Comparing Simulation Training of Bronchoscopy-Guided Percutaneous Dilatational Tracheostomy Using Conventional Versus 3D Printed Simulators (TRAC-Sim Study).

Background: Individual implementation rate of bronchoscopy-guided percutaneous dilatational tracheostomy (PDT) varies among intensivists. Simulation training (ST) can increase the safety of medical procedures by reducing stress levels of the performing team. The aim of this study was to evaluate the benefit of ST in PDT regarding procedural time, quality of performance, and percepted feelings of safety of the proceduralist and to compare conventional simulators (CSIM) with simulators generated from 3D printers (3DSIM). Methods: We conducted a prospective, single-center, randomized, blinded cross-over study comparing the benefit of CSIM versus 3DSIM for ST of PDT. Participants underwent a standardized theoretical training and were randomized to ST with CSIM (group A) or 3DSIM (group B). After ST, participants' performance was assessed by two blinded examiners on a porcine trachea regarding time required for successful completion of PDT and correct performance (assessed by a performance score). Percepted feelings of safety were assessed before and after ST. This was followed by a second training and second assessment of the same aspects with crossed groups. Results: 44 participants were included: 24 initially trained with CSIM (group A) and 20 with 3DSIM (group B). Correctness of the PDT performance increased significantly in group B (p < .01) and not significantly in group A (p = .14). Mean procedural time required for performing a PDT after their second ST compared to the first assessment (p < .01) was lower with no difference between group A and group B and irrespective of the participants' previous experience regarding PDT, age, and sex. Moreover, percepted feelings of safety increased after the first ST in both groups (p < .001). Conclusions: ST can improve procedural skills, procedural time, and percepted feelings of safety of the proceduralist in simulated PDT.

A Systematic Review and Meta-Analysis of Heparin-Bonded Expanded Polytetrafluoroethylene Grafts for Below-The-Knee Femoral Bypass Surgery.

BACKGROUND: Heparin-bonded expanded polytetrafluoroethylene (hb-ePTFE) synthetic grafts are an alternative to autologous vein grafts (AVG) for surgical bypass interventions in lower limb peripheral arterial disease (LLPAD). However, the clinical benefits of hb-ePTFE grafts have not been reviewed systematically for patients undergoing below-the-knee (BK) surgical bypass. This study aimed to meta-analyze available data on the utility of hb-ePTFE in patients undergoing BK surgical bypass. METHODS: Medline, Embase, and Cochrane databases were searched, restricted to material in English with no date restriction. In addition, proceedings from relevant congresses were screened going back 2 years. The search was performed in December 2021. Eligible studies included prospective or retrospective comparative studies or prospective single-arm cohorts with an hb-ePTFE arm. Methodological quality was assessed with the ROBINS-I criteria. Outcomes included primary patency, amputation/limb salvage, and overall survival. Clinical outcomes were expressed as event rates. Studies were compared using meta-analysis to generate a standardized mean event rate for each outcome, with its 95% confidence interval (95% CI), using a random-effects model. RESULTS: Following deduplication, 10,263 records were identified and 261 were assessed as full texts. No prospective comparative studies were identified. The level of evidence was uniformly low. Seventeen publications describing data from 9 individual patient cohorts met the inclusion criteria. These cohorts included a total of 1,452 patients undergoing BK surgical bypass with hb-ePTFE. The primary patency rate was 78.9% [95% CI: 72.2-85.7%] at 1 year, 68.2% [95% CI: 62.8-73.6%] at 2 years, decreasing to 48.0% [95% CI: 27.3-68.7%] at 5 years. The secondary patency rate was 84.8% [95% CI: 77.0-92.5%] at 1 year and 68.9% [95% CI: 43.0-94.9%] at 3 years; the 1-year limb salvage rate was 88.3% [95% CI: 79.6-97.1%] at 1 year and 79.0% [95% CI: 56.7-100%] at 3 years. CONCLUSIONS: In patients undergoing BK bypass surgery, hb-ePTFE synthetic grafts, compared to uncoated grafts, perform well for patency and limb salvage. However, the quality of the evidence is low, and well-performed randomized clinical trials are needed to inform clinical decision-making on the choice of synthetic graft.

