Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients.

OBJECTIVE: Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which is modified post-translationally by glycosylation. This study aimed to characterize the glycoproteome of the aortic ECM from patients with MFS and relate it to aortopathy. Approach and Results: ECM extracts of aneurysmal ascending aortic tissue from patients with and without MFS were enriched for glycopeptides. Direct N-glycopeptide analysis by mass spectrometry identified 141 glycoforms from 47 glycosites within 35 glycoproteins in the human aortic ECM. Notably, MFAP4 (microfibril-associated glycoprotein 4) showed increased and more diverse N-glycosylation in patients with MFS compared with control patients. MFAP4 mRNA levels were markedly higher in MFS aortic tissue. MFAP4 protein levels were also increased at the predilection (convexity) site for ascending aorta aneurysm in bicuspid aortic valve patients, preceding aortic dilatation. In human aortic smooth muscle cells, MFAP4 mRNA expression was induced by TGF (transforming growth factor)-β1 whereas siRNA knockdown of MFAP4 decreased FBN1 but increased elastin expression. These ECM changes were accompanied by differential gene expression and protein abundance of proteases from ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family and their proteoglycan substrates, respectively. Finally, high plasma MFAP4 concentrations in patients with MFS were associated with a lower thoracic descending aorta distensibility and greater incidence of type B aortic dissection during 68 months follow-up. CONCLUSIONS: Our glycoproteomics analysis revealed that MFAP4 glycosylation is enhanced, as well as its expression during the advanced, aneurysmal stages of MFS compared with control aneurysms from patients without MFS

Type 2 Endoleak With or Without Intervention and Survival After Endovascular Aneurysm Repair

Objective: The aims of the present study were to examine the impact of type 2 endoleaks (T2EL) on overall survival and to determine the need for secondary intervention after endovascular aneurysm repair (EVAR). Methods: A multicentre retrospective cohort study in the Netherlands was conducted among patients with an infrarenal abdominal aortic aneurysm (AAA) who underwent EVAR between 2007 and 2012. The primary endpoint was overall survival for patients with (T2EL+) or without (T2EL-) a T2EL. Secondary endpoints were sac growth, AAA rupture, and secondary intervention. Kaplan–Meier survival and multivariable Cox regression analysis were used. Results: A total of 2 018 patients were included. The median follow up was 62.1 (range 0.1 – 146.2) months. No difference in overall survival was found between T2EL+ (n = 388) and T2EL- patients (n = 1630) (p =.54). The overall survival estimates at five and 10 years were 73.3%/69.4% and 45.9%/44.1% for T2EL+/T2EL- patients, respectively. Eighty-five of 388 (21.9%) T2EL+ patients underwent a secondary intervention. There was no difference in overall survival between T2EL+ patients who underwent a secondary intervention and those who were treated conservatively (p =.081). Sac growth was observed in 89 T2EL+ patients and 44/89 patients (49.4%) underwent a secondary intervention. In 41/44 cases (93.1%), sac growth was still observed after the intervention, but was left untreated. Aneurysm rupture occurred in 4/388 T2EL patients. In Cox regression analysis, higher age, ASA classification, and maximum iliac diameter were significantly associated with worse overall survival. Conclusion: No difference in overall survival was found between T2EL+ and T2EL- patients. Also, patients who underwent a secondary intervention did not have better survival compared with those who did not undergo a secondary intervention. This study reinforces the need for conservative treatment of an isolated T2EL and the importance of a prospective study to determine possible advantages of the intervention

Optimization of Suture-Free Laser-Assisted Vessel Repair by Solder-Doped Electrospun Poly(ε-caprolactone) Scaffold

Poor welding strength constitutes an obstacle in the clinical employment of laser-assisted vascular repair (LAVR) and anastomosis. We therefore investigated the feasibility of using electrospun poly(ε-caprolactone) (PCL) scaffold as reinforcement material in LAVR of medium-sized vessels. In vitro solder-doped scaffold LAVR (ssLAVR) was performed on porcine carotid arteries or abdominal aortas using a 670-nm diode laser, a solder composed of 50% bovine serum albumin and 0.5% methylene blue, and electrospun PCL scaffolds. The correlation between leaking point pressures (LPPs) and arterial diameter, the extent of thermal damage, structural and mechanical alterations of the scaffold following ssLAVR, and the weak point were investigated. A strong negative correlation existed between LPP and vessel diameter, albeit LPP (484 ± 111 mmHg) remained well above pathophysiological pressures. Histological analysis revealed that thermal damage extended into the medial layer with a well-preserved internal elastic lamina and endothelial cells. Laser irradiation of PCL fibers and coagulation of solder material resulted in a strong and stiff scaffold. The weak point of the ssLAVR modality was predominantly characterized by cohesive failure. In conclusion, ssLAVR produced supraphysiological LPPs and limited tissue damage. Despite heat-induced structural/mechanical alterations of the scaffold, PCL is a suitable polymer for weld reinforcement in medium-sized vessel ssLAVR

