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Animal models have significantly advanced our understanding of the mechanisms of atherosclerosis formation and the evaluation of therapeutic options. The current focus of research is on preventive strategies and includes pharmacologic and biologic interventions directed primarily against smooth-muscle cell proliferation, endovascular devices for recanalization and/or drug delivery, and an integrated approach using both devices and pharmacobiologic agents. The experience over many decades with animal models in vascular research has established that a single, ideal, naturally available model for atherosclerosis does not exist. The spectrum ranges from large animals such as pigs to small animal experiments with genetically modified rodents such as the ApoE−/− mouse with correspondingly differently pronounced changes in their lipid and lipoprotein levels. The development of transgenic variants of currently available models, e.g., an ApoE-deficient rabbit line, has widened our options. Nevertheless, an appreciation of the individual features of natural or stimulated disease in each species is of importance for the proper design and execution of relevant experiments.

This study aimed to determine predictors and outcomes associated with spinal cord ischemia (SCI) after elective fenestrated or branched endovascular aneurysm repair (F/BEVAR) of thoracoabdominal aortic aneurysm (TAAA), abdominal aortic aneurysm (AAA), or aortic dissection.Health insurance claims data of Germany's third largest insurance provider, DAK-Gesundheit, were used to investigate SCI in elective F/BEVAR performed between 2008 and 2017. The International Classification of Diseases and German Operation and Procedure Classification System were used. We stratified the results into F/BEVAR with one or two (AAA) vs three or more (TAAA) fenestrations or branches.A total of 877 patients (18.9% female; 5.8% with SCI) matching the inclusion criteria were identified during the study period. SCI occurred more often after F/BEVAR of TAAA vs AAA (10.7% vs 3.0%; P .001). SCI was associated with female sex in the AAA group (odds ratio, 3.87; 95% confidence interval [CI], 1.25-11.15; P = .014) and with cardiac arrhythmias in the TAAA group (odds ratio, 2.98; 95% CI, 1.24-7.06; P = .013). Compared with patients without SCI, SCI patients were more likely to suffer from drug use disorders (eg, opioids, cannabinoids, sedatives) in the TAAA group (17.6% vs 2.1%; P .05). After F/BEVAR of TAAA, the occurrence of SCI was associated with higher 90-day mortality (14.7% vs 1.1%; P .05), longer postoperative hospital stay (22 vs 9 days; P .05), and severe adverse events, such as acute respiratory insufficiency (44.1% vs 12.7%), acute renal failure (35.3% vs 11.3%), and pneumonia (29.4% vs 4.9%; all P .05). In adjusted analyses, SCI was associated with worse long-term survival after F/BEVAR for TAAA (hazard ratio, 2.54; 95% CI, 1.37-4.73; P .003).Female AAA patients and TAAA patients with cardiac arrhythmias are at highest risk for development of SCI after F/BEVAR. The occurrence of this event was strongly associated with higher major complication rates and worse short-term and long-term survival. This emphasizes a need to further illuminate the value of spinal cord protection protocols in F/BEVAR.

Background We investigated changes of cortical thickness and its association with cognitive performance in patients with high-grade carotid artery stenosis without ischemic brain lesions. Methods We studied 25 patients with unilateral carotid artery stenosis ≥50% and 25 age-matched controls. All subjects underwent T1-weighted MRI, and cortical thickness was measured in 33 regions of interest in each hemisphere, as well as in brain regions belonging to the vascular territory of the middle cerebral artery (MCA). General linear mixed models were fitted to the dependent variable cortical thickness. Cognitive assessment comprised the Stroop Test and Trail Making Test B. Results In the linear mixed model, presence of carotid stenosis had no effect on cortical thickness. There was a significant interaction of stenosis and region with a trend towards lower cortical thickness in the MCA region on the side of carotid stenosis. Patients with carotid stenosis performed significantly worse on the Stroop test than controls, but there was no correlation with cortical thickness. Conclusion In patients with carotid stenosis without ischemic brain lesions, neither a clear pattern of reduced cortical thickness nor an association of cortical thickness with cognitive function was observed. Our data do not support the hypothesized association of cortical thinning and cognitive impairment in carotid stenosis. Electronic supplementary material The online version of this article (10.1186/s12872-019-1127-y) contains supplementary material, which is available to authorized users.