HeRO graft-The results of the cologne single center study.

OBJECTIVE: The HeRO graft is a technique for vascular access in patients with limited treatment options; however, the published results with the HeRO graft are diverging. We therefore conducted a single-center study. METHODS: Patient records between July 2014 and February 2020 from Vascular Access Unit of the Department of Vascular and Endovascular Surgery of University Clinic of Cologne (Germany) were reviewed. Retrospective data was analysed from patients with a HeRo graft (n = 18). RESULTS: Eighteen patients were enrolled in the study. The mean age of the patients was 62.8 ± 17.24 years. During the follow-up period, no patients died from complications related to the HeRO graft. Each patient had a mean of 1.94 concomitant diseases. The primary patency rates of the HeRO graft at 3, 6, 12, 18, and 24 months were 61.1%, 50%, 16.7%, 11.1%, and 5.6%, respectively. The secondary patency rates at the same time intervals were 77.8%, 72.8%, 55.6% 55.6%, and 55.6%, respectively. There were 44 re-operations per year, or 2.4 operations per patient. The main cause of acute complications was acute graft occlusions after HERO graft implantation. An infection after the graft implantation occurred in five (27.7%) patients, leading to graft explanation in 2 cases. CONCLUSION: The use of the HERO graft is a valuable alternative method for providing a durable dialysis access in patients with limited access options. The secondary patency and survival are good with a low infection rate.

Implications of aortic neck dilation following thoracic endovascular aortic repair.

OBJECTIVE: This article reports on a retrospective observational study designed to evaluate the incidence, etiology, and clinical implications of aortic neck dilation following thoracic endovascular aortic repair (TEVAR) for aneurysms with landing zones II and III. METHODS: The study included 37 patients who underwent TEVAR and had postoperative computed tomography angiography available within 30 days and at least one computed tomography angiography at 1 year postoperatively. The primary end point was proximal aortic dilation (defined as growth ≥5 mm or ≥10% of the original diameter), and secondary end points included annual growth of the aneurysmal sac, device migration, endoleak, and reintervention with additional neck-related adverse events. The measurements taken during follow-up included the maximum diameter of the aneurysm and aortic diameter at various locations relative to the stent graft. RESULTS: During follow-up, a significant increase in aortic diameter was observed at the proximal edge of TEVAR. The estimated freedom from 5 mm or 10% proximal aortic neck growth at 1, 2, and 3 years was 81%, 70%, and 65%, respectively. At the proximal edge of TEVAR the type III aortic arch was significantly associated with 5 mm growth during follow-up (P = .047) and this growth (5 mm or 10%) as well as a 10% increase at +20 mm were significantly associated with more aortic-related reinterventions. Moreover, an aortic diameter at the start <36 mm was associated with a greater increase during follow-up (area under curve in receiver operating characteristic >80%; P < .05). CONCLUSIONS: The study concludes that proximal aortic dilation after TEVAR is a common and progressive phenomenon, and the management strategies for aortic neck dilation, including surveillance, secondary interventions, and open conversion, should be considered carefully to optimize patient outcomes and improve the long-term success of the procedure.

Favorable Remodeling After TEVAR in Uncomplicated Acute and Subacute Type B Aortic Dissection in Comparison to Conservative Treatment: A Midterm Analysis.

