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Early survivors of acute type A aortic dissection (AAAD) remain at risk for late death and late aortic events. However, the frequency and long-term effects of warfarin anticoagulation on long-term outcome in post-surgical AAAD survivors have not been elucidated.Two tertiary care centers performed a retrospective observational cohort study of warfarin anticoagulation in AAAD in 243 persons with early survival of surgical repair (WATAS). Serial postoperative tomographic imaging was available in 106 persons.A total of 88 postoperative AAAD survivors (36%) were on long-term warfarin anticoagulation. The indication for anticoagulation was a mechanical aortic prosthesis in 46 (52%), atrial fibrillation in 33 (38%), stroke in 7 (8%), and pulmonary embolism in 1 (1%). The indication for anticoagulation remained unclear in 1 person (1%). Survival and aortic event free survival were 98.3±0.01 and 98.7±0.01 at 1 year, and 76.4±0.03 and 91.8±0.02 at 5 years, respectively, with no differences irrespective of warfarin anticoagulation. Multivariate Cox regression analysis established higher age (P0.001), and operation extending into the descending aorta (P=0.030) as independent predictors of late death. Follow-up without tomographic imaging independently predicted increased long-term mortality (P0.001) and lower rates of documented aortic events (P=0.003). Kaplan-Meyer analysis showed a relationship of aortic diameter growth ≥0.5 cm per year with late death (P=0.041) and with late aortic events (P0.001). However, rapid aortic growth did not relate to warfarin anticoagulation.Warfarin anticoagulation is frequent in postsurgical AAAD and it is administered for vital indications. Warfarin anticoagulation does not relate to late mortality or to late aortic events. Rapid aortic growth predicts late mortality and late aortic events, but warfarin anticoagulation is not associated with aortic growth. Follow-up tomographic imaging is mandatory for long-term survival after surgical repair of AAAD.

Das Kompartmentsyndrom kann nach der Ursache, dem zeitlichen Verlauf, dem klinischen Schweregrad und nach der betroffenen Korperregion klassifiziert werden.

Abstract. Background: Perioperative evaluation in peripheral artery disease (PAD) by common vascular diagnostic tools is limited by open wounds, medial calcinosis or an altered collateral supply of the foot. Indocyanine green fluorescent imaging (ICG-FI) has recently been introduced as an alternative tool, but so far a standardized quantitative assessment of tissue perfusion in vascular surgery has not been performed for this purpose. The aim of this feasibility study was to investigate a new software for quantitative assessment of tissue perfusion in patients with PAD using indocyanine green fluorescent imaging (ICG-FI) before and after peripheral bypass grafting. Patients and methods: Indocyanine green fluorescent imaging was performed in seven patients using the SPY Elite system before and after peripheral bypass grafting for PAD (Rutherford III-VI). Visual and quantitative evaluation of tissue perfusion was assessed in an area of low perfusion (ALP) and high perfusion (AHP), each by three independent investigators. Data assessment was performed offline using a specially customized software package (Institute for Laser Technology, University Ulm, GmbH). Slope of fluorescent intensity (SFI) was measured as time-intensity curves. Values were compared to ankle-brachial index (ABI), slope of oscillation (SOO), and time to peak (TTP) obtained from photoplethysmography (PPG). Results: All measurements before and after surgery were successfully performed, showing that ABI, TTP, and SOO increased significantly compared to preoperative values, all being statistically significant (P < 0.05), except for TTP (p = 0.061). Further, SFI increased significantly in both ALP and AHP (P < 0.05) and correlated considerably with ABI, TTP, and SOO (P < 0.05). Conclusions: In addition to ABI and slope of oscillation (SOO), the ICG-FI technique allows visual assessment in combination with quantitative assessment of tissue perfusion in patients with PAD. Ratios related to different perfusion patterns and SFI seem to be useful tools to reduce factors disturbing ICG-FI measurements.

Objective The aim of this study was to assess the immediate postoperative and midterm outcome of complex aortic aneurysm treatment necessitating four-vessel revascularization with either a total endovascular approach (fenestrated-branched stent graft [FBSG]) or a hybrid technique of visceral debranching plus stenting. Methods The clinical data of consecutively treated patients presenting with a complex aortic aneurysm that necessitated four-vessel revascularization between 2010 and 2015 were retrospectively analyzed. Results There were 98 patients (65 men [68%]) with a mean age of 70.65 ± 4 years who presented with aortic aneurysm (Crawford type I, 12; type II, 18; type III, 12; type IV, 24; type V, 6; and juxtarenal and suprarenal, 26) and were treated with either FBSG (76/98 [77.5%]) or hybrid repair (22/98 [22.4%]). Twenty-six patients were symptomatic (16, pain; 10, contained rupture). The mean maximum aneurysm diameter was 65 ± 15 mm, and 53% of the patients had a prior aortic intervention. In FBSG-treated patients, 15 off-the-shelf multibranched stent grafts, 3 surgeon-modified fenestrated stent grafts, and 58 custom-made devices tailored to the patient's anatomy were used. Four fenestrations, four branches, and their combination were used in 38 cases, 30 cases, and 8 cases, respectively. A total of 304 target vessels were addressed, with technical success rate of 96% (292/304). In most hybrid cases (18/22 [82%]), a two-stage procedure was undertaken. All target vessels were successfully revascularized with 88 bypasses. The 30-day mortality was 15.3% (15/98), and the early target vessel occlusion was 9.1% (2 in FBSG, 7 in hybrid). After multivariate analysis, type of procedure (hybrid) was independently associated with higher early mortality (odds ratio, 6.3; P = .01). The morbidity was mainly attributed to pulmonary complications (16.3%), lower extremity weakness (16.3%), mesenteric ischemia (6.1%), dialysis on discharge (6.1%), and complete paraplegia (4.3%). Acute renal failure (2.6% vs 18%; P = .03) and mesenteric ischemia (3% vs 23%; P = .001) presented more commonly in the hybrid group. The mean follow-up was 16.4 ± 5 months, and the mortality rate was 19.4% (12% in the FBSG group vs 45% in the hybrid group; P = .05). The graft and stent graft patency rate was 87.8% (three branches and nine bypasses were occluded). Conclusions FBSG and hybrid technique seem to be feasible treatment options for complex aortic aneurysms that necessitate four-vessel revascularization. FBSG may be associated with lower mortality and morbidity rates in comparison to the hybrid procedure. FBSG should be the treatment of choice for complex aneurysms in patients with comorbidities, whereas hybrid repair should be considered for acute cases unsuitable for endovascular repair.

