Follicle-stimulating hormone receptor expression in advanced atherosclerotic plaques.

Experimental evidence indicates that follicle-stimulating hormone (FSH), an essential hormone for reproduction, can act directly on endothelial cells inducing atherosclerosis activation and development. However, it remains unknown whether the FSH-receptor (FSHR) is expressed in human atherosclerosis plaques. To demonstrate the FSHR presence, we used immunohistochemical and immunoelectron microscopy involving a specific monoclonal antibody FSHR1A02 that recognizes an epitope present in the FSHR-ectodomain. In all 55 patients with atherosclerotic plaques located in carotid, coronary, femoral arteries, and iliac aneurysm, FSHR was selectively expressed in arterial endothelium covering atherosclerotic plaques and endothelia lining intraplaque neovessels. Lymphatic neovessels were negative for FSHR. M1-macrophages, foam cells, and giant multinucleated cells were also FSHR-positive. FSHR was not detected in normal internal thoracic artery. Immunoelectron microscopy performed in ApoEKO/hFSHRKI mice with atherosclerotic plaques, after injection in vivo with mouse anti-hFSHR monoclonal antibody FSHR1A02 coupled to colloidal gold, showed FSHR presence on the luminal surface of arterial endothelial cells covering atherosclerotic plaques. Therefore, FSHR can bind, internalize, and deliver into the plaque circulating ligands to FSHR-positive cells. In conclusion, we report FSHR expression in endothelial cells, M1-macrophages, M1-derived foam cells, giant multinucleated macrophages, and osteoclasts associated with human atherosclerotic plaques.

First Result of a Tailored Progressive Multistep Approach for the Treatment of Aorto-esophageal Fistulae.

BACKGROUND: Aorto-esophageal fistulae (AEFs) are a rare but serious and life-threatening disease of the mediastinum. Especially, AEF in the presence of infected stent grafts, for example, after thoracic endovascular aortic repair (TEVAR) is only curable by a multistage interdisciplinary surgical approach. This study presents the results of our four-stage approach consisting of bridging TEVAR, esophagectomy, complete stent removal followed by total bovine tube aortic replacement (TBTAR), and finally esophageal reconstruction. METHODS: A case series of four patients from our department receiving a four-stage treatment of AEF is presented in this study. Retrospective database analysis focusing on overall survival, duration of intensive care unit and total hospital stay until discharge, complications, surgical time frame, and completion of chosen surgical treatment course was performed. RESULTS: Overall, four patients surgically treated for AEF since May 2015 were included. A 30-day mortality was 0%, and overall survival at 1 year was 75%. All patients survived more than 5 months and could be discharged after TEVAR and esophagectomy. TBTAR could be performed in two of four patients (50%). Esophageal reconstruction was completed in all patients. Average follow-up was 20.3 ± 1.7 months or until death. CONCLUSION: The acute management of AEF using this approach seems satisfactory, especially for reducing acute short-term mortality. Complete restoration of the circulatory system and digestive tract remains challenging and is associated with high morbidity. We support the application of bridging TEVAR with a staggered approach to further surgical treatment individually tailored to the patient.

Increase of urinary TIMP-2 and IGFBP7 as potential predictor of acute kidney injury requiring renal replacement therapy and patients' outcome following complex endovascular and open thoracic abdominal aortic aneurysm surgery - a prospective observational study.

