Perceptions, Experiences, Barriers and Facilitators Regarding Nutritional Intake of Patients with Chronic Limb Threatening Ischemia: A Qualitative Study.

BACKGROUND: Patients with chronic limb threatening ischemia (CLTI) are at high risk for amputation and other cardiovascular adverse events. Nutrition-related symptoms and malnutrition are common in the CLTI population, and lead to worse clinical outcomes. Understanding of the factors influencing nutritional intake is required to determine whether optimization of nutritional intake in this population requires interventions. Therefore, this study aimed to describe perceptions and experiences on nutrition of patients with CLTI, and to identify perceived barriers and facilitators influencing their nutritional intake. METHODS: In this phenomenological qualitative study, individual semi-structured, face-to-face interviews were conducted with patients with CLTI who lived independently. Interviews were transcribed verbatim, and reflexive thematic analysis was performed. RESULTS: Twelve participants were interviewed. Five themes were generated: (1) lack of nutritional risk perception, (2) role of nutrition for health, functioning, and surviving, (3) multiple factors influencing nutritional intake, (4) limited nutritional advice, and (5) no intention to change current nutritional intake. CONCLUSIONS: Patients with CLTI perceive nutritional intake as a necessity to survive and function. Patients express limited risk perception regarding adequate nutritional intake and undernutrition. Nutritional intake is mainly based on non-health-related factors, as habits and taste, and multiple barriers hinder nutritional intake. Patients received no or only limited nutritional advice. Together this leads to an expressed lack of intention to change nutritional intake. Findings of this study stress the urgency for patient-centered nutritional support, to increase nutrition-related knowledge and motivation, to prevent or treat undernutrition, and may improve clinical outcomes in patients with CLTI.

Palladium-Catalyzed Cascade to Benzoxepins by Using Vinyl-Substituted Donor-Acceptor Cyclopropanes.

A palladium-catalyzed intermolecular cascade (4+3) cyclocondensation of salicylaldehydes and vinylcyclopropanes is reported. A key feature of the reaction is the use of a phosphonate group as an acceptor moiety on the cyclopropane, exploiting its propensity to undergo olefination with aldehydes. Subsequent O-allylation enabled the formation of a range of substituted benzoxepinsWith a novel chiral ligand, the products were obtained in generally good yield and with reasonable enantioselectivity.

Incidence, natural course, and outcome of type II endoleaks in infrarenal endovascular aneurysm repair based on the ENGAGE registry data.

OBJECTIVE: The purpose of this study was to report the incidence, natural history, and outcome of type II endoleaks in the largest prospective real-world cohort to date. METHODS: Patients were extracted from the prospective Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE). Two groups were analyzed: first, patients with an isolated type II endoleak; and second, patients with a type II endoleak who later presented with a type I endoleak. A health status analysis between patients with an early type II endoleak and patients with no endoleak was performed. Second, an attempt was made to identify risk factors in patients with a type II endoleak who later presented with a type I endoleak. RESULTS: Through 5 years of follow-up, a total of 197 (15.6%) patients with isolated type II endoleaks were identified. Most were detected within the first 30 days (n = 73 [37.1%]) and through the first year (n = 73 [37.1%]), with the remainder being detected after 1 year of follow-up (n = 51 [25.8%]). Patients with a type II endoleak had a higher incidence of aneurysm growth and more secondary endovascular procedures (15.4% vs 7.5% at 5 years; P < .001). Overall survival was higher in the isolated type II endoleak group compared with patients with no endoleak (77.2% vs 67.0% at 5 years; P = .010). Twenty-two patients (10%) with a type II endoleak were diagnosed with a late type I endoleak (type IA, n = 10; type IB, n = 12), with a secondary intervention rate of 67.5% through 5 years. There was no difference in health status scores between patients with an early type II endoleak and patients without any type of endoleak at 1-year follow-up. CONCLUSIONS: In the ENGAGE registry, isolated type II endoleaks are present in 15.6% of patients during follow-up. The majority do not require secondary intervention, and an early isolated type II endoleak does not have an impact on health status through 1 year. However, a small group of patients with a type II endoleak will present with a type I endoleak, resulting in a high secondary intervention rate and significant risk of aneurysm-related complications.

The Use of Iliac Branched Devices in the Acute Endovascular Repair of Ruptured Aortoiliac Aneurysms.

