Regionalization of Emergent Vascular Surgery for Patients With Ruptured AAA Improves Outcomes.

PubMed

Warner, Courtney J; Roddy, Sean P; Chang, Benjamin B; Kreienberg, Paul B; Sternbach, Yaron; Taggert, John B; Ozsvath, Kathleen J; Stain, Steven C; Darling, R Clement

2016-09-01

Safe and efficient endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (r-AAA) requires advanced infrastructure and surgical expertise not available at all US hospitals. The objective was to assess the impact of regionalizing r-AAA care to centers equipped for both open surgical repair (r-OSR) and EVAR (r-EVAR) by vascular surgeons. A retrospective review of all patients with r-AAA undergoing open or endovascular repair in a 12-hospital region. Patient demographics, transfer status, type of repair, and intraoperative variables were recorded. Outcomes included perioperative morbidity and mortality. Four hundred fifty-one patients with r-AAA were treated from 2002 to 2015. Three hundred twenty-one patients (71%) presented initially to community hospitals (CHs) and 130 (29%) presented to the tertiary medical center (MC). Of the 321 patients presenting to CH, 133 (41%) were treated locally (131 OSR; 2 EVAR) and 188 (59%) were transferred to the MC. In total, 318 patients were treated at the MC (122 OSR; 196 EVAR). At the MC, r-EVAR was associated with a lower mortality rate than r-OSR (20% vs 37%, P = 0.001). Transfer did not influence r-EVAR mortality (20% in r-EVAR presenting to MC vs 20% in r-EVAR transferred, P > 0.2). Overall, r-AAA mortality at the MC was 20% lower than CH (27% vs 46%, P < 0.001). Regionalization of r-AAA repair to centers equipped for both r-EVAR and r-OSR decreased mortality by approximately 20%. Transfer did not impact the mortality of r-EVAR at the tertiary center. Care of r-AAA in the US should be centralized to centers equipped with available technology and vascular surgeons.

Outcome after open surgery repair in endovascular-suitable patients with ruptured abdominal aortic aneurysms.

PubMed

Krenzien, Felix; Matia, Ivan; Wiltberger, Georg; Hau, Hans-Michael; Freitas, Bruno; Moche, Michael; Schmelzle, Moritz; Jonas, Sven; Fellmer, Peter T

2013-11-01

Endovascular aneurysm repair (EVAR) has been suggested in several studies to be superior to open surgery repair (OSR) for the treatment of ruptured abdominal aortic aneurysms (rAAAs), but this finding might be affected by selection bias based on aneurysm morphology and patient characteristics. We tested rAAA anatomy according to EVAR suitability in patients undergoing OSR to assess the impact on mortality. This retrospective analysis reports on 83 patients with rAAAs treated between November 2002 and July 2013. Pre-operative computed tomography (CT) scans were evaluated based on EVAR suitability and were determined by blinded independent reviewers. CT scans were lacking due to acquisition in an external institution with no availability (n = 9) or solely ultrasound evaluations (n = 8). In addition patient characteristics and outcomes were assessed. All patients who underwent OSR and who had available preoperative CT scans were included in the study (n = 66). In summary, 42 % of the patients (28/66; 95 % confidence interval [CI], 30.5 - 54.4) were considered eligible for EVAR according to pre-operative CT scans and 58 % of the patients (38/66; 95 % CI, 45.6 - 69.5) were categorized as unsuitable for endovascular repair. Patients suitable for EVAR had a significantly lower prevalence of in-hospital deaths (25 % [7/28]; 95 % CI, 9 - 41) in contrast to patients unsuitable for EVAR (53 % [20/38]; 95 % CI, 36.8 - 68.5; p = 0.02). EVAR-suitable patients had a highly significant mortality reduction undergoing OSR. Thus, the present study proposes that EVAR suitability is a positive predictor for survival after open repair of rAAA.

Variations in Abdominal Aortic Aneurysm Care: A Report From the International Consortium of Vascular Registries

PubMed Central

Sedrakyan, Art; Mao, Jialin; Venermo, Maarit; Faizer, Rumi; Debus, Sebastian; Behrendt, Christian-Alexander; Scali, Salvatore; Altreuther, Martin; Schermerhorn, Marc; Beiles, Barry; Szeberin, Zoltan; Eldrup, Nikolaj; Danielsson, Gudmundur; Thomson, Ian; Wigger, Pius; Björck, Martin; Cronenwett, Jack L.; Mani, Kevin

2016-01-01

Background: This project by the ICVR (International Consortium of Vascular Registries), a collaboration of 11 vascular surgical quality registries, was designed to evaluate international variation in the contemporary management of abdominal aortic aneurysm (AAA) with relation to recommended treatment guidelines from the Society for Vascular Surgery and the European Society for Vascular Surgery. Methods: Registry data for open and endovascular AAA repair (EVAR) during 2010 to 2013 were collected from 11 countries. Variations in patient selection and treatment were compared across countries and across centers within countries. Results: Among 51 153 patients, 86% were treated for intact AAA (iAAA) and 14% for ruptured AAA. Women constituted 18% of the entire cohort (range, 12% in Switzerland–21% in the United States; P<0.01). Intact AAAs were repaired at diameters smaller than recommended by guidelines in 31% of men (<5.5 cm; range, 6% in Iceland–41% in Germany; P<0.01) and 12% of women with iAAA (<5 cm; range, 0% in Iceland–16% in the United States; P<0.01). Overall, use of EVAR for iAAA varied from 28% in Hungary to 79% in the United States (P<0.01) and for ruptured AAA from 5% in Denmark to 52% in the United States (P<0.01). In addition to the between-country variations, significant variations were present between centers in each country in terms of EVAR use and rate of small AAA repair. Countries that more frequently treated small AAAs tended to use EVAR more frequently (trend: correlation coefficient, 0.51; P=0.14). Octogenarians made up 23% of all patients, ranging from 12% in Hungary to 29% in Australia (P<0.01). In countries with a fee-for-service reimbursement system (Australia, Germany, Switzerland, and the United States), the proportions of small AAA (33%) and octogenarians undergoing iAAA repair (25%) were higher compared with countries with a population-based reimbursement model (small AAA repair, 16%; octogenarians, 18%; P<0.01). In general, center-level variation within countries in the management of AAA was as important as variation between countries. Conclusions: Despite homogeneous guidelines from professional societies, significant variation exists in the management of AAA, most notably for iAAA diameter at repair, use of EVAR, and the treatment of elderly patients. ICVR provides an opportunity to study treatment variation across countries and to encourage optimal practice by sharing these results. PMID:27784712

[Incidence and risk factors of ischemic colitis after AAA repair in our cohort of patients from 2005 through 2009].

PubMed

Biros, E; Staffa, R

2011-12-01

Using retrospective analysis, we sought to investigate the incidence, risk factors and therapeutic outcomes of ischemic colitis in patients after surgical and endovascular repair of abdominal aortic aneurysms (AAA). The complete inpatient and outpatient medical records of all patients undergoing surgical or endovascular AAA repair in our Department from January 2005 to December 2009 were retrospectively reviewed. We selected all patients who had developed an acute or chronic form of postoperative large or small bowel ischemia. We carried out data analysis and focused on determining the incidence and risk factors of this complication and the outcomes of its treatment. Two hundred and seven AAA repairs were performed in the 2nd Department of Surgery of St. Anne's University Hospital in Brno and the Faculty of Medicine of Masaryk University in Brno during the studied period. This number includes endovascular AAA repairs (13 patients; 6.3%) as well as one robot-assisted operation, and also the whole clinical spectrum of AAA manifestations, from non-symptomatic forms to ruptured aneurysm forms. The rest of the patients underwent open operation. Bowel ischemia developed in a total of 11 patients (5.3 %), who all underwent open AAA repair. Six of these patients presented with non-ruptured AAA and the remaining 5 with ruptured AAA. In 3 patients, bowel ischemia was diagnosed with a delay of several months from the original revascularization operation in the clinical form of postischemic stricture of the large bowel (2 patients) or postischemic colitis (1 patient). 8 patients were diagnosed with acute ischemic colitis affecting an isolated segment of the small bowel in one patient, extended segments of the large bowel (descending colon + sigmoid colon + rectum) in 2 patients, and typically the descending and sigmoid colon in 5 patients. None of the three patients with late manifestation of ischemic colitis died. Of the 8 patients with acute presentation, resection of the ischemic bowel +/- the rectum was performed in 6 patients. 3 of them died and 3 survived the operation and have been followed up in our outpatient department. 2 patients with acute manifestation did not undergo bowel resection. Both of them died. The overall mortality of all patients with ischemic colitis was 45.5% (5 patients out of 11 died) in our study. When considering only patients suffering from the acute form of ischemic colitis, the mortality rate in our studied cohort amounts to 62.5% (5 patients out of 8 died). Bowel ischemia after AAA repair remains to be a serious complication. Besides the acute form of ischemic colitis, its possible late clinical manifestation in the form of postischemic stricture of the large bowel or postischemic large bowel colitis must also be kept in mind when following up patients. The analysis of our patient's data shows that conditions requiring the use of vasopressors and an increased need of transfusions (more than 7 units of packed red blood cells) intraoperatively represent important predictors of colon ischemia after AAA repair.

A multiantioxidant supplementation reduces damage from ischaemia reperfusion in patients after lower torso ischaemia. A randomised trial.

PubMed

Wijnen, M H W A; Roumen, R M H; Vader, H L; Goris, R J A

2002-06-01

open repair of intra-abdominal aortic aneurysm (AAA) is associated with lower torso ischaemia and reperfusion. to examine the effect of antioxidants on the activation and sequestration of white blood cells and muscle injury during AAA repair. forty-two patients undergoing elective infrarenal aneurysm repair, were randomised to either standard therapy (22 patients) or standard therapy with additional multiantioxidant supplementation (20 patients). Vitamin E and C, Allopurinol, N-acetylcysteine and mannitol was administered perioperatively. White blood cell count (WBC), serum creatine kinase, aspartateaminotransferase, lactate and lipofuscine were measured. WBC remained higher after reperfusion in the antioxidant group (p = 0.008). CK, ASAT and lipofuscine levels were significantly lower after reperfusion in the antioxidant group (p = 0.02, p = 0.018, p = 0.017). multi-antioxidant supplementation was associated with a reduction in serum CK and ASAT after AAA repair. This is likely due to a reduction in oxidative stress and a decreased leucocyte sequestration and activation. Copyright 2002 Elsevier Science Ltd.

High-intensity interval exercise training before abdominal aortic aneurysm repair (HIT-AAA): protocol for a randomised controlled feasibility trial.

PubMed

Tew, Garry A; Weston, Matthew; Kothmann, Elke; Batterham, Alan M; Gray, Joanne; Kerr, Karen; Martin, Denis; Nawaz, Shah; Yates, David; Danjoux, Gerard

2014-01-10

In patients with large abdominal aortic aneurysm (AAA), open surgical or endovascular aneurysm repair procedures are often used to minimise the risk of aneurysm-related rupture and death; however, aneurysm repair itself carries a high risk. Low cardiopulmonary fitness is associated with an increased risk of early post-operative complications and death following elective AAA repair. Therefore, fitness should be enhanced before aneurysm repair. High-intensity interval exercise training (HIT) is a potent, time-efficient strategy for enhancing cardiopulmonary fitness. Here, we describe a feasibility study for a definitive trial of a pre-operative HIT intervention to improve post-operative outcomes in patients undergoing elective AAA repair. A minimum of 50 patients awaiting elective repair of a 5.5-7.0 cm infrarenal AAA will be allocated by minimisation to HIT or usual care control in a 1:1 ratio. The patients allocated to HIT will complete three hospital-based exercise sessions per week, for 4 weeks. Each session will include 2 or 4 min of high-intensity stationary cycling followed by the same duration of easy cycling or passive recovery, repeated until a total of 16 min of high-intensity exercise is accumulated. Outcomes to be assessed before randomisation and 24-48 h before aneurysm repair include cardiopulmonary fitness, maximum AAA diameter and health-related quality of life. In the post-operative period, we will record destination (ward or critical care unit), organ-specific morbidity, mortality and the durations of critical care and hospital stay. Twelve weeks after the discharge, participants will be interviewed to reassess quality of life and determine post-discharge healthcare utilisation. The costs associated with the exercise intervention and healthcare utilisation will be calculated. Ethics approval was secured through Sunderland Research Ethics Committee. The findings of the trial will be disseminated through peer-reviewed journals, and national and international presentations. Current Controlled Trials ISRCTN09433624.

Mid-term cost-effectiveness analysis of open and endovascular repair for ruptured abdominal aortic aneurysm.

PubMed

Rollins, K E; Shak, J; Ambler, G K; Tang, T Y; Hayes, P D; Boyle, J R

2014-02-01

Emergency endovascular repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA) may have lower operative mortality rates than open surgical repair. Concerns remain that the early survival benefit after EVAR for rAAA may be offset by late reinterventions. The aim of this study was to compare reintervention rates and cost-effectiveness of EVAR and open repair for rAAA. A retrospective analysis was undertaken of patients with rAAA undergoing EVAR or open repair over 6 years. A health economic model developed for the cost-effectiveness of elective EVAR was used in the emergency setting. Sixty-two patients (mean age 77·9 years) underwent EVAR and 85 (mean age 75·9 years) had open repair of rAAA. Median follow-up was 42 and 39 months respectively. There was no significant difference in 30-day mortality rates after EVAR and open repair (18 and 26 per cent respectively; P = 0·243). Reintervention rates were also similar (32 and 31 per cent; P = 0·701). The mean cost per patient was €26,725 for EVAR and €30,297 for open repair, and the cost per life-year gained was €7906 and €9933 respectively (P = 0·561). Open repair had greater initial costs: longer procedural times (217 versus 178·5 min; P < 0·001) and intensive care stay (5·0 versus 1·0 days; P = 0·015). Conversely, EVAR had greater reintervention (€156,939 versus €35,335; P = 0·001) and surveillance (P < 0·001) costs. There was no significant difference in reintervention rates after EVAR or open repair for rAAA. EVAR was as cost-effective at mid-term follow-up. The increased procedural costs of open repair are not outweighed by greater surveillance and reintervention costs after EVAR. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Hypothermia is associated with increased mortality in patients undergoing repair of ruptured abdominal aortic aneurysm.

PubMed

Quiroga, Elina; Tran, Nam T; Hatsukami, Thomas; Starnes, Benjamin W

2010-06-01

To evaluate the impact of hypothermia on mortality in patients presenting with ruptured abdominal aortic aneurysms (rAAA). Between July 2007 and September 2009, 73 patients with ruptured AAAs presented to our Emergency Department (ED). Thirteen patients did not receive surgical treatment; of the 60 patients (46 men; mean age 76 years, range 63-90) who did, 35 had endovascular aneurysm repair (EVAR) and 25 open repair. Body temperatures, which were recorded upon arrival to the ED and operating room, during the procedure, and just prior to leaving the operating room, were analyzed for any association with mortality or hypotension. The primary outcome measure was the 30-day mortality rate. Six (17%) patients in the EVAR group and 10 (40%) patients in the open group died during the 30-day period. Temperature upon arrival to OR, lowest temperature recorded during the procedure, and temperature at the end of the procedure were higher among survivors (p<0.005), independent of the repair technique implemented. Patients in the EVAR group left the OR with a mean temperature of 35.5 degrees C versus 35.0 degrees C for patients in the open group (p = 0.12). Hypothermia is associated with increased mortality after repair of rAAA. Efforts to correct hypothermia are more frequently successful in patients undergoing EVAR. Increased communication with anesthesia providers, as well as aggressive measures to correct hypothermia, including active intravascular rewarming methods, should be considered to improve mortality in this gravely ill patient population.

Risk-adjusted predictive models of mortality after index arterial operations using a minimal data set.

PubMed

Prytherch, D R; Ridler, B M F; Ashley, S

2005-06-01

Reducing the data required for a national vascular database (NVD) without compromising the statistical basis of comparative audit is an important goal. This work attempted to model outcomes (mortality and morbidity) from a small and simple subset of the NVD data items, specifically urea, sodium, potassium, haemoglobin, white cell count, age and mode of admission. Logistic regression models of risk of adverse outcome were built from the 2001 submission to the NVD using all records that contained the complete data required by the models. These models were applied prospectively against the equivalent data from the 2002 submission to the NVD. As had previously been found using the P-POSSUM (Portsmouth POSSUM) approach, although elective abdominal aortic aneurysm (AAA) repair and infrainguinal bypass (IIB) operations could be described by the same model, separate models were required for carotid endarterectomy (CEA) and emergency AAA repair. For CEA there were insufficient adverse events recorded to allow prospective testing of the models. The overall mean predicted risk of death in 530 patients undergoing elective AAA repair or IIB operations was 5.6 per cent, predicting 30 deaths. There were 28 reported deaths (chi(2) = 2.75, 4 d.f., P = 0.600; no evidence of lack of fit). Similarly, accurate predictions were obtained across a range of predicted risks as well as for patients undergoing repair of ruptured AAA and for morbidity. A 'data economic' model for risk stratification of national data is feasible. The ability to use a minimal data set may facilitate the process of comparative audit within the NVD. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

The effect of surgeon specialization on outcomes after ruptured abdominal aortic aneurysm repair.

PubMed

Hawkins, Alexander T; Smith, Ann D; Schaumeier, Maria J; de Vos, Marit S; Hevelone, Nathanael D; Nguyen, Louis L

2014-09-01

Although mortality after elective abdominal aortic aneurysm (AAA) repair has steadily declined, operative mortality for a ruptured AAA (rAAA) remains high. Repair of rAAA at hospitals with a higher elective aneurysm workload has been associated with lower mortality rates irrespective of the mode of treatment. This study sought to determine the association between surgeon specialization and outcomes after rAAA repair. The American College of Surgeons National Surgical Quality Improvement Project database from 2005 to 2010 was used to examine the 30-day mortality and morbidity outcomes of patients undergoing rAAA repair by vascular and general surgeons. Multivariable logistic regression analysis was performed for each death and morbidity, adjusting for all independently predictive preoperative risk factors. Survival curves were compared using the log-rank test. We identified 1893 repairs of rAAAs, of which 1767 (96.1%) were performed by vascular surgeons and 72 (3.9%) were performed by general surgeons. There were no significant differences between patients operated on by general vs vascular surgeons in preoperative risk factors or method of repair. Overall 30-day mortality was 34.3% (649 of 1893). After risk adjustment, mortality was significantly lower in the vascular surgery group compared with the general surgery group (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.30-0.86; P = .011). The risk of returning to the operating room (OR, 0.58; 95% CI, 0.35-0.97; P = .038), renal failure (OR, 0.54; 95% CI, 0.31-0.95; P = .034), and a cardiac complication (OR, 0.53; 95% CI, 0.28-0.99; P = .047) were all significantly less in the vascular surgery group. Despite similar preoperative risk factors profiles, patients who were operated on by vascular surgeons had lower mortality, less frequent returns to the operating room, and decreased incidences of postoperative renal failure and cardiac events. These data add weight to the case for further centralization of vascular services. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Regional Differences in Case Mix and Peri-operative Outcome After Elective Abdominal Aortic Aneurysm Repair in the Vascunet Database.