PURPOSE: The purpose of the study was to evaluate the midterm and long-term outcomes of patients who underwent thoracic endovascular aortic repair (TEVAR) procedure to treat an uncomplicated acute and subacute type B aortic dissection (uATBAD) with high risk for subsequent aortic complications compared with the group of patients who received a conservative treatment protocol during the same period. MATERIALS AND METHODS: Between 2008 and 2019, 35 patients who had TEVAR due to uATBAD and those with conservative procedure (n=18) were included in a retrospective analysis and follow-up study. The primary endpoints were false lumen thrombosis/perfusion, true lumen diameter, and aortic dilatation. The aortic-related mortality, reintervention, and long-term survival were the secondary endpoints. RESULTS: In the study period, 53 patients (22 females) with a mean age of 61.1±13 years were included. No 30-day and in-hospital mortality was recorded. Permanent neurological deficits occurred in 2 patients (5.7%). In the TEVAR group (n=35) and in a median follow-up period of 34 months, a significant reduction of maximum aortic and false lumen diameter as well as a significant increase of true lumen diameter were detected (p<0.001 each). Complete false lumen thrombosis increased from 6% preoperatively to 60% at follow-up. The median difference in aortic, false lumen, and true lumen diameter was -5 mm (interquartile range [IQR]=-28 to 8 mm), -11 mm (IQR=-53 to 10 mm), and 7 mm (IQR=-13 to 17 mm), respectively. In 3 patients (8.6%), a reintervention was needed. Two patients (1 aortic-related) died during follow-up. The estimated survival according to Kaplan-Meyer analysis was 94.1% after 3 years and 87.5% after 5 years. Similar to the TEVAR group, no 30-day or in-hospital mortality was recorded in the conservative group. During follow-up, 2 patients died and 5 patients underwent conversion-TEVAR (28%). In a median follow-up period of 26 months (range=150), a significant increase of maximum aortic diameter (p=0.006) and a tendency to augmentation of the false lumen (p=0.06) were noted. No significant reduction of the true lumen was seen. CONCLUSIONS: Thoracic endovascular aortic repair in patients at high risk of subsequent aortic complications in uncomplicated acute and subacute type B aortic dissection is safe and is associated with favorable midterm outcomes regarding aortic remodeling. CLINICAL IMPACT: In a retrospective, single center analysis of prospectively collected data with follow-up, we compared 35 patients with high-risk features who recieved TEVAR in acute and sub-acute uncomplicated type B aortic dissection to a control-group (n=18). The TEVAR group showed a significant positive remoduling (reduction of max. aortic and false lumen diameter and increase of true lumen diameter (p<0.001 each)) during follow-up with an estimated survival of 94.1% after 3 years and 87.5% after 5 years.

Surgical Versus Interventional Treatment of Major Access Site Complications During Transfemoral TAVI Procedures at a Large Volume Center.

PURPOSE: Access-related vascular complications in transfemoral transcatheter aortic valve implantation (TAVI) can be treated endovascularly or surgically. The aim of this study was to evaluate the short- and long-term outcomes of endovascular treatment compared with surgical repair for access-related vascular complications. METHODS: This retrospective study was performed from January 1, 2018, to December 31, 2020. All transfemorally treated TAVI patients in whom a surgical or endovascular treatment for an access site complication was needed were included. The primary outcome was the need for any related vascular re-operation. RESULTS: In total, 1219 transfemoral TAVI procedures were conducted during the study period. 19 patients suffered an access complication requiring endovascular treatment, while 54 patients required surgical repair. No differences were seen with regard to re-operations (endovascular 15.8% vs surgical 14.8%; p=0.919), wound infections (endovascular 0% vs surgical. 11.1%; p=0.129), and wound healing disorders (endovascular 15.8% vs surgical 29.6%; p=0.237). Patients undergoing endovascular treatment were discharged earlier (endovascular 11.2 vs surgical 14.9 days; p=0.028). After surgical repair, patients received significantly more blood transfusions than endovascularly treated patients (endovascular 1.00 vs surgical 3.1 red blood cell concentrate bags; p<0.001). No differences were found regarding the new onset of walking pain, rest pain, and ischemic ulcers during follow-up. CONCLUSION: In this retrospective cohort, endovascular treatment of access-related vascular complications of transfemoral TAVI procedures was safe and feasible. During the hospital stay, endovascularly treated patients received fewer blood transfusions and were discharged faster than surgically treated patients. No differences regarding clinical outcomes and re-intervention rates were seen during the follow-up. CLINICAL IMPACT: Given the in this retrospective study demonstrated safety and feasibility of endovascular treatment for major access-related vascular complications, along with the in-hospital benefits and absence of follow-up disadvantages compared to surgical treatment, endovascular treatment should be considered in cases of major access-related vascular complications in transfemoral TAVI patients.

Meta-analysis and meta-regression of the total endovascular aortic repair in aortic arch.