Background: Acute kidney injury (AKI) as complication after open and endovascular repair of thoracoabdominal aortic aneurysm (TAAA) is one major predictor of mortality and postoperative complications. We evaluated tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as combined early biomarker for AKI detection and predictor of patients' outcome. Patients and methods: Between 2014 and 2015, 52 patients have been enrolled in this observational study, of whom 29 (55.8%) underwent elective open repair and 23 (44.2%) endovascular repair. TIMP2 × IGFBP7 were measured until 48 hours after admission on intensive-care unit (ICU) and were analyzed regarding their predictive ability for AKI (defined according to the KDIGO criteria) requiring temporary renal replacement therapy (RRT) and 90-day mortality using ROC curves. Results: Mean patient age was 64.5 years (Min: 43, Max: 85), endovascular treated patients were older (p <0.0001). 40.4% (n = 21) developed AKI, and 21.2% (n = 11) required renal replacement therapy. In-hospital and total mortality rates were 7.7% (n = 4) and 9.6% (n = 5), respectively. At no time a significant difference in TIMP2 × IGFB7 levels between patients undergoing open or endovascular surgery was observed. The predictive quality of the TIMP2 × IGFBP7 value on ICU admission was sound regarding AKI requiring temporary renal replacement therapy (sensitivity: 55.56% [38.1-72.1%], specificity: 90.91% [58.7-99.8%] with an area under the curve [AUC]: 0.694 [0.543-0.820]). Mean follow-up was 13.2 months (Min: 2, Max: 20), regarding the 90-day mortality, the predictive property of the TIMP2 × IGFBP7 value was not sufficient (sensitivity: 80% [28.4-99.5%], specificity: 52.38% [36.4-68%], and AUC: 0.607 [0.454-0.746]). Conclusions: TIMP2 × IGFBP7 level measured 6-12 hrs postoperatively may be useful as an early detectable biomarker for AKI requiring temporary renal replacement therapy. It seems not suited to predict patients' outcome following complex thoracoabdominal aortic surgery, regardless if performed by open or endovascular repair.

Zinc supplementation ameliorates lung injury by reducing neutrophil recruitment and activity.

INTRODUCTION: Zinc is well known for its anti-inflammatory effects, including regulation of migration and activity of polymorphonuclear neutrophils (PMN). Zinc deficiency is associated with inflammatory diseases such as acute lung injury (ALI). As deregulated neutrophil recruitment and their hyper-activation are hallmarks of ALI, benefits of zinc supplementation on the development of lipopolysaccharides (LPS)-induced ALI were tested. METHODS: 64 C57Bl/6 mice, split into eight groups, were injected with 30 µg zinc 24 hours before exposure to aerosolised LPS for 4 hours. Zinc homoeostasis was characterised measuring serum and lung zinc concentrations as well as metallothionein-1 expression. Recruitment of neutrophils to alveolar, interstitial and intravascular space was assessed using flow cytometry. To determine the extent of lung damage, permeability and histological changes and the influx of protein into the bronchoalveolar lavage fluid were measured. Inflammatory status and PMN activity were evaluated via tumour necrosis factor α levels and formation of neutrophil extracellular traps. The effects of zinc supplementation prior to LPS stimulation on activation of primary human granulocytes and integrity of human lung cell monolayers were assessed as well. RESULTS: Injecting zinc 24 hours prior to LPS-induced ALI indeed significantly decreased the recruitment of neutrophils to the lungs and prevented their hyperactivity and thus lung damage was decreased. Results from in vitro investigations using human cells suggest the transferability of the finding to human disease, which remains to be tested in more detail. CONCLUSION: Zinc supplementation attenuated LPS-induced lung injury in a murine ALI model. Thus, the usage of zinc-based strategies should be considered to prevent detrimental consequences of respiratory infection and lung damage in risk groups.

Management strategies for true and dissecting visceral artery aneurysms.

