Cf Vahl

Should intentional endovascular stent-graft coverage of the left subclavian artery be preceded by prophylactic revascularisation?

Thoracic endovascular aortic repair (TEVAR) has emerged as a promising therapeutic alternative to conventional open aortic replacement but it requires suitable proximal and distal landing zones for stent-graft anchoring. Many aortic pathologies affect in the immediate proximity of the left subclavian artery (LSA) limiting the proximal landing zone site without proximal vessel coverage. In patients in whom the distance between the LSA and aortic lesion is too short, extension of the landing zone can be obtained by covering the LSAs origin with the endovascular stent graft (ESG). This manoeuvre has the potential for immediate and delayed neurological and vascular symptoms. Some authors, therefore, propose prophylactic revascularisation of the LSA by transposition or bypass, while others suggest prophylactic revascularisation only under certain conditions, and still others see no requirement for prophylactic revascularisation in anticipation of LSA ostium coverage. In this review about LSA revascularisation in TEVAR patients with coverage of the LSA, we searched the electronic databases MEDLINE and EMBASE historically until the end date of May 2010 with the search terms left subclavian artery, covering, endovascular, revascularisation and thoracic aorta. We have gathered the most complete scientific evidence available used to support the various concepts to deal with this issue. After a review of the current available literature, 23 relevant articles were found, where we have identified and analysed three basic treatment concepts for LSA revascularisation in TEVAR patients (prophylactic, conditional prophylactic and no prophylactic LSA revascularisation). The available evidence supports prophylactic revascularisation of the LSA before ESG LSA coverage when preoperative imaging reveals abnormal supra-aortic vascular anatomy or pathology. We further conclude that elective patients undergoing planned coverage of the LSA during TEVAR should receive prophylactic LSA transposition or LSA-to-left-common-carotid-artery (LCCA) bypass surgery to prevent severe neurological complications, such as paraplegia or brain stem infarction.

Subendothelial infiltration of neutrophil granulocytes and liberation of matrix-destabilizing enzymes in an experimental model of human neo-intima

It was the objective of this study to examine the role of human neutrophil granulocytes (PMN) in an in-vitro model of human neo-intima developed for the study of atherosclerosis. Human granulocytes were subjected to a co-culture model of human endothelial and smooth muscle cells. Subendothelial lipid accumulation was achieved by addition of native LDL to the culture medium. Tissue samples were analyzed by immunohistochemistry and scanning/transmission electron microscopy, and culture supernatants were examined for the presence of interleukin-8 (IL-8), MCP-1, GRO-alpha, elastase and matrixmetalloproteinase-8 (MMP-8). Following addition of 2 mg/ml LDL, adherence, transmigration and infiltration depth of PMN was increased significantly when compared to controls. LDL challenging was paralleled by a time- and dose-dependent secretion of IL-8 from intimal smooth muscle cells. PMN infiltration was mediated by the IL-8-signalling pathway and accompanied by release of elastase and MMP-8 into the supernatant and induction of endothelial cell apoptosis. In conclusion, LDL-induced secretion of IL-8 by intimal smooth muscle cells provides a potential mechanism of PMN-recruitment into culprit lesions. The concomitant release of potent matrix-degrading enzymes and the induction of EC apoptosis may have implications for plaque destabilization and cardiovascular events.

Management of Patients With Aortic Dissection

INTRODUCTION The incidence of acute diseases of the aorta will continue to rise as our population ages. METHODS Selective literature review. RESULTS/DISCUSSION At centers specializing in maximum care, it is important that a specific strategy should be established in cases of clinically suspected, acute aortic diseases, and non-invasive diagnostic measures should be taken without delay. If an acute aortic dissection is diagnosed, the necessary treatment must be provided immediately. As this disease is life-threatening, a cooperating network of referring physicians and institutions should be set up in order to ensure optimal treatment for these desperately ill patients. Acute type A aortic dissections generally require surgery, while the primary treatment of uncomplicated type B dissections is conservative and complicated type B dissections can be treated primarily with stent-graft implantation. The referring medical specialists and institutions should follow the patients closely after treatment so that any problems that may develop can be recognized and treated in timely fashion.