Objective Type II endoleak after endovascular aneurysm repair (EVAR) is frequently caused by persistent flow from the inferior mesenteric artery (IMA). The aim of this study was to assess the perioperative and midterm efficacy of laparoscopic ligation of the IMA for treatment of endoleak. Methods MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane databases and key references were searched with Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology for studies reporting on laparoscopic ligation of the IMA for treatment of type II endoleak after EVAR. Results Eight case studies and one study of a retrospective nature were identified. In total, 20 patients (18 men; mean age, 73.6 ± 2 years; with a mean abdominal aortic aneurysm diameter of 64.3 ± 10 mm) who underwent post-EVAR laparoscopic ligation of the IMA for type II endoleak were analyzed. The mean time from EVAR until intervention ranged from 6 to 18 months. All but one patient were asymptomatic; in 9, the aneurysm sac was enlarged, and in 11, the endoleak was considered persistent without sac enlargement. The mean procedural duration was 99 ± 24 minutes, with technical success rate of 90% (18/20); in two cases, the patients were successfully reoperated on laparoscopically in 24 hours. The mean hospitalization was 3.6 ± 1.2 days, with 0% (0/20) perioperative and 30-day mortality. No patient underwent open conversion or showed signs of intestinal ischemia. During follow-up of 32.6 ± 12 months, 13 of 20 patients had aneurysm sac regression, whereas the rest had a stable sac diameter without evidence of persistent type II endoleak. Conclusions Laparoscopic ligation of the IMA for treatment of type II endoleak after EVAR is a feasible and safe technique in specialized centers with high technical success rate and good midterm outcomes.

Diabetes mellitus is a frequent cause for chronic, difficult-to-treat wounds. New therapies for diabetic wounds are urgently needed and in-vitro or ex-vivo test systems are essential for the initial identification of new active molecules. The aim of this study is to compare in-vitro and ex-vivo test systems for their usability for early drug screening and to investigate the efficacy of a birch bark triterpene extract (TE) that has been proven ex-vivo and clinically to accelerate non-diabetic wound healing (WH), in a diabetic context. We investigated in-vitro models for diabetic WH, i.e. scratch assays with human keratinocytes from diabetic donors or cultured under hyperglycaemic conditions and a newly developed porcine ex-vivo hyperglycaemic WH model for their potential to mimic delayed diabetic WH and for the influence of TE in these test systems. We show that keratinocytes from diabetic donors often fail to exhibit significantly delayed WH. For cells under hyperglycaemic conditions significant decrease is observed but is influenced by choice of medium and presence of supplements. Also, donor age plays a role. Interestingly, hyperglycaemic effects are mainly hyperosmolaric effects in scratch assays. Ex-vivo models under hyperglycaemic conditions show a clear and substantial decrease of WH, and here both glucose and hyperosmolarity effects are involved. Finally, we provide evidence that TE is also beneficial for ex-vivo hyperglycaemic WH, resulting in significantly increased length of regenerated epidermis to 188±16% and 183±11% (SEM; p

In den kommenden 20 Jahren wird mit einer starken Zunahme kardiovaskularer Erkrankungen zu rechnen sein. Parallel hat sich das therapeutische Armamentarium sowohl der medikamentosen als auch der invasiven Therapieoptionen erheblich erweitert. Beides erfordert eine Neuorientierung der klinischen Gefaschirurgie und Gefasmedizin, da die tradierten Fachergrenzen von heute der Komplexitat der Therapievielfalt nicht mehr gerecht werden. Die Erweiterung klassischer Fachgrenzen und die Konzeption organorientierter Behandlungseinrichtungen kann diese Entwicklung aufnehmen. Die alleinige Fokussierung auf technische Kernkompetenzen und Teilbereiche der Organerkrankung weicht in diesem Modell einem ganzheitlichen Therapieansatz. Dies ist fur die beteiligten Primardisziplinen auf der einen Seite mit dem Weitergeben von Kompetenzen, aber auch mit dem Aufnehmen von bisher fachfremden Fachinhalten verbunden. Da das periphere Gefassystem sowohl anatomisch als auch physiologisch und pathophysiologisch eine funktionelle Einheit mit dem Herzen darstellt, erscheint daruber hinaus die Bildung fachlich und organisatorisch eng zusammenarbeitender Herz- und Gefaszentren als sinnvolle Erganzung.

Die offene Operation stellt aktuell den „Goldstandard“ fur die Versorgung der Aorta ascendens und des Aortenbogens dar. Die konventionellen Operationstechniken erfordern allerdings einen hypothermen Kreislaufstillstand, der mit relevanten Komplikationen assoziiert ist. Die minimalinvasive Therapie von pathologischen Veranderungen des Aortenbogens bedeutet aufgrund der komplexen Probleme dieser vaskularen Region eine technische Herausforderung. Die aus dem Aortenbogen abgehenden Abzweigungen versorgen u. a. das Gehirn, das eine minimale Ischamietoleranz hat. Weiterhin ist der Aortenbogen weit, gebogen, starker pulsatil und weiter von den Femoralarterien entfernt. Die endovaskularen Therapieoptionen zur Behandlung von pathologischen Veranderungen der Aorta ascendens und des Aortenbogens sind Hybridtechniken im Aortenbogen, Chimney-Prozeduren fur die supraaortalen Aste, In-situ-Fenestration von thorakalen Stent-Prothesen sowie individuell angefertigte fenestrierte und gebranchte Stent-Prothesen. Individuell angefertigte fenestrierte und gebranchte Stent-Prothesen sind eine sehr gute Option fur Patienten, die fur offene Operation nicht geeignet sind, und konnten in der Zukunft die endovaskuare Therapie der Wahl werden. Eine gute praoperative Planung, die exakte Kenntnis der individuellen anatomischen Verhaltnisse sowie das Verstandnis der Besonderheiten der Aorta ascendens und des Aortenbogens sind fur die erfolgreiche endovaskulare Versorgung entscheidend.