PubMed

Mani, K; Venermo, M; Beiles, B; Menyhei, G; Altreuther, M; Loftus, I; Björck, M

2015-06-01

National differences exist in the outcome of elective abdominal aortic aneurysm (AAA) repair. The role of case mix variation was assessed based on an international vascular registry collaboration. All elective AAA repairs with aneurysm size data in the Vascunet database in the period 2005-09 were included. AAA size and peri-operative outcome (crude and age adjusted mortality) were analysed overall and in risk cohorts, as well as per country. Glasgow Aneurysm Score (GAS) was calculated as risk score, and patients were stratified in three equal sized risk cohorts based on GAS. Predictors of peri-operative mortality were analysed with multiple regression. Missing data were handled with multiple imputation. Patients from Australia, Finland, Hungary, Norway, Sweden and the UK (n = 5,895) were analysed; mean age was 72.7 years and 54% had endovascular repair (EVAR). There were significant variations in GAS (lowest = Finland [75.7], highest = UK [79.4], p for comparison of all regions < .001), proportion of AAA < 5.5 cm (lowest = UK [6.4%], highest = Hungary [29.0%]; p < .001), proportion undergoing EVAR (lowest = Finland [10.1%], highest = Australia [58.9%]; p < .001), crude mortality (lowest = Norway [2.0%], highest = Finland [5.0%]; p = .006), and age adjusted mortality (lowest = Norway [2.5%], highest = Finland [6.0%]; p = .048). Both aneurysm size and peri-operative mortality were highest among patients with a GAS >82. Of those with a GAS >82, 8.4% of men and 20.8% of women had an AAA <5.5 cm. Important regional differences exist in case selection for elective AAA repair, including variations in AAA size and patient risk profile. These differences partly explain the variations in peri-operative mortality. Further audit is warranted to assess the underlying reasons for the regional variation in case-mix. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Patient and Aneurysm Characteristics Predicting Prolonged Length of Stay After Elective Open AAA Repair in the Endovascular Era.

PubMed

Casillas-Berumen, Sergio; Rojas-Miguez, Florencia A; Farber, Alik; Komshian, Sevan; Kalish, Jeffrey A; Rybin, Denis; Doros, Gheorghe; Siracuse, Jeffrey J

2018-01-01

Open aortic aneurysm repair (AAA) repair can be resource intensive and associated with a prolonged length of stay (LOS). We sought to examine patient and aneurysm predictors of prolonged LOS to better identify those at risk in the preoperative setting. Patient data were obtained from the targeted AAA American College of Surgery National Surgical Quality Improvement Program database from 2012 to 2014 of patients undergoing open AAA repair. Multivariable logistic regression was used to determine predictors of prolonged postoperative LOS defined as greater than 10 days (75th percentile). There were 1172 open AAA repairs identified. The majority (54%) of patients were older than 70 years and male (74%). Surgical approach was transperitoneal (70.9%) and retroperitoneal (29.1%). Aneurysms were 51.4% infrarenal, 33% juxtarenal, 5.7% pararenal, 7.4% suprarenal, and 2.5% type IV thoracoabdominal. Mean and median LOS were 9.1 ± 7.4 and 7 (0-72) days, respectively. Independently associated with extended LOS factors were visceral revascularization (odds ratio [OR]: 5.32, 95% confidence interval [CI]: 2.77-10.22, P < .001), type IV thoracoabdominal extent (OR: 3.09, 95% CI: 1.01-9.46, P = .048), suprarenal extent (OR: 1.89, 95% CI: 1.07-3.34, P = .029) and juxtarenal (OR: 1.43, 95% CI: 1.01-2.02, P = .004), non-Caucasian race (OR: 2.80, 95% CI: 1.77-4.41, P < .001), chronic obstructive pulmonary disease (OR: 1.76, 95% CI: 1.20-2.59, P = .004), not-from-home admission (OR: 1.91, 95% CI: 1.13-3.24), and age greater than 70 (OR: 1.49, 95% CI: 1.08-2.05, P = .014). We identified patient and aneurysm characteristics independently associated with protracted LOS following open AAA repair. Prospective identification of high-risk patients may allow physicians and hospitals to engage in multidisciplinary collaborations preoperatively to try to improve LOS in this resource-intensive population.

Postoperative Aortic Neck Dilation: Myth or Fact?

PubMed

Ribner, A S; Tassiopoulos, A K

2018-06-01

The abdominal aorta is the most common site of an aortic aneurysm. The visceral and most proximal infrarenal segment (aneurysm neck) are usually spared and considered more resistant to aneurysmal degeneration. However, if an abdominal aortic aneurysm (AAA) is left untreated, the natural history of the aortic neck is progressive dilatation and shortening. This may have significant implications for patients undergoing endovascular repair of AAAs (EVAR) as endograft stability and integrity of the repair are dependent on an intact proximal seal zone. Compromised seal zones, caused by progressive diameter enlargement and foreshortening of the aortic neck, may lead to distal endograft migration, type Ia endoleak, aortic sac repressurization, and, ultimately, aortic rupture.

The effect of aortic morphology on peri-operative mortality of ruptured abdominal aortic aneurysm.

PubMed

2015-06-01

To investigate whether aneurysm shape and extent, which indicate whether a patient with ruptured abdominal aortic aneurysm (rAAA) is eligible for endovascular repair (EVAR), influence the outcome of both EVAR and open surgical repair. The influence of six morphological parameters (maximum aortic diameter, aneurysm neck diameter, length and conicality, proximal neck angle, and maximum common iliac diameter) on mortality and reinterventions within 30 days was investigated in rAAA patients randomized before morphological assessment in the Immediate Management of the Patient with Rupture: Open Versus Endovascular strategies (IMPROVE) trial. Patients with a proven diagnosis of rAAA, who underwent repair and had their admission computerized tomography scan submitted to the core laboratory, were included. Among 458 patients (364 men, mean age 76 years), who had either EVAR (n = 177) or open repair (n = 281) started, there were 155 deaths and 88 re-interventions within 30 days of randomization analysed according to a pre-specified plan. The mean maximum aortic diameter was 8.6 cm. There were no substantial correlations between the six morphological variables. Aneurysm neck length was shorter in those undergoing open repair (vs. EVAR). Aneurysm neck length (mean 23.3, SD 16.1 mm) was inversely associated with mortality for open repair and overall: adjusted OR 0.72 (95% CI 0.57, 0.92) for each 16 mm (SD) increase in length. There were no convincing associations of morphological parameters with reinterventions. Short aneurysm necks adversely influence mortality after open repair of rAAA and preclude conventional EVAR. This may help explain why observational studies, but not randomized trials, have shown an early survival benefit for EVAR. ISRCTN 48334791. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Comparative analysis of the outcomes of elective abdominal aortic aneurysm repair in England and Sweden

PubMed Central

Karthikesalingam, A.; Holt, P. J.; Vidal‐Diez, A.; Thompson, M. M.; Wanhainen, A.; Bjorck, M.; Mani, K.

2018-01-01

Background There is substantial international variation in mortality after abdominal aortic aneurysm (AAA) repair; many non‐operative factors influence risk‐adjusted outcomes. This study compared 90‐day and 5‐year mortality for patients undergoing elective AAA repair in England and Sweden. Methods Patients were identified from English Hospital Episode Statistics and the Swedish Vascular Registry between 2003 and 2012. Ninety‐day mortality and 5‐year survival were compared after adjustment for age and sex. Separate within‐country analyses were performed to examine the impact of co‐morbidity, hospital teaching status and hospital annual caseload. Results The study included 36 249 patients who had AAA treatment in England, with a median age of 74 (i.q.r. 69–79) years, of whom 87·2 per cent were men. There were 7806 patients treated for AAA in Sweden, with a median of age 73 (68–78) years, of whom 82·9 per cent were men. Ninety‐day mortality rates were poorer in England than in Sweden (5·0 versus 3·9 per cent respectively; P < 0·001), but were not significantly different after 2007. Five‐year survival was poorer in England (70·5 versus 72·8 per cent; P < 0·001). Use of EVAR was initially lower in England, but surpassed that in Sweden after 2010. In both countries, poor outcome was associated with increased age. In England, institutions with higher operative annual volume had lower mortality rates. Conclusion Mortality for elective AAA repair was initially poorer in England than Sweden, but improved over time alongside greater uptake of EVAR, and now there is no difference. Centres performing a greater proportion of EVAR procedures achieved better results in England. PMID:29468657

The inflammatory response to ruptured abdominal aortic aneurysm is altered by endovascular repair.

PubMed

Makar, R R; Badger, S A; O'Donnell, M E; Soong, C V; Lau, L L; Young, I S; Hannon, R J; Lee, B

2013-01-01

Introduction. Ruptured abdominal aortic aneurysm (rAAA) causes a significant inflammatory response. The study aims to investigate this response following endovascular and open repair of ruptured AAA. Patients and Methods. Consecutive rAAA patients had either endovascular aneurysm repair (EVAR) or open repair (OR). Blood samples were taken for cytokines, lipid hydroperoxides (LOOH), antioxidants, and neutrophil elastase/ α 1-anti-trypsin complexes (NE/AAT) before surgery, 6 hours after clamp release and 1, 3, 5 days postoperatively. Results. 30 patients were included in the study, with 14 undergoing eEVAR and 16 eOR, with comparable baseline comorbidities, age, and parameters. IL-6 peaked higher in eOR patients (P = 0.04), while p75TNFr was similar between groups except at day 5 (P = 0.04). The NE/AAT concentrations were higher in eOR patients (P = 0.01), particularly in the first postoperative day, and correlated with blood (r = 0.398, P = 0.029) and platelet (r = 0.424, P = 0.020) volume transfused. C-reactive protein rose and lipid hydroperoxide fell in both groups without significant intergroup difference. Vitamins C and E, lycopene, and β -carotene levels were similar between groups. Conclusion. EVAR is associated with lower systemic inflammatory response compared to OR. Its increased future use may thereby improve outcomes for patients.

The Inflammatory Response to Ruptured Abdominal Aortic Aneurysm Is Altered by Endovascular Repair

PubMed Central

Makar, R. R.; Badger, S. A.; O'Donnell, M. E.; Soong, C. V.; Lau, L. L.; Young, I. S.; Hannon, R. J.; Lee, B.

2013-01-01

Introduction. Ruptured abdominal aortic aneurysm (rAAA) causes a significant inflammatory response. The study aims to investigate this response following endovascular and open repair of ruptured AAA. Patients and Methods. Consecutive rAAA patients had either endovascular aneurysm repair (EVAR) or open repair (OR). Blood samples were taken for cytokines, lipid hydroperoxides (LOOH), antioxidants, and neutrophil elastase/α1-anti-trypsin complexes (NE/AAT) before surgery, 6 hours after clamp release and 1, 3, 5 days postoperatively. Results. 30 patients were included in the study, with 14 undergoing eEVAR and 16 eOR, with comparable baseline comorbidities, age, and parameters. IL-6 peaked higher in eOR patients (P = 0.04), while p75TNFr was similar between groups except at day 5 (P = 0.04). The NE/AAT concentrations were higher in eOR patients (P = 0.01), particularly in the first postoperative day, and correlated with blood (r = 0.398, P = 0.029) and platelet (r = 0.424, P = 0.020) volume transfused. C-reactive protein rose and lipid hydroperoxide fell in both groups without significant intergroup difference. Vitamins C and E, lycopene, and β-carotene levels were similar between groups. Conclusion. EVAR is associated with lower systemic inflammatory response compared to OR. Its increased future use may thereby improve outcomes for patients. PMID:24363936

Experience with endovascular abdominal aortic aneurysm repair in nonagenarians.

PubMed

Baril, Donald T; Palchik, Eugene; Carroccio, Alfio; Olin, Jeffrey W; Ellozy, Sharif H; Jacobs, Tikva S; Ponzio, Marc M; Teodorescu, Victoria J; Marin, Michael L

2006-06-01

To report a single-institution experience with endovascular abdominal aortic aneurysm (AAA) repair (EVAR) in nonagenarians. A retrospective review was performed of all patients >90 years old undergoing EVAR over an 8-year period at a major academic medical center. The patient population was investigated for the presence of various comorbidities, initial aneurysm size, successful aneurysm exclusion, perioperative complications, disposition, endoleaks, secondary interventions, and overall survival. EVAR was performed in 18 male nonagenarians (mean age 92.4 years, range 90- 95). Mean aneurysm diameter was 7.3 cm (range 5.5-9.8). The cohort had an average of 3.2 comorbid conditions. Sixteen patients were treated electively, while 2 patients underwent emergent repair for contained rupture and bleeding aortoenteric fistula, respectively. Immediate technical success was 100%. Perioperative local/vascular complications occurred in 4 (22%) patients. Perioperative systemic complications occurred in 3 (17%) patients. There were 2 (11%) perioperative (<30 days) deaths. Three (17%) patients required secondary interventions. Mean survival in patients who expired during the follow-up period beyond the first 30 days was 34 months (range 8-78). Mean survival in 8 patients who are still alive is 17.4 months (range 9-39). Endovascular AAA repair in nonagenarians is associated with a high rate of technical success and relatively low morbidity rate. Survival times following successful hospital discharge are significant. Suitable patients over 90 years of age may benefit from an endovascular AAA repair.

Surgery insight: advances in endovascular repair of abdominal aortic aneurysms.

PubMed

Baril, Donald T; Jacobs, Tikva S; Marin, Michael L

2007-04-01

Despite improvements in diagnostic and therapeutic methods and an increased awareness of their clinical significance, abdominal aortic aneurysms (AAAs) continue to be a major source of morbidity and mortality. Endovascular repair of AAAs, initially described in 1990, offers a less-invasive alternative to conventional open repair. The technology and devices used for endovascular repair of AAAs have progressed rapidly and the approach has proven to be safe and effective in short to midterm investigations. Furthermore, several large trials have demonstrated that elective endovascular repair is associated with lower perioperative morbidity and mortality than open repair. The long-term benefits of endovascular repair relative to open repair, however, continue to be studied. In addition to elective repair, the use of endovascular repair for ruptured AAAs has been increasing, and has been shown to be associated with reduced perioperative morbidity and mortality. Advances in endovascular repair of AAAs, including the development of branched and fenestrated grafts and the use of implantable devices to measure aneurysm-sac pressures following stent-graft deployment, have further broadened the application of the technique and have enhanced postoperative monitoring. Despite these advances, endovascular repair of AAAs remains a relatively novel technique, and further long-term data need to be collected.

Follow-up after endovascular aortic aneurysm repair can be stratified based on first postoperative imaging.

PubMed

Baderkhan, H; Haller, O; Wanhainen, A; Björck, M; Mani, K

2018-05-01

Lifelong postoperative surveillance is recommended following endovascular aneurysm repair (EVAR). Although the purpose is to prevent and/or identify complications early, it also results in increased cost and workload. This study was designed to examine whether it may be possible to identify patients at low risk of complications based on their first postoperative CT angiogram (CTA). All patients undergoing EVAR in two Swedish centres between 2001 and 2012 were identified retrospectively and categorized based on the first postoperative CTA as at low risk (proximal and distal sealing zone at least 10 mm and no endoleak) or high risk (sealing zone less than 10 mm and/or presence of any endoleak) of complications. Some 326 patients (273 men) with a CTA performed less than 1 year after EVAR were included (low risk 212, 65·0 per cent; high risk 114, 35·0 per cent). There was no difference between the groups in terms of sex, age, co-morbidities, abdominal aortic aneurysm (AAA) diameter, preoperative AAA neck anatomy, stent-graft type or duration of follow-up (mean(s.d.) 4·8(3·2) years). Five-year freedom from AAA-related adverse events was 97·1 and 47·7 per cent in the low- and high-risk groups respectively (P < 0·001). The corresponding freedom from AAA-related reintervention was 96·2 and 54·1 per cent (P < 0·001). The method had a sensitivity of 88·3 per cent, specificity of 77·0 per cent and negative predictive value of 96·6 per cent to detect AAA-related adverse events. The number of surveillance imaging per AAA-related adverse event was 168 versus 11 for the low-risk versus high-risk group. Two-thirds of patients undergoing EVAR have an adequate seal and no endoleak on the first postoperative CTA, and a very low risk of AAA-related events up to 5 years. Less vigilant follow-up after EVAR may be considered for these patients. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Financial Impact of PEVAR Compared With Standard Endovascular Repair in Canadian Hospitals.

PubMed

Roche-Nagle, Graham; Hazel, Maureen; Rajan, Dheeraj K

2018-05-01

The percutaneous endovascular abdominal aortic repair (PEVAR) approach is a minimally invasive technique that has demonstrated clinical benefit over traditional surgical cut down associated with standard endovascular abdominal aortic aneurysm (AAA) repair (EVAR). The objective of our study was to evaluate the budget impact to a Canadian hospital of changing the technique for AAA repair from the EVAR approach to the PEVAR approach. We examined the budget impact of replacing the EVAR approach with the PEVAR approach in a Canadian hospital that performs 100 endovascular AAA repairs annually. The model incorporates the costs associated with surgery, length of stay, and postoperative complications occurring within 30 days. The use of PEVAR in AAA repair is associated with increased access device costs when compared with the EVAR approach (CAD$1000 vs CAD$400). However, AAA repair completed with the PEVAR approach demonstrates reduced operating time (101 minutes vs 133 minutes), length of stay (2.2 days vs 3.5 days), time in the recovery room (174 minutes vs 193 minutes), and postoperative complications (6% vs 30%), which offset the increased device costs. The model establishes that switching to the PEVAR approach in a Canadian hospital performing 100 AAA repairs annually would result in a potential cost avoidance of CAD$245,120. A change in AAA repair technique from EVAR to PEVAR can be a cost-effective solution for Canadian hospitals. Copyright © 2017 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

A pull-back algorithm to determine the unloaded vascular geometry in anisotropic hyperelastic AAA passive mechanics.

PubMed

Riveros, Fabián; Chandra, Santanu; Finol, Ender A; Gasser, T Christian; Rodriguez, Jose F

2013-04-01

Biomechanical studies on abdominal aortic aneurysms (AAA) seek to provide for better decision criteria to undergo surgical intervention for AAA repair. More accurate results can be obtained by using appropriate material models for the tissues along with accurate geometric models and more realistic boundary conditions for the lesion. However, patient-specific AAA models are generated from gated medical images in which the artery is under pressure. Therefore, identification of the AAA zero pressure geometry would allow for a more realistic estimate of the aneurysmal wall mechanics. This study proposes a novel iterative algorithm to find the zero pressure geometry of patient-specific AAA models. The methodology allows considering the anisotropic hyperelastic behavior of the aortic wall, its thickness and accounts for the presence of the intraluminal thrombus. Results on 12 patient-specific AAA geometric models indicate that the procedure is computational tractable and efficient, and preserves the global volume of the model. In addition, a comparison of the peak wall stress computed with the zero pressure and CT-based geometries during systole indicates that computations using CT-based geometric models underestimate the peak wall stress by 59 ± 64 and 47 ± 64 kPa for the isotropic and anisotropic material models of the arterial wall, respectively.

Colorectal cancer associated with abdominal aortic aneurysm: results of EVAR followed by colectomy.

PubMed

Illuminati, Giulio; Ceccanei, Gianluca; Pacilè, Maria A; Pizzardi, Giulia; Palumbo, Piergaspare; Vietri, Francesco

2013-01-01

The association of colorectal cancer and abdominal aortic aneurysm (AAA) is infrequent but poses special problems of priority of treatment under elective circumstances. The purpose of this study was to retrospectively evaluate the outcome of 16 consecutive patients undergoing endovascular aneurysm repair (EVAR) followed by colectomy. Operative mortality was nil. Operative morbidity included two transient rise of serum creatinine level and one extraperitoneal anastomotic leakage which evolved favourably with conservative treatment. EVAR allowed a very short delay of treatment of colorectal cancer after aneurysm repair, minimizing operative complications.

Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair.

PubMed

Bhat, Javaid Y; Thieulin-Pardo, Gabriel; Hartl, F Ulrich; Hayer-Hartl, Manajit

2017-01-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO 2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO 2 molecule and binding of a Mg 2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are "misfire" products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins.

One-year outcomes after ruptured abdominal aortic aneurysms repair: is evar the best choice? A single-center experience.

PubMed

Martinelli, O; Fenelli, C; Ben-Hamida, J; Fresilli, M; Irace, F G; Picone, V; Malaj, A; Gossetti, B; Irace, L

2018-06-06

Treatment of ruptured abdominal aortic aneurysms (rAAAs) is still burdened by high morbidity and mortality. Although endovascular aortic repair (EVAR) offers encouraging results in elective setting, its role as first line strategy to treat rAAA is still debated. Our aim was to compare early and late outcomes in patients undergoing open surgical repair (OSR) compared with those submitted to vs EVAR for rAAAs. A retrospective review of data extracted from medical records identified 105 consecutive patients with rAAA who were submitted to open or endovascular repairs from 2008 to 2016. Primary endpoint was to assess the rAAA-related mortality in the immediate postoperative, within 1 month and 1 year after ORS and EVAR Secondary endpoints included: length of stay, AAA-related postoperative complications such as acute limb ischemia, myocardial infarction, renal and respiratory failure and rAAA-related re-interventions. Statistical analysis was performed using the Fisher exact test,χ2 test and logistic regression calculations. Early and midterm survival rates were assessed with Cox model. Of the 105 patients with rAAA 70.48% underwent OSR including 41.89% which was hemodynamically (Hd) unstable and the remaining 29.52% was submitted to rEVAR. (all Hd stable). Compared EVAR group, the OSR group had a higher RAAA-related mortality rate for both Hd stable and Hd unstable patients: 18.92% vs 6.45% at 24 hours; (P = .185) 39.19% vs 19.35% at 30 days (P = .082); 44.59% vs 38.71% at 1 year (P = .734) If only Hd stable patients were considered, mortality following OSR and EVAR was: 6.98% vs 6.45% at 24 hours (P = .703); 27.91% vs 19.35% at 30 days (P = .567); 32.56% vs 38.71% at 1 year (P = .764). Mean length of stay for patients was 15 days after OSR and 10 days after rEVAR (P = .002). At 1-year follow-up, the overall rAAA-related complications incidence was higher in the rEVAR group than in the OSR group (47.85% vs 18.33%; P = .008); re-interventions were 18.33% in OSR group vs 21.82% in EVAR group (P = .917). Cox model showed that instability and coronary artery disease were predictors of overall mortality of rAAAs. EVAR does not independently reduce 1-year mortality in comparison with OSR in Hd-stable patients. Urgent EVAR for rAAAs in unstable patients can be limited by logistical problems. It follows that patients selected for OSR have a more complex aortic anatomy and worse Hd status than those sumitted to rEVAR. rEVAR burdened by a higher incidence of procedure-related complications than OSR. Reconfiguration of acute aortic services and establishment of standardized institutional protocols might be advisable for improvements in the management of ruptured AAA. A carefully evaluation of whether the benefits of an endovascular strategy translate into longer term benefit is needed before definitive conclusions can be drawn about the advantages of EVAR as first-line strategy for ruptured aneurysms. Copyright © 2018 Elsevier Inc. All rights reserved.

Abdominal aortic aneurysm repair - open

MedlinePlus

AAA - open; Repair - aortic aneurysm - open ... Open surgery to repair an AAA is sometimes done as an emergency procedure when there is bleeding inside your body from the aneurysm. You may have an ...

Ruptured abdominal aortic aneurysm: Is endovascular aneurysm repair the answer for everybody?

PubMed

Aziz, Faisal

2016-03-01

Treatment paradigms for elective repair of asymptomatic abdominal aortic aneurysms (AAA) have evolved during the past 2 decades, with endovascular aneurysm repair as the preferred treatment modality. The patient care strategy for emergent treatment for ruptured AAA is not as straightforward, due in part to surgeon expertise and stent-graft availability at the institution. Although most reports have extrapolated elective endovascular aneurysm repair feasibility data to the ruptured AAA patient and the aneurysm anatomy, these expectations should be interpreted with caution. In the absence of level I evidence, and lack of adequate local hospital resources, endovascular aneurysm repair-first policy might not be feasible for all the patients who present with ruptured AAA. Copyright © 2016 Elsevier Inc. All rights reserved.

Epidemiology of abdominal aortic aneurysms in a Chinese population during introduction of endovascular repair, 1994 to 2013: A retrospective observational study.

PubMed

Tam, Greta; Chan, Yiu Che; Chong, Ka Chun; Lee, Kam Pui; Cheung, Grace Chung-Yan; Cheng, Stephen Wing-Keung

2018-03-01

The aim of this study was to examine changes in abdominal aortic aneurysm repair and mortality during a period when endovascular aneurysm repair (EVAR) was introduced.Open repair surgery was the mainstay of treatment for abdominal aortic aneurysm (AAA), but EVAR is increasingly utilized. Studies in the Western population have reported improved short-term or postoperative mortality and shorter length of hospital stay with EVAR. However, scant data are available in the Chinese population.We conducted a retrospective observational study using the database of the Hospital Authority, which provides public health care to most of the Hong Kong population. AAA patients admitted to public hospitals for intact repair or rupture from 1994 to 2013 were included in this study. We calculated the incidence of ruptured AAA, annual repair rates according to type of AAA and surgery, as well as death rates (operative and overall short-term). We calculated whether there were significant changes over time and compared short-term mortality between open surgery and EVAR.One thousand eight hundred eighty-five patients were admitted for intact repair and 1306 patients were admitted for AAA rupture, of whom 795 underwent rupture repair. Intact repair rates significantly increased in all age groups (7.3-37.8%, P < .001) over the study period.The incidence of ruptured AAA increased, in all age groups, except in < 64 years old. By 2013, 85% of intact repairs and 55.4% of rupture repair were done by EVAR. Over time, there was a significant decrease in operative mortality for intact repair (16.5 in 1994 to 7.1 in 2013, P = .01) and rupture repair (59.7 in 1994 to 30.8 in 2013, P = .003). Over the same time period, short-term AAA-related deaths decreased by more than half (73% in 1994 to 24% in 2013, P < .001), with a significant decline in all age groups, except < 64 years old. Short-term mortality was significantly lower for EVAR than for open repair (17.2% vs 40.3%, P < .01).Short-term AAA-related deaths have declined likely due to decreased operative mortality and rupture deaths during the period of EVAR introduction and expansion.

Impact of graft composition on the systemic inflammatory response after an elective repair of an abdominal aortic aneurysm

PubMed Central

Baek, Jong Kwan; Kwon, Hyunwook; Ko, Gi-Young; Kim, Min Joo; Han, Youngjin; Chung, Young Soo; Park, Hojong; Kwon, Tae-Won

2015-01-01

Purpose The present study aimed to evaluate the risk factors and the role of graft material in the development of an acute phase systemic inflammatory response, and the clinical outcome in patients who undergo endovascular aneurysm repair (EVAR) or open surgical repair (OSR) of an abdominal aortic aneurysm (AAA). Methods We retrospectively evaluated the risk factors and the role of graft material in an increased risk of developing systemic inflammatory response syndrome (SIRS), and the clinical outcome in patients who underwent EVAR or OSR of an AAA. Results A total of 308 consecutive patients who underwent AAA repair were included; 178 received EVAR and 130 received OSR. There was no significant difference in the incidence of SIRS between EVAR patients and OSR patients. Regardless of treatment modality, SIRS was observed more frequently in patients treated with woven polyester grafts. Postoperative hospitalization was significantly prolonged in patients that experienced SIRS. In multivariate analyses, the initial white blood cell count (P = 0.001) and the use of woven polyester grafts (P = 0.005) were significantly associated with an increased risk of developing SIRS in patients who underwent EVAR. By contrast, the use of woven polyester grafts was the only factor associated with an increased risk of developing SIRS in patients who underwent OSR, although this was not statistically significant (P = 0.052). Conclusion The current study shows that the graft composition plays a primordial role in the development of SIRS, and it leads to prolonged hospitalization in both EVAR and OSR patients. PMID:25553321

Notch γ-Secretase Inhibitor Dibenzazepine Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm in ApoE Knockout Mice by Multiple Mechanisms

PubMed Central

Zheng, Yue-Hong; Li, Fang-Da; Tian, Cui; Ren, Hua-Liang; Du, Jie; Li, Hui-Hua

2013-01-01

Abdominal aortic aneurysm (AAA) is a life-threatening aortic disease in the elderly. Activation of Notch1 pathway plays a critical role in the development of AAA, but the underlying mechanisms remain poorly understood. In the present study, we explored the mechanisms by which Notch1 activation regulates angiotensin II (Ang II)-induced AAA formation and evaluated the therapeutic potential of a new Notch γ-secretase inhibitor, dibenzazepine (DBZ), for the treatment of AAA. Apolipoprotein E knockout (Apo E−/−) mice infused for 4 weeks with Ang II (1000 ng/kg/min, IP) using osmotic mini-pumps were received an intraperitoneal injection of either vehicle or 1 mg/kg/d DBZ. Notch1 signaling was activated in AAA tissue from both Ang II-infused Apo E−/− mice and human undergoing AAA repair in vivo, with increased expression of Notch intracellular domain (NICD) and its target gene Hes1, and this effect was effectively blocked by DBZ. Moreover, infusion of Ang II markedly increased the incidence and severity of AAA in Apo E−/− mice. In contrast, inhibition of Notch activation by DBZ prevented AAA formation in vivo. Furthermore, DBZ markedly prevented Ang II-stimulated accumulation of macrophages and CD4+ T cells, and ERK-mediated angiogenesis, simultaneously reversed Th2 response, in vivo. In conclusion, these findings provide new insight into the multiple mechanisms of Notch signaling involved in AAA formation and suggest that γ-secretase inhibitor DBZ might be a novel therapeutic drug for treating AAAS. PMID:24358274

National trends in open surgical, endovascular, and branched-fenestrated endovascular aortic aneurysm repair in Medicare patients.

PubMed

Suckow, Bjoern D; Goodney, Philip P; Columbo, Jesse A; Kang, Ravinder; Stone, David H; Sedrakyan, Art; Cronenwett, Jack L; Fillinger, Mark F

2018-06-01

Open repair effectively prevents rupture for patients with abdominal aortic aneurysm (AAA) and is commonly studied as a metric reflecting hospital and surgeon expertise in cardiovascular care. However, given recent advances in endovascular aneurysm repair (EVAR), such as branched-fenestrated EVAR, it is unknown how commonly open surgical repair is still used in everyday practice. We analyzed trends in open AAA repair, EVAR, and branched-fenestrated EVAR for AAA in Medicare beneficiaries from 2003 to 2013. We used Medicare Part B claims to ascertain counts of these repair types annually during the study period. We assessed regional and national trends in characteristics of the patients and procedure volume. Between 2003 and 2013, the total number of AAA repairs performed in fee-for-service Medicare patients declined by 26% from 31,582 to 23,421 (P < .001), after a peak number of 32,540 was performed in 2005 (28% decline since 2005). The number of open AAA repairs steadily declined by a total of 76%, from 20,533 in 2003 to 4916 in 2013 (P < .001). Whereas the number of EVARs increased from 11,049 in 2003 to 19,247 in 2011 (P < .001), it has since declined a total of 15% to only 16,362 repairs in 2013 (P < .001). After its introduction in 2011, the number of branched-fenestrated EVAR cases continuously rose from 335 procedures in 2011 to 2143 procedures in 2013 (P < .001). By 2013, virtually all hospital referral regions in the United States had rates of open AAA repair that would have been in the lowest quintile of volume in 2003. The number of open AAA repairs fell by nearly 80% during the last decade, whereas traditional EVAR declined slightly and branched-fenestrated EVAR rapidly disseminated into national practice. These results suggest that open AAA repair is now performed too infrequently to be used as a metric in the assessment of hospital and surgeon quality in cardiovascular care. Furthermore, surgical training paradigms will need to reflect the changing dynamics necessary to ensure that surgeons and interventionists can safely perform these high-risk surgical procedures. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Postoperative Development of Abdominal Compartment Syndrome among Patients Undergoing Endovascular Aortic Repair for Ruptured Abdominal Aortic Aneurysms.

PubMed

Miranda, Elizabeth; Manzur, Miguel; Han, Sukgu; Ham, Sung Wan; Weaver, Fred A; Rowe, Vincent L

2018-05-01

Abdominal compartment syndrome (ACS) has a reported incidence of 9%-14% among trauma patients. However, in patients with similar hemodynamic changes, the incidence of ACS remains unclear. Our aim was to determine the incidence of ACS among patients undergoing endovascular aortic repair (EVAR) for ruptured abdominal aortic aneurysms (rAAAs) and to identify associated risk factors. A retrospective review was performed for consecutive patients who underwent EVAR for rAAA from March 2010 to November 2016 at our institution. The development of ACS was diagnosed based on a variety of factors, including bladder pressure, laboratory abnormalities, hemodynamic monitoring, and clinical evaluation. Previously validated risk factors for ACS development in trauma and EVAR patients (preoperative hypotension, aggressive fluid resuscitation, postoperative anemia, use of an aorto-uniiliac graft, and placement of an aortic occlusive balloon) were analyzed. Association between patient characteristics and ACS development was analyzed using the Fisher's exact test. During the study period, 25 patients had image-confirmed rAAA and underwent emergent EVAR. Mortality rate was 28% (n = 7), and ACS incidence was 12% (n = 3). Of the analyzed risk factors, hypotension on arrival (P = 0.037), transfusion of 3 or more units of packed red blood cells (P = 0.037), and postoperative anemia (P = 0.02) were all significantly associated with postoperative ACS development. In addition, having greater than 3 of the studied risk factors was associated with increased odds of developing ACS (P = 0.015), and having greater than 4 of the studied risk factors showed the strongest association with ACS development (P = 0.0017). Overresuscitation should be avoided in patients with rAAA. In addition, patients who present with multiple risk factors for ACS should be monitored very closely with serial bladder pressures and may require decompression laparotomy immediately after EVAR. Copyright © 2018 Elsevier Inc. All rights reserved.

External validation of Vascular Study Group of New England risk predictive model of mortality after elective abdominal aorta aneurysm repair in the Vascular Quality Initiative and comparison against established models.

PubMed

Eslami, Mohammad H; Rybin, Denis V; Doros, Gheorghe; Siracuse, Jeffrey J; Farber, Alik

2018-01-01

The purpose of this study is to externally validate a recently reported Vascular Study Group of New England (VSGNE) risk predictive model of postoperative mortality after elective abdominal aortic aneurysm (AAA) repair and to compare its predictive ability across different patients' risk categories and against the established risk predictive models using the Vascular Quality Initiative (VQI) AAA sample. The VQI AAA database (2010-2015) was queried for patients who underwent elective AAA repair. The VSGNE cases were excluded from the VQI sample. The external validation of a recently published VSGNE AAA risk predictive model, which includes only preoperative variables (age, gender, history of coronary artery disease, chronic obstructive pulmonary disease, cerebrovascular disease, creatinine levels, and aneurysm size) and planned type of repair, was performed using the VQI elective AAA repair sample. The predictive value of the model was assessed via the C-statistic. Hosmer-Lemeshow method was used to assess calibration and goodness of fit. This model was then compared with the Medicare, Vascular Governance Northwest model, and Glasgow Aneurysm Score for predicting mortality in VQI sample. The Vuong test was performed to compare the model fit between the models. Model discrimination was assessed in different risk group VQI quintiles. Data from 4431 cases from the VSGNE sample with the overall mortality rate of 1.4% was used to develop the model. The internally validated VSGNE model showed a very high discriminating ability in predicting mortality (C = 0.822) and good model fit (Hosmer-Lemeshow P = .309) among the VSGNE elective AAA repair sample. External validation on 16,989 VQI cases with an overall 0.9% mortality rate showed very robust predictive ability of mortality (C = 0.802). Vuong tests yielded a significant fit difference favoring the VSGNE over then Medicare model (C = 0.780), Vascular Governance Northwest (0.774), and Glasgow Aneurysm Score (0.639). Across the 5 risk quintiles, the VSGNE model predicted observed mortality significantly with great accuracy. This simple VSGNE AAA risk predictive model showed very high discriminative ability in predicting mortality after elective AAA repair among a large external independent sample of AAA cases performed by a diverse array of physicians nationwide. The risk score based on this simple VSGNE model can reliably stratify patients according to their risk of mortality after elective AAA repair better than other established models. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Abdominal Aortic Aneurysm: Evolving Controversies and Uncertainties.

PubMed

Carino, Davide; Sarac, Timur P; Ziganshin, Bulat A; Elefteriades, John A

2018-06-01

Abdominal aortic aneurysm (AAA) is defined as a permanent dilatation of the abdominal aorta that exceeds 3 cm. Most AAAs arise in the portion of abdominal aorta distal to the renal arteries and are defined as infrarenal. Most AAAs are totally asymptomatic until catastrophic rupture. The strongest predictor of AAA rupture is the diameter. Surgery is indicated to prevent rupture when the risk of rupture exceeds the risk of surgery. In this review, we aim to analyze this disease comprehensively, starting from an epidemiological perspective, exploring etiology and pathophysiology, and concluding with surgical controversies. We will pursue these goals by addressing eight specific questions regarding AAA: (1) Is the incidence of AAA increasing? (2) Are ultrasound screening programs for AAA effective? (3) What causes AAA: Genes versus environment? (4) Animal models: Are they really relevant? (5) What pathophysiology leads to AAA? (6) Indications for AAA surgery: Are surgeons over-eager to operate? (7) Elective AAA repair: Open or endovascular? (8) Emergency AAA repair: Open or endovascular?

Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair

PubMed Central

Bhat, Javaid Y.; Thieulin-Pardo, Gabriel; Hartl, F. Ulrich; Hayer-Hartl, Manajit

2017-01-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO2 molecule and binding of a Mg2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are “misfire” products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins. PMID:28443288

Fenestrated endovascular aortic repair and clinical trial devices for complex abdominal aortic aneurysms.

PubMed

Brinster, Clayton J; Milner, Ross

2018-06-01

Endovascular aortic repair (EVAR) has revolutionized the treatment of infrarenal abdominal aortic aneurysm (AAA), with consistently low reported perioperative morbidity and mortality. Universal applicability of EVAR to treat AAA is hindered by several specific anatomic constraints, however, and many patients cannot be treated with commercially available stent-grafts within the device specific instructions for use. Treatment of these complex pararenal aneurysms is increasingly accomplished by extension of EVAR into the visceral segment of the abdominal aorta with branches or fenestrations that allow perfusion of the visceral and renal arteries. Fenestrated endovascular aneurysm repair (FEVAR) was initially developed to treat high-risk patients unfit for open surgery and anatomically ineligible for standard infrarenal EVAR, but this technique has evolved over the past decade into a mature treatment option for complex AAA. High-volume, single-center reports, multicenter series and clinical reviews have demonstrated that FEVAR is a safe and effective technique with favorable results at proficient centers. Generalizability of these outcomes to less advanced centers remains unproven, and reintervention rates following FEVAR in the mid- and long-term, even among the most experienced centers, remain a concern. Several off-the-shelf devices that are undergoing clinical trial seek to broaden the anatomic applicability and overall availability of FEVAR. A significant number of patients are not candidates for off-the-shelf or customized stent-grafts, however, stressing the need for continued refinement of existing devices, development of novel devices with broader indications for use, and maintenance of open surgical skills.