A novel in vitro model for the study of plaque development in atherosclerosis

For the study of atherogenesis in vitro, coculture systems have been devised, in which two or more cell types can be cultured in close contact to each other. Herein, we describe a novel in vitro model that aims at the simulation of the morphology of a normal muscular artery allowing for the study of the initial events in atherosclerosis. Using a modified fibrin gel as a scaffold for the coculture of endothelial cells (ECs) and smooth muscle cells (SMCs), we generated an autologous in vitro model with a multilayer growth of SMCs (intima-like structure) covered by an endothelium. The production of extracellular matrix (ECM) could be visualized histologically and verified by (i) ascorbic-acid dependent secretion of procollagen I into the supernatant and (ii) deposition of collagens I and III as well as laminin in the gel as assessed by immunohistochemistry. By BrdU-incorporation and Ki67 expression, the SMCs exhibited minimal proliferative activity, even when the culture period was extended to 6 weeks. Lipoprotein insudation was investigated under simulated hypo-, normo- and hypercholesterolemic conditions through addition of 0.5, 1 or 2 mg/mL LDL to the medium with subsequent time and dose dependent insudation of LDL. When human monocytes were added to the culture medium, infiltration and foam cell formation of macrophages and SMCs as well as expression of interleukin-8 (IL-8) was demonstrated. The in vitro model of the human vascular wall described herein appears to be suitable for the study of pivotal events in atherosclerotic plaque development. The applicability for long-term culture, the ability to study cell-matrix interactions and the opportunities for histomorphological and immunohistochemical examinations represent additional advantages of this model.

Patency of renal and visceral vessels after open thoracoabdominal aortic replacement

OBJECTIVE In thoracoabdominal aortic aneurysms (TAAAs), a paradigm shift is observed from open surgery toward total endovascular aortic repair using fenestrated and branched endografts. Whereas outcome after open replacement in terms of mortality and paraplegia has been evaluated extensively, no studies exist addressing long-term patency of visceral and renal vessels. To enable comparison of target vessel patency between open and endovascular treatment, we analyzed our series of open TAAA replacements. METHODS Our vascular surgery database was screened for patients who received open TAAA replacement between 1998 and 2012, and patient records were analyzed retrospectively. All available imaging scans (computed tomography and magnetic resonance angiography: preoperative, postoperative, and follow-up) were evaluated for graft and vessel patency. RESULTS We identified 62 patients (mean age, 66 ± 10 years; 40 men) who had been operated on for aneurysms of Crawford types I (8), II (13), III (13), and IV (24) and Safi type V (4). A total of 181 vessels were revascularized by either patch inclusion (n = 147) or selective revascularization (bypass or transposition, n = 34); 48 survived the procedure, resulting in a number of vessels available for follow-up of 154 (patch, 126; selective revascularization, 28). The respective patency rates for overall, patch, and selective revascularization were 95.2%, 94.2%, and 100% at 5 years and 83.7%, 81.3%, and 100% at 10 years, respectively. In addition, a trend for better performance of selective revascularization (bypass or transposition) was evident as all vessel occlusions were observed in cases of patch inclusion, whereas all selectively revascularized vessels were patent. The respective patency rates for the celiac trunk, superior mesenteric artery, and left and right renal artery were 100%, 97.5%, 92.3%, and 90.3% at 5 years. CONCLUSIONS In our series of open thoracoabdominal aortic replacement, excellent patency rates for revascularized renal and visceral vessels were observed during long-term follow-up. We were able to provide a reference value of long-term target vessel patency that can and should be taken into account to judge the efficacy of endovascular repair in TAAA.

A Follicular Dendritic Cell Sarcoma of the Mediastinum With Immature T Cells and Association With Myasthenia Gravis

Follicular dendritic cell (FDC) sarcoma is a very rare neoplasm showing morphologic and phenotypic features of FDCs. It occurs primarily in lymph nodes but also in extranodal sites. So far, there have been no reports on FDC sarcoma associated with myasthenia gravis. In the following we will present a case of an FDC tumor of the mediastinum associated with paraneoplastic myasthenia gravis in a 39-year-old man. The tumor contained a major proportion of immature T cells, which may be connected to this patients very unusual clinical presentation with autoimmune phenomena. Extranodal FDC sarcomas still seem hardly noticed, and their clinical and pathologic characteristics remain to be better defined.