BACKGROUND: The objective of this study was to evaluate the feasibility and midterm outcomes of iliac branch devices (IBDs) to preserve the internal iliac artery perfusion in emergent endovascular repair of ruptured aorto-iliac aneurysms. METHODS: Between December 2012 and July 2017, a total of 8 IBDs were implanted in 6 patients (the median age 65 years; all men) in a single tertiary referral center. The indication for IBD implantation was a ruptured abdominal aortic aneurysm with a concomitant common iliac artery aneurysm (n = 4) or isolated CIA aneurysms (n = 2). The main outcome measures were technical and clinical success. The secondary outcomes were primary and primary assisted patency, the occurrence of type I/III endoleaks, and reinterventions. RESULTS: All patients were hemodynamically stable during the procedures, which were performed under local anesthesia. Technical success was achieved in all cases (the median total procedure time of 188 min and the median IBD procedure time of 28 min). The median follow-up was 34 months (interquartile range 19-78). There were no deaths during the follow-up and no major complications unrelated to the IBD. Two (25%) secondary interventions were performed for IBD occlusion in patients with bilateral IBDs. The other reintervention was a type II endoleak embolization in 1 of these 2 patients. The freedom from reintervention estimate was 75% through 2 years. The overall primary assisted patency was 100% through 3 years. CONCLUSIONS: The use of IBDs in the acute setting is feasible to exclude ruptured aortoiliac aneurysms while maintaining pelvic circulation. The secondary intervention rate is considerable; however, the midterm assisted primary patency rates are promising. Further studies are needed to guide patient selection and to evaluate longer term outcomes.

Editor's Choice - Spinal Cord Ischaemia in Endovascular Thoracic and Thoraco-abdominal Aortic Repair: Review of Preventive Strategies.

INTRODUCTION: The incidence of spinal cord ischaemia (SCI) and subsequent paraplegia after thoracic endovascular aneurysm repair (TEVAR) and thoraco-abdominal endovascular aneurysm repair is estimated to be between 2.5% and 8%. The aim of this review is to provide an overview of SCI preventive strategies in TEVAR and thoraco-abdominal repair and recommend an optimal strategy. METHODS: Medline, Embase, and the Cochrane Library were searched for studies on TEVAR, thoraco-abdominal endovascular repair, and the use of SCI preventive measures. The review was reported according to the PRISMA statement. RESULTS: The final analysis included 43 studies (7168 patients). All studies are cohort studies (non-comparative cohorts n = 37, comparative cohorts n = 6) and largely performed retrospectively (n = 27). The included studies had an average MINORS score of 9 (range 6-13) for non-comparative studies and 15.5 (range 12-18) for comparative studies. Transient SCI occurred in 5.7% (450/7,168, 95% CI 4.5-6.9%), permanent SCI in 2.2% (232/7,168, 95% CI 1.6-2.8%). There was a trend towards increased SCI incidence for more "high risk" cohorts. Avoidance of hypotension resulted in a slightly lower permanent SCI rate 1.8% (102/4216, 95% CI 1.2-2.3%) than the overall cohort. A very low SCI estimate (transient and permanent) was found in the subgroup of studies (2 studies, n = 248) using (mild) peri-operative hypothermia (transient SCI 0.8%, permanent SCI 0.4%). In the subgroup using temporary permissive endoleak, there was a transient SCI estimate (15.4%), with a permanent SCI estimate of 4.8%. The remaining preventive measures did not significantly impact transient or permanent SCI estimates. CONCLUSION: Low overall transient and permanent SCI rates are achieved during endovascular thoracic and thoraco-abdominal aortic repair. Based on the presented data, the use of selective spinal fluid drainage in high risk patients seems justified. Peri-operative hypotension should be avoided and treated where possible. The use of mild hypothermia is promising in small cohorts, but requires further evaluation. Further high quality data are essential to establish a definitive preventive strategy.

Midterm results of the fenestrated Anaconda endograft for short-neck infrarenal and juxtarenal abdominal aortic aneurysm repair.