Endovascular strategy for the elective treatment of concomitant aortoiliac aneurysm and symptomatic large bowel diverticular disease.

PubMed

Illuminati, Giulio; Ricco, Jean-Baptiste; Schneider, Fabrice; Caliò, Francesco G; Ceccanei, Gianluca; Pacilè, Maria A; Pizzardi, Giulia; Palumbo, Piergaspare; Vietri, Francesco

2014-07-01

The purpose of this study was to evaluate the strategy for treatment of patients presenting with asymptomatic diverticular disease of the large bowel associated with an asymptomatic aortoiliac aneurysmal (AAA) disease. Sixty-nine patients were included in this retrospective study. The patients were divided into 5 groups according to the type and sequence of the surgical treatment: 32 patients (47%) underwent colectomy followed by a staged open AAA repair (group A); 10 patients (14%) were treated with open AAA repair followed by a staged colectomy (group B); 13 patients (18%) received endovascular aneurysm repair (EVAR) followed by a staged bowel resection (group C); 8 patients (12%) had a bowel resection followed by staged EVAR (group D); and 6 patients (9%) underwent simultaneous open AAA repair and bowel resection (group E). Primary end points were mortality and complications after any of the procedures. Secondary end point was the time interval between the staged procedures. The cumulative death rate for delayed treatment of AAA was 6.5% and 0% for delayed treatment of diverticular disease [P=0.22]. The mean time interval between the staged procedures was 11 days for EVAR/colon resection (group C and group D) and 73 days for open AAA repair/colon resection (group A and group B; P<0.01). EVAR allows a significant reduction in the time required between AAA repair and colon resection, but no definite rule can be established regarding the sequence of staged procedures. Combined procedures should be reserved for selected cases. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of Three Contemporary Risk Scores for Mortality Following Elective Abdominal Aortic Aneurysm Repair

PubMed Central

Grant, S.W.; Hickey, G.L.; Carlson, E.D.; McCollum, C.N.

2014-01-01

Objective/background A number of contemporary risk prediction models for mortality following elective abdominal aortic aneurysm (AAA) repair have been developed. Before a model is used either in clinical practice or to risk-adjust surgical outcome data it is important that its performance is assessed in external validation studies. Methods The British Aneurysm Repair (BAR) score, Medicare, and Vascular Governance North West (VGNW) models were validated using an independent prospectively collected sample of multicentre clinical audit data. Consecutive, data on 1,124 patients undergoing elective AAA repair at 17 hospitals in the north-west of England and Wales between April 2011 and March 2013 were analysed. The outcome measure was in-hospital mortality. Model calibration (observed to expected ratio with chi-square test, calibration plots, calibration intercept and slope) and discrimination (area under receiver operating characteristic curve [AUC]) were assessed in the overall cohort and procedural subgroups. Results The mean age of the population was 74.4 years (SD 7.7); 193 (17.2%) patients were women and the majority of patients (759, 67.5%) underwent endovascular aneurysm repair. All three models demonstrated good calibration in the overall cohort and procedural subgroups. Overall discrimination was excellent for the BAR score (AUC 0.83, 95% confidence interval [CI] 0.76–0.89), and acceptable for the Medicare and VGNW models, with AUCs of 0.78 (95% CI 0.70–0.86) and 0.75 (95% CI 0.65–0.84) respectively. Only the BAR score demonstrated good discrimination in procedural subgroups. Conclusion All three models demonstrated good calibration and discrimination for the prediction of in-hospital mortality following elective AAA repair and are potentially useful. The BAR score has a number of advantages, which include being developed on the most contemporaneous data, excellent overall discrimination, and good performance in procedural subgroups. Regular model validations and recalibration will be essential. PMID:24837173

Comparison of three contemporary risk scores for mortality following elective abdominal aortic aneurysm repair.

PubMed

Grant, S W; Hickey, G L; Carlson, E D; McCollum, C N

2014-07-01

A number of contemporary risk prediction models for mortality following elective abdominal aortic aneurysm (AAA) repair have been developed. Before a model is used either in clinical practice or to risk-adjust surgical outcome data it is important that its performance is assessed in external validation studies. The British Aneurysm Repair (BAR) score, Medicare, and Vascular Governance North West (VGNW) models were validated using an independent prospectively collected sample of multicentre clinical audit data. Consecutive, data on 1,124 patients undergoing elective AAA repair at 17 hospitals in the north-west of England and Wales between April 2011 and March 2013 were analysed. The outcome measure was in-hospital mortality. Model calibration (observed to expected ratio with chi-square test, calibration plots, calibration intercept and slope) and discrimination (area under receiver operating characteristic curve [AUC]) were assessed in the overall cohort and procedural subgroups. The mean age of the population was 74.4 years (SD 7.7); 193 (17.2%) patients were women and the majority of patients (759, 67.5%) underwent endovascular aneurysm repair. All three models demonstrated good calibration in the overall cohort and procedural subgroups. Overall discrimination was excellent for the BAR score (AUC 0.83, 95% confidence interval [CI] 0.76-0.89), and acceptable for the Medicare and VGNW models, with AUCs of 0.78 (95% CI 0.70-0.86) and 0.75 (95% CI 0.65-0.84) respectively. Only the BAR score demonstrated good discrimination in procedural subgroups. All three models demonstrated good calibration and discrimination for the prediction of in-hospital mortality following elective AAA repair and are potentially useful. The BAR score has a number of advantages, which include being developed on the most contemporaneous data, excellent overall discrimination, and good performance in procedural subgroups. Regular model validations and recalibration will be essential. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Rupture of abdominal aortic aneurysm: concurrent comparison of outcome of those occurring after endovascular repair versus those occurring without previous treatment in an 11-year single-center experience.

PubMed

May, James; White, Geoffrey H; Stephen, Michael S; Harris, John P

2004-11-01

The purpose of this single-center study was to compare findings at presentation and surgical outcome in patients in whom abdominal aortic aneurysms (AAAs) ruptured after endovascular repair and patients in whom AAAs ruptured before any treatment, over a defined period. From May 1992 to September 2003, 1043 patients underwent elective repair of intact infrarenal AAAs. Endovascular repair was performed in 609 patients, and open repair in 434 patients. Eighteen of 609 patients (3%) who underwent endovascular AAA repair required treatment because of rupture of the aneurysm after a mean of 29 months (group 1). During the same 11-year period, another 91 patients without previous treatment required urgent repair of a ruptured AAA (group 2). Rupture was diagnosed at contrast material-enhanced computed tomography or by presence of extramural extravasation of blood at open repair. Except for a higher incidence of women in group 2, patients in both groups were similar with regard to demographics and clinical characteristics but differed in findings at presentation. Eight patients in group 1 had a known endoleak before AAA rupture, whereas contrast-enhanced computed tomography, performed in 15 patients at presentation, demonstrated an endoleak in all. Hypotension (systolic blood pressure <100 mm Hg) was noted at presentation in 4 of 18 patients (22%) in group 1 and 76 of 91 patients (84%) in group 2. All patients underwent open repair via a transperitoneal approach, except for 4 patients in group 1 and 3 patients in group 2 who underwent endovascular repair of ruptured AAAs. The proportion of patients with hypotension at presentation in group 1 (4 of 18) was significantly less than in group 2 (76 of 91; P < .01). The difference in perioperative (30 day) mortality rate in group 1 (3 of 18; 16.6%) compared with group 2 (49 of 91; 53.8%) was also significant (P < .01). The outcome in group 1 was therefore superior to that in group 2. This study confirms that endovascular AAA repair complicated by endoleak does not prevent rupture. The data suggest, however, that rupture, when it occurs in these circumstances, may not be accompanied by such major hemodynamic changes and high mortality as rupture of an untreated AAA. Further long-term follow-up and analysis in a larger group of patients are required to confirm the apparent intermediate level of protection afforded by failed endovascular repair, which does not prevent rupture but enhances survival after operation to treat rupture, possibly by ameliorating the hemodynamic changes associated with the rupture process.

Epidemiology and outcome of aortic aneurysms in Hong Kong.

PubMed

Cheng, Stephen W K; Ting, Albert C W; Tsang, Simon H Y

2003-02-01

The objective of this study was to determine epidemiology and mortality statistics for abdominal aortic aneurysms (AAAs) in Hong Kong. Data from three sources were obtained and analyzed: (1) Hong Kong Hospital Authority discharge statistics for 1999 and 2000; (2) a survey on aortic aneurysms in public hospitals conducted by the Working Group of Vascular Surgery; and (3) the Department of Surgery, University of Hong Kong Medical Center aortic aneurysm database. The disease pattern, distribution, and operative mortality were determined. The annual incidence of AAA in Hong Kong is 13.7 per 100,000 population and 105 per 100,000 for those aged 65 and above. About 10% of the AAAs that presented were ruptured. The mean age of the AAA patients was 74 years, with 84% of them over age 65. The operative repair rate for AAAs was low, being only 8% for intact aneurysms and 54% for ruptured ones. Overall, 45% of all aneurysm repairs were performed for a ruptured AAA. There is diverse practice between major vascular centers and smaller regional hospitals. The territory-wide operative mortality rates for intact and ruptured aneurysms were 10% (range 4-24%) and 70% (range 38--100%), respectively. There was no gender bias in the rupture and operative rates. The overall mortality was 17% for intact AAAs and 78% for ruptured AAAs. The average length of hospital stay was 19 days for elective AAA surgery and 13 days for ruptured AAAs. The number of operations in high-volume centers is increasing with a concomitant decrease in operative mortality. There are no definitive data to indicate that the incidence of AAAs is rising, but a trend toward an increasing number of operations in referral centers is noted. The low repair rates for intact AAAs and the high proportion of repairs for ruptured aneurysms suggest that AAAs are undertreated in Hong Kong.

Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue.

PubMed

O'Leary, Siobhan A; Mulvihill, John J; Barrett, Hilary E; Kavanagh, Eamon G; Walsh, Michael T; McGloughlin, Tim M; Doyle, Barry J

2015-02-01

Varying degrees of calcification are present in most abdominal aortic aneurysms (AAAs). However, their impact on AAA failure properties and AAA rupture risk is unclear. The aim of this work is evaluate and compare the failure properties of partially calcified and predominantly fibrous AAA tissue and investigate the potential reasons for failure. Uniaxial mechanical testing was performed on AAA samples harvested from 31 patients undergoing open surgical repair. Individual tensile samples were divided into two groups: fibrous (n=31) and partially calcified (n=38). The presence of calcification was confirmed by fourier transform infrared spectroscopy (FTIR). A total of 69 mechanical tests were performed and the failure stretch (λf), failure stress (σf) and failure tension (Tf) were recorded for each test. Following mechanical testing, the failure sites of a subset of both tissue types were examined using scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) to investigate the potential reasons for failure. It has been shown that the failure properties of partially calcified tissue are significantly reduced compared to fibrous tissue and SEM and EDS results suggest that the junction between a calcification deposit and the fibrous matrix is highly susceptible to failure. This study implicates the presence of calcification as a key player in AAA rupture risk and provides further motivation for the development of non-invasive methods of measuring calcification. Copyright © 2014 Elsevier Ltd. All rights reserved.

External validation of a 5-year survival prediction model after elective abdominal aortic aneurysm repair.

PubMed

DeMartino, Randall R; Huang, Ying; Mandrekar, Jay; Goodney, Philip P; Oderich, Gustavo S; Kalra, Manju; Bower, Thomas C; Cronenwett, Jack L; Gloviczki, Peter

2018-01-01

The benefit of prophylactic repair of abdominal aortic aneurysms (AAAs) is based on the risk of rupture exceeding the risk of death from other comorbidities. The purpose of this study was to validate a 5-year survival prediction model for patients undergoing elective repair of asymptomatic AAA <6.5 cm to assist in optimal selection of patients. All patients undergoing elective repair for asymptomatic AAA <6.5 cm (open or endovascular) from 2002 to 2011 were identified from a single institutional database (validation group). We assessed the ability of a prior published Vascular Study Group of New England (VSGNE) model (derivation group) to predict survival in our cohort. The model was assessed for discrimination (concordance index), calibration (calibration slope and calibration in the large), and goodness of fit (score test). The VSGNE derivation group consisted of 2367 patients (70% endovascular). Major factors associated with survival in the derivation group were age, coronary disease, chronic obstructive pulmonary disease, renal function, and antiplatelet and statin medication use. Our validation group consisted of 1038 patients (59% endovascular). The validation group was slightly older (74 vs 72 years; P < .01) and had a higher proportion of men (76% vs 68%; P < .01). In addition, the derivation group had higher rates of advanced cardiac disease, chronic obstructive pulmonary disease, and baseline creatinine concentration (1.2 vs 1.1 mg/dL; P < .01). Despite slight differences in preoperative patient factors, 5-year survival was similar between validation and derivation groups (75% vs 77%; P = .33). The concordance index of the validation group was identical between derivation and validation groups at 0.659 (95% confidence interval, 0.63-0.69). Our validation calibration in the large value was 1.02 (P = .62, closer to 1 indicating better calibration), calibration slope of 0.84 (95% confidence interval, 0.71-0.97), and score test of P = .57 (>.05 indicating goodness of fit). Across different populations of patients, assessment of age and level of cardiac, pulmonary, and renal disease can accurately predict 5-year survival in patients with AAA <6.5 cm undergoing repair. This risk prediction model is a valid method to assess mortality risk in determining potential overall survival benefit from elective AAA repair. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Reconsidering gender relative to risk of rupture in the contemporary management of abdominal aortic aneurysms.

PubMed

Skibba, Afshin A; Evans, James R; Hopkins, Steven P; Yoon, H Richard; Katras, Tony; Kalbfleisch, John H; Rush, Daniel S

2015-12-01

Abdominal aortic aneurysms (AAAs) may rupture at smaller diameters in women than in men, and women may be at higher risk and have poorer outcomes in elective and emergent interventions because of age and comorbidities. Practice guidelines recommending elective AAA repair at >5.5 cm are gender neutral and may not adequately reflect increased risks in women or the potential advantages of elective lower risk endovascular procedures. Patients with a diagnosis of AAA discharged from a single referral hospital during a 14-year period were identified for retrospective analysis. A total of 2121 patients with AAAs were studied, 499 women (23.5%) and 1622 men (76.5%). Women were older and had a greater incidence of hypertension, smoking, chronic obstructive pulmonary disease, dyslipidemia, and renal insufficiency. Intact AAAs in 467 women had a mean diameter of 4.4 ± 1.3 cm compared with 1538 men at 5.0 ± 1.4 cm (P < .01). The ruptured AAAs in 32 women (6.4%) had a mean diameter of 6.1 ± 1.5 cm compared with 84 men (5.2%) at 7.7 ± 1.9 cm (P < .01). Women had a twofold increased frequency of AAA rupture than men at all size intervals (P < .01). The frequency of ruptured AAAs <5.5 cm among 10 of 32 women with ruptured AAAs was 31.3%; among 7 of 84 men with ruptured AAAs, it was 8.3% (P < .01). The frequency of ruptured AAAs <5.5 cm in all 383 women with AAAs <5.5 cm was 2.6%; in 1042 men, it was 0.6% (P < .01). Of the 1211 AAA repairs, 574 (47.4%) were open aneurysm repair (OAR) and 637 (52.6%) were endovascular aneurysm repair (EVAR). Mortality after elective OAR in 475 patients of both sexes was 5.1%; for EVAR in 676 patients, mortality was 1.6% (P < .01). No differences in mortality with respect to OAR or EVAR were found between the female and male cohorts in either intact or ruptured AAAs. Women with AAAs are older and have a higher frequency of cardiovascular risk factors than men. Women rupture AAAs with a greater frequency than men at all size intervals and have a fourfold increased frequency of rupture at <5.5 cm. No differences in surgical mortality between women and men were found. Current practice guidelines for elective AAA operative intervention should be reconsidered and stratified by gender. Published by Elsevier Inc.

Endo-exuberance and abdominal aortic aneurysm management: have we gone too far?

PubMed

Sternbergh, W Charles

2003-11-01

new technology, such as endovascular abdominal aortic aneurysm repair (EVAR) may promote an 'irrational exuberance' for its application. nonsuprarenal AAA repairs performed at a single institution over a 7 year period were retrospectively studied. Method of repair, 30-day mortality and EVAR aortic neck anatomy were assessed. 431 AAA repairs were performed between January 1996 and June 2002, 238 (55%) open and 193 (45%) EVAR. The percentage of EVAR increased steadily from approximately 20% in 1996 and 1997 to a peak of 69.5% in 2000. However, in 2001-2002 the percentage of EVAR fell to approximately 40% of total repairs. In this time period our selection criteria for EVAR became more conservative, with treatment of fewer patients with short aortic necks (12.8 vs. 28.9% with neck length < or = 20 mm, p = 0.05; 3.8 vs. 10.8% with neck length < or = 15 mm, p = 0.1) or highly angulated necks (3.8 vs. 28.9% with neck angulation > or = 40 degrees, p = 0.04) in 2001-2002 versus 1999-2000, respectively. Institutional volume of AAA repairs doubled over the study period (p = 0.001). 30-day mortality over the study period for nonruptured EVAR and open AAA repair was 2.6 and 3.3%, respectively (p = NS). The complexity of open repairs increased significantly during the final 3 years of the review. the application of EVAR has fallen from a high of 69.5% of our AAA repairs in 2000 to approximately 40% in 2001-2002. More prudent patient selection in recent years regarding unfavorable aortic neck anatomy was felt to be a primary etiology of changes in overall EVAR utilization. The anticipated improvement in long-term results from EVAR await multi-year follow-up.

Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery

PubMed Central

Stone, David H.; Goodney, Philip P.; Schanzer, Andres; Nolan, Brian W.; Adams, Julie E.; Powell, Richard J.; Walsh, Daniel B.; Cronenwett, Jack L.

2017-01-01

Objectives Persistent variation in practice surrounds preoperative clopidogrel management at the time of vascular surgery. While some surgeons preferentially discontinue clopidogrel citing a perceived risk of perioperative bleeding, others will proceed with surgery in patients taking clopidogrel for an appropriate indication. The purpose of this study was to determine whether preoperative clopidogrel use was associated with significant bleeding complications during peripheral arterial surgery. Methods We reviewed a prospective regional vascular surgery registry recorded by 66 surgeons from 15 centers in New England from 2003 to 2009. Preoperative clopidogrel use within 48 hours of surgery was analyzed among patients undergoing carotid endarterectomy (CEA), lower extremity bypass (LEB), endovascular abdominal aortic aneurysm repair (EVAR), and open abdominal aortic aneurysm repair (oAAA). Ruptured AAAs were excluded. Endpoints included postoperative bleeding requiring reoperation, as well as the incidence and volume of blood transfusion. Statistical analysis was performed using analysis of variance, Fisher exact, χ2, and Wilcoxon rank-sum tests. Results Over the study interval, a total of 10,406 patients underwent surgery, including 5264 CEA, 2883 LEB, 1125 EVAR, and 1134 oAAA repair. Antiplatelet use among all patients varied, with 19% (n = 2010) taking no antiplatelet agents, 69% (n = 7132) taking aspirin (ASA) alone, 2.2% (n = 229) taking clopidogrel alone, and 9.7% (n = 1017) taking both ASA and clopidogrel. Clopidogrel alone or as dual antiplatelet therapy was most frequently used prior to CEA and least frequently prior to oAAA group (CEA 16.1%, LEB 9.0%, EVAR 6.5%, oAAA 5%). Reoperation for bleeding was not significantly different among patients based on antiplatelet regimen (none 1.5%, ASA 1.3%, clopidogrel 0.9%, ASA/clopidogrel 1.5%, P = .74). When analyzed by operation type, no difference in reoperation for bleeding was seen across antiplatelet regimens. There was also no difference in the incidence of transfusion among antiplatelet treatment groups (none 18%, ASA 17%, clopidogrel 0%, ASA/clopidogrel 24%, P = .1) and none when analyzed by individual operation type. Among patients who did require transfusion, there was no significant difference in the mean number of units of packed red blood cells required (none 0.7 units, ASA 0.5 units, clopidogrel 0 units, ASA/clopidogrel 0.6 units, P = .1) or when stratified by operation type. Conclusions Patients undergoing peripheral arterial surgery in whom clopidogrel was continued either alone or as part of dual antiplatelet therapy did not have significant bleeding complications compared with patients taking no antiplatelet therapy or ASA alone at the time of surgery. These data suggest that clopidogrel can safely be continued preoperatively in patients with appropriate indications for its use, such as symptomatic carotid disease or recent drug-eluting coronary stents. PMID:21571492

Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery.