Background: The total endovascular repair of the aortic arch is becoming more and more an acceptable alternative to the open repair in selected patients. The aim of the present study is to perform a meta-analysis of the available data on the outcomes of the various endovascular techniques used to treat the pathologies in this challenging anatomical area. Patients and methods: An extensive electronic search in PubMed/MEDLINE, Science Direct Databases, and the Cochrane Library was conducted. All papers published up to January 2022 on the endovascular techniques in the aortic arch (chimney-thoracic endovascular aortic repair (ChTEVAR), fenestrated/branched grafts as custom made devices (CMD) and surgeon modified TEVAR (SM TEVAR) providing information about at least one of the essential outcomes defined in the inclusion criteria. Results: Out of the 5078 studies found through the search in the databases and registers, 26 studies with a total number of patients of 2327 with 3497 target vessels were included in the analysis. The studies reported a high technical success rate with an estimated proportion of 95.8% (95% CI, 93-97.6%). Moreover, the pooled estimation of the early type Ia/III endoleak was 8.1% (95% CI, 5.4-12.1%). The pooled mortality was 4.6% (95 CI, 3.2-6.6%) with a significant heterogeneity and the stroke had an estimated proportion (major and minor combined) of 4.8% (95% CI, 3.5-6.6%). A meta-regression analysis showed no significant variation between the groups in mortality (P=.324) showed however a significant difference between the therapeutic methods regarding stroke P<.001 (lower rate in ChTEVAR and SM vs. CMD). Conclusions: The present meta-analysis could demonstrate good short- and long-term outcomes of the multiple total endovascular repair methods used in the aortic arch.

Gut Microbiota-Associated Activation of TLR5 Induces Apolipoprotein A1 Production in the Liver.

RATIONALE: Dysbiosis of gut microbiota plays an important role in cardiovascular diseases but the molecular mechanisms are complex. An association between gut microbiome and the variance in HDL-C (high-density lipoprotein-cholesterol) level was suggested in a human study. Besides, dietary fat was shown to increase both HDL-C and LDL-C (low-density lipoprotein-cholesterol) levels. We speculate that certain types of gut bacteria responding to dietary fat may help to regulate HDL-C level and potentially affect atherosclerotic development. OBJECTIVE: We aimed to investigate whether and how high-fat diet (HFD)-associated gut microbiota regulated HDL-C level. METHODS AND RESULTS: We found that HFD increased gut flagellated bacteria population in mice. The increase in HDL-C level was adopted by mice receiving fecal microbiome transplantation from HFD-fed mouse donors. HFD led to increased hepatic but not circulating flagellin, and deletion of TLR5 (Toll-like receptor 5), a receptor sensing flagellin, suppressed HFD-stimulated HDL-C and ApoA1 (apolipoprotein A1) levels. Overexpression of TLR5 in the liver of TLR5-knockout mice was able to partially restore the production of ApoA1 and HDL-C levels. Mechanistically, TLR5 activation by flagellin in primary hepatocytes stimulated ApoA1 production through the transcriptional activation responding to the binding of NF-κB (nuclear factor-κB) on Apoa1 promoter region. Furthermore, oral supplementation of flagellin was able to stimulate hepatic ApoA1 production and HDL-C level and decrease atherosclerotic lesion size in apolipoprotein E-deficient (Apoe-/-) mice without triggering hepatic and systemic inflammation. The stimulation of ApoA1 production was also seen in human ApoA1-transgenic mice treated with oral flagellin. CONCLUSIONS: Our finding suggests that commensal flagellated bacteria in gut can facilitate ApoA1 and HDL-C productions in liver through activation of TLR5 in hepatocytes. Hepatic TLR5 may be a potential drug target to increase ApoA1.

Ovine Biosynthetic Grafts for Aortoiliac Reconstructions in Nonsterile Operative Fields.