Die zunehmende Okonomisierung des Gesundheitswesens, anstehende gesetzliche Novellierungen und ein inhomogenes Patientenkollektiv verlangen nach leistungsfahigen Methoden der Qualitatssicherung und Versorgungsforschung in der Gefasmedizin. Mehr als 12 etablierte internationale Registerprojekte zeigen bereits seit Jahren, wie wichtig klinische Register als komplementare Methode zu den randomisierten kontrollierten Studien („randomized controlled trial“, RCT) sind. In Nordamerika beispielsweise konnte durch Ableitung von Behandlungsparametern die Rezidivstenoserate bei der Versorgung der extrakraniellen Karotisstenose signifikant gesenkt werden. In England fuhrte die registerbasierte Qualitatssteigerung bei der elektiven Versorgung des Bauchaortenaneurysmas (BAA) zu einer Senkung der Mortalitatsrate von 7,5 auf etwa 2,4 % innerhalb von 4 Jahren. Im Gegensatz zu vielen Landern im europaischen und ausereuropaischen Ausland verfugt Deutschland derzeit noch uber kein gemeinsames populationsbezogenes Register fur alle vaskularen Behandlungen. Mit dem prospektiven BAA-Register wird derzeit nur ein kleiner Teil des vaskularen Versorgungsspektrums erfasst. Die verpflichtende sektorenubergreifende Qualitatssicherung zur Karotisrevaskularisation bietet mit jahrlich etwa 33.000 Datensatzen zwar ein annahernd vollstandiges Bild der deutschen Karotisversorgung, in die Auswertung gehen allerdings nur Sekundardaten mit eingeschrankter Validitat ein. Mit dem gemeinsamen Gefasregister fur Deutschland GermanVasc konnen die Versorgungsrealitat des einwohnerreichsten europaischen Landes erfasst und bisher unbeantwortete Fragestellungen besser beantwortet werden.

Fragestellung Die folgende Ubersicht nimmt zu geschlechtsspezifischen Unterschieden hinsichtlich Pravalenz, Epidemiologie, Risikofaktoren und Therapie bei Patienten mit peripherer arterieller Verschlusskrankheit (PAVK) Stellung.

To describe an innovative technique to occlude distal backflow into a false lumen aneurysm by controlled rupture of the dissection membrane after stent-graft implantation.The "Knickerbocker technique" involves relining the true lumen in the descending aorta with an oversized thoracic tubular endograft, followed by controlled rupture of the dissection membrane using a large compliant balloon within the graft's midsection. This maneuver, which allows expansion of the stent-graft's midsection into the false lumen, was developed in order to occlude the large false lumen distally and thus prevent continued false lumen perfusion through distal abdominal entry tears. The technique has been successfully used in 3 patients with ruptured or symptomatic chronic false lumen aneurysm in type B aortic dissection. There was no short-term mortality associated with the procedure. After a mean follow-up of 8 months, the false lumen aneurysm remained thrombosed, with no mortality after a mean clinical follow-up of 22 months.The Knickerbocker technique appears to be feasible and effective in inducing false lumen thrombosis in selected patients who undergo stent-grafting for chronic type B aortic dissection.

Objective:To describe our experience with consensus-based decision-making for treatment of internal carotid artery (ICA) stenosis by neurologists, interventional neuroradiologists, vascular surgeons, and neurosurgeons in a multidisciplinary neurovascular board and to study adherence to treatment recommendations in the context of uncertainty with respect to the best treatment option.Methods:We established a multidisciplinary neurovascular board meeting twice a week with structured documentation of consensus decisions. Over a time period of 53 months, 614 cases with ICA stenosis were discussed, with 285 (46%) symptomatic and 279 (45%) asymptomatic cases.Results:Recommendation for symptomatic ICA stenosis was revascularization in 76%, medical management alone in 8%, and further diagnostics in 16%. For asymptomatic ICA stenosis, recommendation was randomization in a clinical trial in 29%, revascularization in 27%, medical management alone in 23%, and further diagnostics in 22%. Treatment recommendations were followed in 94% of symptomatic ICA stenosis and 69% of asymptomatic ICA stenosis. Patients in whom carotid artery stenting was recommended for revascularization were younger and showed a higher rate of severe (≥70%) ICA stenosis.Conclusions:Interdisciplinary board decisions are a helpful and transparent tool to assure adherence to guideline recommendations, and to provide consensus-based individualized treatment strategies in clinical practice in the absence of unequivocal evidence.

Yskert von Kodolitsch,1 Meike Rybczynski,1 Marina Vogler,2 Thomas S Mir,3 Helke Schüler,1 Kerstin Kutsche,4 Georg Rosenberger,4 Christian Detter,5 Alexander M Bernhardt,5 Axel Larena-Avellaneda,6 Tilo Kölbel,6 E Sebastian Debus,6 Malte Schroeder,7,8 Stephan J Linke,9,10 Bettina Fuisting,9 Barbara Napp,1 Anna Lena Kammal,11 Klaus Püschel,11 Peter Bannas,12 Boris A Hoffmann,13 Nele Gessler,13 Eva Vahle-Hinz,14 Bärbel Kahl-Nieke,14 Götz Thomalla,15 Christina Weiler-Normann,16 Gunda Ohm,17 Stefan Neumann,18 Dieter Benninghoven,19 Stefan Blankenberg,1 Reed E Pyeritz20 1Clinic of Cardiology, University Heart Centre, 2Marfan Hilfe Deutschland e.V., Zentrumsehstärke, 3Clinic for Pediatric Cardiology, University Heart Centre, 4Institute of Human Genetics, 5Clinic of Cardiovascular Surgery, University Heart Centre, 6Clinic of Vascular Medicine, University Heart Centre, 7Department of Trauma, Hand, and Reconstructive Surgery, 8Department of Orthopedics, 9Clinic of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 10Smilow Center for Translational Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 11Department of Legal Medicine, 12Diagnostic and Interventional Radiology Department and Clinic, 13Clinic of Electrophysiology, University Heart Centre, 14Department of Orthodontics, Center for Dental and Oral Medicine, 15Clinic of Neurology, 16Martin Zeitz Center for Rare Diseases, 17Strategic Business Development, 18Business Unit Quality Management, University Medical Center Hamburg-Eppendorf, 19Mühlenberg-Clinic for Rehabilitation, Bad Malente-Gremsmühlen, 20Zentrumsehstärke, Hamburg, Germany Abstract: Marfan syndrome (MFS) is a rare, severe, chronic, life-threatening disease with multiorgan involvement that requires optimal multidisciplinary care to normalize both prognosis and quality of life. In this article, each key team member of all the medical disciplines of a multidisciplinary health care team at the Hamburg Marfan center gives a personal account of his or her contribution in the management of patients with MFS. The authors show how, with the support of health care managers, key team members organize themselves in an organizational structure to create a common meaning, to maximize therapeutic success for patients with MFS. First, we show how the initiative and collaboration of patient representatives, scientists, and physicians resulted in the foundation of Marfan centers, initially in the US and later in Germany, and how and why such centers evolved over time. Then, we elucidate the three main structural elements; a team of coordinators, core disciplines, and auxiliary disciplines of health care. Moreover, we explain how a multidisciplinary health care team integrates into many other health care structures of a university medical center, including external quality assurance; quality management system; clinical risk management; center for rare diseases; aorta center; health care teams for pregnancy, for neonates, and for rehabilitation; and in structures for patient centeredness. We provide accounts of medical goals and standards for each core discipline, including pediatricians, pediatric cardiologists, cardiologists, human geneticists, heart surgeons, vascular surgeons, vascular interventionists, orthopedic surgeons, ophthalmologists, and nurses; and of auxiliary disciplines including forensic pathologists, radiologists, rhythmologists, pulmonologists, sleep specialists, orthodontists, dentists, neurologists, obstetric surgeons, psychiatrist/psychologist, and rehabilitation specialists. We conclude that a multidisciplinary health care team is a means to maximize therapeutic success. Keywords: multidisciplinary, Marfan syndrome, health care, team, profession, sociology, management