The main objective of this study was to define a role of sphingosine-1-phosphate receptor 1 (S1PR1) in the arterial injury response of a human artery. The hypotheses were tested that injury induces an expansion of S1PR1-positive cells and that these cells accumulate toward the lumen because they follow the sphingosine-1-phosphate gradient from arterial wall tissue (low) to plasma (high).A humanized rat model was used in which denuded human internal mammary artery (IMA) was implanted into the position of the abdominal aorta of immunosuppressed Rowett nude rats. This injury model is characterized by medial as well as intimal hyperplasia, whereby intimal cells are of human origin. At 7, 14, and 28 days after implantation, grafts were harvested and processed for fluorescent immunostaining for S1PR1 and smooth muscle α-actin. Nuclei were stained with 4',6-diamidine-2'-phenylindole dihydrochloride. Using digitally reconstructed, complete cross sections of grafts, intimal and medial areas were measured, whereby the medial area had virtually been divided into an outer (toward adventitia) and inner (toward lumen) layer. The fraction of S1PR1-positive cells was determined in each layer by counting S1PR1-positive and S1PR1-negative cells.The fraction of S1PR1-postive cells in naive IMA is 58.9% ± 6.0% (mean ± standard deviation). At day 28 after implantation, 81.6% ± 4.4% of medial cells were scored S1PR1 positive (P .01). At day 14, the ratio between S1PR1-positive and S1PR1-negative cells was significantly higher in the lumen-oriented inner layer (9.3 ± 2.1 vs 6.0 ± 1.0; P .01). Cells appearing in the intima at day 7 and day 14 were almost all S1PR1 positive. At day 28, however, about one-third of intimal cells were scored S1PR1 negative.From these data, we conclude that denudation of IMA specifically induces the expansion of S1PR1-positive cells. Based on the nonrandom distribution of S1PR1-positive cells, we consider the possibility that much like lymphocytes, S1PR1-positive smooth muscle cells also use S1PR1 to recognize the sphingosine-1-phosphate gradient from tissue (low) to plasma (high) and so migrate out of the media toward the intima of the injured IMA.

The aim of this study was to determine the survival of patients after use of paclitaxel coated devices (PCX), as a recent meta-analysis of randomised trials reported higher mortality in patients treated with PCX balloons and stents METHODS: A retrospective health insurance claims analysis of patients covered by the second largest insurance fund in Germany, BARMER, was used to identify index femoropopliteal arterial interventions between 1 January 2010 and 31 December 2018. To ensure first PCX exposure, patients with prior deployment of PCX were excluded. The study cohort was stratified into patients with chronic limb threatening ischaemia (CLTI) and intermittent claudication (IC), then into balloons vs. stents cohorts. Within each stratum PCX were compared with uncoated devices. Propensity score matching was used to balance the study groups. Survival was evaluated using the Kaplan-Meier method and Cox regression.There were 37 914 patients (mean age 73.3 years; 48.8% female) included in the study. The annual proportion of PCX use increased from 3% to 39% during the study period for CLTI and from 4% to 48% for IC (both p .001). Paclitaxel coated balloons and stents were associated with improved overall survival (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.77-0.90), amputation free survival (HR 0.85, 95% CI 0.78-0.91), and freedom from major cardiovascular events (HR 0.82, 95% CI 0.77-0.89) vs. uncoated devices at five years for CLTI. In IC cohort, mortality was significantly lower after using drug coated balloons (DCB) (HR 0.87, 95% CI 0.76-0.99) or combined DCB and drug eluting stents (HR 0.88, 95% CI 0.80-0.98).In this large health insurance claims analysis, rapid adoption of PCX, higher long term survival, better amputation free survival, and lower rates of major cardiovascular events were seen after their use for the treatment of CLTI.