PubMed

Stone, David H; Goodney, Philip P; Schanzer, Andres; Nolan, Brian W; Adams, Julie E; Powell, Richard J; Walsh, Daniel B; Cronenwett, Jack L

2011-09-01

Persistent variation in practice surrounds preoperative clopidogrel management at the time of vascular surgery. While some surgeons preferentially discontinue clopidogrel citing a perceived risk of perioperative bleeding, others will proceed with surgery in patients taking clopidogrel for an appropriate indication. The purpose of this study was to determine whether preoperative clopidogrel use was associated with significant bleeding complications during peripheral arterial surgery. We reviewed a prospective regional vascular surgery registry recorded by 66 surgeons from 15 centers in New England from 2003 to 2009. Preoperative clopidogrel use within 48 hours of surgery was analyzed among patients undergoing carotid endarterectomy (CEA), lower extremity bypass (LEB), endovascular abdominal aortic aneurysm repair (EVAR), and open abdominal aortic aneurysm repair (oAAA). Ruptured AAAs were excluded. Endpoints included postoperative bleeding requiring reoperation, as well as the incidence and volume of blood transfusion. Statistical analysis was performed using analysis of variance, Fisher exact, χ(2), and Wilcoxon rank-sum tests. Over the study interval, a total of 10,406 patients underwent surgery, including 5264 CEA, 2883 LEB, 1125 EVAR, and 1134 oAAA repair. Antiplatelet use among all patients varied, with 19% (n = 2010) taking no antiplatelet agents, 69% (n = 7132) taking aspirin (ASA) alone, 2.2% (n = 229) taking clopidogrel alone, and 9.7% (n = 1017) taking both ASA and clopidogrel. Clopidogrel alone or as dual antiplatelet therapy was most frequently used prior to CEA and least frequently prior to oAAA group (CEA 16.1%, LEB 9.0%, EVAR 6.5%, oAAA 5%). Reoperation for bleeding was not significantly different among patients based on antiplatelet regimen (none 1.5%, ASA 1.3%, clopidogrel 0.9%, ASA/clopidogrel 1.5%, P = .74). When analyzed by operation type, no difference in reoperation for bleeding was seen across antiplatelet regimens. There was also no difference in the incidence of transfusion among antiplatelet treatment groups (none 18%, ASA 17%, clopidogrel 0%, ASA/clopidogrel 24%, P = .1) and none when analyzed by individual operation type. Among patients who did require transfusion, there was no significant difference in the mean number of units of packed red blood cells required (none 0.7 units, ASA 0.5 units, clopidogrel 0 units, ASA/clopidogrel 0.6 units, P = .1) or when stratified by operation type. Patients undergoing peripheral arterial surgery in whom clopidogrel was continued either alone or as part of dual antiplatelet therapy did not have significant bleeding complications compared with patients taking no antiplatelet therapy or ASA alone at the time of surgery. These data suggest that clopidogrel can safely be continued preoperatively in patients with appropriate indications for its use, such as symptomatic carotid disease or recent drug-eluting coronary stents. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Editor's Choice - Prolonged ICU Length of Stay after AAA Repair: Analysis of Time Trends and Long-term Outcome.

PubMed

Gavali, H; Mani, K; Tegler, G; Kawati, R; Covaciu, L; Wanhainen, A

2017-08-01

The aim of the study was to investigate the frequency and outcome of prolonged intensive care unit (ICU) length of stay (LOS) after abdominal aortic aneurysm (AAA) repair in the endovascular era. All patients operated on for AAA between 1999 and 2013 at Uppsala University hospital were identified. Data were retrieved from the Swedish Vascular registry, the Swedish Intensive Care registry, the National Population registry, and case records. Prolonged ICU LOS was defined as ≥ 48 h during the primary hospital stay. Patients surviving ≥ 48 h after AAA surgery were included in the analysis. A total of 725 patients were identified, of whom 707 (97.5%) survived ≥ 48 h; 563 (79.6%) underwent intact AAA repair and 144 (20.4%) ruptured AAA repair. A total of 548 patients (77.5%) required < 48 h of intensive care, 115 (16.3%) 2-6 days and 44 (6.2%) ≥ 7 days. The rate of prolonged ICU LOS declined considerably over time, from 41.4% of all AAA repairs in 1999 to 7.3% in 2013 (p < .001) whereas the use of endovascular aortic repair (EVAR) increased from 6.9% in 1999 to 78.0% in 2013 (p < .001). The 30 day survival rate was 98.2% for those with < 48 h ICU stay versus 93.0% for 2-6 days versus 81.8% for ≥ 7 days (p < .001); the corresponding 90 day survival was 97.1% versus 86.1% versus 63.6% (p < .001) respectively. For patients surviving 90 days after repair, there was no difference in long-term survival between the groups. During the period of progressively increasing use of EVAR, a simultaneous significant reduction in frequency of prolonged ICU LOS occurred. Although prolonged ICU LOS was associated with a high short-term mortality, long-term outcome among those surviving the initial 90 days was less affected. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Jaundice as a Rare Indication for Aortic Aneurysm Repair.

PubMed

Rieß, Henrik C; Tsilimparis, Nikolaos; Behrendt, Christian A; Wipper, Sabine; Debus, Eike S; Larena-Avellaneda, Axel

2015-10-01

Compression of adjacent anatomic structures by an abdominal aortic aneurysm (AAA) can result in a variety of symptoms. We describe the case of an 88-year-old Caucasian woman with jaundice, elevated laboratory parameters for extrahepatic and intrahepatic cholestasis, and concomitant juxtarenal AAA compressing the liver hilum. Following exclusion of other common causes for cholestasis, the patient was considered to have a symptomatic AAA. Open abdominal aortic surgery revealed a contained rupture and was repaired. Obstructive jaundice secondary to a compromising AAA is a rare condition and to the best of our knowledge has not been reported to date. Copyright © 2015 Elsevier Inc. All rights reserved.

Endovascular abdominal aortic aneurysm repair (EVAR) procedures: counterbalancing the benefits with the costs.

PubMed

Paraskevas, Kosmas I; Bessias, Nikolaos; Giannoukas, Athanasios D; Mikhailidis, Dimitri P

2010-05-01

Endovascular abdominal aortic aneurysm (AAA) repair (EVAR) is associated with lower 30-day mortality rates compared with open repair. Despite that, there are no significant differences in mortality rates between the two procedures at 2 years. On the other hand, EVAR is associated with considerably higher costs compared with open repair. The lack of significant long-term differences between the two procedures together with the substantially higher cost of EVAR may question the appropriateness of EVAR as an alternative to open surgical repair in patients fit for surgery. With several thousands of AAA procedures performed worldwide, the employment of EVAR for the management of all AAAs irrespective of the patient's surgical risk may hold implications for several national health economies. The lower perioperative mortality and morbidity rates associated with EVAR should thus be counterbalanced against the considerable costs of these procedures.

Abdominal aortic aneurysm: An update

PubMed

Chuen, Jason; Theivendran, Mayo

2018-05-01

Abdominal aortic aneurysm (AAA) remains one of the hallmark pathologies in vascular surgery and an area of intense research interest. Treatment options have expanded in recent years to increase the range of morphology suitable for endovascular aneurysm repair (EVAR), and with potential implications on treatment thresholds. This article is the first of two that will outline current treatment options for AAA, including areas of controversy and research in AAA disease, to inform the development of Australasian clinical guidelines and health policy. Medical therapy options remain limited and no aneurysm-specific pharmacotherapy is currently available. Recent years have witnessed a significant shift in AAA surgery from open repair to EVAR and expansion of EVAR techniques. General management of cardiovascular risk factors remains key to reducing all-cause mortality for patients with AAA.

The INNOVATION Trial: four-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System for endovascular repair.

PubMed

Pratesi, Giovanni; Pratesi, Carlo; Chiesa, Roberto; Coppi, Gioacchino; Scheinert, Dierk; Brunkwall, Jan S; van der Meulen, Stefaan; Torsello, Giovanni

2017-10-01

This paper reports the 4-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System (Cordis Corp., Milpitas, CA, USA), an ultra-low-profile device for the treatment of abdominal aortic aneurysms. The INNOVATION Trial is the prospective, first-in-human, multicenter trial to evaluate the safety and effectiveness of the INCRAFT® System. Patients underwent annual clinical and computed tomography angiography examination as part of the study protocol. The INCRAFT® AAA Stent-Graft System is a customizable tri-modular design, with an ultra-low profile (14-Fr) delivery system. Patient were treated under approved protocol, the prescribed clinical and imaging follow-up at annually through 5 years. Results analyzed and adjudicated by a clinical events committee, independent core laboratory, and a data safety and monitoring board. This manuscript reports results through 4 years of follow-up. A total of 60 patients were enrolled in the trial, all of whom were successfully treated. Follow-up rates at 1 and 4 years were 93% (56/60) and 85% (51/60), respectively. All-cause mortality at 4 years was 17.6% and no death was AAA-, device-, or procedure-related. The secondary reintervention rate at 1 year was 4.6%, primarily the result of stent thrombosis. In total, 10 patients required 13 post-procedure interventions within 4-years of follow-up (2 to repair a type I endoleak, 4 to repair a type II endoleak, 1 for stent thrombosis, 1 for renal stenosis, 1 for aneurysm enlargement, 2 for limb migration and 2 for prosthesis stenosis or occlusion). There were 4 cases (10%) of aneurysm enlargement reported at the 4 year follow-up. At 4 years, 38 out of 39 patients were free from type I and III endoleaks. There were no proximal type I or type III endoleaks at 4-year follow-up. Core laboratory evaluation of the postoperative imaging studies indicated absence of endograft migration while a single fracture was demonstrated without any clinical sequelae. The INCRAFT® AAA Stent-Graft System provides a minimally invasive and durable solution for patients undergoing EVAR that has been associated with a low frequency of device-related events through 4 years of follow-up.

Mortality from ruptured abdominal aortic aneurysms: clinical lessons from a comparison of outcomes in England and the USA.

PubMed

Karthikesalingam, Alan; Holt, Peter J; Vidal-Diez, Alberto; Ozdemir, Baris A; Poloniecki, Jan D; Hinchliffe, Robert J; Thompson, Matthew M

2014-03-15

The outcome of patients with ruptured abdominal aortic aneurysm (rAAA) varies by country. Study of practice differences might allow the formulation of pathways to improve care. We compared data from the Hospital Episode Statistics for England and the Nationwide Inpatient Sample for the USA for patients admitted to hospital with rAAA from 2005 to 2010. Primary outcomes were in-hospital mortality, mortality after intervention, and decision to follow non-corrective treatment. In-hospital mortality and the rate of non-corrective treatment were analysed by binary logistic regression for each health-care system, after adjustment for age, sex, year, and Charlson comorbidity index. The study included 11,799 patients with rAAA in England and 23,838 patients with rAAA in the USA. In-hospital mortality was lower in the USA than in England (53·05% [95% CI 51·26-54·85] vs 65·90%; p<0·0001). Intervention (open or endovascular repair) was offered to a greater proportion of cases in the USA than in England (19,174 [80·43%] vs 6897 [58·45%]; p<0·0001) and endovascular repair was more common in the USA than in England (4003 [20·88%] vs 589 [8·54%]; p<0·0001). Postintervention mortality was similar in both countries (41·77% for England and 41·65% for USA). These observations persisted in age-matched and sex-matched comparisons. In both countries, reduced mortality was associated with increased use of endovascular repair, increased hospital caseload (volume) for rAAA, high hospital bed capacity, hospitals with teaching status, and admission on a weekday. In-hospital survival from rAAA, intervention rates, and uptake of endovascular repair are lower in England than in the USA. In England and the USA, the lowest mortality for rAAA was seen in teaching hospitals with larger bed capacities and doing a greater proportion of cases with endovascular repair. These common factors suggest strategies for improving outcomes for patients with rAAA. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-term survival following open repair of ruptured abdominal aortic aneurysm.

PubMed

Englund, Raymond; Katib, Nedal

2017-05-01

Long-term results for patients being managed for ruptured compared to elective abdominal aortic aneurysms (AAA) are unclear. We hypothesize that patients who survive 30 days or more following repair of ruptured AAA (RAAA) performed by open technique have a life expectancy no different to those patients surviving 30 days or more following elective AAA repair, or compared to a general age-matched population. Between 1987 and December 2014, 620 consecutive patients were treated by the principal author for aortic aneurysmal disease. Two subgroups were selected from this population, elective open abdominal repair (215) and RAAA open repair (105). Comparable age-matched life curves with the general population were used from the Australian Bureau of Statistics for each patient according to gender, age and date of presentation. Statistical comparison was by Kaplan-Meier survival analysis. Both the open and RAAA groups were well matched for age and sex. There was no statistical difference between RAAA survival and an age-matched population P = 0.23, or was there any difference between open repair and an age-matched population, P = 0.1. Survival curves for RAAA and open repair were similar, P = 0.98. For elective open repair 1-, 5-, 10-, 15- and 20-year survival was 93.6, 71.2, 40, 17 and 2% respectively. Corresponding results for RAAA were 92.5, 74, 36.7, 13.5 and 5% respectively. Open AAA repair for RAAA or elective aneurysm treatment restores predicted life expectancy for those patients surviving 30 days or more and is therefore a durable method of treatment for this condition. © 2016 Royal Australasian College of Surgeons.

Aortic aneurysm repair - endovascular

MedlinePlus

EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... to guide the stent graft up into your aorta, to where the aneurysm is located. Next open ...

On the effect of computed tomography resolution to distinguish between abdominal aortic aneurysm wall tissue and calcification: A proof of concept.

PubMed

Barrett, H E; Cunnane, E M; O Brien, J M; Moloney, M A; Kavanagh, E G; Walsh, M T

2017-10-01

The purpose of this study is to determine the optimal target CT spatial resolution for accurately imaging abdominal aortic aneurysm (AAA) wall characteristics, distinguishing between tissue and calcification components, for an accurate assessment of rupture risk. Ruptured and non-ruptured AAA-wall samples were acquired from eight patients undergoing open surgical aneurysm repair upon institutional review board approval and informed consent was obtained from all patients. Physical measurements of AAA-wall cross-section were made using scanning electron microscopy. Samples were scanned using high resolution micro-CT scanning. A resolution range of 15.5-155μm was used to quantify the influence of decreasing resolution on wall area measurements, in terms of tissue and calcification. A statistical comparison between the reference resolution (15.5μm) and multi-detector CT resolution (744μm) was also made. Electron microscopy examination of ruptured AAAs revealed extremely thin outer tissue structure <200μm in radial distribution which is supporting the aneurysm wall along with large areas of adjacent medial calcifications far greater in area than the tissue layer. The spatial resolution of 155μm is a significant predictor of the reference AAA-wall tissue and calcification area measurements (r=0.850; p<0.001; r=0.999; p<0.001 respectively). The tissue and calcification area at 155μm is correct within 8.8%±1.86 and 26.13%±9.40 respectively with sensitivity of 87.17% when compared to the reference. The inclusion of AAA-wall measurements, through the use of high resolution-CT will elucidate the variations in AAA-wall tissue and calcification distributions across the wall which may help to leverage an improved assessment of AAA rupture risk. Copyright © 2017 Elsevier B.V. All rights reserved.

Aortic stent grafting: a new approach to a deadly diagnosis: one hospital's findings in defining new care processes.

PubMed

Kalinowski, H

2001-01-01

Ruptured abdominal aortic aneurysm (AAA) is the 13th leading cause of death in the United States. Diagnosis is the key to prevention of death from AAA. Millions of Americans harbor this silent, potentially lethal aneurysm. For over 50 years, conventional open surgical repair has been performed for ruptured aortic abdominal aneurysm. It is a major operation with an extended hospital stay and recovery period. An alternative approach to AAA repair has evolved over the past 10 years that combines advances in catheter and stent technologies. With the AAA aortic stent graft, patients usually do not require intensive care and are discharged home within 48 hours of the procedure. This article describes the AAA aortic stent graft procedure, in the formation of a case management team to develop a clinical pathway and standing orders for these patients and defines the outcomes of care.

Renal Fenestration Closure Technique in Fenestrated Endovascular Repair for Pararenal Aortic Aneurysm.

PubMed

Gallitto, Enrico; Gargiulo, Mauro; Faggioli, Gianluca; Sonetto, Alessia; Mascoli, Chiara; Pini, Rodolfo; Abualhin, Mohamhed; Stella, Andrea

2018-05-01

To describe an endovascular technique to close a renal artery fenestration during fenestrated endograft implant for a pararenal abdominal aortic aneurysm (p-AAA) without interfering with other visceral vessels. A 76-year-old man with p-AAA underwent repair by a 4 fenestrations custom-made endograft. At the intraprocedural angiography, the right renal artery was occluded. To avoid a high-flow endoleak from fenestration, we performed the following technique: a 9F-steerable sheath was used to advance a 7F sheath through the fenestration into aneurism. A balloon-expandable covered stent was deployed across the fenestration and then occluded by 2 vascular plugs. At the completion angiography, there was no endoleak from the right renal fenestration, and at 6-month period, p-AAA remained completely excluded. The present technique can be a safe and effective therapeutic option to propose in cases of impossible target visceral vessels cannulation during p-AAA repair using a custom-made device to avoid the aneurysmal sac perfusion. Copyright © 2018 Elsevier Inc. All rights reserved.

Cost-effectiveness of intensive smoking cessation therapy among patients with small abdominal aortic aneurysms.

