for VEGFR and 45% negative for EGFR. Primary tumors revealed positive staining for PDGFRalpha in 88%, for PDGFRbeta in 59%, for VEGFR in 0% and for EGFR in 18%. Our investigation of a pilot character represents a 'biomarker-based' analysis of pulmonary metastases of different primary tumors; we conclude that an immediate 'tumor profiling' at initial diagnosis should be considered in order to guide tumor therapy individually.

Background: Hybrid procedures for thoracoabdominal aortic aneurysms (TAAA) have been previously described as an attractive alternative to open reconstruction. Patients and Methods: Between 1999 and 2009, 16 patients with a median age of 67years underwent hybrid repair of a TAAA (Crawford type I: 3, type II: 3, type III: 1, and type IV: 9). In 94%, 3 and more severe comorbidities were present, with previous aortic surgery in 56% of the patients; elective/urgent repair was done in 10 and emergent surgery in 6 patients. Results: Primary technical success was 100%, with 31 vessels grafted. Elective/urgent mortality was 20% (2 of 10) and emergent mortality 50% (3 of 6). During follow-up time (median: 12 months) 2 patients died and 2 patients had to undergo secondary interventions. Conclusion: In high-risk patients especially after prior aortic surgery hybrid repair of TAAA is feasible. However, due to high mortality rates especially in the emergent situation this procedure should be reserved only for decidedly selected patients.

Bernd Muehling1, Alexander Oberhuber1, Hubert Schelzig1, Gisela Bischoff1, Nikolaus Marx2, Ludger Sunder-Plassmann1, Karl H Orend11Department of Thoracic and Vascular surgery; 2Department of Internal Medicine, University of Ulm, Ulm, GermanyBackground and aims: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL).Methods: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter.Results: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter.Conclusion: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurismal disease remains to be elucidated.Keywords: biomarkers, aneurismal disease, statin therapy

Background: Aortic occlusion causes ischemia/reperfusion injury, kidney and spinal cord being the most vulnerable organs. Erythropoietin improved ischemia/reperfusion injury in rodents, which, however, better tolerate ischemia/reperfusion than larger species. Therefore, we investigated whether erythropoietin attenuates porcine aortic occlusion ischemia/reperfusion injury. Materials and Methods: Before occluding the aorta for 45 mins by inflating intravascular balloons, we randomly infused either erythropoietin (n = 8; 300 IU/kg each over 30 mins before and during the first 4 hrs of reperfusion) or vehicle (n = 6). During aortic occlusion, mean arterial pressure was maintained at 80% to 120% of baseline by esmolol, nitroglycerine, and adenosine 5’-triphosphate. During reperfusion, noradrenaline was titrated to keep mean arterial pressure >80% of baseline. Kidney perfusion and function were assessed by fractional Na-excretion, p-aminohippuric acid and creatinine clearance, spinal cord function by lower extremity reflexes and motor evoked potentials. Blood isoprostane levels as well as blood and tissue catalase and superoxide dismutase activities allowed evaluation of oxidative stress. After 8 hrs of reperfusion, kidney and spinal cord specimens were taken for histology (hematoxylin–eosin, Nissl staining) and immunohistochemistry (TUNEL assay for apoptosis). Results: Parameters of oxidative stress and antioxidative activity were comparable. Erythropoietin reduced the noradrenaline requirements to achieve the hemodynamic targets and may improve kidney function despite similar organ blood flow, histology, and TUNEL staining. Neuronal damage and apoptosis was attenuated in the thoracic spinal cord segments without improvement of its function. Conclusion: During porcine aortic occlusion-induced ischemia/reperfusion erythropoietin improved kidney function and spinal cord integrity. The lacking effect on spinal cord function was most likely the result of the pronounced neuronal damage associated with the longlasting ischemia.