OBJECTIVE: The fenestrated Anaconda endograft (Vascutek, Renfrewshire, Scotland) was introduced in 2010 and showed promising short-term results with high technical success and low morbidity rates. The aim of this study was to present the midterm results, with a minimum of 12 months follow-up, for all patients treated with the fenestrated Anaconda endograft in The Netherlands. METHODS: Patients treated with the fenestrated Anaconda endograft between May 2011 and February 2015 were included. Follow-up consisted of computed tomography angiography at 1 month and 1 year, and duplex ultrasound yearly thereafter with additional computed tomography angiography if indicated using a standard protocol. RESULTS: A total of 60 patients were included; 48 patients (80.0%) were treated for juxtarenal aneurysms, and 12 (20.0%) were short-neck infrarenal aneurysms. Mean aneurysm size was 64 ± 9 mm. A total of 140 fenestrations were incorporated. Median follow-up was 16.4 months (interquartile range, 11.9-27.4). The 30-day mortality was 3.4% (n = 2). Kaplan-Meier estimates for 1-year, 2-year, and 3-year survival were 91.4%, 89.5%, and 86.3%, respectively, without aneurysm-related mortality during follow-up. Main body primary and secondary endograft patencies were 98.3% and 100%, respectively. Target vessel primary and secondary patencies were 95.0% and 98.6%, respectively. Early type IA endoleaks occurred in seven patients (11.7%) and spontaneously resolved in all patients. At 1-year follow-up 4 (6.7%) type II endoleaks persisted. One patient experienced aneurysm rupture because of a late type III endoleak attributable to a dislodged renal stent and subsequently underwent successful conversion to open surgery. CONCLUSIONS: The fenestrated Anaconda is a viable treatment option for complex abdominal aortic aneurysms. Acceptable mortality and morbidity and low reintervention rates contribute to good midterm results. Occurrence of early type I endoleak was relatively common, but these resolved spontaneously in all patients.

Initial Experience With Covered Endovascular Reconstruction of the Aortic Bifurcation in Conjunction With Chimney Grafts.

PURPOSE: To show feasibility of the covered endovascular repair of the aortic bifurcation (CERAB) technique in conjunction with chimney grafts in aortic side branches for complex aortoiliac occlusive disease. METHODS: Two European centers and one facility located in New Zealand participated in a retrospective observational study that enrolled 14 consecutive patients (mean age 61.2±8.9 years; 11 men) treated with CERAB in conjunction with chimney graft(s) between December 2012 and May 2015. Indications for treatment included disabling claudication in 9 and critical limb ischemia in 5. Lesions were classified as TransAtlantic Inter-Society Consensus II B (n=1), C (n=1), or D (n=12). RESULTS: A total of 15 chimney grafts were used to perfuse the inferior mesenteric artery (n=8), the right renal artery (n=4), and the left renal artery (n=3). Technical success was achieved in all cases. Procedural complications included 5 unintended dissections and 1 vessel thrombosis, all of which were successfully treated intraoperatively. Five patients developed access-site hematoma/ecchymosis (3 at the brachial access). Mean follow-up was 12 months (range 6-24) without death or loss to follow-up. One patient suffered occlusion of a CERAB limb and an IMA chimney graft; the former was recanalized, but the IMA graft was not; there were no signs of bowel ischemia. Ankle-brachial indices significantly increased from 0.54 (range 0.47-0.60) preoperatively to 0.97 (range 0.90-1.00) in 11 patients examined at 12 months, and all patients had an improvement in the Rutherford category. All CERAB limbs, including the one recanalized, were patent at the most recent follow-up, as were 14 of 15 chimney grafts. CONCLUSION: Chimney-CERAB is technically feasible and may offer an alternative to open surgery for complex aortoiliac occlusive disease. Further prospective studies are needed to confirm these findings.

One-Year Outcomes of Endovascular Aneurysm Repair in High-Risk Patients Using the Endurant Stent-Graft: Comparison of the ASA Classification and SVS/AAVS Medical Comorbidity Grading System for the Prediction of Mortality and Adverse Events.