Introduction To correctly interpret plasma- or serum-sphingosine-1-phosphate (S1P) concentrations measured in clinical studies it is critical to understand all major determinants in healthy controls. Methods Serum- and plasma-S1P from 174 healthy blood donors was measured by liquid chromatography-tandem mass spectrometry and correlated to clinical laboratory data. Selected plasma samples, 10 with high and 10 with low S1P concentrations, were fractionated into very low-density lipoprotein (VLDL)-, low density lipoprotein (LDL)-, high density lipoprotein (HDL)-, and lipoprotein-free fractions. S1P was then measured in each fraction to determine its distribution. Results The mean S1P concentration in serum (1.04 ± 0.24 nmol/mL) was found 39% higher compared with plasma (0.75 ± 0.16 nmol/mL) and overall was not different between men and women. Only when stratified for age and gender, older women were found to exhibit higher circulatory S1P levels than men. In plasma, S1P levels correlate to red blood cell (RBC) counts but not to platelet counts. Conversely, serum-S1P correlates to platelet counts but not to RBC counts. In addition, eosinophil counts are strongly associated with serum-S1P concentrations. Both serum- and plasma-S1P correlate to total cholesterol but not to HDL-C. The distribution of S1P between VLDL-, LDL-, HDL-, and lipoprotein-free fractions is independent of total plasma-S1P concentrations. S1P concentrations in HDL but not in LDL are highly variable. Conclusion These data indicate S1P concentrations in plasma and serum to be differentially associated with cell counts and S1P carrier proteins. Besides platelets, eosinophil counts are identified as a novel determinant for serum-S1P concentrations further suggesting a role for S1P in eosinophil pathologies.

Introduction There is evidence suggesting a detrimental effect of asymptomatic carotid artery stenosis on cognitive function even in the absence of ischemic cerebral lesions. Hypoperfusion has been suggested as pathophysiological mechanism causing cognitive impairment. We aimed to assess cognitive performance and cerebral perfusion changes in patients with carotid artery stenosis without ischemic lesions by arterial spin labeling (ASL) and contrast enhanced (CE) perfusion MRI before and after revascularization therapy. Methods 17 asymptomatic patients with unilateral high-grade (≥70%) carotid artery stenosis without evidence of structural brain lesions underwent ASL and CE perfusion MRI and cognitive testing (MMSE, DemTect, Clock-Drawing Test, Trail-Making Test, Stroop Test) before and 6–8 weeks after revascularization therapy by endarterectomy or stenting. Multiparametric perfusion maps (ASL: cerebral blood flow (ASL-CBF), bolus arrival time (ASL-BAT); CE: cerebral blood flow (CE-CBF), mean transit time (CE-MTT), cerebral blood volume (CE-CBV)) were calculated and analyzed by vascular territory. Relative perfusion values were calculated. Results Multivariate analysis revealed a significant impact of revascularization therapy on all perfusion measures analyzed. At baseline post-hoc testing showed significant hypoperfusion in MCA borderzones as assessed by ASL-CBF, ASL-BAT, CE-MTT and CE-CBV. All perfusion alterations normalized after revascularization. We did not observe any significant correlation of cognitive test results with perfusion parameters. There was no significant change in cognitive performance after revascularization. Conclusion We found evidence of traceable perfusion alterations in patients with high grade carotid artery stenosis in the absence of structural brain lesions, which proved fully reversible after revascularization therapy. In this cohort of asymptomatic patients we did not observe an association of hypoperfusion with cognitive performance., Highlights • In patients with high grade unilateral carotid artery stenosis there was a significant impact of revascularization therapy on brain perfusion • All perfusion alterations normalized after revascularization. • We did not observe any significant correlation of cognitive test results with perfusion parameters. • There was no significant change in cognitive performance after revascularization.