Background: Fast track programs, multimodal therapy strategies, have been introduced in many surgical fields to minimize postoperative morbidity and mortality. In terms of lung resections no randomized controlled trials exist to evaluate such patient care programs. Methods: In a prospective, randomized controlled pilot study a conservative and fast track treatment regimen in patients undergoing lung resections was compared. Main differences between the two groups consisted in preoperative fasting (6 h vs 2 h) and analgesia (patient controlled analgesia vs patient controlled epidural analgesia). Study endpoints were pulmonary complications (pneumonia, atelectasis, prolonged air leak), overall morbidity and mortality. Analysis was performed in an intention to treat. Results: Both study groups were similar in terms of age, sex, preoperative forced expiratory volume in one second (FEV1), American Society of Anesthesiologists score and operations performed. The rate of postoperative pulmonary complications was 35% in the conservative and 6.6% in the fast track group (p = 0.009). A subgroup of patients with reduced preoperative FEV1 (

Fast-track programs have been introduced in many surgical fields to minimize postoperative morbidity and mortality. Morbidity after elective open infrarenal aneurysm repair is as high as 30%; mortality ranges up to 10%. In terms of open infrarenal aneurysm repair, no randomized controlled trials exist to introduce and evaluate such patient care programs.This study involved prospective randomization of 82 patients in a "traditional" and a "fast-track" treatment arm. Main differences consisted in preoperative bowel washout (none vs. 3 l cleaning solution) and analgesia (patient controlled analgesia vs. patient controlled epidural analgesia). Study endpoints were morbidity and mortality, need for postoperative mechanical ventilation, and length of stay (LOS) on intensive care unit (ICU).The need for assisted postoperative ventilation was significantly higher in the traditional group (33.3% vs. 5.4%; p = 0.011). Median LOS on ICU was shorter in the fast-track group, 41 vs. 20 h. The rate of postoperative medical complications was significantly lower in the fast-track group, 16.2% vs. 35.7% (p = 0.045).We introduced and evaluated an optimized patient care program for patients undergoing open infrarenal aortic aneurysm repair which showed a significant advantage for "fast-track" patients in terms of postoperative morbidity.

Objective This study examined effects and functional outcome of recombinant human erythropoietin (rhEPO) and carbamylated erythropoietin fusion protein (cEPO-FC) preconditioning in a rabbit model for spinal cord ischemia and resulting paraplegia. This model was chosen because only a small surgical effect is needed to cause paraplegia in rabbits, which facilitates postoperative observation of animals. Methods Anesthetized but spontaneously breathing New Zealand White rabbits randomly received cEPO-FC (50 μg/kg; n = 8), rhEPO (5000 IU/kg; n = 10), or vehicle (control; n = 10) 30 minutes before and after infrarenal aortic clamping. Ideal clamping time of 22 minutes was identified from preceding clamping tests (15-25 minutes). Postoperative observation time was 96 hours. Spinal cord function was assessed by neurologic evaluation of hind limb motor function every 12 hours using a modified Tarlov score. Spinal cord tissue damage was evaluated after 96 hours using hematoxylin and eosin, elastica van Gieson, Nissl, Masson-Goldner, and hemosiderin staining. Plasma levels of cell senescence markers stathmin, chitinase 1/3, elongation factor 1-α were determined. Results Rabbits that received rhEPO showed significant improvement of spontaneous lower limb movements until 36 hours of reperfusion and improved histologic scores upon examination of the lumbar spinal cord compared with the control group. In contrast, cEPO-FC treatment showed comparable outcome to the control group concerning movements of the lower limbs and histology. Senescence markers were elevated in the control group, but not in the treatment groups, except for chitinase 3 in the rhEPO group. Only stathmin showed no significant effect. Markers for senescence might increase after acute ischemic injury. Attenuation of senescence markers might not come alone from improvement of the spinal cord. Conclusions Preconditioning with rhEPO attenuates ischemia/reperfusion injury of the spinal cord, whereas the carbamylated derivative (cEPO-FC) showed no positive effect on spinal cord function.

Purpose: To describe a contralateral femoral approach for iliac branch device implantation using a steerable sheath in the setting of an existing bifurcated stent-graft. Technique: The method is demonstrated in an 80-year-old man who developed a 4-cm iliac aneurysm 3 years after implantation of an Endurant bifurcated stent-graft. Both femoral arteries were cannulated after surgical cutdown. The steerable sheath was advanced from the contralateral side over the neobifurcation of the bifurcated stent-graft. A 0.014-inch Roadrunner wire was used as a through-and-through wire to stabilize the curve of the sheath and to get proper push. The bridging stent-graft for the iliac branch was advanced over this sheath to seal the iliac aneurysm. During the entire procedure, the sheath was stable over the neobifurcation without pulling it down. Conclusion: The contralateral femoral approach for iliac branch graft implantation is feasible in cases with an extant bifurcated stent-graft using a steerable sheath and a through-and-through wire.