PubMed

Mani, Kevin; Wanhainen, Anders; Lundkvist, Jonas; Lindström, David

2011-09-01

Smoking cessation is one of the few available strategies to decrease the risk for expansion and rupture of small abdominal aortic aneurysms (AAAs). The cost-effectiveness of an intensive smoking cessation therapy in patients with small AAAs identified at screening was evaluated. A Markov cohort simulation model was used to compare an 8-week smoking cessation intervention with adjuvant pharmacotherapy and annual revisits vs nonintervention among 65-year-old male smokers with a small AAA identified at screening. The smoking cessation rate was tested in one-way sensitivity analyses in the intervention group (range, 22%-57%) and in the nonintervention group (range, 3%-30%). Literature data on the effect of smoking on AAA expansion and rupture was factored into the model. The intervention was cost-effective in all tested scenarios and sensitivity analyses. The smoking cessation intervention was cost-effective due to a decreased need for AAA repair and decreased rupture rate even when disregarding the positive effects of smoking cessation on long-term survival. The incremental cost/effectiveness ratio reached the willingness-to-pay threshold value of €25,000 per life-year gained when assuming an intervention cost of > €3250 or an effect of ≤ 1% difference in long-term smoking cessation between the intervention and nonintervention groups. Smoking cessation resulted in a relative risk reduction for elective AAA repair by 9% and for rupture by 38% over 10 years of follow-up. An adequate smoking cessation intervention in patients with small AAAs identified at screening can cost-effectively increase long-term survival and decrease the need for AAA repair. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Comparison of Conscious Sedation and Asleep-Awake-Asleep Techniques for Awake Craniotomy.

PubMed

Dilmen, Ozlem Korkmaz; Akcil, Eren Fatma; Oguz, Abdulvahap; Vehid, Hayriye; Tunali, Yusuf

2017-01-01

Since awake craniotomy (AC) has become a standard of care for supratentorial tumour resection, especially in the motor and language cortex, determining the most appropriate anaesthetic protocol is very important. The aim of this retrospective study is to compare the effectiveness of conscious sedation (CS) to "awake-asleep-awake" (AAA) techniques for supratentorial tumour resection. Forty-two patients undergoing CS and 22 patients undergoing AAA were included in the study. The primary endpoint was to compare the CS and AAA techniques with respect to intraoperative pain and agitation in patients undergoing supratentorial tumour resection. The secondary endpoint was comparison of the other intraoperative complications. This study results show that the incidence of intraoperative agitation and seizure were lower in the AAA group than in the CS group. Intraoperative blood pressures were significantly higher in the CS group than in the AAA group during the pinning and incision, but the level of blood pressures did not need antihypertensive treatment. Otherwise, blood pressures were significantly higher in the AAA group than in the CS group during the neurological examination and the severity of hypertension needed statistically significant more antihypertensive treatment in the AAA group. As a result of hypertension, the amount of intraoperative bleeding was higher in the AAA group than in the CS group. In conclusion, the AAA technique may provide better results with respect to agitation and seizure, but intraoperative hypertension needed a vigilant follow-up especially in the wake-up period. Copyright © 2016 Elsevier Ltd. All rights reserved.

Patients with end-stage renal disease have poor outcomes after endovascular abdominal aortic aneurysm repair.

PubMed

Komshian, Sevan; Farber, Alik; Patel, Virendra I; Goodney, Philip P; Schermerhorn, Marc L; Blazick, Elizabeth A; Jones, Douglas W; Rybin, Denis; Doros, Gheorghe; Siracuse, Jeffrey J

2018-06-23

Although endovascular repair of abdominal aortic aneurysms (AAAs) has been demonstrated to have favorable outcomes, not all cohorts of patients with AAA fare equally well. Our goal was to investigate perioperative and 1-year outcomes in patients with end-stage renal disease (ESRD) on dialysis, who have traditionally fared worse after vascular interventions, to assess how ESRD affects outcomes in a large modern cohort of endovascular aneurysm repair (EVAR) patients. The Vascular Quality Initiative database was queried for all patients undergoing EVAR from 2010 to 2017. ESRD patients were compared with patients not on dialysis. Propensity-matched scoring and multivariable analysis were used to isolate the effects of ESRD. Of 28,683 EVARs identified, there were 321 (1.12%) patients with ESRD on dialysis. Patients with ESRD had no difference in presenting AAA size (57.5 ± 12.7 mm vs 56.7 ± 17.2 mm; P = .44); however, they had more urgent/emergent repairs (20.6% vs 13.6%; P = .002) than those without ESRD. ESRD patients were more often younger, nonwhite, and nonobese and less likely to have commercial insurance (P < .05). ESRD patients more often had hypertension, coronary artery disease, congestive heart failure, previous lower extremity bypass, aneurysm repair, and carotid interventions (P < .05). There was no difference in the rate of concomitant procedures. Matching based on demographics, comorbidities, and operative details showed that ESRD patients had longer hospital length of stay (4.8 ± 9.4 days vs 4.1 ± 12.6 days; P = .026) and higher 30-day mortality (7% vs 2.4%; P < .001). There was no difference in cardiac, pulmonary, lower extremity, bowel, and stroke complications or return to the operating room. On multivariable analysis, ESRD was associated with 30-day mortality (odds ratio, 4.1; 95% confidence interval, 2.6-6.7; P < .001). Of the 24,750 elective EVARs, 1.04% had ESRD on dialysis. Matched data for elective EVAR show increased postoperative length of stay, hospital mortality, and 30-day mortality for ESRD patients on dialysis compared with those who are not. There was no association with postoperative myocardial infarction or pulmonary complications. At 1 year, patients with ESRD on dialysis had worse survival (78% vs 94%; P < .001), and ESRD was associated with higher mortality (hazard ratio, 3.3; 95% confidence interval, 2.5-4.2; P < .001). Among patients undergoing EVAR, ESRD is independently associated with higher perioperative and 1-year mortality despite not being associated with higher postoperative complications. This should be taken into account during informed consent for EVAR and risk-benefit considerations in this high-risk population, particularly for elective repair. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Calculating when elective abdominal aortic aneurysm repair improves survival for individual patients: development of the Aneurysm Repair Decision Aid and economic evaluation.

PubMed

Grant, Stuart W; Sperrin, Matthew; Carlson, Eric; Chinai, Natasha; Ntais, Dionysios; Hamilton, Matthew; Dunn, Graham; Buchan, Iain; Davies, Linda; McCollum, Charles N

2015-04-01

Abdominal aortic aneurysm (AAA) repair aims to prevent premature death from AAA rupture. Elective repair is currently recommended when AAA diameter reaches 5.5 cm (men) and 5.0 cm (women). Applying population-based indications may not be appropriate for individual patient decisions, as the optimal indication is likely to differ between patients based on age and comorbidities. To develop an Aneurysm Repair Decision Aid (ARDA) to indicate when elective AAA repair optimises survival for individual patients and to assess the cost-effectiveness and associated uncertainty of elective repair at the aneurysm diameter recommended by the ARDA compared with current practice. The UK Vascular Governance North West and National Vascular Database provided individual patient data to develop predictive models for perioperative mortality and survival. Data from published literature were used to model AAA growth and risk of rupture. The cost-effectiveness analysis used data from published literature and from local and national databases. A combination of systematic review methods and clinical registries were used to provide data to populate models and inform the structure of the ARDA. Discrete event simulation (DES) was used to model the patient journey from diagnosis to death and synthesised data were used to estimate patient outcomes and costs for elective repair at alternative aneurysm diameters. Eight patient clinical scenarios (vignettes) were used as exemplars. The DES structure was validated by clinical and statistical experts. The economic evaluation estimated costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) from the NHS, social care provider and patient perspective over a lifetime horizon. Cost-effectiveness acceptability analyses and probabilistic sensitivity analyses explored uncertainty in the data and the value for money of ARDA-based decisions. The ARDA outcome measures include perioperative mortality risk, annual risk of rupture, 1-, 5- and 10-year survival, postoperative long-term survival, median life expectancy and predicted time to current threshold for aneurysm repair. The primary economic measure was the ICER using the QALY as the measure of health benefit. The analysis demonstrated it is feasible to build and run a complex clinical decision aid using DES. The model results support current guidelines for most vignettes but suggest that earlier repair may be effective in younger, fitter patients and ongoing surveillance may be effective in elderly patients with comorbidities. The model adds information to support decisions for patients with aneurysms outside current indications. The economic evaluation suggests that using the ARDA compared with current guidelines could be cost-effective but there is a high level of uncertainty. Lack of high-quality long-term data to populate all sections of the model meant that there is high uncertainty about the long-term clinical and economic consequences of repair. Modelling assumptions were necessary and the developed survival models require external validation. The ARDA provides detailed information on the potential consequences of AAA repair or a decision not to repair that may be helpful to vascular surgeons and their patients in reaching informed decisions. Further research is required to reduce uncertainty about key data, including reintervention following AAA repair, and assess the acceptability and feasibility of the ARDA for use in routine clinical practice. The National Institute for Health Research Health Technology Assessment programme.

The Abdominal Aortic Aneurysm Statistically Corrected Operative Risk Evaluation (AAA SCORE) for predicting mortality after open and endovascular interventions.

PubMed

Ambler, Graeme K; Gohel, Manjit S; Mitchell, David C; Loftus, Ian M; Boyle, Jonathan R

2015-01-01

Accurate adjustment of surgical outcome data for risk is vital in an era of surgeon-level reporting. Current risk prediction models for abdominal aortic aneurysm (AAA) repair are suboptimal. We aimed to develop a reliable risk model for in-hospital mortality after intervention for AAA, using rigorous contemporary statistical techniques to handle missing data. Using data collected during a 15-month period in the United Kingdom National Vascular Database, we applied multiple imputation methodology together with stepwise model selection to generate preoperative and perioperative models of in-hospital mortality after AAA repair, using two thirds of the available data. Model performance was then assessed on the remaining third of the data by receiver operating characteristic curve analysis and compared with existing risk prediction models. Model calibration was assessed by Hosmer-Lemeshow analysis. A total of 8088 AAA repair operations were recorded in the National Vascular Database during the study period, of which 5870 (72.6%) were elective procedures. Both preoperative and perioperative models showed excellent discrimination, with areas under the receiver operating characteristic curve of .89 and .92, respectively. This was significantly better than any of the existing models (area under the receiver operating characteristic curve for best comparator model, .84 and .88; P < .001 and P = .001, respectively). Discrimination remained excellent when only elective procedures were considered. There was no evidence of miscalibration by Hosmer-Lemeshow analysis. We have developed accurate models to assess risk of in-hospital mortality after AAA repair. These models were carefully developed with rigorous statistical methodology and significantly outperform existing methods for both elective cases and overall AAA mortality. These models will be invaluable for both preoperative patient counseling and accurate risk adjustment of published outcome data. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Higher surgeon annual volume, but not years of experience, is associated with reduced rates of postoperative complications and reoperations after open abdominal aortic aneurysm repair.

PubMed

Dubois, Luc; Allen, Britney; Bray-Jenkyn, Krista; Power, Adam H; DeRose, Guy; Forbes, Thomas L; Duncan, Audra; Shariff, Salimah Z

2018-06-01

Volume-outcome relationships for open abdominal aortic aneurysm (AAA) repair have received less attention in publicly funded health systems. Furthermore, the roles of surgeon seniority (years of experience) and composite volume (encompassing all major arterial cases) on outcomes after open AAA repair are less well known. We sought to determine the effects of surgeon volume, surgeon years of experience, and composite volume on outcomes after elective open AAA repairs performed in Ontario, Canada. Using a population-based, prospectively collected health administrative database, all elective open AAA repairs occurring in the province of Ontario from 2005 to 2014 were identified. Surgeon annual volume was classified by quintiles, with the highest volume quintile acting as the reference category. Multivariable logistic regression modeling was used, adjusting for patient factors (age, sex, comorbidities, year of procedure, income) to investigate the relationship between surgeon annual volume and 30-day mortality, 30-day major complications, 30-day reoperations, 1-year mortality, and 1-year reoperations (related to index procedure). The potential effects of annual surgeon composite volume and surgeon years of experience on postoperative outcomes were also explored. A total of 7211 elective open AAA repairs performed by 101 surgeons were identified between 2005 and 2014. Most of the operations were performed by vascular surgeons (81.5%), followed by cardiac (12.1%) and general surgeons (6.1%). Median number of procedures in the lowest quintile group was 3 repairs/y, whereas the highest quintile group performed 54 repairs/y. Overall 30-day mortality was 3%. No difference in mortality was detected in comparing the lowest with the highest volume groups (1.89% vs 3.01%; adjusted odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27-1.33). The lowest volume group exhibited a higher 30-day complication rate (28.0% vs 20.4%; OR, 1.54; 95% CI, 1.15-2.06) and 30-day reoperation rate (10.53% vs 6.73%; OR, 1.64; 95% CI, 1.13-2.38) compared with the highest volume group. No effect of surgeon volume on 1-year mortality or 1-year reoperation was observed. Similarly, composite volume and surgeon years of experience were not associated with postoperative outcomes. In a single-payer system with a relatively high number of open AAA repairs/surgeon per year, surgeon annual volume had no effect on postoperative mortality but was associated with lower postoperative complication and reoperation rates. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Mortality rates and risk factors for emergent open repair of abdominal aortic aneurysms in the endovascular era.

PubMed

Pecoraro, Felice; Gloekler, Steffen; Mader, Caecilia E; Roos, Malgorzata; Chaykovska, Lyubov; Veith, Frank J; Cayne, Neal S; Mangialardi, Nicola; Neff, Thomas; Lachat, Mario

2018-03-01

The background of this paper is to report the mortality at 30 and 90 days and at mean follow-up after open abdominal aortic aneurysms (AAA) emergent repair and to identify predictive risk factors for 30- and 90-day mortality. Between 1997 and 2002, 104 patients underwent emergent AAA open surgery. Symptomatic and ruptured AAAs were observed, respectively, in 21 and 79% of cases. Mean patient age was 70 (SD 9.2) years. Mean aneurysm maximal diameter was 7.4 (SD 1.6) cm. Primary endpoints were 30- and 90-day mortality. Significant mortality-related risk factor identification was the secondary endpoint. Open repair trend and its related perioperative mortality with a per-year analysis and a correlation subanalysis to identify predictive mortality factor were performed. Mean follow-up time was 23 (SD 23) months. Overall, 30-day mortality was 30%. Significant mortality-related risk factors were the use of computed tomography (CT) as a preoperative diagnostic tool, AAA rupture, preoperative shock, intraoperative cardiopulmonary resuscitation (CPR), use of aortic balloon occlusion, intraoperative massive blood transfusion (MBT), and development of abdominal compartment syndrome (ACS). Previous abdominal surgery was identified as a protective risk factor. The mortality rate at 90 days was 44%. Significant mortality-related risk factors were AAA rupture, aortocaval fistula, peripheral artery disease (PAD), preoperative shock, CPR, MBT, and ACS. The mortality rate at follow-up was 45%. Correlation analysis showed that MBT, shock, and ACS are the most relevant predictive mortality factor at 30 and 90 days. During the transition period from open to endovascular repair, open repair mortality outcomes remained comparable with other contemporary data despite a selection bias for higher risk patients. MBT, shock, and ACS are the most pronounced predictive mortality risk factors.

Aortic outflow occlusion predicts rupture of abdominal aortic aneurysm.

PubMed

Crawford, Jeffrey D; Chivukula, Venkat Keshav; Haller, Stephen; Vatankhah, Nasibeh; Bohannan, Colin J; Moneta, Gregory L; Rugonyi, Sandra; Azarbal, Amir F

2016-12-01

Current threshold recommendations for elective abdominal aortic aneurysm (AAA) repair are based solely on maximal AAA diameter. Peak wall stress (PWS) has been demonstrated to be a better predictor than AAA diameter of AAA rupture risk. However, PWS calculations are time-intensive, not widely available, and therefore not yet clinically practical. In addition, PWS analysis does not account for variations in wall strength between patients. We therefore sought to identify surrogate clinical markers of increased PWS and decreased aortic wall strength to better predict AAA rupture risk. Patients treated at our institution from 2001 to 2014 for ruptured AAA (rAAA) were retrospectively identified and grouped into patients with small rAAA (maximum diameter <6 cm) or large rAAA (>6 cm). Patients with large (>6 cm) non-rAAA were also identified sequentially from 2009 for comparison. Demographics, vascular risk factors, maximal aortic diameter, and aortic outflow occlusion (AOO) were recorded. AOO was defined as complete occlusion of the common, internal, or external iliac artery. Computational fluid dynamics and finite element analysis simulations were performed to calculate wall stress distributions and to extract PWS. We identified 61 patients with rAAA, of which 15 ruptured with AAA diameter <60 mm (small rAAA group). Patients with small rAAAs were more likely to have peripheral arterial disease (PAD) and chronic obstructive pulmonary disease (COPD) than were patients in the large non-rAAA group. Patients with small rAAAs were also more likely to have AOO compared with non-rAAAs >60 mm (27% vs 8%; P = .047). Among all patients with rAAAs, those with AOO ruptured at smaller mean AAA diameters than in patients without AOO (62.1 ± 11.8 mm vs 72.5 ± 16.4 mm; P = .024). PWS calculations of a representative small rAAA and a large non-rAAA showed a substantial increase in PWS with AOO. We demonstrate that AOO, PAD, and COPD in AAA are associated with rAAAs at smaller diameters. AOO appears to increase PWS, whereas COPD and PAD may be surrogate markers of decreased aortic wall strength. We therefore recommend consideration of early, elective AAA repair in patients with AOO, PAD, or COPD to minimize risk of early rupture. Copyright © 2016. Published by Elsevier Inc.

Maximal aortic diameter affects outcome after endovascular repair of abdominal aortic aneurysms.

PubMed

Huang, Ying; Gloviczki, Peter; Duncan, Audra A; Kalra, Manju; Oderich, Gustavo S; Fleming, Mark D; Harmsen, William S; Bower, Thomas C

2017-05-01

The purpose of this study was to evaluate whether maximal aortic diameter affects outcome after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA). Clinical data of patients undergoing EVAR between 1997 and 2011 for nonruptured asymptomatic AAAs in a tertiary center were reviewed. Patients were classified according to diameter of AAA: group 1, <5.0 cm; group 2, 5.0 to 5.4 cm; group 3, 5.5 to 5.9 cm; and group 4, ≥6.0 cm. The primary end point was all-cause mortality; secondary end points were complications, reinterventions, and ruptures. There were 874 patients studied (female, 108 [12%]; group 1, 119; group 2, 246; group 3, 243; group 4, 266); mean age was 76 ± 7.2 years. The 30-day mortality rate was 1.0%, not significantly different between groups (P = .22); complication and reintervention rates were 13% and 4.1%, respectively, similar between groups (P < .05). Five-year survival was 68%; freedom from complications and reinterventions was 65% and 74%, respectively; rupture rate was 0.5%. Multivariate analysis revealed that factors associated with all-cause mortality included maximal aortic diameter, age, gender, surgical risk, cancer history, and endograft type (P < .05). Group 4 had increased risks of mortality (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.38-2.85; P = .002) and complications (HR, 1.6; 95% CI, 1.2-2.7; P = .009) relative to group 1. Reinterventions were more frequent for aneurysms ≥6.0 cm (HR, 2.0; 95% CI, 1.2-3.3; P = .01). Late rupture rate after EVAR was not different between groups. Maximal aortic diameter is associated with long-term outcomes after elective EVAR. Patients with large AAAs (≥6.0 cm) have higher all-cause mortality, complication, and reintervention rates after EVAR than those with smaller aneurysms. We continue to recommend that AAAs be repaired when they reach 5.5 cm as recommended by the guidelines of the Society for Vascular Surgery. On the basis of our data, EVAR should be considered even in high-risk patients with a maximal aortic diameter between 5.5 and 6.0 cm because surgical risk with aneurysm size above 6.0 cm will increase significantly. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Endovascular Repair of Abdominal Aortic Aneurysms

PubMed Central

Sternbergh, W. Charles; Yoselevitz, Moises; Money, Samuel R.