We present a partitioned approach to fluid-structure interaction problems arising in analyses of blood flow in arteries. Several strategies to accelerate the convergence of the fixed-point iteration resulting from the coupling of the fluid and the structural sub-problem are investigated. The Aitken relaxation and variants of the interface quasi-Newton -least-squares method are applied to different test cases. A hybrid variant of two well-known variants of the interface quasi-Newton-least-squares method is found to perform best. The test cases cover the typical boundary value problem faced when simulating the fluid-structure interaction in arteries, including a strong added mass effect and a wet surface which accounts for a large part of the overall surface of each sub-problem. A rubber-like Neo Hookean material model and a soft-tissue-like Holzapfel-Gasser-Ogden material model are used to describe the artery wall and are compared in terms of stability and computational expenses. To avoid any kind of locking, high-order finite elements are used to discretize the structural sub-problem. The finite volume method is employed to discretize the fluid sub-problem. We investigate the influence of mass-proportional damping and the material model chosen for the artery on the performance and stability of the acceleration strategies as well as on the simulation results. To show the applicability of the partitioned approach to clinical relevant studies, the hemodynamics in a pathologically deformed artery are investigated, taking the findings of the test case simulations into account.

Objective The aim of this study was to determine the survival of patients after use of paclitaxel coated devices (PCX), as a recent meta-analysis of randomised trials reported higher mortality in patients treated with PCX balloons and stents Methods A retrospective health insurance claims analysis of patients covered by the second largest insurance fund in Germany, BARMER, was used to identify index femoropopliteal arterial interventions between 1 January 2010 and 31 December 2018. To ensure first PCX exposure, patients with prior deployment of PCX were excluded. The study cohort was stratified into patients with chronic limb threatening ischaemia (CLTI) and intermittent claudication (IC), then into balloons vs. stents cohorts. Within each stratum PCX were compared with uncoated devices. Propensity score matching was used to balance the study groups. Survival was evaluated using the Kaplan–Meier method and Cox regression. Results There were 37 914 patients (mean age 73.3 years; 48.8% female) included in the study. The annual proportion of PCX use increased from 3% to 39% during the study period for CLTI and from 4% to 48% for IC (both p Conclusion In this large health insurance claims analysis, rapid adoption of PCX, higher long term survival, better amputation free survival, and lower rates of major cardiovascular events were seen after their use for the treatment of CLTI.

OBJECTIVES Gender disparities in risk factors and outcomes following aortic repair are important issues in healthcare. To date, no large-scale multicentre study addresses this topic in complex endovascular aortic repair. We aimed to determine the outcomes following fenestrated or branched endovascular aortic repair of aneurysms and dissections in female and male patients. METHODS Health insurance claims data of Germany's third largest insurance provider, DAK-Gesundheit, were used to investigate gender disparities in elective fenestrated or branched endovascular aortic repair of thoraco-abdominal or abdominal aortic aneurysms or dissections performed between 2008 and 2017. Elixhauser comorbidities and the linear van Walraven score were used to adjust for confounders in the multivariable analyses. RESULTS There were 959 patients in the cohort, in whom 163 (17%) were female. The mean age was 73 ± 8 years with no differences between females and males. No gender disparities were observed regarding the van Walraven comorbidity score (6.9 vs 6.8, P = 0.83), but complications occurred more frequently in females. Acute renal failure (relative risk 1.71, 95% confidence interval 1.06-2.77), paraplegia (relative risk 2.71, 95% confidence interval 1.28-5.77) and bleeding or anaemia requiring transfusion (relative risk 1.76, 95% confidence interval 1.39-2.22) were more common in women. In multivariable models, female patients were at a higher risk of in-hospital death (odds ratio 3.206, P