PURPOSE: To evaluate the outcome and survival of patients with extensive comorbid conditions after endovascular aneurysm repair (EVAR) and objectify which of 2 medical comorbidity classifications is more accurate in predicting adverse outcomes. METHODS: All 1263 patients (mean age 73.1 years; 1129 men) treated using the Endurant Stent Graft system and entered in the prospective global postmarketing ENGAGE registry (ClinicalTrials.gov identifier NCT00870051) were grouped using the American Society of Anesthesiologists (ASA) classification and the Society for Vascular Surgery/American Association for Vascular Surgery (SVS/AAVS) medical comorbidity grading system. Patients assigned to ASA III and IV and SVS/AAVS 2 and 3 categories were considered high risk. Primary outcome was 1-year all-cause mortality. Secondary outcomes included technical and clinical success, major adverse events (MAE), aneurysm rupture, endoleaks, and secondary endovascular procedures. One-year follow-up of the entire ENGAGE cohort was the endpoint of the study. RESULTS: A total of 1263 patients were included. The overall technical success rate was high, the lowest being 97.4% in the ASA I group. The overall 30-day and 1-year Kaplan-Meier survival estimates were 98.7% and 92.5%, respectively. All cause 1-year mortality was higher in the ASA III and IV groups, but this did not reach statistical significance (5.2% and 5.7% for ASA I and II vs 9.0% and 9.9% for ASA III and IV, p=0.12). In the SVS/AAVS groups, 1-year all-cause mortality significantly increased with the SVS/AAVS score to 11.3% in the SVS/AAVS 3 group (p=0.002). There were significantly more MAEs in the SVS/AAVS 3 group at 1 year (p<0.001 for group 1 vs 3 and group 2 vs 3). CONCLUSION: Endovascular aneurysm repair has evolved, and high technical success and low mortality and morbidity can be achieved in high-risk patients. When treating high-risk patients, the perioperative risks should always be weighed against the expected gains. In contrast to the ASA classification, the SVS/AAVS medical comorbidity grading system is a useful tool to predict occurrence of MAEs and 1-year survival in patients undergoing EVAR.

Dutch experience with the fenestrated Anaconda endograft for short-neck infrarenal and juxtarenal abdominal aortic aneurysm repair.

OBJECTIVE: In the past decennium, the management of short-neck infrarenal and juxtarenal aortic aneurysms with fenestrated endovascular aneurysm repair (FEVAR) has been shown to be successful, with good early and midterm results. Recently, a new fenestrated device, the fenestrated Anaconda (Vascutek, Renfrewshire, Scotland), was introduced. The aim of this study was to present the current Dutch experience with this device. METHODS: A prospectively held database of patients treated with the fenestrated Anaconda endograft was analyzed. Decision to treat was based on current international guidelines. Indications for FEVAR included an abdominal aortic aneurysm (AAA) with unsuitable neck anatomy for EVAR. Planning was performed on computed tomography angiography images using a three-dimensional workstation. RESULTS: Between May 2011 and September 2013, 25 patients were treated in eight institutions for juxtarenal (n = 23) and short-neck AAA (n = 2). Median AAA size was 61 mm (59-68.5 mm). All procedures except one were performed with bifurcated devices. A total of 56 fenestrations were incorporated, and 53 (94.6%) were successfully cannulated and stented. One patient died of bowel ischemia caused by occlusion of the superior mesenteric artery. On completion angiography, three type I endoleaks and seven type II endoleaks were observed. At 1 month of follow-up, all endoleaks had spontaneously resolved. Median follow-up was 11 months (range, 1-29 months). There were no aneurysm ruptures or aneurysm-related deaths and no reinterventions to date. Primary patency at 1 month of cannulated and stented target vessels was 96%. CONCLUSIONS: Initial and short-term results of FEVAR using the fenestrated Anaconda endograft are promising, with acceptable technical success and short-term complication rates. Growing experience and long-term results are needed to support these findings.

Endovascular aneurysm sealing for juxtarenal aneurysm using the Nellix device and chimney covered stents.

PURPOSE: To show the feasibility of the Nellix device in conjunction with a chimney technique for treating juxtarenal aneurysms in two patients who were deemed unsuitable for fenestrated endovascular aneurysm repair or open surgery. CASE REPORTS: Two men aged 83 and 81 years were referred with a juxtarenal abdominal aortic aneurysm (66 and 69 mm, respectively). Both were considered for open surgery as well as custom-made fenestrated stent-graft but deemed unsuitable for both options. They were both treated using the Nellix endoprosthesis in combination with chimney grafts to preserve the renal arteries. Technical success was achieved in both cases, with successful aneurysm exclusion and target vessel preservation (the right renal artery in the first case and both renal arteries in the second). At 6 months, duplex ultrasound and computed tomographic angiography of the first patient showed no signs of endoleak and patent renal arteries. The second patient developed a right retroperitoneal hematoma with minor extravasation near the lower pole of the right kidney for which coil embolization was necessary. The subsequent clinical sequelae led to respiratory insufficiency and ultimately death. CONCLUSION: The use of the Nellix endoprosthesis combined with chimney grafts is technically feasible. The addition of chimney grafts can increase the applicability of endovascular aneurysm sealing to treat short-neck and juxtarenal aneurysms. Further studies are needed to confirm these findings and establish longer term outcome.