1999-01-01

Endovascular treatment of abdominal aortic aneurysms (AAAs) is an exciting new minimally invasive treatment option for patients with this disease. Ochsner Clinic has been the only institution in the Gulf South participating in FDA clinical trials of these investigational devices. Early results with endovascular AAA repair demonstrate a trend towards lower mortality and morbidity when compared with traditional open surgery. Length of stay has been reduced by two-thirds with a marked reduction in postoperative pain and at-home convalescence. If the long-term data on efficacy and durability of these devices are good, most AAAs in the future will be treated with this minimally invasive technique. PMID:21845135

Abdominal aortic aneurysm neck remodeling after open aneurysm repair.

PubMed

Falkensammer, Juergen; Oldenburg, W Andrew; Biebl, Matthias; Hugl, Beate; Hakaim, Albert G; Crook, Julia E; Berland, Todd L; Paz-Fumagalli, Ricardo

2007-05-01

Proximal endovascular aortic graft fixation and maintenance of hemostatic seal depends on the long-term stability of the aortic neck. Previous investigations of aortic neck dilation mostly focused on the infrarenal aortic diameter. Fenestrated and branched stent grafts facilitate suprarenal graft fixation and may thereby improve the long-term integrity of the aortic attachment site. For these devices, the natural history of the suprarenal aortic segment is also of interest. We investigated the natural history of the supra- and infrarenal aortic segment after open abdominal aortic aneurysm (AAA) repair. For this retrospective analysis, we reviewed the preoperative and the initial postoperative as well as the most recent CT series that were obtained from 52 patients undergoing conventional repair of an infrarenal abdominal aortic aneurysm between January 1998 and December 2002. Measurements were performed using electronic calipers on a "split screen", allowing direct comparison of subsequent CT series at corresponding levels along the vessel. Main outcome measures were changes in postoperative measures of the supra- and infrarenal aortic diameters. The first postoperative exam was at a mean (+/-SD) of 7.0 +/- 3.5 months, and the final exams were at 44.4 +/- 21 months. Over this time period, the estimated rate of change in suprarenal diameter was 0.18 mm/ y with 95% confidence interval (CI) from 0.08 to 0.27. The estimated rate of change for the infrarenal diameter was 0.16 (95% CI: 0.05 to 0.27). A clinically relevant diameter increase of >or=3 mm was observed in seven patients (13%). There was evidence of larger diameter increases associated with larger AAA diameters (P = .003 and <.001 for suprarenal and infrarenal diameters), an inverted funnel shape (P = .002 and <.001), and marginal evidence of association with a history of inguinal hernia (P = .043 and .066). Although there is statistically significant evidence of increases in the supra- and infrarenal aortic diameters after conventional AAA repair, mean annual increases tended to be small and clinically relevant increases of 3 mm or more were observed in only a small proportion of cases.

Hepatorenal revascularization enables EVAR repair on a patient with AAA and an ectopic right renal artery.

PubMed

Lazaris, A M; Moulakakis, K; Mantas, G; Poulou, K; Alexiou, E; Vasdekis, S; Geroulakos, G

2018-06-07

The last thirty years the endovascular repair (EVAR) has become the standard method of treatment of abdominal aortic aneurysms (AAA). Nevertheless, the method has limitations based mainly on the anatomic characteristics of the specific aneurysm. In these cases a combination of endovascular and open techniques can be used. We describe a case of a patient with an infrarenal AAA and an ectopic right renal artery emerging from within the aneurysm sac. The patient was treated with a combination of endovascular and open techniques. In particular, he underwent a hepatorenal revascularization followed by a standard EVAR procedure, with a successful final outcome. For the treatment of AAA disease, the combination of open and endovascular procedures can overcome difficulties where a standard EVAR cannot be an option. Copyright © 2018 Elsevier Inc. All rights reserved.

Epidemiology and contemporary management of abdominal aortic aneurysms.

PubMed

Ullery, Brant W; Hallett, Richard L; Fleischmann, Dominik

2018-05-01

Abdominal aortic aneurysm (AAA) is most commonly defined as a maximal diameter of the abdominal aorta in excess of 3 cm in either anterior-posterior or transverse planes or, alternatively, as a focal dilation ≥ 1.5 times the diameter of the normal adjacent arterial segment. Risk factors for the development of AAA include age > 60, tobacco use, male gender, Caucasian race, and family history of AAA. Aneurysm growth and rupture risk appear to be associated with persistent tobacco use, female gender, and chronic pulmonary disease. The majority of AAAs are asymptomatic and detected incidentally on various imaging studies, including abdominal ultrasound, and computed tomographic angiography. Symptoms associated with AAA may include abdominal or back pain, thromboembolization, atheroembolization, aortic rupture, or development of an arteriovenous or aortoenteric fistula. The Screening Abdominal Aortic Aneurysms Efficiently (SAAAVE) Act provides coverage for a one-time screening abdominal ultrasound at age 65 for men who have smoked at least 100 cigarettes and women who have family history of AAA disease. Medical management is recommended for asymptomatic patients with AAAs < 5 cm in diameter and focuses on modifiable risk factors, including smoking cessation and blood pressure control. Primary indications for intervention in patients with AAA include development of symptoms, rupture, rapid aneurysm growth (> 5 mm/6 months), or presence of a fusiform aneurysm with maximum diameter of 5.5 cm or greater. Intervention for AAA includes conventional open surgical repair and endovascular aortic stent graft repair.

Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm.

PubMed

Montan, C; Hammar, U; Wikman, A; Berlin, E; Malmstedt, J; Holst, J; Wahlgren, C M

2016-11-01

The aim was to study blood transfusions and blood product ratios in massively transfused patients treated for ruptured abdominal aortic aneurysms (rAAAs). This was a registry based cohort study of rAAA patients repaired at three major vascular centres between 2008 and 2013. Data were collected from the Swedish Vascular Registry, hospitals medical records, and local transfusion registries. The transfusion data were analysed for the first 24 h of treatment. Massive transfusion (MT) was defined as 4 or more units of red blood cell (RBC) transfused within 1 h, or 10 or more RBC units within 24 h. Logistic regression was used to calculate the odds ratio of 30 day mortality associated with the ratios of blood products and timing of first units of platelets (PLTs) and fresh frozen plasma (FFP) transfused. Three hundred sixty nine rAAA patients were included: 80% men; 173 endovascular aneurysm repairs (EVARs) and 196 open repairs (ORs) with median RBC transfusion 8 units (Q1-Q3, 4-14) and 14 units (Q1-Q3, 8-28), respectively. A total of 261 (71%) patients required MT. EVAR patients with MT (n = 96) required less transfusion than OR patients (n = 165): median RBC 10 units (Q1-Q3, 6-16.5) vs. 15 units (Q1-Q3, 9-26) (p = .002), FFP 6 units (Q1-Q3, 2-14.5) vs. 13 units (Q1-Q3, 7-24) (p < .001), and PLT 0 units (Q1-Q3, 0-2) vs. 2 units (Q1-Q3, 0-4) (p = .01). Median blood product ratios in MT patients were FFP/RBC (EVAR group 0.59 [0.33-0.86], OR group 0.84 [0.67-1.2]; p < .001], and PLT/RBC (EVAR 0 [0-0.17], OR 0.12 (0-0.18); p < .001]. In patients repaired by OR a FFP/RBC ratio close to 1 was associated with reduced 30 day mortality (p = .003). The median PLT/RBC ratio was higher during the later part of the study period (p < .001, median test), whereas there was no significant difference in median FFP/RBC ratio (p = .101, median test). The majority of rAAA patients undergoing EVAR required MT. EVAR patients treated with MT had lower FFP/RBC and PLT/RBC ratios than OR patients with MT. The mortality risk was lower with FFP/RBC ratio close to 1:1 in open repaired patients requiring MT. The 24 h PLT/RBC ratio increased over the study period. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm

PubMed Central

Muehling, Bernd; Oberhuber, Alexander; Schelzig, Hubert; Bischoff, Gisela; Marx, Nikolaus; Sunder-Plassmann, Ludger; Orend, Karl H

2008-01-01

Background and aims: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL). Methods: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter. Results: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter. Conclusion: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurismal disease remains to be elucidated. PMID:19337556

Micromanaging Abdominal Aortic Aneurysms

PubMed Central

Maegdefessel, Lars; Spin, Joshua M.; Adam, Matti; Raaz, Uwe; Toh, Ryuji; Nakagami, Futoshi; Tsao, Philip S.

2013-01-01

The contribution of abdominal aortic aneurysm (AAA) disease to human morbidity and mortality has increased in the aging, industrialized world. In response, extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of the diseased aorta. This work aims to develop novel diagnostic and therapeutic strategies to limit AAA expansion and, ultimately, rupture. Contributions from multiple research groups have uncovered a complex transcriptional and post-transcriptional regulatory milieu, which is believed to be essential for maintaining aortic vascular homeostasis. Recently, novel small noncoding RNAs, called microRNAs, have been identified as important transcriptional and post-transcriptional inhibitors of gene expression. MicroRNAs are thought to “fine tune” the translational output of their target messenger RNAs (mRNAs) by promoting mRNA degradation or inhibiting translation. With the discovery that microRNAs act as powerful regulators in the context of a wide variety of diseases, it is only logical that microRNAs be thoroughly explored as potential therapeutic entities. This current review summarizes interesting findings regarding the intriguing roles and benefits of microRNA expression modulation during AAA initiation and propagation. These studies utilize disease-relevant murine models, as well as human tissue from patients undergoing surgical aortic aneurysm repair. Furthermore, we critically examine future therapeutic strategies with regard to their clinical and translational feasibility. PMID:23852016

Direct health costs and clinical outcomes of open surgery in patients with abdominal aortic aneurysm in Spain. The RECAPTA study.

PubMed

Egea, Marta; Fernández-Samos, Rafael; Lechón, José Antonio; Reparaz, Luis; Álvarez, María; Cairols, Marc

2018-06-18

Abdominal aortic aneurysm (AAA) is a chronic, progressive disease that often requires surgical repair. This study aimed to assess the healthcare costs and clinical outcomes of open AAA repair in Spain. Observational, retrospective, multicenter study with a one-year follow-up. Healthcare resource use and costs related to the surgical procedure, hospital stay, and follow-up period were assessed. Ninety patients with asymptomatic AAA who underwent open repair were recruited between 2003 and 2009 at three Spanish hospitals. Four patients (4.44%) died in the first 30 postoperative days. Mean [standard deviation] procedure time was 292.83 [72.10] minutes and mean hospital length of stay was 11.44 days [5.42]. Thirty two patients (35.56%) presented in-hospital complications and three patients (3.45%) underwent re-intervention during follow-up. The mean overall cost per patient during the study period was €21,622.59, of which 42.40% (€9,168.19), 52.08% (€11,261.74), and 5.52% (€1,192.66) corresponded to the surgical procedure, the inpatient stay, and the study follow-up period, respectively. Given the economic burden imposed by the treatment of patients admitted with AAA on the Spanish health system, additional efforts comparing the cost of open repair with endovascular treatments are needed to ensure greater efficiency.

Self-efficacy is an independent predictor for postoperative six-minute walk distance after elective open repair of abdominal aortic aneurysm.

PubMed

Hayashi, Kazuhiro; Kobayashi, Kiyonori; Shimizu, Miho; Tsuchikawa, Yohei; Kodama, Akio; Komori, Kimihiro; Nishida, Yoshihiro

2018-05-01

Open surgery is performed to treat abdominal aortic aneurysm (AAA), although the subsequent surgical stress leads to worse physical status. Preoperative self-efficacy has been reported to predict postoperative physical status after orthopedic surgery; however, it has not been sufficiently investigated in patients undergoing abdominal surgery. The purpose of the present study is to investigate the correlation between preoperative self-efficacy and postoperative six-minute walk distance (6MWD) in open AAA surgery. Seventy patients who underwent open AAA surgery were included. Functional exercise capacity was measured using preoperative and 1 week postoperative 6MWD. Self-efficacy was preoperatively measured using self-efficacy for physical activity (SEPA). The correlations of postoperative 6MWD with age, height, BMI, preoperative 6MWD, SEPA, Hospital Anxiety and Depression Scale (HADS) score, operative time, and blood loss were investigated using multivariate analysis. Single regression analysis showed that postoperative 6MWD was significantly correlated with age (r = -0.553, p ≤ 0.001), height (r = 0.292, p = 0.014), Charlson's comorbidity index (r = -0.268, p = 0.025), preoperative 6MWD (r = 0.572, p ≤ 0.001), SEPA (r = 0.586, p ≤ 0.001), and HADS-depression (r = -0.296, p = 0.013). Multiple regression analysis showed that age (p = 0.002), preoperative 6MWD (p = 0.013), and SEPA (p = 0.043) score were significantly correlated with postoperative 6MWD. Self-efficacy was an independent predictor for postoperative 6MWD after elective open AAA surgery. This suggests the importance of assessing not only physical status but also psychological factors such as self-efficacy. Implications for Rehabilitation Preoperative self-efficacy has been limited to reports after orthopedic surgery. We showed that preoperative self-efficacy predicted postoperative 6MWD after AAA surgery. Treatment to improve self-efficacy might be useful in patients receiving AAA surgery in rehabilitation.

Abdominal aortic aneurysms: pre- and post-procedural imaging.

PubMed

Hallett, Richard L; Ullery, Brant W; Fleischmann, Dominik

2018-05-01

Abdominal aortic aneurysm (AAA) is a relatively common, potentially life-threatening disorder. Rupture of AAA is potentially catastrophic with high mortality. Intervention for AAA is indicated when the aneurysm reaches 5.0-5.5 cm or more, when symptomatic, or when increasing in size > 10 mm/year. AAA can be accurately assessed by cross-sectional imaging including computed tomography angiography and magnetic resonance angiography. Current options for intervention in AAA patients include open surgery and endovascular aneurysm repair (EVAR), with EVAR becoming more prevalent over time. Cross-sectional imaging plays a crucial role in AAA surveillance, pre-procedural assessment, and post-EVAR management. This paper will discuss the current role of imaging in the assessment of AAA patients prior to intervention, in evaluation of procedural complications, and in long-term follow-up of EVAR patients.

Update on Abdominal Aortic Aneurysm Research: From Clinical to Genetic Studies

PubMed Central

Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Hinterseher, Irene; Smelser, Diane T.; Tromp, Gerard

2014-01-01

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person's risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks. PMID:24834361

Mechanism of Enzyme Repair by the AAA+ Chaperone Rubisco Activase.

PubMed

Bhat, Javaid Y; Miličić, Goran; Thieulin-Pardo, Gabriel; Bracher, Andreas; Maxwell, Andrew; Ciniawsky, Susanne; Mueller-Cajar, Oliver; Engen, John R; Hartl, F Ulrich; Wendler, Petra; Hayer-Hartl, Manajit

2017-09-07

How AAA+ chaperones conformationally remodel specific target proteins in an ATP-dependent manner is not well understood. Here, we investigated the mechanism of the AAA+ protein Rubisco activase (Rca) in metabolic repair of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits containing eight catalytic sites. Rubisco is prone to inhibition by tight-binding sugar phosphates, whose removal is catalyzed by Rca. We engineered a stable Rca hexamer ring and analyzed its functional interaction with Rubisco. Hydrogen/deuterium exchange and chemical crosslinking showed that Rca structurally destabilizes elements of the Rubisco active site with remarkable selectivity. Cryo-electron microscopy revealed that Rca docks onto Rubisco over one active site at a time, positioning the C-terminal strand of RbcL, which stabilizes the catalytic center, for access to the Rca hexamer pore. The pulling force of Rca is fine-tuned to avoid global destabilization and allow for precise enzyme repair. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk assessment and risk scores in the management of aortic aneurysms.

PubMed

Von Meijenfeldt, Gerdine C I; Van Der Laan, Maarten J; Zeebregts, Clark J; Balm, Ron; Verhagen, Hence J M

2016-04-01

The decision whether to operate a patient or not can be challenging for a clinician for both ruptured abdominal aortic aneurysms (AAAs) as well as elective AAAs. Prior to surgical intervention it would be preferable that the clinician exactly knows which clinical variables lower or increase the chances of morbidity and mortality postintervention. To help in the preoperative counselling and shared decision making several clinical variables can be identified as risk factors and with these, risk models can be developed. An ideal risk score for aneurysm repair includes routinely obtained physiological and anatomical variables, has excellent discrimination and calibration, and is validated in different geographical areas. For elective AAA repair, several risk scores are available, for ruptured AAA treatment, these scores are far less well developed. In this manuscript, we describe the designs and results of published risk scores for elective and open repair. Also, suggestions for uniformly reporting of risk factors and their statistical analyses are described. Furthermore, the preliminary results of a new risk model for ruptured aortic aneurysm will be discussed. This score identifies age, hemoglobin, cardiopulmonary resuscitation and preoperative systolic blood pressure as risk factors after multivariate regression analysis. This new risk score can help to identify patients that would not benefit from repair, but it can also potentially identify patients who would benefit and therefore lower turndown rates. The challenge for further research is to expand on validation of already existing promising risk scores in order to come to a risk model with optimal discrimination and calibration.

Endovascular repair of abdominal aortic aneurysms: vascular anatomy, device selection, procedure, and procedure-specific complications.

PubMed

Bryce, Yolanda; Rogoff, Philip; Romanelli, Donald; Reichle, Ralph

2015-01-01

Abdominal aortic aneurysm (AAA) is abnormal dilatation of the aorta, carrying a substantial risk of rupture and thereby marked risk of death. Open repair of AAA involves lengthy surgery time, anesthesia, and substantial recovery time. Endovascular aneurysm repair (EVAR) provides a safer option for patients with advanced age and pulmonary, cardiac, and renal dysfunction. Successful endovascular repair of AAA depends on correct selection of patients (on the basis of their vascular anatomy), choice of the correct endoprosthesis, and familiarity with the technique and procedure-specific complications. The type of aneurysm is defined by its location with respect to the renal arteries, whether it is a true or false aneurysm, and whether the common iliac arteries are involved. Vascular anatomy can be divided more technically into aortic neck, aortic aneurysm, pelvic perfusion, and iliac morphology, with grades of difficulty with respect to EVAR, aortic neck morphology being the most common factor to affect EVAR appropriateness. When choosing among the devices available on the market, one must consider the patient's vascular anatomy and choose between devices that provide suprarenal fixation versus those that provide infrarenal fixation. A successful technique can be divided into preprocedural imaging, ancillary procedures before AAA stent-graft placement, the procedure itself, postprocedural medical therapy, and postprocedural imaging surveillance. Imaging surveillance is important in assessing complications such as limb thrombosis, endoleaks, graft migration, enlargement of the aneurysm sac, and rupture. Last, one must consider the issue of radiation safety with regard to EVAR. (©)RSNA, 2015.

Inflammatory Cells and Proteases in Abdominal Aortic Aneurysm and its Complications.

PubMed

Haiying, Jiang; Sasaki, Takeshi; Jin, Enze; Kuzuya, Masafumi; Cheng, Xianwu

2018-05-30

Abdominal aortic aneurysm (AAA), a common disease among elderly individuals, involves the progressive dilatation of the abdominal aorta as a consequence of degeneration. The mechanisms of AAA formation, development and rupture are largely unknown. Surgical repair is the only available method of treatment since the lack of knowledge regarding the pathogenesis of AAA has hindered the development of suitable medical treatments, particularly the development of drugs. In this review, we describe the inflammatory cells and proteases that may be involved in the formation and development of AAA. This knowledge can contribute to the development of new drugs for AAA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Predictive models for mortality after ruptured aortic aneurysm repair do not predict futility and are not useful for clinical decision making.