In den letzten Jahren sind als neue orale Antikoagulanzien Dabigatran, Rivaroxaban und Apixaban fur die Schlaganfall- und Thrombembolieprophylaxe, Rivaroxaban auch fur die Thrombembolietherapie zugelassen worden. Umfangreiche Studien legen hinreichend nahe, dass die neuen Substanzen im Vergleich zu den bisherigen Medikamenten das Risiko schwerer Blutungsereignisse, insbesondere intrakranieller Blutungen sowie Schlaganfalle und Thrombembolien trotz eines begrenzten Anstiegs leichter Blutungen reduzieren. Zusatzlich weisen sie betrachtliche Vorteile in der Anwendung auf, wahrend die Nachteile beherrschbar erscheinen.

To describe the deployment technique for a single side branch arch endograft in a porcine model and prove the concept of transseptal or transapical antegrade access for catheterization and introduction of the mating stent-graft.Six domestic pigs were operated with retrograde delivery of a single side branch arch endograft and antegrade introduction of a mating stent-graft using transseptal access (n=3) and transapical access (n=3). Technical feasibility, operating time, radiation parameters, and hemodynamic changes were studied.Transseptal and transapical access techniques were feasible in all animals. Catheterization and introduction of the mating stent-graft was feasible in 2 of 3 animals in the transseptal group and all animals in the transapical group. Technical feasibility was better in the transapical group, with shorter operating and fluoroscopy times and less hemodynamic impact during endograft deployment. Hemodynamic changes were short and reversible in all animals in both groups.Antegrade transcardiac access to the aortic arch for implantation of mating stent-grafts in branched arch endografting is feasible in a porcine model with reversible impact on hemodynamic measures during deployment. Transapical access was technically easier, with shorter operating and fluoroscopy times.

Purpose: To describe and prove the concept of a technique for complete transapical deployment of a single-branch aortic arch endograft in a porcine model. Methods: Eight domestic pigs underwent antegrade transapical delivery of a single-branch arch endograft, including a mating stent-graft to the innominate artery. Technical feasibility, operating time, radiation parameters, and hemodynamic changes were studied according to a standardized protocol during baseline (T0), after establishing the transapical access and through-and-through wire (T1), and after stent-graft deployment (T2). Myocardial and cerebral blood flow status was assessed using fluorescent microspheres (FM) and transit-time flow measurement (TTFM) monitoring. Results: Transapical access, introduction and deployment of the endograft, side branch catheterization, and deployment of the mating stent-graft were feasible in 6 of 8 animals. One animal died due to irreversible heart rhythm disorders and one due to accidental graft rotation during deployment, resulting in unintended coverage of the innominate artery. The mean operating and fluoroscopy times were 223±11 minutes and 27.2±6.3 minutes, respectively. During introduction and deployment of the stent-graft, transient aortic valve insufficiency occurred in all animals. Hemodynamic stability recovered within 10 minutes after retrieval of the delivery system in all animals. The innominate artery was patent, with unchanged TTFM measurements throughout the procedure. FM evaluation revealed stable cerebral blood flow. Conclusion: An antegrade transapical access to the aortic arch for implantation of a single-branch endograft is feasible in a porcine model with reversible impact on hemodynamic measures during deployment. Transapical access allows deployment of a complex endograft through a single large-bore access site in a porcine model.

Objective— Intraplaque neovascularization contributes to the progression and rupture of atherosclerotic lesions. Glutamate carboxypeptidase II (GCPII) is strongly expressed by endothelial cells of tumor neovasculature and plays a major role in hypoxia-induced neovascularization in rodent models of benign diseases. We hypothesized that GCPII expression may play a role in intraplaque neovascularization and may represent a target for imaging of atherosclerotic lesions. The aim of this study was to determine frequency, pattern, and clinical correlates of vessel wall uptake of a 68 Ga-GCPII ligand for positron emission tomographic imaging. Approach and Results— Data from 150 patients undergoing 68 Ga-GCPII ligand positron emission tomography were evaluated. Tracer uptake in various arterial segments was analyzed and was compared with calcified plaque burden, cardiovascular risk factors, and immunohistochemistry of carotid specimens. Focal arterial uptake of 68 Ga-GCPII ligand was identified at 5776 sites in 99.3% of patients. The prevalence of uptake sites was highest in the thoracic aorta; 18.4% of lesions with tracer uptake were colocalized with calcified plaque. High injected dose ( P =0.0005) and obesity ( P =0.007) were significantly associated with 68 Ga-GCPII ligand accumulation, but other cardiovascular risk factors showed no association. The number of 68 Ga-GCPII ligand uptake sites was significantly associated with overweight condition ( P =0.0154). Immunohistochemistry did not show GCPII expression. Autoradiographic blocking studies indicated nonspecific tracer binding. Conclusions— 68 Ga-GCPII ligand positron emission tomography does not identify vascular lesions associated with atherosclerotic risk. Foci of tracer accumulation are likely caused by nonspecific tracer binding and are in part noise-related. Taken together, GCPII may not be a priority target for imaging of atherosclerotic lesions.