BACKGROUND: Prosthetic vascular grafts placed surgically or via endovascular techniques can be subject to the risk of life-threatening graft infections. The Omniflow II vascular prosthesis is a biosynthetic graft that was reported to have favorable properties in resisting infections. MATERIALS AND METHODS: We retrospectively reviewed our 3 years' experience of using the Omniflow II prostheses for aortoiliac reconstructions in patients considered to carry a substantial risk of subsequent prosthetic graft infections (prevention group) as well as in patients with actively infected prosthetic vascular grafts (treatment group). RESULTS: Aorto-bi-iliac (n = 4) and aortobifemoral (n = 12) vascular reconstructions were performed using bifurcated Omniflow II prostheses in nine patients in the prevention group and seven patients in the treatment group. During mean follow-up of 28.6 ± 17.2 months, there was one case of graft infection (6.3%) and graft thrombosis (6.3%) with subsequent successful thrombectomy. Early and late surgical revisions were required in eight (50%) and two (12.6%) patients, respectively. All graft prostheses were patent at last follow-up. CONCLUSION: Using bifurcated Omniflow II vascular prostheses in patients with or at a high risk of vascular graft infection is advisable, and is associated with acceptable reinfection and patency rates.

Long-Term Outcomes after Thoracic Endovascular Aortic Repair Using Chimney Grafts for Aortic Arch Pathologies: 10 Years of Single-Center Experience.

BACKGROUND: This study reports the early- and long-term outcomes of the thoracic endovascular aortic repair using the Chimney-Graft technique (ChTEVAR) for the treatment of aortic arch pathologies. METHODS: From January 2010 to December 2019, patients who underwent aortic ChTEVAR technique in our institution were included. Early, mid, and long-term outcomes in this group of patients were evaluated. Patient follow-up data were obtained by imaging follow-up that are routinely performed after 3-6 months following initial surgery and then at yearly intervals. RESULTS: Aortic arch repair with a ChTEVAR was performed in 54 patients. The 30-day mortality was 18.5% (n = 10). All-cause 30-day mortality was higher in the subgroup of patients operated urgently (33% vs. 14%) without a significant difference (P = 0.141). Permanent neurological deficit (PND) was observed in 15% (8/54 patients); stroke in 11% (6/54), and paraplegia 4% (2/54). During follow-up the primary and primary-assisted chimney-graft patency was 96.8% and 97.8%, respectively. The multivariate analysis identified the age >70 years and the aortic diameter as independent risk factors for elevated mortality during the follow-up (P = 0.015 and 0.001, respectively). The PND was an independent predictor for 30-day mortality (P = 0.014, hazard ratio 13.5, 95% confidence interval 1.7-106.6). CONCLUSIONS: The ChTEVAR has noninferior results to other open and endovascular aortic arch repair methods with an acceptable long-term survival especially in elective procedures.

[Debate on Infrarenal AAA in Young and Fit Patients ('Fit for Open Repair'): Open Repair is Safe and Long-term Results are Better]. / Debatte infrarenales AAA bei jüngeren Patienten ("fit for open repair"): Der offene Aortenersatz ist sicher und hat ein besseres Langzeitergebnis.

Endovascular aortic repair, initially developed for patients at prohibitively high risk for an open repair, has undergone significant technical evolution and refinement and has emerged as the preferred treatment option for patients with an infrarenal aortic aneurysm. However, analysis of long-term data of the randomised studies revealed inferior results with regards to survival and freedom-from-reintervention after eight years. Open aortic repair has been performed for more than seven decades and especially for the younger patients with few comorbidities, results are excellent. Potential drawbacks of open repair like incisional hernias, erectile dysfunction and quality of life can either be effectively prevented (mesh reinforcement) or actually failed to show a significant difference compared to open repair in recent studies. Therefore, meticulous assessment of patient comorbidites using validated parameters is the key element for decision-making and parameters such as young age, low comorbidity profile, large aneurysm and presence of atopic renal arteries or a dominant inferior mesenteric artery should prompt a recommendation of open repair.

[Pro Endo: No Need for Open Any More... Surveillance is All Important]. / Pro Endo: No Need for Open Any More ... Surveillance is All Important.