Hypertensive extracorporeal limb perfusion for critical limb ischemia.

OBJECTIVE: This article reports the early results in humans of hypertensive extracorporeal limb perfusion (HELP) technology in the prevention of major limb amputation due to ischemia. The short-term aim was to dilate pre-existing collateral channels, and the long-term aim was to stimulate remodeling and new collateral development by increasing endothelial shear stress and wall tension. METHODS: This study evaluated 20 patients with critical limb ischemia who were treated with HELP. These patients had no other option but major amputation, as determined by at least two vascular surgeons. The arterial circulation to the ischemic limb was isolated from the systemic circulation by the use of an endoluminal balloon catheter in seven patients and by an implantable, inflatable, occlusive cuff in 13. The limbs were hyperperfused through the peripheral access system with an extracorporeal pump, producing a minimally pulsatile waveform at 200% to 300% of the mean arterial pressure. This was performed repeatedly in sessions of 24 to 36 hours, up to a maximum of 74 hours. The primary end point was avoidance of major amputation. The secondary end points were the clinical improvements in rest pain, ulcer healing, and claudication distance. Patients were analyzed and reviewed using infrared thermography and ultrasound imaging parameters of the limb. RESULTS: Given adequate arterial access, 39 of 40 connections developed flows four to eight times those supplied to the limb by the normal cardiac output. A progressive decrease was noted in peripheral resistance. All patients developed a pain-free, warm foot or hand while on the pump in the short-term. In the longer term at a mean of 22 months (range, 12-54 months), eight of 20 patients (40%) had avoided major amputation and four more had a delay in amputation of an average of 4 months. The ankle-brachial index changed from 0.04 ± 0.07 (range, 0.00-0.94) to 0.63 ± 0.39 (t-test, P < .05). Bleeding, infection, premature cessation of the treatment, and poor patient selection resulted in the failures. There were two short-term unrelated deaths that occurred at 1 and 3 months follow-up. CONCLUSIONS: The collateral circulation of ischemic limbs can be augmented and regulated by a connection to an extracorporeal centrifugal pump, with isolation from the systemic circulation provided by balloons and with an access system providing repeatable pump connections. Major amputation may be avoided in selected cases.

Long-Term Survival and Quality of Life After Fenestrated Endovascular Repair for Complex Abdominal Aortic Aneurysms.

OBJECTIVES: Fenestrated endovascular repair (FEVAR) has become a widely used treatment option for complex abdominal aortic aneurysms (AAA) but long-term survival and quality of life (QoL) outcomes are scarce. This single center cohort study aims to evaluate both long-term survival and QoL after FEVAR. METHODS: All juxtarenal and suprarenal AAA patients treated with FEVAR in a single-center between 2002 and 2016 were included. QoL scores, measured by the RAND 36-Item Short Form Survey (SF-36), were compared with baseline data of the SF-36 provided by RAND. RESULTS: A total of 172 patients were included at a median follow-up of 5.9 years (IQR 3.0-8.8). Follow-up at 5 and 10 years post-FEVAR yielded survival rates of 59.9% and 18%, respectively. Younger patient age at surgery had a positive influence on 10-year survival and most patients died due to cardiovascular pathology. Emotional well-being was better in the research group as compared to baseline RAND SF-36 1.0 data (79.2 ± 12.4 vs 70.4 ± 22.0; P < 0.001). Physical functioning (50 (IQR 30-85) vs 70.6 ± 27.4; P = 0.007) and health change (51.6 ± 17.0 vs 59.1 ± 23.1; P = 0.020) were worse in the research group as compared to reference values. CONCLUSIONS: Long-term survival was 60% at 5-years follow-up, which is lower than reported in recent literature. An adjusted positive influence of younger age at surgery was found on long-term survival. This could have consequences for future treatment indication in complex AAA surgery but further large-scale validation is necessary.

A high-throughput processing service for retention time alignment of complex proteomics and metabolomics LC-MS data.