BACKGROUND: Visceral artery aneurysms (VAA) are rare and the literature regarding management strategies is limited. The study aim was to evaluate our 13-year experience with VAA treatment including conservative, open surgical and endovascular therapy. METHODS: This retrospective single-center study included 37 patients (31 male, median age 70 years [46-79 years]) with true and dissecting VAA treated between January 2006 and December 2018. Indications for invasive therapy were ruptured (N.=1) and symptomatic (N.=8) VAA or asymptomatic VAA>20 mm (N.=15). The decision on the treatment type was made after interdisciplinary (vascular surgeons/radiologists) discussion. RESULTS: The aneurysms affected the celiac trunk (N.=18, 49%), the splenic artery (N.=11, 30%), the superior mesenteric artery (SMA, N.=6, 16%), the hepatic artery (N.=5, 14%) and proximal SMA side branches (N.=2, 5%). Six patients had multiple VAA, one had an intrahepatic artery aneurysm and one had peripheral mesocolic artery aneurysms plus a VAA. 46% of the patients (N.=17) had coexisting aneurysms in other vascular territories. Thirteen patients were managed conservatively (median VAA diameter 15 [14-25] mm), 18 underwent open surgery with venous or prosthetic bypass or interposition graft implantation and 6 were treated by endovascular means (coiling [N.=3] or endograft [N.=3]). Median follow-up (FU) was 21 months (4-123 months). In-hospital mortality was 0%. Median length of hospital stay was 11 days (5-28 days) after surgical and 3 days (2-71 days) after endovascular treatment. Complications included an early type I endoleak, 3 secondary open abdominal surgeries for bleeding/peritonitis after endovascular treatment of a ruptured intrahepatic aneurysm, an asymptomatic aorto-truncal bypass occlusion and aneurysm recurrence after a venous SMA interposition graft. None of the conservatively treated VAA required invasive treatment during FU. CONCLUSIONS: Small (<20 mm) asymptomatic VAA can be managed conservatively. Whenever invasive treatment is indicated, both open and endovascular treatments can be performed with low complication rates. In order to choose the optimal therapeutic approach, anatomical features and patient comorbidities should be considered and, ideally, discussed interdisciplinarily.

Update on diagnosis and treatment strategies in patients with post-thrombotic syndrome due to chronic venous obstruction and role of endovenous recanalization.

OBJECTIVE: After a first episode of lower extremity deep venous thrombosis, post-thrombotic syndrome (PTS) develops in 20% to 50% of patients despite adequate anticoagulation. Symptoms of PTS can vary from leg swelling to venous ulceration with disabling venous claudication. It significantly affects the patient's quality of life and has considerable socioeconomic consequences. This review gives an update on diagnosis and current treatment strategies in patients with PTS due to chronic venous obstruction, in particular regarding the role of endovenous procedures. METHODS: This review article is based on a selective literature search in PubMed and the Cochrane Library. The terms "postthrombotic syndrome," "post-thrombotic syndrome," "chronic venous obstruction," "venous outflow obstruction," and "venous stent" were used as keywords. Selected publications addressed the diagnosis of and therapy for PTS. Acute deep venous thrombosis, thrombolysis, case reports, complications as a result of caval vein filters, animal experiments, PTS of the upper extremity, and PTS in children were excluded. RESULTS: In addition to conservative treatment of PTS, the following invasive procedures are also available: open surgical reconstructions, hybrid procedures, and endovenous recanalization of the occluded iliocaval venous tract with stent angioplasty. Since introduction of dedicated venous stents in 2012, technical success, patency rates, and improvement in quality of life have been at least as good as results of open surgical reconstruction if not better. CONCLUSIONS: First-line treatment should be conservative therapy. In case of therapy-resistant PTS with poor quality of life, the possibility of an invasive treatment should be evaluated. All invasive procedures are recommended with low levels of evidence. Therefore, deciding on an invasive treatment and type of procedure should be made individually. Because PTS is rarely a threat to life or limb, a minimally invasive treatment is preferred. Therefore, endovenous recanalization appears to be appropriate as the therapy of choice. In patients with involvement of the femoral confluence, endophlebectomy of the common femoral vein in addition to venous recanalization is inevitable to ensure an adequate inflow into the recanalized venous tract. It also secures a sufficient drainage of blood from the peripheral venous system. Because this hybrid procedure is burdened with a significantly higher risk of complications, strict criteria must be fulfilled to legitimize the indication for this procedure. For the best possible results to be achieved, the following perioperative and postoperative management must be considered: therapeutic anticoagulation, early mobilization, compression therapy, and systematic follow-up with duplex ultrasound.