Since its first report in 1991, endovascular aneurysm repair (EVAR) has become an established and preferred treatment modality for many patients. Several randomised controlled trials comparing EVAR and open repair have shown an early survival benefit, lower perioperative morbidity and shorter hospital stay with EVAR. As a result, EVAR has become the most common method of elective repair of BAAs in most vascular centres. Despite its widespread use, there are still subgroups of the patient population for whom the benefit of EVAR has not been clearly demonstrated. The most frequently discussed subgroup in this context is the patient with few risk factors - due to concerns about the durability and need of reinterventions. EVAR can provide durability and long-term survival similar to open repair in these younger patients, as long as the aneurysm anatomy and instructions for use are followed. The evidence on the effects of follow-up on patient survival is currently controversial. With increasing knowledge about the behavior of endoprostheses and factors that influence the complications of the endograft, changes in follow-up protocols have been made. A more patient-specific follow-up strategy and less compliance with a rigorous follow up scheme are required.

Contemporary results with the biosynthetic glutaraldehyde denatured ovine collagen graft (Omniflow II) in femoropopliteal position.

OBJECTIVE: The objective of this study was to analyze the outcome of a contemporary series of femoropopliteal bypass operations with the glutaraldehyde denatured polyester mesh-reinforced ovine collagen prosthesis (OCP; Omniflow II [LeMaitre Vascular, Inc, Burlington, Mass]). The experience of two tertiary centers regarding long-term graft function, secondary reinterventions, and biodegeneration of the OCP prosthesis is presented. METHODS: Between January 2006 and January 2014, a series of 205 consecutive operations with the OCP in the femoropopliteal position (54 above knee and 151 below knee) were performed in 194 patients in 202 limbs for disabling claudication (72), chronic critical ischemia (105), acute ischemia (18), popliteal artery aneurysm (4), degeneration of a venous or prosthetic graft (5), and infection of a synthetic bypass graft (1). Grafts were observed with duplex ultrasound scan supplemented by additional angiography in case of recurrent ischemia with prospective documentation of follow-up data in a computerized vascular database. Retrospective analysis of graft patency, limb salvage, and diagnosis of aneurysmal graft degeneration was performed. RESULTS: The 30-day mortality was 3.9%. Early thrombotic bypass occlusion occurred in 8.2% of cases. Four early graft infections could be successfully managed by local treatment with graft preservation. After a mean (median) follow-up of 56 (55) months (range, 1-135 months), primary patency, primary assisted patency, secondary patency, and limb salvage were 71%, 78%, 78%, and 91% for above-knee bypass and 40%, 50%, 63%, and 87% for below-knee bypass at 5 years. Biodegeneration in the form of graft aneurysm or graft stenosis was detected in 26 grafts (12.6%), resulting in secondary open or endovascular procedures in 16 cases. CONCLUSIONS: The OCP provides satisfactory medium- and long-term patency and limb salvage in the femoropopliteal position. Aneurysmal degeneration or graft stenosis may develop over time, demanding lifelong duplex ultrasound surveillance and secondary intervention if needed. Its possible infection-resistant behavior in a contaminated field combined with an acceptable graft patency and limb salvage justifies the use of this graft in the absence of autologous vein.

[The Future of Vascular Medicine - Role of 3D Printing]. / Gefäßmedizin in der Zukunft ­ Möglichkeiten mit 3D-Druckverfahren.

Digitalisation is one of the key challenges in current surgery and will impact the future of surgical care as well as upcoming generations of surgeons. 3D printing is a technology that has recently been transferred from industrial prototyping into cardiovascular medicine. The digital model of the anatomical structure which needs to be engineered represents the inherent link of 3D printing to digital medicine. 3D printing technology is able to provide the surgeon with patient-specific models of anatomy and disease for surgical planning and patient informed consent as well as training templates for students and residents, surgical templates and even ready-to-use surgical implants. In our service, we have established a full-inhouse workflow for 3D printing and we currently use this technology for the generation of patient-specific models, training templates and for patient education, as will be presented in this article. Future advances in software solutions, printing polymers and easy-to-handle printers will further propagate and expand the applicability of this technology in cardiovascular medicine.

External polytetrafluoroethylene reinforcement of varicose autologous vein grafts in peripheral bypass surgery produces durable bypass function.