UNLABELLED: Warp2D is a novel time alignment approach, which uses the overlapping peak volume of the reference and sample peak lists to correct misleading peak shifts. Here, we present an easy-to-use web interface for high-throughput Warp2D batch processing time alignment service using the Dutch Life Science Grid, reducing processing time from days to hours. This service provides the warping function, the sample chromatogram peak list with adjusted retention times and normalized quality scores based on the sum of overlapping peak volume of all peaks. Heat maps before and after time alignment are created from the arithmetic mean of the sum of overlapping peak area rearranged with hierarchical clustering, allowing the quality control of the time alignment procedure. Taverna workflow and command line tool are provided for remote processing of local user data. AVAILABILITY: online data processing service is available at http://www.nbpp.nl/warp2d.html. Taverna workflow is available at myExperiment with title '2D Time Alignment-Webservice and Workflow' at http://www.myexperiment.org/workflows/1283.html. Command line tool is available at http://www.nbpp.nl/Warp2D_commandline.zip. CONTACT: p.l.horvatovich@rug.nl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The use of a novel short dilator tip on the distal bifurcated component during fenestrated aortic repair to avoid reno-visceral bridging stents.

BACKGROUND: The aim of this study was to evaluate the feasibility and efficacy of a modified delivery system of the distal bifurcated FEVAR component where the dilator tip was shortened to prevent damage to the renovisceral bridging stents. METHODS: All consecutive patients from a tertiary referral center that underwent a FEVAR with a custom delivery system of the distal bifurcated endograft with a short tip between November 2017 and July 2019 were retrospectively analyzed. Only patients with complete fluoroscopic loops of the insertion and deployment of the distal endograft were included. The primary study endpoint was the degree of crossing of the fenestration bridging stent-grafts, that was graded as 'not crossing', 'partial crossing' and 'complete crossing' relative to the lowermost placed fenestration. Secondary endpoints included fenestration related adverse events, secondary interventions, changes in renal function, aneurysm related mortality and overall mortality. RESULTS: 23 patients were included (21 (91%) juxta-renal aneurysms, 2 TAAA type IV (9%). The lowermost fenestration was crossed in 4 (17.3%), partially crossed in 9 (39.1%) and not crossed in 10 (43.4%) cases. Partial compression or inadequate flaring of a fenestration stent-graft was identified in the intraoperative cone beam CT in 6 (26.0%) patients and corrected peri-operatively. Technical success was 100%. Median follow-up was 34 (27-38) months with two non-aneurysm related deaths during this period. Four patients (17.3%) underwent a secondary intervention related to a fenestration bridging stent-graft. CONCLUSIONS: The use of a custom short dilator introducer tip on the bifurcated device during FEVAR reduces the need to cross the fenestration bridging stent-grafts and may result in less fenestration related adverse events. However, the reno-visceral segment is still frequently crossed by the iliac extension which may lead to adverse events. This could likely be avoided by a similar adaptation on the iliac extension delivery system.

Crushing of a bridging stent during follow-up of endovascular branched aortic arch repair: A novel mode of failure.

A 68-year-old man developed aneurysmal degeneration of the aortic arch and proximal descending aorta after an open ascending graft for a type A aortic dissection. A three-branched endovascular aortic arch repair was performed with patency of all branches despite some degree of initial misalignment of the branches in relation to the target vessels. At 6 months postoperatively, an asymptomatic partial crushing of the left common carotid bridging grafts was observed on computed tomography angiography. This was treated by reinforcing the branch with a balloon-expandable endograft. The postoperative course was uneventful but a computed tomography angiography after 1 month showed recurrent asymptomatic compression. A left carotid-subclavian bypass was eventually performed. We have reported a new failure mode of an inner branch arch repair of residual type A chronic dissection.

Supra- and Infra-Renal Aortic Neck Diameter Increase after Endovascular Repair of a Ruptured Abdominal Aortic Aneurysm.

Hypovolemia-induced hypotension may lead to an aortic diameter decrease in patients with a ruptured abdominal aortic aneurysm (rAAA). This study investigates the changes in supra- and infra-renal aortic neck diameters before and after endovascular aortic aneurysm repair (EVAR) for rAAA and the possible association with endograft apposition. A retrospective cohort study was conducted including 74 patients treated between 2010 and 2019 in two large European vascular centers. Outer-to-outer wall diameters were measured at +40, +10, 0, −10, and −20 mm relative to the lowest renal artery baseline on the last pre- and first post-EVAR computed tomography angiography (CTA) scan in a vascular workstation. Endograft apposition was determined on the first post-EVAR CTA scan. The post-operative diameter was significantly (p < 0.001) larger than the preoperative diameter at all aortic levels. The aortic diameter at +40 mm (supra-renal) and −10 mm (infra-renal) increased by 6.2 ± 7.3% and 12.6 ± 9.8%, respectively. The aortic diameter at +40 mm increased significantly more in patients with low preoperative systolic blood pressure (<90 mmHg; p = 0.005). A shorter apposition length was associated with a higher aortic diameter increase (R = −0.255; p = 0.032). Hypovolemic-induced hypotension results in a significant decrease in the aortic diameter in patients with an rAAA, which should be taken into account when oversizing the endograft.