Comparison of urine and serum neutrophil gelatinase-associated lipocalin after open and endovascular thoraco-abdominal aortic surgery and their meaning as indicators of acute kidney injury.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has been described as a potential biomarker of acute kidney injury (AKI) in different settings, but its behaviour under influence of open and endovascular repair of thoraco-abdominal aortic aneurysms (TAAA) has not been assessed yet. In this study, the course of NGAL was observed and differences of serum- (sNGAL) and urine-NGAL (uNGAL) levels following TAAA repair, especially with regard to AKI, were evaluated. PATIENTS AND METHODS: In this retrospective single centre study, 52 patients (mean age 64.5 years, [43-85 years]), including 39 (75 %) men, were enrolled (2014-2015, 13.2 months mean follow-up). Levels of sNGAL and uNGAL were measured perioperatively for 48 hours on intensive care unit. Twenty-three patients were treated by endovascular and 29 by open TAAA-repair. RESULTS: Logistic regression revealed an increase in NGAL (sNGAL p = 0.0263, uNGAL p = 0.0080) corresponding with an increase in serum creatinine within the first 48 hours. Fourteen patients (26.9 %) developed AKI and 11 (21.1 %) required dialysis. The course of NGAL differed significantly (uNGAL p < .0001, sNGAL p = 0.0002) between patients suffering from AKI requiring dialysis and patients without AKI. The predictive power of uNGAL was three times higher than that of sNGAL (estimate of the regression slope 0.1382 vs. 0.0460). No significant difference between patients undergoing open or endovascular TAAA repair regarding the perioperative course of sNGAL and uNGAL was observed. CONCLUSION: serum-NGAL and urine-NGAL correlate with serum creatinine levels and AKI requiring dialysis. Furthermore, the postoperative course of sNGAL and uNGAL after open and endovascular TAAA repair is not significantly different. Taken together, the results indicate that uNGAL and, to a lesser extent, sNGAL could be considered biomarkers for early detection of perioperative AKI after open and endovascular TAAA surgery.

[Delayed Occluding Membrane (DOM) - A New Concept to Prevent Spinal Cord Ischaemia During Endovascular Aortic Aneurysm Repair]. / Delayed Occluding Membrane (DOM) ­ ein neuer Ansatz zur Protektion der spinalen Ischämie bei endovaskulärem Aortenrepair.

INTRODUCTION: The risk of spinal cord ischemia is a relevant problem in in fields of open and endovascular thoracoabdominal aortic aneurysm repair (TAAA). Despite all efforts, no therapeutical concept exists, which enables a complete treatment of the TAAA without open branches or fenestrations, and reduces the risk for a spinal cord ischemia (SCI) to the minimum. In this article, we would like to present a new concept based on slow-occluding hydrogel-textile membrane, which could help to reduce the SCI risk during endovascular TAAA repair. CONCEPT: A hydrogel textile membrane is under development, which could be used a functional unit of endovascular stentprosthesis. If in contact with blood, glutathion induces swelling of the induces ongoing swelling of the membrane because of the triggered degradation of the crosslinker. Due to the resulting water uptake of the hydrogel textile membrane and mass increase of the gel, the swelling leads to a stabilization of the membrane. In vitro studies show, that the swelling of the hydrogel textile membrane should lead to a controlled decreasing flow into the aneurysm sac. After a pre-defined period, the membrane is occluded and the aneurysm sac perfusion stops. So, by using the hydrogel textile membrane, a complete treatment of the TAAA can be realized in one procedure without further re-intervention or pre-interventional measures. Furthermore, the risk of a SCI would be minimized. As this treatment concept is under development, only interim results are presented. CONCLUSION: The successful development and usage of a slow-occluding hydrogel textile membrane as a part of endovascular stentprosthesis could help to reduce the risk SCI during endovascular TAAA surgery.

Closed Incision Negative Pressure Therapy Reduces Surgical Site Infections in Vascular Surgery: A Prospective Randomised Trial (AIMS Trial).