OBJECTIVE: Use of autologous veins as peripheral bypass graft may become critical in the presence of significant varicose degeneration of the harvested vein. External support of such dilated veins with standard polytetrafluoroethylene (PTFE) prostheses was recommended as an option to use these veins for peripheral bypass. A single-center experience with this technique regarding long-term graft function, secondary reinterventions, and potential graft degeneration is presented. METHODS: Between January 1995 and January 2006, there were 54 patients with varicose veins who underwent 57 consecutive infrainguinal vein bypass operations with PTFE reinforcement in 57 limbs. Indications for surgery consisted of disabling claudication (5), chronic critical ischemia (40), popliteal aneurysm (11), and acute ischemia (1). Grafts were observed with duplex ultrasound scan supplemented by additional angiography in case of recurrent ischemia, with prospective documentation of follow-up data in a computerized vascular database. Graft patency, limb salvage, and possible degeneration of the vein grafts were retrospectively analyzed. RESULTS: Mean follow-up was 79 months (range, 1-219 months). The 30-day mortality was 2%. Secondary procedures to maintain or to restore bypass patency were necessary in 12 grafts (21%). Primary, primary assisted, and secondary patency rates were 54%, 73%, and 73% after 5 years for all bypasses, with a limb salvage rate for limbs operated on for chronic critical or acute ischemia of 83%. Significant stenosis of a reinforced vein segment was detected in one case after 56 months, with subsequent replacement of the vein graft with a biologic vascular prosthesis. CONCLUSIONS: Good late graft patency and limb salvage combined with a low rate of late vein graft degeneration justify the use of external PTFE reinforcement of varicose vein segments in infrainguinal bypass surgery.

Human neutrophil elastase induces endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded protein response.

Human neutrophil elastase impacts on atherosclerotic plaque stability by inducing apoptosis in endothelial cells. Our aim was to investigate the proapoptotic mechanism of elastase on endothelial cells and to evaluate the presence of elastase in human plaque material. Human endothelial cells were treated with purified human neutrophil elastase. Apoptosis was assayed by capsase-3/7 activation, TUNEL, and sub-G1 assay. Activation of unfolded protein response (UPR) effector molecules binding Ig protein, soluble X-binding protein-1, protein kinase RNA-like ER kinase (PERK), and C/EBP-homologous protein (CHOP) was analyzed by RT-PCR, immunocytochemistry, and Western blot. Genetic silencing of CHOP was achieved by small interfering RNA. Elastase induces autophagic-apoptotic forms of endothelial cell death in a time- and dose-dependent manner, in conjunction with a significant increase in phosphorylation/expression of the canonical UPR-activation markers PERK and CHOP. By using CHOP knockdown, we identified CHOP as a key mediator of elastase-induced endothelial cell death. Immunohistochemical analysis of human rupture-prone plaque specimens confirmed the presence of elastase and colocalization with apoptosis. We have demonstrated for the first time that the PERK-CHOP branch of the UPR is causally involved in elastase-induced apoptosis of endothelial cells. Ex vivo analysis of human rupture-prone plaques confirmed the presence of elastase and its colocalization with markers of apoptosis. This novel role of elastase underlines the potential of combined targeting of elastase and endoplasmic reticulum stress in the prevention of plaque progression and cardiovascular events.-Grechowa, I., Horke, S., Wallrath, A., Vahl, C.-F., Dorweiler, B. Human neutrophil elastase induces endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded protein response.

Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis.

The first ATP-competitive p38α MAPK/MAPK14 inhibitor with excellent in vivo efficacy and selectivity, skepinone-L, is now available. We investigated the impact of selective p38α MAPK/MAPK14 inhibition on enzymatically modified LDL (eLDL) stimulated human monocytes with its implications for atherosclerosis. Among the different p38 MAPK isoforms, p38α/MAPK14 was the predominantly expressed and activated isoform in isolated human peripheral blood monocytes. Moreover, eLDL colocalized with macrophages positive for p38α MAPK/MAPK14 in human carotid endarterectomy specimens. Using the human leukemia cell line THP-1 and/or primary monocyte-derived macrophages, skepinone-L inhibited eLDL-induced activation of the p38 MAPK pathway, inhibited eLDL induced expression of both cluster of differentiation 36 (CD36) and ATP-binding cassette, subfamily A, member 1 (ABCA1), without a net effect on foam cell formation, had a cell- and time-dependent effect on eLDL-triggered apoptosis, and inhibited eLDL-stimulated secretion of IL-8 and MIP-1ß/CCL4 (macrophage inflammatory protein-1ß/chemokine, CC motif, ligand 4). Inhibition of a key signaling molecule of the p38 MAPK pathway, p38α MAPK/MAPK14, by selective inhibitors like skepinone-L, conclusively facilitates elucidation of the impact of the complex network of p38 MAPK signaling on atherogenesis and might provide a promising therapeutic tool to prevent inflammatory cascades in atherosclerosis.-Cheng, F., Twardowski, L., Fehr, S., Aner, C., Schaeffeler, E., Joos, T., Knorpp, T., Dorweiler, B., Laufer, S., Schwab, M., Torzewski, M. Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis.