Demographic developments have led to an exponential increase of cardiovascular illness. Additionally, the technical development of conservative and invasive treatment modalities has added to an increase of differentiated therapy. The development of vascular centres led to optimised processes in diagnostic and therapy according to their essential requirements. A further development is an increased specialisation and new orientation of vascular specialties through a combination of vascular surgery, endovascular therapy and angiology. The concept of the Hamburg model implements this development by introduction of an organ-orientated clinic for vascular medicine, located within the heart centre of the University of Hamburg's Eppendorf Hospital.

The purpose of this paper is to describe the technique of transapical deployment of a thoracic endograft and to discuss the specifics of this access. The technique of endograft deployment through a transapical access is demonstrated in a patient with a symptomatic 14-cm aortic arch aneurysm. The 73-year-old patient, with concomitant chronic obstructive airway disease and cardiovascular disease, had been denied open surgery. Femoral artery access was deemed contraindicated because of a more distal concomitant type III thoracoabdominal aneurysm, borderline renal failure and heavily calcified iliac arteries. Bilateral iliac–subclavian debranching and thoracic endografting via a combined transapical and left subclavian access successfully excluded the thoracic aortic aneurysm. The patient died within 24 hours postoperatively due to a massive myocardial infarction. In conclusion, transapical access for thoracic endograft delivery is feasible. Combined with complex debranching procedures in a challenging aneurysmal anatomy, it carries a high risk for periprocedural complications.

Ischemic changes of the abdominal organs are crucial since they develop slowly and are therefore often diagnosed at a late stage. Due to this general aspect, mortality from this disease could not be significantly reduced over the last decade. One of the main causes of these high mortality rates is the insufficient integration of the overall clinical picture into the diagnostic work-up. Acute mesenteric ischemia should be differentiated from chronic visceral ischemia. Acute intestinal ischemia is a vascular emergency with a mortality rate of 60-80%. The incidence of chronic visceral vascular disorders accounts for approximately 1-2% of all abdominal conditions and has to be differentiated from the acute form, since intestinal ischemia has a progressive nature and usually is related to general atherosclerotic disease. Therefore, this condition is associated with an increase of arteriosclerotic-related multimorbidity in an increasingly elderly population. Due to excellent collateralization, extensive chronic occlusion processes affecting the visceral arteries can be asymptomatically treated on a long-term basis.

Repair of blunt shoulder trauma with transection of the subclavian or proximal axillary artery poses a surgical challenge, especially in instable patients. Endovascular treatment for initial damage control in arterial transection has evolved as a promising technique to improve outcome, but technical success can be limited in cases of complete transection as the lesion cannot be passed by a guidewire. This report describes an endovascular approach using a through-and-through brachial–femoral wire to control complete traumatic transection of the proximal axillary artery in a hemodynamically unstable patient. Endovascular therapy is used as a bridging method for open surgical repair three days later under optimized conditions with an interdisciplinary team. The brachial–femoral guidewire technique helps to overcome limitations in endovascular therapy in patients with blunt traumatic transection of thoracic outlet arteries.

Introduction: The formation of capsular fibrosis around silicone breast implants is a common complication in reconstructive and plastic surgery. Foreign body reaction-induced infections are quite common because of the hydrophobic surface properties of silicone and are, in addition, considered to be a causative factor of capsular fibrosis. Methods: In this experimental pilot study, 2 groups of 7 Sprague-Dawley rats were established to evaluate the periprosthetic collagen synthesis after implantation of coated silicone implants. In the first group, the textured minisilicone implants were implanted submuscularly. The second group received the biotechnologically, surface-modified phosphorylcholine (PC)-coated implants. After a 3-month period, all the rats were killed, and the capsules were examined in a histologic (hematoxylin-eosin and Masson-trichrom) and immunohistologic way (CD4, CD8, CD68, TGF-beta, fibroblasts, collagen type I, and collagen type III). Results: Significant differences were found to occur between the PC-coated and standard, textured implants with respect to the inflammatory reaction and collagen synthesis. Conclusions: The production of hydrophilic surfaces in silicone implants by way of PC-coating causes a decrease in the inflammatory reaction, and thus, a reduction of periprosthetic fibrosis. This could form the basis of a cost-effective, preventive, and therapeutic strategy with respect to the decrease in capsular fibrosis occurrence.

Erratum to: Gefasschirurgie (2018) https://doi.org/10.1007/s00772-018-0387-7 The article was wrongly published under the article type “Review”. Please note that the article is an “Original Paper”. The publisher apologizes to the authors and …

INTRODUCTION: Fast track (FT) is a modern concept to enhance postoperative recovery after elective surgery. It has been approved during the last years. Beside its medical benefits, fast-track (FT) concepts may provide an economic incentive, -although a cost-benefit analysis in the daily clinical routine has not yet been realised. In addition to this an elevated consumption of resources is postulated. PATIENTS AND METHODS: In 2007 we prospectively studied the implementation of the FT concept for elective colonic surgery in the daily clinical rou-tine at the Department of General Surgery of Nurem-berg Hospital. In a representative subgroup of patients studied, we performed a cost-cost analysis by comparing these patients to a retro-spectively analysed group that had been treated in a conventional traditional manner in 2002. RESULTS: 369 patients were included and treated according to the FT concept. Discharge criteria were met at the 4 th postoperative day in median (SD 3.9 days, minimum 1, maxiumum 29 days). The rate of general postoperative complications was 24.4 % (16 % minor complications) for all pa-tients and 6.6 % in the group of patients who were discharged within 9 postoperative days or less (n = 182). With respect to the main FT items, implementation of the FT concept was considered as effective. Cost-cost analyses showed a cost reduction of 32 % in favour of patients treated with the FT concept. CONCLUSION: This study clearly shows the clinical and economic benefits of the FT concept consid-er-ing health services research. Therefore further clin-ical implementation of the FT concept seems beneficial, not only in the view of medical aspects, but also for economic reasons.