Intraoperative C-arm cone-beam computed tomography in fenestrated/branched aortic endografting.

OBJECTIVES: To evaluate the use of intraoperative guidance by means of C-arm cone-beam computed tomography (CT) (cone-beam computed tomography [CBCT]) and the use of postoperative CBCT to assess for successful aneurysm exclusion in fenestrated branched endovascular aneurysm repair (FEVAR). METHODS: Patients with FEVAR who underwent CBCT were retrospectively evaluated and categorized into one of two groups. The CBCT-fusion group was comprised of patients who underwent preprocedural CBCT to guide FEVAR using fusion imaging with multidetector computed tomography (MDCT). The postprocedure CBCT group consisted of patients undergoing CBCT following deployment of the endograft. Outcomes from the CBCT-fusion group were compared with historical controls. These controls were patients who underwent FEVAR for similar groups of abdominal and thoracoabdominal aortic aneurysms in the 12 months preceding the initiation of a CBCT program. The findings on postprocedural CBCT were compared with those on predischarge MDCT. Results are expressed as mean ±standard error of the mean, or as median and interquartile range. RESULTS: Forty patients were included in the "CBCT-fusion" group and compared with the historical cohort. The use of perioperative guidance of FEVAR by means of CBCT resulted in a significantly lower contrast dose (94 cc [72-131] vs 136 cc [96-199]; P = .001). While there was a trend toward lower operative (330 minutes [273-522] vs 387 minutes [290-477]; P = .651) and fluoroscopy times (81 min [54-118] vs 90 minutes (46-128), P = .932); this difference did not reach statistical significance. Nineteen patients were included in the "postprocedural CBCT" group and compared with predischarge MDCT. Postoperative CBCT identified eight endoleaks. Type I and III (n = 6) endoleaks were identified and treated during the primary procedure. When CBCT did not show an endoleak, this was confirmed by MDCT. The use of CBCT required significantly less contrast compared to MDCT (50 cc [set amount] vs 100 cc [80-125]; P < .0001). Mean skin dose was 0.27 (0.011) Gy for preoperative CBCT and 0.552 (0.036) Gy for postoperative CBCT. CONCLUSIONS: CBCT is a valuable addition to complicated aortic interventions such as FEVAR. Intraoperative use utilizing fusion imaging limits contrast dosage and postdeployment CBCT is of sufficient quality to evaluate successful aneurysm exclusion and for detection of early complications after FEVAR. With the information we are able to obtain from the CBCT at the completion of the FEVAR, we can intervene on problems earlier and potentially decrease the subsequent need for reintervention.

Comparison of isotope-labeled amino acid incorporation rates (CILAIR) provides a quantitative method to study tissue secretomes.

Adipose tissue is an endocrine organ involved in regulation of whole-body energy metabolism via storage of lipids and secretion of various peptide hormones (adipokines). We previously characterized the adipose tissue secretome and showed that [(13)C]lysine incorporation into secreted proteins can be used to determine the origin of identified proteins. In the present study we determined the effect of insulin on the secretome by comparing incorporation rates of (13)C-labeled lysine in the presence and absence of insulin. Human visceral adipose tissue from one patient was divided over six dishes. After subsequent washes to remove serum proteins, [(13)C]lysine-containing medium was added. Three dishes also received 60 nm insulin. The other three were controls. After 72 h of culture, media were collected and processed separately, involving concentration by ultrafiltration and fractionation by SDS-PAGE followed by in-gel digestion of excised bands and LC-MS/MS analyses. The obtained spectra were used for database searching and calculation of heavy/light ratios. The three control data sets shared 342 proteins of which 156 were potentially secreted and contained label. The three insulin-derived data sets shared 361 proteins of which 141 were potentially secreted and contained label. After discarding secreted proteins with very low label incorporation, 121 and 113 proteins remained for control and insulin data sets, respectively. The average coefficient of variation for control triplicates was 10.0% and for insulin triplicates was 18.3%. By comparing heavy/light ratios in the absence and presence of insulin we found 24 up-regulated proteins and four down-regulated proteins, and 58 proteins showed no change. Proteins involved in the endoplasmic reticulum stress response and in extracellular matrix remodeling were up-regulated by insulin. In conclusion, comparison of isotope-labeled amino acid incorporation rates (CILAIR) allows quantitative assessment of changes in protein secretion without the need for 100% label incorporation, which cannot be reached in differentiated tissues or cells.