Adjunct Perfusion Branch for Reduction of Spinal Cord Ischemia in the Endovascular Repair of Thoracoabdominal Aortic Aneurysms.

BACKGROUND: To analyze utilization of a perfusion branch for temporary sac perfusion to reduce the spinal cord ischemia (SCI) in the endovascular repair of thoracoabdominal aortic aneurysms (TAAAs). METHODS: Between January 2012 and August 2016, 30 patients (18, men; median age 72 years) were treated for TAAAs with total endovascular repair using customized branched/fenestrated endografts in our institution. The median aneurysm size was 6.6 cm. Types of TAAA were: type I, 9 (30%), type II, 5 (16.6%), type III, 4 (13.3%), type IV, 6 (20%), and type V, 6 (20%). Ten patients received a perfusion branch to create an intentional endoleak, which was occluded with vascular plugs in mean interval time of 8.2 weeks (range: 6-10). Staged procedure and automated cerebrospinal fluid drainage were used in 23 (77%) and 24 (80%) patients, respectively. RESULTS: The technical success was 97%; 107 renovisceral target vessels were revascularized (32 fenestrations, 75 branches). At the time of the planned reinterventions, the mean arterial pressure (MAP) gradients were measured between the temporarily perfused aneurysm sac and the aortic endografts, and they were significantly higher (mean gradients 42.5 ± 10 mm Hg; range: 30-60) within the aortic grafts. The in-hospital and 30-day mortality was 3.3%. The incidence of postoperative SCI was 3/20 (15%) in the standard group and 0% in the group of the perfusion branch (p = 0.28). The mean follow-up was 12 months (range: 2-51). CONCLUSION: We experience that the use of a dedicated perfusion branch is feasible and may serve as protective adjunct to reduce the risk of SCI in endovascular treatment of TAAA. The risk of rupture in interval appears to be low. Larger series and multicenter studies are warranted to corroborate these results.

Three-Dimensional Analysis of Component Stability of the Nellix Endovascular Aneurysm Sealing System After Treatment of Infrarenal Abdominal Aortic Aneurysms.

PURPOSE: To assess short-term stability and conformational changes of the Nellix EndoVascular Aneurysm Sealing (EVAS) System using 3-dimensional (3D) analysis. METHODS: Postoperative computed tomography (CT) scans obtained at 0, 3, and 12 months in 24 patients (mean age 75±7 years; 22 men) who underwent EVAS between December 2013 and December 2014 for intact abdominal aortic aneurysm (within the instructions for use) were evaluated for stent-graft deviation in multiple planes using dedicated 3D analysis software. In addition, 2D analysis using an anatomically fixed reference landmark was performed to assess craniocaudal migration. Clinical and follow-up data of the patients were recorded and matched with results of the imaging analysis. RESULTS: Overall stability of the Nellix endografts was promising. Relevant conformational changes in the majority of cases were limited to the iliac graft segment and were clinically benign in all cases. Conversely, the only deviation of the proximal stent-graft segment was found in a patient with type Ia endoleak. Additional 2D analysis found relevant (≥5 mm) caudal migration of the Nellix stent-graft in 6 patients, including the one with the type Ia endoleak. In 3 patients, 3D analysis demonstrated the absence of relevant conformational changes of the endografts despite caudal migration. CONCLUSION: Overall stability of the separate EVAS stent-grafts is promising in the short term. Relevant conformational changes (stent-graft deviation) in the majority of cases were benign and confined to the iliac segment.