Die Intimahyperplasie (IH) ist eines der Hauptprobleme nach Eingriffen am Gefassystem. Obwohl man zahlreiche pathophysiologische Vorgange mit der IH in Verbindung bringen kann, sind die genauen molekularen Mechanismen weitestgehend unbekannt. Zur detaillierten Erforschung dieser Prozesse werden unter anderem Knock-out-Mausmodelle mit artifizieller arterieller Lasion verwendet, mit denen eine gezielte Analyse individueller Gene moglich ist. Es konnte nachgewiesen werden, dass das Ausmas der IH zwischen verschiedenen Inzuchtstammen variiert. Somit konnen heute Genloci identifiziert werden, die mit der IH korrelieren. Als Zielgefas fur die arterielle Verletzung eignet sich in der Maus besonders die A. carotis. Dabei gibt es verschiedene Wege, die IH zu erzeugen: Endothelfreilegung durch Nylonschlinge oder Fuhrungsdraht, Ligatur der A. carotis communis, Angioplastie mittels Ballonkatheter und Veneninterponate. Im vorliegenden Artikel werden zwei wichtige Forschungsgebiete naher erlautert. Zunachst wird auf die Bedeutung des bioaktiven Lipids Sphingosin-1-Phosphat (S1P) eingegangen. Den Studienergebnissen nach ist S1P fur die Differenzierung der glatten Muskelzellen (GM) der Media uber eine Aktivierung des Typ-2-Rezeptors verantwortlich. Die auf diese Weise induzierte Expression von GM-Differenzierungsgenen scheint die Proliferation der GM zu hemmen, und somit die IH zu limitieren. Als zweites Forschungsgebiet wird die Rolle der Stammzellen im Rahmen der IH diskutiert. So wurden in den intimalen Lasionen der Mausarterie endotheliale Progenitorzellen (EPC) und aus dem Knochenmark stammende mesenchymale Stammzellen gefunden. Die Funktion dieser Zellen ist jedoch noch unklar. Ein auf den ersten Blick irritierender Aspekt in der IH-Forschung ist die Beobachtung, dass nicht nur die Art der Verletzung, sondern auch die Topografie des Gefases das Ausmas der IH beeinflusst. Zusammenfassend definieren also verschiedene Parameter die Reaktion des Gefases auf die Verletzung. Die Mechanismen, die zur Ausbildung der IH fuhren, scheinen demnach keineswegs so einheitlich zu sein, wie bisher angenommen.

Nous presentons une prothese vasculaire en silicone qui peut etre optimisee de diverses manieres. Ce travail decrit les bases theoriques, le processus de fabrication, et les proprietes mecaniques de cette nouvelle prothese, permettant une comparaison avec les materiaux employes en chirurgie vasculaire. Un processus d'enduction de protheses en polyester avec de l’elastomere de silicone (polydimethylsiloxane, PDMS) a ete etabli. D'autres modifications (ameliorations de surface, incorporation de medicaments pour relargage) peuvent etre faites en chimie humide. La mesure des proprietes physiques a inclus la stabilite et l'elasticite longitudinale et circulaire, la force de retention de suture et la resistance a la ponction (force tensile), la permeabilite, et la compliance (modele de circulation). Les protheses peuvent etre enduites de couches multiples de PDMS. Des niveaux suffisamment bas de permeabilite ( 15 mg/cm2. Considerant la stabilite, l'elasticite, et la compliance, les protheses ayant une teneur en elastomere de silicone de 15-20 mg/cm2 sont comparables aux protheses conventionnelles, etanches d'emblee. L'enduction de PDMS diminue la force de retention des sutures et la resistance a la ponction comparees aux materiaux alloplastiques conventionnelles (polyester enduit de collagene et polytetrafluoroethylene expanse). L'enduit de silicone entoure les fils de passage (« surface a obturation automatique ») et resiste au traumatisme du clampage. Les procedures de mesure decrites permettent la comparaison des nouveaux materiaux avec les conventionnels et permettent d'objectiver les caracteristiques de manipulation des implants. Les protheses etanches enduites de silicone peuvent etre comparees aux materiaux conventionnels enduits de collagene bovin sans inconvenients concernant les proprietes physiques.

We introduce a silicone-based vascular prosthesis that may be optimized in various ways. The current work describes the theoretical background, the fabrication process, and the mechanical properties of these new prostheses, allowing objectification and comparison of materials used in vascular surgery. A production process to coat polyester prostheses with silicone-rubber (polydimethylsiloxane, PDMS) was established. Further modifications (surface improvements, drug incorporation for release) can be performed wet-chemically. Measurement of the physical properties included longitudinal and circumferential stability and elasticity, suture retention strength and puncture resistance (tensile testing machine), permeability, and compliance (circulation model). Prostheses can be multiply coated with PDMS. Sufficiently low levels of permeability (5 mL/cm(2)/min at 120 mm Hg) were achieved with a PDMS content15 mg/cm(2). Considering stability, elasticity, and compliance, prostheses with a silicone-rubber content of 15-20 mg/cm(2) are comparable to conventional, primarily tight prostheses. Coating with PDMS decreases suture retention strength and puncture resistance compared to conventional alloplastic materials (collagen-coated polyester and expanded polytetrafluorethylene) materials. The silicone coating surrounds the passing threads ("self-sealing surface") and is resistant to clamping trauma. The complete measurement procedures described here allow for a comparison of new materials with conventional ones and allow the handling characteristics of implants to be objectified. The primarily tight, silicone-coated prostheses can be compared to conventional bovine-coated materials without drawbacks regarding physical properties.

En este articulo se presenta una protesis vascular de silicona que puede ser optimizada de diversas maneras. Se describen su fundamento teorico, el proceso de fabricacion y las propiedades mecanicas de estas nuevas protesis, lo que permite la evaluacion objetiva y su comparacion con otros materiales protesicos utilizados en cirugia vascular. Se establecio un proceso de produccion para el recubrimiento de las protesis de poliester con silicona plastificada (polidimetilsiloxano, PDMS), asi como modificaciones adicionales (en la superficie, incorporacion de medicamentos para su liberacion, etc.) mediante procedimientos quimicos. La determinacion de las propiedades fisicas incluyo la estabilidad y elasticidad longitudinal y circunferencial, la fuerza de retencion de las suturas y la resistencia a las punciones (dispositivo de evaluacion de la tension), la permeabilidad y la adaptabilidad (modelo circulatorio). Las protesis se pueden recubrir con capas multiples de PDMS. Con un contenido de PDMS > 15 mg/cm2 se pueden conseguir niveles suficientemente bajos de permeabilidad (

Spontaneous perforation of a nonaneurysmal abdominal aorta due to a penetrating atherosclerotic ulcer (PAU) is exceedingly rare. We describe the case of a 57-year-old man with a perforating PAU of the infrarenal aortic wall and discuss the clinical presentation, diagnostic pathways, and therapeutic options based on a comprehensive review of the literature. Since a PAU of the aorta can give rise to chronic mild to moderate abdominal or back pain, a computed tomographic scan of the abdomen should be performed in patients with evidence of vascular disease and persistent abdominal or back discomfort. Surgical resection or stent-graft placement is indicated in symptomatic patients or in asymptomatic patients with radiographic signs of progressive PAU.