Covered stents versus Bare-metal stents in chronic atherosclerotic Gastrointestinal Ischemia (CoBaGI): Study protocol for a randomized controlled trial

Background: Chronic mesenteric ischemia (CMI) is the result of insufficient blood supply to the gastrointestinal tract and is caused by atherosclerotic stenosis of one or more mesenteric arteries in > 90% of cases. Revascularization therapy is indicated in patients with a diagnosis of atherosclerotic CMI to relieve symptoms and to prevent acute-on-chronic mesenteric ischemia, which is associated with high morbidity and mortality. Endovascular therapy has rapidly evolved and has replaced surgery as the first choice of treatment in CMI. Bare-metal stents (BMS) are standard care currently, although retrospective studies suggested significantly highe

Psoas Muscle Area as a Prognostic Factor for Survival in Patients with an Asymptomatic Infrarenal Abdominal Aortic Aneurysm: A Retrospective Cohort Study

Objectives: Loss of muscle mass has been associated with poor survival in several surgical patient populations, including those with an abdominal aortic aneurysm (AAA). We wanted to replicate these findings and assess the association between psoas muscle area (PMA) and survival in patients with an asymptomatic AAA. Methods: Patients with an asymptomatic infrarenal AAA who underwent computed tomography (CT) scanning between January 1, 2007, and December 31, 2013, were included in this single-centre retrospective cohort study. PMA was measured with thresholding on an axial image at the centre level of the third lumbar vertebra. The lowest tertile of PMA in all patients was used as a cutoff value for a low PMA. Then, in separate analyses for conservatively and surgically managed patients, survival was estimated with the Kaplane-Meier method. Differences in survival between patients with and without a low PMA were tested with the log-rank test. Results: Of 228 patients, 104 were managed conservatively and 124 underwent AAA repair. Seventy-seven patients (62%) had an endovascular repair. In these 228 patients, the median PMA was 16.83 cm(2), while the cutoff value for low PMA was 14.56 cm(2). Patients who were managed conservatively were more often classified as having low PMA (45/104, 43%, vs. 31/124, 25%; p = .004) and were significantly older (mean 73.4 +/- 49.05 years vs. 69.03 +/- 7.46 years; p <.001). Low PMA was not associated with survival, either in patients managed conservatively, or in those who underwent AAA repair (p = .512 and p = .311, respectively). Conclusions: The association between low PMA and poor survival could not be replicated; in this study, low PMA was not associated with survival in patients with an asymptomatic AAA. Further research is recommended before PMA can be used for pre-operative risk stratification. (C) 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserve

Lasagna plots to visualize results in surgical studies

A lasagna plot is a graphical tool that can display multiple longitudinal outcomes. To our knowledge, lasagna plots have not been used in publications of surgical studies before. The objective of this study was to demonstrate the results of surgical randomized controlled trials (RCTs) with lasagna plots in order to assess whether this can lead to new observations of the data presented in the original studies. Lasagna plots were created with R for an RCT comparing endovascular and open repair for patients with a ruptured abdominal aortic aneurysm (AJAX trial), an RCT comparing laparoscopy or open surgery combined with either fast track or standard care for patients with colon cancer (LAFA trial) and an RCT comparing preoperative biliary drainage and early surgery for patients with pancreatic cancer (DROP trial). Regarding the AJAX trial, the original article had reported the rate of outcomes at 30 days after repair in two tables. The plots additionally demonstrated the moments of occurrence, increase and decrease of multiple outcomes such as renal replacement therapy and occurrence of death within one plot. These observations were not presented in the original article. The lasagna plots of the LAFA and DROP trial revealed similar new observations on multiple longitudinal outcomes. By revealing new observations of the previously published data, lasagna plots generate new hypotheses and theories regarding the outcomes. As such, lasagna plots may be a useful addition to traditional tables and figures and could improve the interpretation of result

Electrospun poly(ε-caprolactone) scaffold for suture-free solder-mediated laser-assisted vessel repair