Use and durability of femoral vein for autologous reconstruction with infection of the aortoiliofemoral axis

OBJECTIVE To analyze early and late mortality, venous morbidity, reinfection, and freedom from reintervention after using the femoral vein (FV) for vascular reconstruction with infection of the aortoiliofemoral axis. METHODS By reviewing our database, 86 patients could be identified with implantation of FV grafts in infected fields between November 1995 and July 2012. The patient records were retrospectively analyzed and follow-up information obtained from patients or their general physician. Seventy-one patients presented with prosthetic graft infection and 15 with an infected aneurysm. For data analysis, patients were divided into an aortoiliac (n = 67) and a femoral group (n = 19). Study end points assessed were early and late mortality, incidence of deep vein thrombosis of the FV donor limb, graft patency, limb salvage, reinfection, and freedom from reintervention. RESULTS Sixty-seven aortoiliac reconstructions were performed using 84 FV grafts with an operative mortality of 9%. After a mean follow-up of 45 months, survival, patency, limb salvage, and freedom from reintervention were 45%, 97%, 94%, and 91%, respectively, at 5 years. Twenty FV grafts were employed for 19 femoral reconstructions with an operative mortality of 10.5%. Here, mean follow-up was 35 months and survival, patency, limb salvage, and freedom from reintervention were 29%, 87%, 93%, and 81%, respectively, at 5 years. Specimen culture confirmed Staphylococcus (epidermidis and aureus) as the predominant microorganism. Venous morbidity after FV harvest showed an incidence of deep venous thrombosis of 13.7% for popliteal and 10.6% for tibial level at a follow-up of 24 months with only mild clinical symptoms (21% limb swelling). CONCLUSIONS Vascular reconstruction using autologous FV in arterial and graft infection of the aortoiliofemoral axis provides durable long-term results with acceptable mortality and morbidity.

The adenosine deaminase inhibitor erythro-9-[2-hydroxyl-3-nonyl]-adenine decreases intestinal permeability and protects against experimental sepsis: a prospective, randomised laboratory investigation

IntroductionThe treatment of septic conditions in critically ill patients is still one of medicines major challenges. Cyclic nucleotides, adenosine and its receptors play a pivotal role in the regulation of inflammatory responses and in limiting inflammatory tissue destruction. The aim of this study was to verify the hypothesis that adenosine deaminase-1 and cyclic guanosine monophosphate-stimulated phosphodiesterase inhibition by erythro-9-[2-hydroxyl-3-nonyl]-adenine could be beneficial in experimental endotoxicosis/sepsis.MethodWe used two established animal models for endotoxicosis and sepsis. Twenty-four male Wistar rats that had been given intravenous endotoxin (Escherichia coli lipopolysaccharide) were treated with either erythro-9-[2-hydroxyl-3-nonyl]-adenine infusion or 0.9% saline during a study length of 120 minutes. Sepsis in 84 female C57BL/6 mice was induced by caecal ligation and puncture. Animals were treated with repeated erythro-9-[2-hydroxyl-3-nonyl]-adenine injections after 0, 12 and 24 hours or 4, 12 and 24 hours for delayed treatment.ResultsIn endotoxaemic rats, intestinal production of hypoxanthine increased from 9.8 +/- 90.2 μmol/l at baseline to 411.4 +/- 124.6 μmol/l and uric acid formation increased from 1.5 +/- 2.3 mmol/l to 13.1 +/- 2.7 mmol/l after 120 minutes. In endotoxaemic animals treated with erythro-9-[2-hydroxyl-3-nonyl]-adenine, we found no elevation of adenosine metabolites. The lactulose/L-rhamnose ratio (14.3 versus 4.2 in control animals; p = 2.5 × 10-7) reflects a highly permeable small intestine and through the application of erythro-9-[2-hydroxyl-3-nonyl]-adenine, intestinal permeability could be re-established. The lipopolysaccharide animals had decreased L-rhamnose/3-O-methyl-D-glucose urine excretion ratios. Erythro-9-[2-hydroxyl-3-nonyl]-adenine reduced this effect. The mucosa damage score of the septic animals was higher compared with control and therapy animals (p < 0.05). Septic shock induction by caecal ligation and puncture resulted in a 160-hour survival rate of about 25%. In contrast, direct adenosine deaminase-1 inhibition resulted in a survival rate of about 75% (p = 0.0018). A protective effect was still present when erythro-9-[2-hydroxyl-3-nonyl]-adenine treatment was delayed for four hours (55%, p = 0.029).ConclusionsWe present further evidence of the beneficial effects achieved by administering erythro-9-[2-hydroxyl-3-nonyl]-adenine, an adenosine deaminase-1 and cyclic guanosine monophosphate-stimulated phosphodiesterase inhibitor, in an endotoxicosis and sepsis animal model. This suggests a potential therapeutic option in the treatment of septic conditions.