BACKGROUND: Surgical site infections (SSIs) of the groin remain a crucial problem in vascular surgery, prompting great interest in preventative techniques, such as closed incision negative pressure therapy (ciNPT). This prospective randomised study aimed to assess the potential benefits of ciNPT application after groin incisions for vascular surgery. METHOD: The study included 204 patients who underwent vascular surgery for peripheral artery disease (PAD) at two sites between July 2015 and May 2017. These patients received post-operative treatment with ciNPT (intervention group) or standard wound dressings (control group). After exclusion, 188 patients were assessed for SSIs using the Szilagyi classification. RESULTS: The mean patient age was 66.6 ± 9.4 years (range 43-85 years), and 70% were male (n = 132). Regarding PAD stage, 52% were stage IIB, 28% stage III, and 19% stage IV. Among the patients, 45% (n = 85) had had a previous groin incision. Bacterial swabs were performed in each case of suspected SSI (22.8% [43/188]), while 76.7% (33/188) were negative, there were 5% [5/98] positive swabs in the intervention group and 5.5% [5/90] in the control group). Antibiotics were given to 13.2% of the intervention group, and 31.1% of the control group (p = .004). The control group experienced more frequent SSIs (33.3%; 30/90) than the intervention group (13.2%; 13/98; p = .0015; absolute risk difference -20.1 per 100; 95% CI -31.9 to 8.2). This difference was based on an increased rate of Szilagyi I SSI in the control group (24.6% vs. 8.1%, p = .0012). CONCLUSION: The results confirmed a reduced superficial SSI rate after vascular surgical groin incision using ciNPT compared with standard wound dressings.

Recovery of lost motor evoked potentials in open thoracoabdominal aortic aneurysm repair using intercostal artery bypass.

Ischemia of the spinal cord remains a disastrous complication in thoracoabdominal aortic aneurysm (TAAA) surgery. We report a case of open type I TAAA repair during which no motor evoked potentials were detectable for >1 hour after aortic cross-clamping. The creation of three intercostal artery bypasses restored spinal cord perfusion. As the patient showed only moderate clinical signs of spinal cord ischemia afterward, we underline the role of neuromonitoring to guide intercostal artery bypass implantation during TAAA surgery as the combined use of neuromonitoring and intercostal artery bypass implantation may prevent paraplegia in specific TAAA cases.

Extra-Thoracic Supra-aortic Bypass Surgery Is Safe in Thoracic Endovascular Aortic Repair and Arterial Occlusive Disease Treatment.

OBJECTIVE: The safety and feasibility of supra-aortic debranching as part of endovascular aortic surgery or as a treatment option for arterial occlusive disease (AOD) remains controversial. The aim of this study was to assess the clinical outcome of this surgery. METHODS: This single centre, retrospective study included 107 patients (mean age 69.2 years, 38.4% women) who underwent supra-aortic bypass surgery (carotid-subclavian bypass, carotid-carotid bypass, and carotid-carotid-subclavian bypass) because of thoracic or thoraco-abdominal endovascular aortic repair (57%; 61/107) or as AOD treatment (42.9%; 46/107) between January 2006 and January 2015. Mortality, morbidity with a focus on neurological complications, and patency rate were assessed. Twenty-six of 107 (14.2%) of the debranching patients were treated under emergency conditions because of acute type B dissection or symptomatic aneurysm. Follow up, conducted by imaging interpretation and telephone interviews, continued till March 2017 (mean 42.1, 0-125, months). RESULTS: The in hospital mortality rate was 10.2% (11/107), all of these cases from the debranching group and related to emergency procedures (p < .0001). One procedure related death of a patient in the debranching group, who had a lethal stroke 72 months post-operatively following bypass occlusion was observed. Early neurological complications were recognised in 10 patients, including two transient cases of Horner syndrome and vocal cord paralysis as well as six cases of phrenic nerve apraxia. Three cases of stenosis and one case of occlusion were successfully treated. In three AOD patients, the graft had to be exchanged because of peri-graft reaction. Primary and secondary patency rates of 96 patients after 36 months were 95% (SE 2.6%) and 98% (SE 1.8%), respectively. CONCLUSIONS: Extra-thoracic supra-aortic bypass surgery involves low complication rates and high mid-term bypass patency rates. It is a safe and feasible treatment option in the form of debranching in combination with endovascular aortic aneurysm repair and in AOD.