Critical limb ischemia (CLI) is growing in global prevalence and is associated with high rates of limb loss and mortality. However, a relevant gap of evidence about the most optimal treatment strategy still exists. The aim of this study of the prospective, multicenter First-Line Treatments in Patients With Critical Limb Ischemia (CRITISCH) registry was to assess the current practice of all first-line treatments strategies in CLI patients in German vascular centers.Between January 2013 and September 2014, five first-line treatment strategies-endovascular revascularization (ER), bypass surgery (BS), femoral/profundal artery patchplasty (FAP), conservative treatment, and primary amputation-were determined among CLI patients in 27 vascular tertiary centers. The main composite end point was major amputation or death, or both, during the hospital stay. Secondary outcomes were hemodynamic failure, major adverse cardiovascular and cerebral events, and reintervention. Univariate logistic models were additionally built to preselect possible risk factors for either event, which were then used as candidates for a multivariate logistic model.The study included 1200 consecutive patients. First-line treatment of choice was ER in 642 patients (53.4%), BS in 284 (23.7%), FAP in 126 (10.5%), conservative treatment in 118 (9.8%), and primary amputation in 30 (2.5%). The composite end point was met in 24 patients (4%) after ER, in 17 (6%) after BS, in 8 (6%) after FAP, and in 9 (8%) after conservative treatment (P = .172). The highest rate of in-hospital death was observed after primary amputation (10%) and of hemodynamic failure after conservative treatment (91%). Major adverse cardiovascular and cerebral events developed in 4% of patients after ER, in 5% after BS, in 6% after FAP, in 5% after conservative treatment, and in 13% after primary amputation. The reintervention rate was 8%, 14%, 6%, 5%, and 3% in each group, respectively. In the multivariate regression model, coronary artery disease (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.42-6.17) and previous myocardial infarction (PMI)6 months (OR, 3.67, 95% CI, 1.51-8.88) were identified as risk factors for the composite end point. Risk factors for amputation were dialysis (OR, 3.31, 95% CI, 1.44-7.58) and PMI (OR, 3.26, 95% CI, 1.23-8.36) and for death, BS compared with ER (OR, 3.32; 95% CI, 1.10-10.0), renal insufficiency without dialysis (OR, 6.34; 95% CI, 1.71-23.5), and PMI (OR, 7.41; 95% CI, 2.11-26.0).The CRITISCH registry revealed ER as the most common first-line approach in CLI patients. Coronary artery disease and PMI6 months were independent risk factors for the composite end point. Special attention should be also paid to CLI patients with renal insufficiency, with or without dialysis, and those undergoing BS.

Inhibition of poly (ADP-ribose) polymerase 1 (PARP-1) improved hemodynamics and organ function in various shock models induced by sepsis or ischemia/reperfusion. PARP-1, however, is also referred to play a pivotal role for the maintenance of genomic integrity. Therefore, we investigated the effect of the PARP-1 blocker INO-1001 on hemodynamics, kidney function, and DNA damage and repair during porcine thoracic aortic cross-clamping. The animals underwent 45 min of aortic cross-clamping after receiving vehicle (n=9) or i.v. INO-1001 (n=9; total dose, 4 mg.kg, administered both before clamping and during reperfusion), data were recorded before clamping, before declamping, and 2 and 4 h after declamping. During reperfusion, continuous i.v. norepinephrine was incrementally adjusted to maintain blood pressure greater than or equal to 80% of the pre-clamping level. The plasma INO-1001 levels analyzed with high-pressure liquid chromatography were 1 to 1.4 micromol/L and 0.4 to 0.6 micromol/L before and after clamping, respectively. Although INO-1001-treated animals required less norepinephrine support, kidney function was comparable in the 2 groups. There was no intergroup difference either in the time course of DNA damage and repair (comet assay) as assessed both in vivo in whole blood before surgery, before clamping, before declamping, 2 h after declamping, and ex vivo in isolated lymphocytes (Ficoll gradient) sampled immediately before clamping and analyzed before, immediately, and 1 and 2 h after exposure to 4 bar 100% O2 for 2 h. There was no difference either in the expression of the cyclin-dependent kinase inhibitor gene, p27, in the kidney (immunohistochemistry). The reduced norepinephrine requirements during reperfusion suggest a positive inotropic effect of INO-1001, as demonstrated by other authors. In our model, INO-1001 proved to be safe with respect to DNA repair.