Background and Objective: The addition of poly(lactic-co-glycolic) acid (PLGA) scaffolds to liquid solder-mediated laser-assisted vascular repair (sLAVR) has been shown to increase soldering strength significantly. Unfortunately, the fast degradation of PLGA is associated with adverse effects such as acidity of the degradation products. This study investigated the possibility of using electrospun poly(ε-caprolactone) (PCL) as reinforcement material in scaffold and solder-mediated LAVR (ssLAVR). Materials and Methods: In vitro sLAVR of 10-mm arteriotomies (n = 62) was performed on 0.3-to 0.6-cm diameter porcine carotid arteries with a 670-nm diode laser. The solder contained 50% bovine serum albumin (BSA) and 0.1-0.7% methylene blue (MB) as a chromophore. The soldering strength was studied as a function of PCL-scaffold thickness, scaffold-fiber diameter, MB concentration, number of laser passes, and different sLAVR techniques. Leaking-point pressures (LPPs) were measured with a fluid-infusion technique. Results: The highest mean ± SD LPP (749 ± 171 mm Hg) was produced by the ssLAVR modality that included the sheathing of the arteriotomy with 30 μL solder containing 50% BSA and 0.5% MB, followed by application of the PCL scaffold (mean ± SD thickness of 187 ± 9 μm and 14-μm fiber diameter) and irradiation with two consecutive continuous-wave laser passes. Conclusions: The study demonstrated the potential applicability of an electrospun PCL scaffold as reinforcement material in ssLAVR. Soldering strength was dependent on the scaffold physical properties, chromophore concentration, the number of laser passes, and the ssLAVR technique.</p

Biodegradable polymer scaffold, semi-solid solder, and single-spot lasing for increasing solder-tissue bonding in suture-free laser-assisted vascular repair

We recently showed the fortifying effect of poly-caprolactone (PCL) scaffold in liquid solder-mediated laser-assisted vascular repair (ssLAVR) of porcine carotid arteries, yielding a mean?+/-?SD leaking point pressure of 488?+/-?111?mmHg. Despite supraphysiological pressures, the frequency of adhesive failures was indicative of weak bonding at the solder-tissue interface. As a result, this study aimed to improve adhesive bonding by using a semi-solid solder and single-spot vs. scanning irradiation. In the first experiment, in vitro ssLAVR (n?=?30) was performed on porcine abdominal aorta strips using a PCL scaffold with a liquid or semi-solid solder and a 670-nm diode laser for dual-pass scanning. In the second experiment, the scanning method was compared to single-spot lasing. The third experiment investigated the stability of the welds following hydration under quasi-physiological conditions. The welding strength was defined by acute breaking strength (BS). Solder-tissue bonding was examined by scanning electron microscopy and histological analysis was performed for thermal damage analysis. Altering solder viscosity from liquid to semi-solid solder increased the BS from 78?+/-?22?N/cm2 to 131?+/-?38?N/cm2. Compared to scanning ssLAVR, single-spot lasing improved adhesive bonding to a BS of 257?+/-?62?N/cm2 and showed fewer structural defects at the solder-tissue interface but more pronounced thermal damage. The improvement in adhesive bonding was associated with constantly stronger welds during two weeks of hydration. Semi-solid solder and single-spot lasing increased welding strength by reducing solder leakage and improving adhesive bonding, respectively. The improvement in adhesive bonding was associated with enhanced weld stability during hydration. Copyright (c) 2011 John Wiley & Sons, Lt

Estimation of Abdominal Aortic Aneurysm Rupture Risk with Biomechanical Imaging Markers

Purpose: To evaluate whether the biomechanical marker known as rupture risk equivalent diameter (RRED) was superior to the actual abdominal aortic aneurysm (AAA) diameter in estimating future rupture risk in patients who had undergone pre-rupture computed tomography (CT) angiography. Materials and Methods: A retrospective study was conducted in 13 patients with ruptured AAAs who had undergone CT angiography before and after rupture between 2001 and 2015. The median time between the 2 scans was 731 days. Biomechanical and geometrical markers such as maximal AAA diameter, peak wall stress (PWS), and RRED were calculated with AAA-dedicated software. The main analyses determined whether RRED was higher than the actual diameter and the threshold diameter for elective surgery (55 mm for men, 50 mm for women) in AAAs before and after rupture. Differences between diameter and biomechanical markers before and after rupture were tested with appropriate statistical tests. Results: RRED before and after rupture was smaller than the actual diameter in 7 of 13 cases. Post-rupture RRED was estimated to be smaller than the threshold diameter for elective repair in 4 cases, again suggesting a low rupture risk. The median PWS before and after rupture was 181.7 kPa (interquartile range [IQR], 152.1-244.2 kPa) and 274.1 kPa (IQR, 172.2-377.2 kPa), respectively. Conclusions: RRED was smaller than the actual diameter in more than half of pre-rupture AAAs, suggesting a lower rupture risk than estimated with the actual diameter. The results suggest that the currently available biomechanical imaging markers might not be ready for use in clinical practice