Endovascular Repair of Paravisceral Aortic Aneurysms Combining Chimney Grafts and the Nellix Endovascular Aneurysm Sealing Technology (Four-Vessel ChEVAS)

Background We demonstrate our initial experience and first results of the endovascular aneurysm sealing (EVAS) technology with chimney grafts for the treatment of paravisceral aneurysms. Methods We present a consecutive series of seven patients with a mean age of 75 years who had been treated by four‐vessel‐chimney EVAS (ChEVAS) between May 2014 and May 2015. All patients were ASA grade ≥ III and were not eligible for fenestrated/branched endovascular aortic repair (fEVAR/brEVAR) due to urgency (n = 5) or anatomical constraints (n = 2). Results Total 28 renovisceral target vessels were treated by balloon‐expandable covered stents and 14 Nellix devices were used to seal the paravisceral aorta. Overall, 16 Nellix (Endologix Inc., Irvine, California, United States) devices and 65 covered stents were implanted with a technical success of 100%. Perioperatively, one patient with ruptured aneurysm died due to respiratory failure following splenic laceration/splenectomy (mortality = 14%) and in one patient, laceration of an axillary access vessel occurred. At a median follow‐up of 6 months, all six surviving patients were well and no reinterventions were necessary. One chimney was found occluded without clinical sequelae resulting in a patency rate of 96%. Conclusion Four‐vessel ChEVAS may serve as alternative treatment option in highly selected cases of either acute paravisceral aortic pathology and/or situations, where the implantation of fEVAR/brEVAR is hampered by anatomical constraints. Further follow‐up and a multicenter study are of course warranted to corroborate these initial results.

Anomalous origin of the left coronary artery from the pulmonary artery: mid-term results after surgical correction

ObjectivesChildren with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) are at risk for myocardial infarction and death. This retrospective study shows the mid-term follow-up after the use of aortic implantation and alternative methods to achieve coronary transfer.MethodsSince 1990 seven consecutive children underwent primary repair of ALCAPA. Age at operation ranged from 2 to 71 months (median 11 months). Operative techniques included ligation (n = 1), intrapulmonary tunnel (n = 1), and aortic implantation (n = 5). One patient with severe mitral valve incompetence underwent additional mitral valve replacement. A 4-month-old patient was successfully treated after the operation with a left heart assist device.ResultsOne death in the series occurred at 2 weeks after intrapulmonary tunneling. The mid-term results were evaluated in the six survivors with a follow-up mean of 98 months (ranged 58–168). In all surviving patients with two-vessel coronary blood supply, left ventricular end-diastolic volume and left ventricular ejection fraction returned to near normal values 2–12 months postoperatively. The mitral valve incompetence decreased in all patients with a native mitral valve. One patient with coronary ligation showed severe mitral valve regurgitation and received additional mitral valve replacement concomitantly. Six years after primary valve replacement of a 21 mm SJM (Saint Jude Medical) a change of the mechanical valve to a 27 mm valve was necessary because of development of severe stenosis due to growth.ConclusionsIt is always preferable to establish an antegrade flow of oxygenated blood through the coronary arteries and to create a two-coronary artery system. Mitral valve annuloplasty or replacement may be necessary for patients with severe mitral valve incompetence.