The MOLGENIS toolkit: rapid prototyping of biosoftware at the push of a button.

BACKGROUND: There is a huge demand on bioinformaticians to provide their biologists with user friendly and scalable software infrastructures to capture, exchange, and exploit the unprecedented amounts of new *omics data. We here present MOLGENIS, a generic, open source, software toolkit to quickly produce the bespoke MOLecular GENetics Information Systems needed. METHODS: The MOLGENIS toolkit provides bioinformaticians with a simple language to model biological data structures and user interfaces. At the push of a button, MOLGENIS' generator suite automatically translates these models into a feature-rich, ready-to-use web application including database, user interfaces, exchange formats, and scriptable interfaces. Each generator is a template of SQL, JAVA, R, or HTML code that would require much effort to write by hand. This 'model-driven' method ensures reuse of best practices and improves quality because the modeling language and generators are shared between all MOLGENIS applications, so that errors are found quickly and improvements are shared easily by a re-generation. A plug-in mechanism ensures that both the generator suite and generated product can be customized just as much as hand-written software. RESULTS: In recent years we have successfully evaluated the MOLGENIS toolkit for the rapid prototyping of many types of biomedical applications, including next-generation sequencing, GWAS, QTL, proteomics and biobanking. Writing 500 lines of model XML typically replaces 15,000 lines of hand-written programming code, which allows for quick adaptation if the information system is not yet to the biologist's satisfaction. Each application generated with MOLGENIS comes with an optimized database back-end, user interfaces for biologists to manage and exploit their data, programming interfaces for bioinformaticians to script analysis tools in R, Java, SOAP, REST/JSON and RDF, a tab-delimited file format to ease upload and exchange of data, and detailed technical documentation. Existing databases can be quickly enhanced with MOLGENIS generated interfaces using the 'ExtractModel' procedure. CONCLUSIONS: The MOLGENIS toolkit provides bioinformaticians with a simple model to quickly generate flexible web platforms for all possible genomic, molecular and phenotypic experiments with a richness of interfaces not provided by other tools. All the software and manuals are available free as LGPLv3 open source at http://www.molgenis.org.

Regulation of adipokine production in human adipose tissue by propionic acid.

BACKGROUND: Dietary fibre (DF) has been shown to be protective for the development of obesity, insulin resistance and type 2 diabetes. Short-chain fatty acids, produced by colonic fermentation of DF might mediate this beneficial effect. Adipose tissue plays a key role in the regulation of energy homeostasis, therefore, we investigated the influence of the short-chain fatty acid propionic acid (PA) on leptin, adiponectin and resistin production by human omental (OAT) and subcutaneous adipose tissue (SAT). As PA has been shown to be a ligand for G-protein coupled receptor (GPCR) 41 and 43, we investigated the role of GPCR's in PA signalling. MATERIALS AND METHODS: Human OAT and SAT explants were obtained from gynaecological patients who underwent surgery. Explants were incubated for 24 h with PA. Adipokine secretion and mRNA expression were determined using ELISA and RT-PCR respectively. RESULTS: We found that PA significantly stimulated leptin mRNA expression and secretion by OAT and SAT, whereas it had no effect on adiponectin. Furthermore, PA reduced resistin mRNA expression. Leptin induction, but not resistin reduction, was abolished by inhibition of Gi/o-coupled GPCR signalling. Moreover, GPCR41 and GPCR43 mRNA levels were considerably higher in SAT than in OAT. CONCLUSIONS: We demonstrate that PA stimulates expression of the anorexigenic hormone leptin and reduces the pro-inflammatory factor resistin in human adipose tissue depots. This suggests that PA is involved in regulation of human energy metabolism and inflammation and in this way may influence the development of obesity and type 2 diabetes.