Editor's Choice - Open Thoracic and Thoraco-abdominal Aortic Repair After Prior Endovascular Therapy.

OBJECTIVE: The aim was to present current results of open thoracic and thoraco-abdominal aortic repair as secondary procedure after prior endovascular therapy. METHODS: This was a retrospective cross border single centre study. From 2006 to July 2017 45 open thoracic aortic (TAA) or thoraco-abdominal aortic aneurysm (TAAA) operations were performed on 44 patients (median age 58 [15-80] years) as secondary surgery after previous endovascular therapy comprising TEVAR (n = 38; 86%), EVAR (n = 3; 7%), fenestrated EVAR (n = 1; 2%) and TEVAR plus EVAR (n = 1; 2%). Eleven patients (25%) had had previous open aortic surgery at the secondary surgery site. Indications for TAA(A) repair were Type I endoleak (n = 10; 23%), post-dissection aneurysm progression due to persisting false lumen perfusion (n = 8; 18%), proximal/distal disease progression (n = 16; 36%), device fracture/dislocation (n = 4; 9%), infection (n = 5; 11%), and initial endograft misplacement (n = 1; 2%). The operations included descending thoracic aortic repair (n = 13, 29%), TAAA Type I (n = 4; 9%), Type II (n = 5; 11%), Type III (n = 13; 29%), Type IV (n = 7; 16%), and Type V repair (n = 3; 7%) with simultaneous arch repair in 18% (n = 8). The median time to secondary surgery was 36 (2-168) months. The median follow up was 39 (3-118) months. RESULTS: In hospital mortality was 20% (n = 9) due to intra-operative aneurysm rupture, pneumonia induced sepsis, hemorrhagic cerebellar infarction, mesenteric ischaemia, broncho-esophageal fistula, and multiorgan failure (1/9) as well as haemorrhage (3/9). Estimated survival was 73% at 1 year and 71% overall. The most frequent complications were pneumonia (n = 19; 43%), bleeding requiring revision (n = 11; 25%) and sepsis (n = 14; 32%). Transient dialysis was required in 32% (n = 14), permanent dialysis in 6% (n = 2). Permanent spinal cord deficit (paraparesis) occurred in 6% (n = 2). Estimated freedom from aortic re-intervention was 86%. CONCLUSION: Open TAA(A) repair as a secondary procedure after previous endovascular aortic therapy is an important treatment option even in the endovascular era. It represents a durable treatment that can produce respectable outcomes. Yet the peri-operative morbidity and mortality are relevant and a specialised team and infrastructure are mandatory for these complex procedures. Therefore, centralisation is required.

Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation.

Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet-neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet-neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation.

Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery.

The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4-99.5%); specificity, 51.2% (35.1-67.1%); AUC, 0.688 (0.534-0.816)] and discharge modality [sensitivity, 87.5% (47.3-99.7%); specificity, 73.7% (56.9-86.6%), AUC, 0.789 (0.644-0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery.

Editor's Choice - Open Thoracic and Thoraco-abdominal Aortic Repair in Patients with Connective Tissue Disease.