The aim of this study was to evaluate the influence of renal ischemia, cold preservation and reperfusion on the degree of renal kidney senescence. An experimental model of ex vivo renal hemoperfusion was used. Expression of p16(INK4a), p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor genes (CDKIGs) was studied immunohistochemically in kidney biopsy samples at baseline and different time points after reperfusion. All three markers were up-regulated in kidney tissue after the reperfusion; however, their activation in different renal cells varied according to the reperfusion time. Expression of p16 was significantly increased in tubular cells at 180 min of reperfusion when compared with the baseline. Activation of p27 was detected in glomerular cells at 15 min and was significantly higher at 60, 120 and 180 min of reperfusion. The marker started increasing in tubular cells at 15 min and was elevated at every time point afterwards. p21 was significantly over-expressed in all renal cells after the reperfusion. It has been shown by the results of the current study that renal ischemia/reperfusion is associated with over-expression of CDKIGs indicating on substantial DNA damage and/or accelerated tissue senescence. For the first time it has been shown that tissue expression of CDKIGs is positively related with the reperfusion time.

Background Abdominal aortic aneurysms (AAAs) are very rare in pediatric patients and can rarely be associated with tuberous sclerosis (TS). Open surgery is the first-line therapy. We report our experience added by a review on current literature. Case Report A 9-year-old boy with TS and history of 2 earlier open repairs for AAA presented to our department with a recurrent juxtarenal aortic aneurysm. We performed a polytetraflourethylene patch plasty. Postoperative course was uneventful. After 8 months, reconstruction was stable, and no recurrent aneurysm developed. Conclusions Recurrent aneurysms may develop after open surgery for TS-associated AAA. However, open surgery is the recommended therapy but requires special techniques and experience in pediatric patients.

Introduction Popliteal artery aneurysms (PAA) are rare. Different surgical techniques for open surgical repair are possible. This study presents a single centre experience using open surgical repair with a medial approach (MA) and outlines differences between symptomatic (SLS) and asymptomatic (ALS) legs. Methods Data collection was performed retrospectively. The investigation period was from 1 January 1996 to 1 January 2013. Patients presented in the Outpatient Department and received a questionnaire concerning their quality of life. Data are presented as mean ± standard deviation. Mann–Whitney test and Cochran–Armitage test for trend was used for data analysis. Kaplan–Meier method was used to calculate limb salvage rates. p, Highlights • 30 day Primary patency rate: 100% asymptomatic legs; 92% for symptomatic legs. • Better quality of life quality for asymptomatic legs in the follow-up. • Better ankle-brachial index for asymptomatic legs on control examination.

BACKGROUND The increasing demand for transplantable organs, especially kidneys, has led to expanded criteria for renal transplant donors. As a result of the expanded criteria, more organs with vascular anomalies and/or pathologies are available for transplant. This retrospective study evaluated the impact of vascular repair on the outcome in kidney transplantation in a single center over a 15-year period. MATERIAL AND METHODS Between January 1997 and May 2012, 1134 deceased donor renal transplantations were performed in the Department for Vascular and Endovascular Surgery of the University of Dusseldorf, Germany. RESULTS A vascular reconstruction of some type was necessary to repair renal vessels or to prepare the recipient site for transplantation in 374 of 1134 (33.0%) renal transplantations. The iliac artery in 12.3% (139/1134) of cases and the renal artery in 10.1% (115/1134) of cases showed severe atherosclerosis and a thrombo-endarterectomy was required. Organ loss occurred in 13 cases (1.1%) due to vascular failure. The 5-year graft survival for kidneys with reconstructed renal arteries was 84.3% in deceased donor renal transplantations (86.1% without arterial reconstruction). CONCLUSIONS The demand for renal transplants has led to more marginal-quality organs and older donors and/or recipients waiting for a second or third transplantation. Thus, the expertise of a vascular surgeon is extremely helpful in a transplantation center because it allows for marginal organ transplantation with acceptable 5-year graft survival rates.