The purpose of this study was to determine effectiveness, tolerability, and safety of electrical stimulation therapy (EST) using an electrical stimulation device to treat wounds under hospitalized and routine ambulatory conditions.This registered study was conducted as a multicenter, retrospective, noncontrolled study of EST for treating complex acute and chronic wounds. Data were collected and entered in a standardized manner in accordance to defined criteria.Ninety-five (n = 95) patients with median wound duration of 13.7 months were treated with EST for an average of 48.1 days. Wound size decreased by 44.7%, complete granulation occurred in 30.4%, and epithelialization (full or partial) increased in 80.4%. Exudate, fibrin, necrosis, and wound odor decreased. Patients described the global effectiveness and treatment tolerability as good (77.2%) or very good (78.5%). A few adverse events occurred, including maceration (4 patients) and pain (1 patient) at the wound edge, where the wound was exposed to the dispersive electrode. Wound status deteriorated in 4 patients. Surgery, mainly second amputations or debridement, were required in 7 cases and were found to be related to a seriously ill patient cohort.Electrical stimulation therapy is a safe and effective treatment for chronic and complicated wounds, and is well tolerated by patients.

Die Letalitat von rupturierten abdominellen Aortenaneurysmen (rAAA) ist hoch. In der vorliegenden Studie wurden Risikofaktoren im Hinblick auf Morbiditat und Letalitat am Wurzburger Krankengut eruiert. Von 8/1990 bis 12/2000 wurden retrospektiv 52 Patienten mit rAAA ausgewertet. 46 Patienten wurden von 12 Chirurgen operiert. Neben vorgegebenen Prognosefaktoren wurden erkrankungsunabhangige Faktoren und der Einfluss des Operateurs auf die Letalitat untersucht. Die 8 weiblichen und 44 mannlichen Patienten waren durchschnittlich 72,0 Jahre alt (SD±10,2). Die haufigsten Begleiterkrankungen waren Hypertonie (n=32), KHK (n=21), pAVK (n=12) und Niereninsuffizienz (n=9). Akutes Nierenversagen (34,8%), Nachblutungen (23,9%), Sepsis (15,2%) und periphere Ischamien (5%) komplizierten den Verlauf. Die 30-Tage-Letalitat bei infrarenalen rAAA lag bei 42,1% und bei interrenalen rAAA bei 50,0%. Einfluss auf das Uberleben hatte ein Alter uber 75 Jahre (p=0,042) und intraoperative Kreislaufschockzustande (p=0,018). Ein zusatzlicher Einflussfaktor war der Operateur (p=0,023). Die Prognose des rAAA ist innerhalb der Klinik nur in geringen Grenzen beeinflussbar. Die zugige Versorgung durch erfahrene Chirurgen spielt eine zentrale Rolle.

Introduction: Fixed intravasal catheters are mainly caused by knots. Removal can be achieved by intervention or surgical exploration, but this is associated with additional morbidity and mortality. Methods: 2 patients were operated for knotted catheters in our institution during the last 2 years, and their records are demonstrated. Treatment options, possible complications, catheter types and locations of knotting are analyzed by a medline search. Results: the search revealed the data from 115 patients. 53 (46.1%) of all "lost" catheters were Swan-Ganz catheters. In 60.9% the catheters could be removed by radiological interventions. Open revision was necessary in 33% of all cases. The catheters were left in place when the clinical condition of the patient did not allow removal (n = 7). However, these patients suffered from a high mortality (5 of 7 patients). Over all mortality reached 8.7%. In the own two cases one removal by sternotomy and one by exploration of the right internal jugular vein were necessary, both operations succeeded without complications. Conclusion: Most of all "lost" intravasal catheters are removed by radiological intervention; only one third needs open surgical therapy. These procedures are harmful for the patient and bear considerable risks for complications.

Einleitung. Kunststoffprothesen stellen in der Bypasschirurgie bis heute Kompromisslosungen dar. Um eine primare Dichtigkeit von Polyesterprothesen zu erreichen, ist die Beschichtung mit bovinem Kollagen oder Gelatine erforderlich. Eine Moglichkeit, auf diese xenogenen Beschichtungssubstanzen zu verzichten, ist ihre Oberflachenmodifikation mit einem oberflachenneutralen Silikonelastomer.

Background and Objectives Atherosclerotic changes of arteries are the leading cause for deaths in cardiovascular disease and greatly impair patient’s quality of life. Sphingosine-1-phosphate (S1P) is a signaling sphingolipid that regulates potentially pro-as well as anti-atherogenic processes. Here, we investigate whether serum-S1P concentrations are associated with peripheral artery disease (PAD) and carotid stenosis (CS). Methods and Results Serum was sampled from blood donors (controls, N = 174) and from atherosclerotic patients (N = 132) who presented to the hospital with either clinically relevant PAD (N = 102) or CS (N = 30). From all subjects, serum-S1P was measured by mass spectrometry and blood parameters were determined by routine laboratory assays. When compared to controls, atherosclerotic patients before invasive treatment to restore blood flow showed significantly lower serum-S1P levels. This difference cannot be explained by risk factors for atherosclerosis (old age, male gender, hypertension, hypercholesteremia, obesity, diabetes or smoking) or comorbidities (Chronic obstructive pulmonary disease, kidney insufficiency or arrhythmia). Receiver operating characteristic curves suggest that S1P has more power to indicate atherosclerosis (PAD and CS) than high density lipoprotein-cholesterol (HDL-C). In 35 patients, serum-S1P was measured again between one and six months after treatment. In this group, serum-S1P concentrations rose after treatment independent of whether patients had PAD or CS, or whether they underwent open or endovascular surgery. Post-treatment S1P levels were highly associated to platelet numbers measured pre-treatment. Conclusions Our study shows that PAD and CS in humans is associated with decreased serum-S1P concentrations and that S1P may possess higher accuracy to indicate these diseases than HDL-C.