OBJECTIVE/BACKGROUND: The aim is to present current results of open complex aortic repair in patients with connective tissue disease (CTD). METHODS: This was a retrospective cross-border, single centre study. From February 2000 to April 2016 72 aortic operations were performed on 65 patients with CTD (41 male, median age 41 years [range 19-70 years]). Fifty-six patients (86%) underwent at least one previous aortic repair (71 open, four endovascular), including 33 patients (51%) operated before at the site of the procedure reported here. The open procedures, counting eight emergency operations (11%), included aortic arch revision (n = 1; 1%), descending thoracic aortic repair (n = 11; 15%), TAAA type I repair (n = 12; 17%), type II repair (n = 29; 40%), type III repair (n = 12; 17%), and type IV repair (n = 5; 7%). Simultaneous repair of the ascending aorta and/or the aortic arch was performed in two (3%) and eight cases (11%), respectively. Seven patients (10%) underwent staged procedures. Median follow-up was 42 months (0.5-180 months). RESULTS: The in hospital mortality was 14% (n = 9) as a result of haemorrhage (n = 3/9), neurological (n = 3/9), cardiac (n = 2/9), and pulmonary (n = 1/9) complications. Paraplegia and paraparesis occurred in one (2%) and three patients (5%), respectively. Seven patients (11%) required temporary dialysis; none needed permanent dialysis. Major complications were revision surgery for bleeding or haematoma (n = 20/65), sepsis (n = 10/65), myocardial infarction/severe cardiac arrhythmia (n = 2/65), stroke (n = 2/65), as well as multiorgan failure, abdominal compartment syndrome, mesenteric and peripheral ischaemia (all n = 1/65). Multivariate analysis identified an operating time > 7 hours (p = .006) as an independent predictor of increased mortality. Freedom from re-intervention was 85%, 1 year survival was 80%, and overall survival was 75%. CONCLUSION: Open TAA(A) repair is a durable therapy for patients with CTD. Often being performed as revision surgery, it can be associated with relevant risks and should therefore be reserved for specialised centres. Staged procedures and thus reducing operating time, if applicable, should be preferred.

Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation.

Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting.

Treatment of blunt thoracic aortic injury in Germany-Assessment of the TraumaRegister DGU®.

PURPOSE: Using the data delivered by the German Trauma Register DGU® from 2002 till 2013, the value of different therapies of blunt thoracic aortic injury (BTAI) in Germany was analyzed. METHODS: Prospectively collected data of patients suffering from BTAI were retrospectively analyzed with focus on the different treatment modalities for grade I-IV injuries. RESULTS: 821 patients suffering from BTAI were identified: 51.6% (424) grade I injury, 35.4% (291) grade II or III injury and 12.9% (106) grade IV injury (77.5% men [44.94 ± 20.6 years]). The main patterns of injury were high- speed accidents and falls (78.0% [n = 640], 21.8% [n = 171] respectively). Significant differences between grade I and grade II/III as well as IV injuries could be assessed for the incidence of cardiopulmonary resuscitation, a Glasgow Coma Scale score below 8 and a systolic blood pressure below 90 mmHg (p-value: <0.001). In the primary admission subgroup, 44.1% (197/447) of the patients received best medical treatment, 55.9% received surgical intervention (250/447): Thereof 37.2% (93/250) received open surgery and 62.8% (147/250) had been treated by endovascular means. Significantly lower 24-h- and in-hospital-mortality rates were encountered after endovascular treatment for all gradings of BTAI (p-value: <0.001). Yet this subgroup of patients showed the lowest incidence of further severe injuries and cardiac arrest. CONCLUSION: Endovascular therapy became the treatment of choice for BTAI in Germany. Patients who have been treated by surgical means showed the highest survival rate, especially endovascular therapy showed a favorable low mortality rate.

Protective Aptitude of Annexin A1 in Arterial Neointima Formation in Atherosclerosis-Prone Mice-Brief Report.

OBJECTIVE: Restenosis as a consequence of arterial injury is aggravated by inflammatory pathways. Here, we investigate the role of the proresolving protein annexin A1 (AnxA1) in healing after wire injury. APPROACH AND RESULTS: Apoe-/- and Apoe-/-Anxa1-/- mice were subjected to wire injury while fed a high-cholesterol diet. Subsequently, localization of AnxA1 and AnxA1 plasma levels were examined. AnxA1 was found to localize within endothelial cells and macrophages in the neointima. Levels of AnxA1 in the plasma and its lesional expression negatively correlated with neointima size, and in the absence of AnxA1, neointima formation was aggravated by the accumulation and proliferation of macrophages. In contrast, reendothelialization and smooth muscle cell infiltration were not affected in Apoe-/-Anxa1-/- mice. CONCLUSIONS: AnxA1 is protective in healing after wire injury and could, therefore, be an attractive therapeutic compound to prevent from restenosis after vascular damage.

Functional Assessment and Evaluation of Outcome After Endovascular Therapy With Coverage of the Left Subclavian Artery in Case of Blunt Thoracic Aortic Injury.