Colonic ischaemia (CI) is a severe complication following abdominal aortic aneurysm (AAA) repair, leading to high morbidity and mortality. The aim of the study was to determine the incidence, predictors, and outcomes of CI following AAA repair.National claims from Germany's third largest insurance provider, DAK-Gesundheit, were used to investigate CI after intact (iAAA) and ruptured (rAAA) AAA repairs. Patients undergoing endovascular (EVAR) or open surgical (OSR) repairs between January 2008 and December 2017 were included in the study.There were 9145 patients (8248 iAAA and 897 rAAA) undergoing EVAR or OSR procedures and the median follow up was 2.28 years. Most patients were male (79.2% iAAA, 79.3% rAAA); the median age was 73.0 years (iAAA group) and 76.0 years (rAAA group). Overall, CI occurred 97 (1.2%) times after iAAA and 95 (10.6%) after rAAA. In univariable analyses CI occurred less often after EVAR than after OSR (0.6% vs. 3.7%; p .001). Acute post-operative renal and respiratory insufficiencies were also related to the occurrence of CI (p .001). CI was associated with greater in hospital mortality (42.2% vs. 2.7% for iAAA, 64.2% vs. 36.3% for rAAA; p .001) and lower long-term survival for iAAA (Kaplan-Meier analysis). In multivariable analyses, rAAA (odds ratio [OR] 5.59), and higher van Walraven comorbidity score (OR 1.09) were independently associated with greater risk of CI occurrence. EVAR use (OR 0.30) was protective. EVAR use remained protective in stratified analyses within iAAA (OR 0.32) and rAAA (OR 0.26).Post-operative CI after AAA repair is not common but is associated with worse in hospital outcomes and lower long-term survival. EVAR was protective after both rAAA and iAAA repairs. When discussing the treatment of AAA with patients the protective effect of EVAR should be considered. Future studies should validate predictive scores and advance preventive strategies.

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.

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

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

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.

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 …

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.

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.

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.

Objective Silver-coated vascular polyester prostheses were developed not only for the treatment of prosthetic graft infections, but also for use as prophylaxes. Although some studies describe the use of these prostheses in cases of infection, there are few data on their prophylactic use. This study compares the performance of the InterGard Silver polyester graft (Intervascular, Datascope, Inc, La Ciotat, France) with that of standard prostheses in routine use. Methods This retrospective study included all patients who received alloplastic bypass for treatment of arterial occlusive disease at the University Hospital in Wurzburg from January 1996 to December 2006. The courses of disease were analyzed by examining the medical records. Follow-up research documented long-term results. Results The cases of 913 patients were analyzed (430 silver grafts, 483 standard grafts). Indications for the operations were claudication (silver: 136, nonsilver: 212), rest pain (49/65), tissue loss (135/148), and acute occlusion (110/58). Prosthetic implantation was performed in the aorto-iliaco-femoral position (silver: 93, nonsilver: 146), in the femorodistal position (309/304), and as multilevel reconstruction (28/33). With regard to perioperative complications, the two groups did not differ significantly. There were no silver release-related complications, such as colored exudation or wound staining. Mean follow-up time was 56.7 ± 1.6 (SEM) months. When corrected for redo procedures, stage of disease, and type of reconstruction, both materials performed equally well: 5-year patency for claudication: silver 91%, nonsilver 95%, femorodistal 47%/41%; 5-year patency for critical ischemia: aortofemoral 88%/93%, femorodistal 31%/35%; 5-year limb salvage (critical ischemia): aortofemoral: 78%/79%; femorodistal: 59%/67%. Graft infections (Szilagyi grade III) were detected in 59 patients (6.4%; silver: n=32, 7.4% vs control: n=27, 5.5%; P = .28) after an average of 321 ± 96 days. One infection occurred out of 93 aortofemoral operations with the silver prosthesis (1.1%) compared to 4.1% (6/146) in the control group ( P = .17). For patients with femorodistal grafts, silver exhibited an infection rate of 9.4% compared to 5.9% ( P = .11). In the multiple regression analysis, two factors influenced the rate of a graft infection significantly: wound healing impairment and revision after bypass implantation. Silver did not prevent a subsequent bypass infection in these cases (silver: 18.1% vs 12.5%, P = .27). Conclusion The silver-coated prosthesis did not differ from standard materials. Silver had no significant effect on the risk of graft infection. Our study showed good results with the silver prosthesis in the aorto-iliaco-femoral position, but in cases of femorodistal grafting, a reduction of prosthetic infections was not achieved. The silver grafts did not prevent subsequent infections in cases of tissue loss or postoperative local complications.