CASE REPORT: We report the case of multiple midgut carcinoids causing segmental intestinal ischaemia in a 77-year-old man. He was admitted to our hospital because of a 2-month history of postprandial abdominal pain with nausea / vomiting and anaemia. The extensive diagnostic examinations (blood tests, ultrasound, computed tomography, hydro magnetic resonance) did not reveal any pathological findings. The small-bowel capsule endoscopy demonstrated multiple areas of bleeding. A laparotomy showed a local ischaemia of the small bowel, a segmental resection of the jejunum / ileum was performed. There were no signs of occlusion of the mesenteric artery. The pathological examination revealed 8 carcinoids of the midgut (jejunum / ileum). Immune histology demonstrated serotonin-synaptophysin-chromogranin-producing carcinoids. The patient was re-operated because of suspected ongoing mesenteric ischaemia, but no further pathologies were found. The postoperative course was uneventful. A subsequent octreotide scan was negative for metastases. DISCUSSION: Carcinoids may become symptomatic mimicking intestinal ischaemia. Although this coincidence is considered to be typical, it is still a rare event. The diagnosis is often delayed. EVS („elastic vascular sclerosis“) of the mesenteric artery is pathognomonic for these carcinoids but, as our case demonstrates, not mandatory. According to the literature, the stage of the disease corresponds to the extent of the intestinal ischaemia.

In this paper, we propose a technique for simulating the fluid-structure interaction in blood vessels. A partitioned approach is used, which allows for an independent discretization of the fluid domain and the structural domain. We choose the finite volume method to solve the Navier-Stokes equations and the p-version of the finite element method (p-FEM) to solve the equations of geometrically nonlinear structural dynamics. The solution strategy can be seen as a first approach towards a comprehensive study of the hemodynamics in vascular substitutes with the goal of improving their long term functionality. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)

To report a technique to create an extra-large vascular plug for occlusion of a large distal false lumen in chronic aortic dissection.The "candy-plug" technique is demonstrated in a 58-year-old multimorbid man with a history of complicated acute type B aortic dissection and a 9-cm chronic thoracic false lumen aneurysm. The patient underwent a staged repair with a cervical debranching procedure as a first step and a thoracic endovascular aortic repair from the innominate artery to the celiac artery as a second step. To occlude the large false lumen from a distal route, a stent-graft was modified on-table with a diameter-restricting suture, giving it a wrapped candy-like shape. This plug was deployed into the false lumen, and the remaining opening was occluded with a standard vascular plug. On 3-month follow-up imaging, the thoracic false lumen aneurysm remained completely thrombosed.The candy-plug technique can facilitate complete occlusion of chronic thoracic false lumen aneurysm by prohibiting distal false lumen backflow.

To report the use of antegrade in situ fenestration as a bailout technique to rescue a renal artery after inadvertent coverage during endovascular aneurysm repair (EVAR).The technique is demonstrated in a patient with a 6-cm infrarenal abdominal aortic aneurysm (AAA) and a short, angulated proximal neck. A type I endoleak persisted on completion angiography after implantation of a bifurcated Zenith stent-graft despite dilation with a compliant balloon. A Giant Palmaz stent mounted on a large compliant balloon successfully resolved the endoleak. After placing the stent, the left renal artery was covered completely by the main aortic graft material, leading to only marginal opacification on angiography. To preserve flow to the renal artery, a transseptal sheath and transseptal needle were introduced from the right femoral artery and used to puncture the abdominal stent-graft antegrade at the site of the left renal artery. A 0.018-inch guidewire could then be introduced into the left renal artery; following a number of maneuvers, a balloon-expandable stent was placed through the fenestration into the target vessel. On computed tomographic angiography 4 days postoperatively, the AAA remained excluded and both renal arteries were patent, with all side branches fully preserved. Renal function was completely restored.Antegrade in situ fenestration can facilitate immediate revascularization of inadvertently covered side branches in EVAR using a transseptal sheath and needle. If the anatomical features are supportive, antegrade in situ fenestration can be a useful bailout technique.

PURPOSE: To evaluate the hemodynamic impact of transseptal sheath access to the ascending aorta using increasing sheath diameters. METHODS: Transseptal puncture was performed in 6 pigs (62±9 kg) facilitating guidewire passage across the left heart to the descending aorta to establish transseptal through-and-through access into the ascending aorta. Hemodynamic parameters were evaluated during 6- to 16-F sheath deployments and after sheath retraction according to a standardized protocol. Fluorescent microspheres were injected for quantitative assessment of myocardial and cerebral perfusion and left-right shunting volume. RESULTS: Cardiac output, heart rate, and central venous pressure (CVP) were stable throughout the study in all animals. The ratio between pulmonary artery pressure and mean arterial pressure was significantly higher during sheath deployment compared to after retraction (p

Objective— The objective of this study was to define a role for sphingosine-1-phosphate receptor 3 (S1PR3) in intimal hyperplasia. Methods and Results— A denudation model of the iliac-femoral artery in wild-type and S1PR3-null mice was used to define a role for S1PR3 in the arterial injury response because we found in humans and mice that expression of S1PR3 was higher in these arteries compared with carotid arteries. At 28 days after surgery, wild-type arteries formed significantly larger lesions than S1PR3-null arteries. Bromodeoxyuridine labeling experiments demonstrated that on injury, wild-type arteries exhibited higher medial as well as intimal proliferation than S1PR3-null arteries. Because S1PR3 expression in vitro was low, we expressed S1PR3 in S1PR3-null smooth muscle cells (SMCs) using retroviral-mediated gene transfer to study the effects of S1PR3 on cell functions and signaling. SMCs expressing S1PR3, but not vector-transfected controls, responded to sphingosine-1-phosphate stimulation with activation of Rac, Erk, and Akt. SMCs expressing S1PR3 also migrated more. Conclusion— In humans and mice, S1PR3 expression was higher in iliac-femoral arteries compared with carotid arteries. S1PR3 promoted neointimal hyperplasia on denudation of iliac-femoral arteries in mice, likely by stimulating cell migration and proliferation through activation of signaling pathways involving Erk, Akt, and Rac.