BACKGROUND: Patients suffering blunt thoracic aortic injury (BTAI) can be treated by use of thoracic endovascular aortic repair (TEVAR). In this setting, the coverage of the left subclavian artery (LSA) is frequently necessary. Nevertheless, the functionality of the upper left extremity after TEVAR had been rarely analyzed. Thus, this study intends to underline the safety of TEVAR as well as to determine the functionality of the left arm after coverage of the LSA. METHODS: All patients suffering from BTAI treated by endovascular means in 3 centers (Aachen [Germany], Maastricht [Netherlands], and Innsbruck [Austria]) between 1996 and 2009 were retrospectively analyzed. The safety of the procedure had been assessed by the morbidity and mortality rate. The mid-term functional status of the upper left extremity was evaluated by using the DASH score (disabilities of the arm shoulder and hand). RESULTS: Forty-six patients (40 male, 6 female), mean age 39.4 ± 16.9 years suffered from BTAI caused by traffic accident (n = 31 [67.39%]), by skiing injury (n = 8 [17.39%]), and by fall (n = 7 [15.21%]). All patients underwent TEVAR, the technical success rate was 100%; 1 carotid-carotid subclavian bypass implantation was necessary. LSA coverage was performed in 76% (35/46) of the cases. Total complication rate was 17.3% (8/46); the endoleak rate was 8.6% (4/46) (2 × Ib, 1 × IIa, 1 × IV). Further complications were bypass and endograft occlusion. The postoperative mortality rate was 6% (3/46), the DASH score was completed in 65% (30/46). The study population reached a mean value of 17 ± 20, which is comparable to a nonharmed reference group (10.10 ± 14.68). A significant correlation between the DASH score and patients age could be demonstrated (2-sided P value: 0.0213). CONCLUSIONS: Endovascular therapy of BTAI revealed a good primary success rate. An adequate mid-term functional status of the upper left extremity could be assessed in comparison to a nonharmed reference group.

Sarcoidosis-Associated Aortoesophageal Fistula-Multistage Interdisciplinary Surgical Therapy for a Rare and Life-Threatening Condition.

Aortoesophageal fistulas (AEFs) are rare and life-threatening conditions. Till date, an association between an AEF and sarcoidosis has not been reported yet. The aim of this report is to demonstrate a case of AEF secondary to sarcoidosis and its multistage interdisciplinary surgical therapy. A 66-year-old male was diagnosed with sarcoidosis in 2014. He has been treated with glucocorticoids since then and no severe health restrictions due to the disease have occurred. In December 2015, the patient presented with acute thoracic pain and hematemesis: an esophagogastroscopy revealed an AEF. First, stent-graft implantation in the thoracic aorta was urgently performed as a "bridging" procedure. Second, esophagectomy and local debridement were performed, followed by explantation of the stent graft and reconstruction by means of xenograft replacement of the stented aorta in a third operation. Finally, retrosternal gastric pull-up was performed in a fourth operative procedure. Sixteen days after the last operation the patient could be discharged to a rehabilitation clinic. Follow-up is uneventful so far; the antibiotic therapy was stopped at the time of hospital discharge. The pathogenesis of sarcoidosis, a rare autoimmunological disease, has not been completely clarified yet. The diagnosis relies on clinical symptoms and radiological as well as histopathological findings. Many cases of sarcoidosis show spontaneous regression, but severe complications may occur. While tracheoesophageal fistulas have been described in the literature, AEFs related to sarcoidosis have not been mentioned yet. Despite surgical and antibiotic treatment, the morbidity and mortality rates of AEF are high. Because the endovascular treatment has been established for emergency procedures of the aorta, it is considered as an appropriate first-line "bridging" treatment option. To achieve good long-term results, surgical treatment has to involve esophagectomy with secondary reconstruction of the upper gastrointestinal tract, as well as open aortic replacement using xenograft or homograft material. Sarcoidosis may lead to AEF as demonstrated in this case. Successful treatment can be realized by a multistage interdisciplinary surgical approach.