Axel Larena-Avellaneda

Evaluation of 68Ga-Glutamate Carboxypeptidase II Ligand Positron Emission Tomography for Clinical Molecular Imaging of Atherosclerotic Plaque Neovascularization

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 68Ga-GCPII ligand for positron emission tomographic imaging. Approach and Results—Data from 150 patients undergoing 68Ga-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 68Ga-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 68Ga-GCPII ligand accumulation, but other cardiovascular risk factors showed no association. The number of 68Ga-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—68Ga-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.

Comparison of In-Vitro and Ex-Vivo Wound Healing Assays for the Investigation of Diabetic Wound Healing and Demonstration of a Beneficial Effect of a Triterpene Extract

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<0.05) compared to controls when using two different TE formulations. In conclusion, our results suggest that microenvironmental influences are important in WH test systems and that therefore the more complex hyperglycaemic ex-vivo model is more suitable for early drug screening. Limitations of the in-vitro and ex-vivo models are discussed. Furthermore our data recommend TE as a promising candidate for in-vivo testings in diabetic wounds.

Complete Antegrade Transapical Deployment of a Branched Aortic Arch Endograft: A Porcine Feasibility Study.

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.

Fenestrated-branched endografts and visceral debranching plus stenting (hybrid) for complex aortic aneurysm repair

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 patients 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.

Incidence, Predictors, and Outcomes of Colonic Ischaemia in Abdominal Aortic Aneurysm Repair

OBJECTIVE/BACKGROUNDnColonic 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.nnnMETHODSnNational claims from Germanys 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.nnnRESULTSnThere 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%; pxa0<xa0.001). Acute post-operative renal and respiratory insufficiencies were also related to the occurrence of CI (pxa0<xa0.001). CI was associated with greater in hospital mortality (42.2% vs. 2.7% for iAAA, 64.2% vs. 36.3% for rAAA; pxa0<xa0.001) 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).nnnCONCLUSIONnPost-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.

Infiziertes arterielles Aneurysma

Gefaschirurgen verwenden meist den Ausdruck „mykotisch“ fur ein Aneurysmen infektioser Genese. Dies ist auf die Erstbeschreibung solcher Aneurysmen durch Osler im Rahmen einer „malignen (mykotischen)“ Endokarditis zuruckzufuhren. Die Verwendung des Begriffs „infiziertes arterielles Aneurysma“ erscheint daher sinnvoll. Eine solche Infektion kann auf verschiedene endogene und exogene Ursachen haben. Weiterhin konnen sich sowohl gesunde, als auch veranderte Gefase infizieren. Die klinische Symptomatik kann unspezifisch sein, die Diagnostik gelingt allerdings mit den bildgebenden Verfahren sicher. Therapeutisch kommen sowohl endovaskulare als auch offene Operationen in Frage, wobei sich insbesondere die Frage des Gefasersatzmaterials stellt. Eine langfristige Antibiotikagabe ist meist indiziert.