A case of lung pecoma (i.e. tumors showing perivascular epithelioid cell differentiation) with extensive 18F-2-deoxy-D-glucose (FDG) uptake in PET/CT study is reported. Pecomas of the lung--which include the better known clear cell 'sugar' tumor--are a subset of extremely rare lung tumors which usually react positively to both melanocytic and smooth muscle markers. Although widely presumed as benign in computed tomography (CT) and positron emission tomography (PET)/CT studies they depict as malignant, thus complicating the preoperative diagnosis. A subset of pecomas could conceal a malignant potential.

The aim of this retrospective study was to evaluate the repair of vascular variations/pathologies in living donor kidney transplantations in a single centre over a 15-year period. Between 01/1997 and 05/2012, 338 living donor renal transplantations were performed in the Department for Endovascular and Vascular Surgery, University of Dusseldorf, Germany. Twenty-four of them showed disorders, like multiple renal arteries (MRA), atherosclerotic stenosis or fibromuscular dysplasia (FMD) needing vascular repair before transplantation. Mean age of donors was 51 ± 11.2, in recipient’s 44 ± 13.9 years. In seven transplantations, renal artery (RA) repair was performed because of MRA. Atherosclerotic stenosis of the RA was apparent in 12 cases needing a repair with disobliteration. FMD was the reason in five transplantations for vascular repair. Complications like renal vessel thrombosis, lymphocele, heamorrhage, distal urinary leakage and ureteral obstruction was not significantly associated with RA reconstruction. Comparison of renal function in kidneys with reconstructed RA compared with kidneys without vascular repair showed no significant difference in primary function and serum creatinine up to the first year after transplantation. Mean follow-up was 75.6 ± 48.1 months. The 5-year graft survival rate for kidneys with RA repair was 88.5 vs. 93.4 % without reconstruction. We could show that RA pathologies, suitable repaired, are not a contraindication for transplantation with acceptable 5-year-graft-survival rates.

Recombinant human erythropoietin (rhEPO) attenuated ischemia/reperfusion (I/R) injury-induced spinal cord damage. Since carbamylated EPO derivatives are stated to be devoid of rhEPO side effects, we tested the hypothesis that a newly developed carbamylated EPO-FC fusion protein (cEPO-FC) would compare favorably with rhEPO.Anesthetized and mechanically ventilated pigs randomly received cEPO-FC (50 μg kg(-1)), rhEPO (5,000 IU kg(-1)) or vehicle (n = 9 per group) 30 min prior to 30 min of aortic occlusion and over the 4 h of reperfusion. During aortic occlusion, mean arterial pressure (MAP) was maintained at 80-120% of baseline values by esmolol, nitroglycerin, and adenosine-5'-triphosphate (ATP). During reperfusion, noradrenaline was titrated to keep MAP at pre-ischemic levels. Spinal cord function was assessed by motor evoked potentials (MEP) and lower limb reflexes. Tissue damage was evaluated using hematoxylin and eosin, Nissl, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. Plasma levels of interleukin-6, tumor necrosis factor-α, and 8-isoprostanes were measured as markers of systemic inflammation and oxidative stress.While only cEPO-FC restored MEP amplitude to values close to pre-occlusion levels, both cEPO-FC and rhEPO comparably restored lower limb reflexes and reduced the percentage of damaged neurons. Infiltration of mononuclear inflammatory cells was moderate without intergroup difference; positive TUNEL staining was barely detectable in any group. I/R injury increased blood cytokine levels without intergroup difference, whereas both cEPO-FC and rhEPO significantly lowered 8-isoprostane levels.In a porcine model of aortic balloon occlusion-induced spinal cord I/R injury, cEPO-FC and rhEPO comparably protected against ischemic spinal cord dysfunction and neuronal damage. This effect coincided with attenuated oxidative stress.