PubMed

Thompson, Patrick C; Dalman, Ronald L; Harris, E John; Chandra, Venita; Lee, Jason T; Mell, Matthew W

2016-12-01

The clinical decision-making utility of scoring algorithms for predicting mortality after ruptured abdominal aortic aneurysms (rAAAs) remains unknown. We sought to determine the clinical utility of the algorithms compared with our clinical decision making and outcomes for management of rAAA during a 10-year period. Patients admitted with a diagnosis rAAA at a large university hospital were identified from 2005 to 2014. The Glasgow Aneurysm Score, Hardman Index, Vancouver Score, Edinburgh Ruptured Aneurysm Score, University of Washington Ruptured Aneurysm Score, Vascular Study Group of New England rAAA Risk Score, and the Artificial Neural Network Score were analyzed for accuracy in predicting mortality. Among patients quantified into the highest-risk group (predicted mortality >80%-85%), we compared the predicted with the actual outcome to determine how well these scores predicted futility. The cohort comprised 64 patients. Of those, 24 (38%) underwent open repair, 36 (56%) underwent endovascular repair, and 4 (6%) received only comfort care. Overall mortality was 30% (open repair, 26%; endovascular repair, 24%; no repair, 100%). As assessed by the scoring systems, 5% to 35% of patients were categorized as high-mortality risk. Intersystem agreement was poor, with κ values ranging from 0.06 to 0.79. Actual mortality was lower than the predicted mortality (50%-70% vs 78%-100%) for all scoring systems, with each scoring system overestimating mortality by 10% to 50%. Mortality rates for patients not designated into the high-risk cohort were dramatically lower, ranging from 7% to 29%. Futility, defined as 100% mortality, was predicted in five of 63 patients with the Hardman Index and in two of 63 of the University of Washington score. Of these, surgery was not offered to one of five and one of two patients, respectively. If one of these two models were used to withhold operative intervention, the mortality of these patients would have been 100%. The actual mortality for these patients was 60% and 50%, respectively. Clinical algorithms for predicting mortality after rAAA were not useful for predicting futility. Most patients with rAAA were not classified in the highest-risk group by the clinical decision models. Among patients identified as highest risk, predicted mortality was overestimated compared with actual mortality. The data from this study support the limited value to surgeons of the currently published algorithms. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

ACR Appropriateness Criteria® Abdominal Aortic Aneurysm: Interventional Planning and Follow-Up.

PubMed

Francois, Christopher J; Skulborstad, Erik P; Majdalany, Bill S; Chandra, Ankur; Collins, Jeremy D; Farsad, Khashayar; Gerhard-Herman, Marie D; Gornik, Heather L; Kendi, A Tuba; Khaja, Minhajuddin S; Lee, Margaret H; Sutphin, Patrick D; Kapoor, Baljendra S; Kalva, Sanjeeva P

2018-05-01

Abdominal aortic aneurysms (AAAs) are a relatively common vascular problem that can be treated with either open, surgical repair or endovascular aortic aneurysm repair (EVAR). Both approaches to AAA repair require dedicated preoperative imaging to minimize adverse outcomes. After EVAR, cross-sectional imaging has an integral role in confirming the successful treatment of the AAA and early detection of complications related to EVAR. CT angiography is the primary imaging modality for both preoperative planning and follow-up after repair. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

The UK EndoVascular Aneurysm Repair (EVAR) trials: randomised trials of EVAR versus standard therapy.

PubMed

Brown, L C; Powell, J T; Thompson, S G; Epstein, D M; Sculpher, M J; Greenhalgh, R M

2012-01-01

To assess the efficacy of endovascular aneurysm repair (EVAR) against standard alternative management in patients with large abdominal aortic aneurysm (AAA). Two national, multicentre randomised trials - EVAR trials 1 and 2. Patients were recruited from 38 out of 41 eligible UK hospitals. Men and women aged at least 60 years, with an AAA measuring at least 5.5 cm on a computerised tomography scan that was regarded as anatomically suitable for EVAR, were assessed for fitness for open repair. Patients considered fit were randomised to EVAR or open repair in EVAR trial 1 and patients considered unfit were randomised to EVAR or no intervention in EVAR trial 2. EVAR, open repair or no intervention. The primary outcome was mortality (operative, all-cause and AAA related). Patients were flagged at the UK Office for National Statistics with centrally coded death certificates assessed by an Endpoints Committee. Power calculations based upon mortality indicated that 900 and 280 patients were required for EVAR trials 1 and 2, respectively. Secondary outcomes were graft-related complications and reinterventions, adverse events, renal function, health-related quality of life and costs. Cost-effectiveness analyses were performed for both trials. Recruitment occurred between 1 September 1999 and 31 August 2004, with targets exceeded in both trials: 1252 randomised into EVAR trial 1 (626 to EVAR) and 404 randomised into EVAR trial 2 (197 to EVAR). Follow-up closed in December 2009 with very little loss to follow-up (1%). In EVAR trial 1, 30-day operative mortalities were 1.8% and 4.3% in the EVAR and open-repair groups, respectively: adjusted odds ratio 0.39 [95% confidence interval (CI) 0.18 to 0.87], p = 0.02. During a total of 6904 person-years of follow-up, 524 deaths occurred (76 AAA related). Overall, there was no significant difference between the groups in terms of all-cause mortality: adjusted hazard ratio (HR) 1.03 (95% CI 0.86 to 1.23), p = 0.72. The EVAR group did demonstrate an early advantage in terms of AAA-related mortality, which was sustained for the first few years, but lost by the end of the study, primarily due to fatal endograft ruptures: adjusted HR 0.92 (95% CI 0.57 to 1.49), p = 0.73. The EVAR procedure was more expensive than open repair (mean difference £1177) and not found to be cost-effective, but the model was sensitive to alternative assumptions. In EVAR trial 2, during a total of 1413 person-years of follow-up, a total of 305 deaths occurred (78 AAA related). The 30-day operative mortality was 7.3% in the EVAR group. However, this group later demonstrated a significant advantage in terms of AAA-related mortality, but this became apparent only after 4 years: overall adjusted HR 0.53 (95% CI 0.32 to 0.89), p = 0.02. Sadly, this advantage did not result in any benefit in terms of all-cause mortality: adjusted HR 0.99 (95% CI 0.78 to 1.27), p = 0.97. Overall, EVAR was more expensive than no intervention (mean difference £10,222) and not found to be cost-effective. EVAR offers a clear operative mortality benefit over open repair in patients fit for both procedures, but this early benefit is not translated into a long-term survival advantage. Among patients unfit for open repair, EVAR is associated with a significant long-term reduction in AAA-related mortality but this does not appear to influence all-cause mortality. Current Controlled Trials ISRCTN 55703451. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 9. See the HTA programme website for further project information.

Fourteen-year outcomes of abdominal aortic endovascular repair with the Zenith stent graft.

PubMed

Verzini, Fabio; Romano, Lydia; Parlani, Gianbattista; Isernia, Giacomo; Simonte, Gioele; Loschi, Diletta; Lenti, Massimo; Cao, Piergiorgio

2017-02-01

Long-term results of abdominal aortic aneurysm (AAA) endovascular repair are affected by graft design renewals that tend to improve the performance of older generation prostheses but usually reset the follow-up times to zero. The present study investigated the long-term outcomes of endovascular AAA repair (EVAR) using the Zenith graft, still in use without major modification, in a single center experience. Between 2000 and 2011, 610 patients underwent elective EVAR using the Zenith endograft (Cook Inc, Bloomington, Ind) and represent the study group. Primary outcomes were overall survival, freedom from AAA rupture, and freedom from AAA-related death. Secondary outcomes included freedom from late (>30 days) reintervention, freedom from late (>30 days) conversion to open repair, freedom from aneurysm sac enlargement >5.0 mm and freedom from EVAR failure, defined as a composite of AAA-related death, AAA rupture, AAA growth >5 mm, and any reintervention. Mean age was 73.2 years. Mean aneurysm diameter was 55.3 mm. There were five perioperative deaths (0.8%) and three intraoperative conversions. At a mean follow-up of 99.2 (range, 0-175) months, seven AAA ruptures occurred, all fatal except one. Overall survival was 92.8% ± 1.1% at 1 year, 70.1% ± 1.9% at 5 years, 37.8% ± 2.9% at 10 years, and 24 ± 4% at 14 years. Freedom from AAA-rupture was 99.8% ± 0.02 at 1 year (one case), 99.4% ± 0.04 at 5 years (three cases), and 98.1% ± 0.07 at 10 and 14 years. Freedom from late reintervention and conversion was 98% ± 0.6 at 1 year, 87.7% ± 1.5 at 5 years, 75.7% ± 3.2 at 10 years, and 69.9% ± 5.2 at 14 years. Freedom from aneurysm sac growth >5.0 mm was 99.8% at 1 year, 96.6% ± 0.7 at 5 years, 81.0% ± 3.4 at 10 years, and 74.1% ± 5.8% at 14 years. EVAR failure occurred in 132 (21.6%) patients at 14 years. At multivariate analysis, independent predictors of EVAR failure resulted type I and III endoleak (hazard ratio [HR], 6.7; 95% confidence interval [CI], 4.6- 9.7; P < .001], type II endoleak (HR, 2.3; 95% CI, 1.6-3.4; P < .001), and American Society of Anesthesiologists grade 4 (HR, 1.6; 95% CI, 1.0-2.6; P = .034). EVAR with Zenith graft represents a safe and durable repair. Risk of rupture and aneurysm-related death is low, whereas overall long-term survival remains poor. Novel endograft models should be tested and evaluated considering that one-fourth of the operated patients will still be alive after 14 years. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Pre-surgical Psychological and Neuroendocrine Predictors of Psychiatric Morbidity Following Major Vascular Surgery: A Prospective Longitudinal Study

PubMed Central

King, Anthony P.; Abelson, James L.; Gholami, Bardia; Upchurch, Gilbert R.; Henke, Peter; Graham, Linda; Liberzon, Israel

2015-01-01

Objective Major life stressors, including major surgeries, are often followed by psychiatric symptoms and disorders. Prior retrospective work found abdominal-aortic aneurysm (AAA) repair is followed by increased psychiatric morbidity, which may adversely influence physical and functional recovery. Identifying risk factors prior to surgery, such as dysregulation in stress response systems, might be useful to improving preventative intervention. Methods Two hundred and sixteen patients receiving open AAA or aortofemoral bypass (AFB) surgeries, endovascular AAA repair (EVAR), or nonsurgical AAA treatment were recruited from two vascular surgery services. Psychiatric symptoms and salivary cortisol measures (waking, 4 pm, and 11 pm, before and after low-dose dexamethasone) were obtained at intake and 3 and 9 month followups. Results Following open surgeries, 18% of patients had new psychiatric disorders, compared to 4% of patients receiving EVAR or nonsurgical treatment (odds ratio = 6.0, 95% CI 1.6 - 22.1, p=.007). Having a history of major depression predicted onset of new disorders in surgical patients. Pre-surgical cortisol levels were associated with both baseline (r=.23, p<.05) and 9 month (r=.32, p<.01) psychiatric symptoms (cortisol B=1.0, SE=0.48, p<.05 in repeated measures mixed model). Conclusion Open AAA repair surgery is prospectively linked to development of psychiatric morbidity, and history of depression elevates risk. Cortisol measures prior to surgery are associated with current and future psychological functioning, suggesting potential neurobiological mechanisms that may contribute to vulnerability. These results can help identify surgical patients at risk, and point to potential targets for risk reduction interventions. PMID:26461854

A Technique of "Chimney Nellix" for the Management of Type 1a Endoleak After EVAR.

PubMed

Joseph, Simon Z; Kwok, C H Ricky; Hockley, Joseph A; Garbowski, Marek W; Ferguson, John; Samuelson, Shaun; Jansen, Shirley J

2018-05-01

This report presents 3 procedures with visceral "chimney stenting" in conjunction with an endovascular aneurysm sealing (EVAS) device, known as chEVAS, for treatment of type 1a endoleak. It includes the first published chEVAS in a patient with previous fenestrated endovascular aneurysm repair (FEVAR). Cases include an 80-year-old man 8 years after FEVAR for a juxtarenal abdominal aortic aneurysm (AAA); an 85-year-old woman 9 months after endovascular aneurysm repair (EVAR) for a ruptured infrarenal AAA; and an 84-year-old woman 3 months after EVAR for a symptomatic infrarenal AAA. Technical success was achieved in all cases, with 1 postoperative death. The remaining 2 patients had no residual type 1a endoleak at 10 and 14 months respectively. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Increasing the Elective Endovascular to Open Repair Ratio of Popliteal Artery Aneurysm.

PubMed

Wrede, Axel; Wiberg, Frans; Acosta, Stefan

2018-02-01

Open repair (OR) for popliteal artery aneurysm (PAA) has recently been challenged by endovascular repair (ER) as the primary choice of treatment. The aim of the present study was to evaluate time trends in treatment modality and compare outcomes between OR and ER among electively operated patients after start of screening in 2010 for abdominal aortic aneurysm (AAA), a disease highly associated with PAA. Between January 1, 2009, and April 30, 2017, 102 procedures and 36 acute and 66 elective repairs for PAA were identified. Over time, a trend ( P = .089) for an increasing elective to acute repair ratio of PAA and an increase in elective ER to OR ratio ( P = .003) was found. Among electively repaired PAAs, the ER group was older ( P = .047) and had a higher ankle-brachial index (ABI; P = .044). The ER group had fewer wound infections ( P = .003), fewer major bleeding complications ( P = .046), and shorter in-hospital stay ( P < .001). After 1 year of follow-up, the ER group had a higher rate of major amputations ( P = .037). Amputation-free survival at the end of follow-up did not differ between groups ( P = .68). Among the 17 patients with PAA eligible for AAA screening, 4 (24%) were diagnosed with PAA through the screening program of AAA. The epidemiology of elective repair of PAA has changed toward increased ER, although ER showed a higher rate of major amputations at 1 year. Confounding was considerable and a randomized trial is needed for evaluation of the best therapeutic option.

Emergency abdominal aortic aneurysm repair with a preferential endovascular strategy: mortality and cost-effectiveness analysis.

PubMed

Kapma, Marten R; Groen, Henk; Oranen, Bjorn I; van der Hilst, Christian S; Tielliu, Ignace F; Zeebregts, Clark J; Prins, Ted R; van den Dungen, Jan J; Verhoeven, Eric L

2007-12-01

To assess mortality and treatment costs of a new management protocol with preferential use of emergency endovascular aneurysm repair (eEVAR) for acute abdominal aortic aneurysm (AAA). From September 2003 until February 2005, 49 consecutive patients (45 men; mean age 71 years) with acute AAA were entered into a prospective study of a new management protocol that featured preferential use of eEVAR (n=18); patients with unsuitable anatomy or who were hemodynamically unstable underwent open repair (n=31). Mortality data and costs of treatment were compared in this mixed prospective group to a historical control group consisting of 147 patients (128 men; mean age 71 years) who underwent open repair from January 1998 to December 2001. All direct medical costs were included from the moment of admission until discharge from the hospital. Mortality in the mixed prospective group (18%) was lower than in the historical control group (31%), but the difference did not reach statistical significance (p=0.099). The mean total cost in the mixed prospective group was 17,164 euro compared to 21,084 euro in the historical open repair group (p=0.255). A preferential eEVAR protocol for acute AAA can decrease mortality and does not increase overall costs during initial treatment, but larger studies are needed to determine if these trends are statistically significant.

Colonic Ischemia After Standard Endovascular Abdominal Aortic Aneurysm Repair, A Rare But Dangerous Complication.

PubMed

Berchiolli, R; Adami, D; Marconi, M; Mari, M; Puta, B; Ferrari, M

2018-05-21

Colonic Ischemia (CI) after abdominal aortic aneurysm (AAA) repair, although rare, is associated with severe prognosis. Endovascular Aneurysm Repair (EVAR) is becoming the standard of practice in most vascular centers, and it also may reduce CI incidence in comparison to conventional open repair. Copyright © 2018 Elsevier Inc. All rights reserved.

Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms.

PubMed

Siennicka, Aldona; Zuchowski, Marta; Kaczmarczyk, Mariusz; Cnotliwy, Miłosław; Clark, Jeremy Simon; Jastrzębska, Maria

2018-03-20

The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Factor levels were measured using enzyme-linked immunosorbent assay of protein extract. Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001; B vs B1, P = .001). Significantly higher tissue plasminogen activator was found in thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of α 2 -antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Risk stratification by pre-operative cardiopulmonary exercise testing improves outcomes following elective abdominal aortic aneurysm surgery: a cohort study.

PubMed

Goodyear, Stephen J; Yow, Heng; Saedon, Mahmud; Shakespeare, Joanna; Hill, Christopher E; Watson, Duncan; Marshall, Colette; Mahmood, Asif; Higman, Daniel; Imray, Christopher He

2013-05-19

In 2009, the NHS evidence adoption center and National Institute for Health and Care Excellence (NICE) published a review of the use of endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). They recommended the development of a risk-assessment tool to help identify AAA patients with greater or lesser risk of operative mortality and to contribute to mortality prediction.A low anaerobic threshold (AT), which is a reliable, objective measure of pre-operative cardiorespiratory fitness, as determined by pre-operative cardiopulmonary exercise testing (CPET) is associated with poor surgical outcomes for major abdominal surgery. We aimed to assess the impact of a CPET-based risk-stratification strategy upon perioperative mortality, length of stay and non-operative costs for elective (open and endovascular) infra-renal AAA patients. A retrospective cohort study was undertaken. Pre-operative CPET-based selection for elective surgical intervention was introduced in 2007. An anonymized cohort of 230 consecutive infra-renal AAA patients (2007 to 2011) was studied. A historical control group of 128 consecutive infra-renal AAA patients (2003 to 2007) was identified for comparison.Comparative analysis of demographic and outcome data for CPET-pass (AT ≥ 11 ml/kg/min), CPET-fail (AT < 11 ml/kg/min) and CPET-submaximal (no AT generated) subgroups with control subjects was performed. Primary outcomes included 30-day mortality, survival and length of stay (LOS); secondary outcomes were non-operative inpatient costs. Of 230 subjects, 188 underwent CPET: CPET-pass n = 131, CPET-fail n = 35 and CPET-submaximal n = 22. When compared to the controls, CPET-pass patients exhibited reduced median total LOS (10 vs 13 days for open surgery, n = 74, P < 0.01 and 4 vs 6 days for EVAR, n = 29, P < 0.05), intensive therapy unit requirement (3 vs 4 days for open repair only, P < 0.001), non-operative costs (£5,387 vs £9,634 for open repair, P < 0.001) and perioperative mortality (2.7% vs 12.6% (odds ratio: 0.19) for open repair only, P < 0.05). CPET-stratified (open/endovascular) patients exhibited a mid-term survival benefit (P < 0.05). In this retrospective cohort study, a pre-operative AT > 11 ml/kg/min was associated with reduced perioperative mortality (open cases only), LOS, survival and inpatient costs (open and endovascular repair) for elective infra-renal AAA surgery.

Risk stratification by pre-operative cardiopulmonary exercise testing improves outcomes following elective abdominal aortic aneurysm surgery: a cohort study

PubMed Central

2013-01-01

Background In 2009, the NHS evidence adoption center and National Institute for Health and Care Excellence (NICE) published a review of the use of endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). They recommended the development of a risk-assessment tool to help identify AAA patients with greater or lesser risk of operative mortality and to contribute to mortality prediction. A low anaerobic threshold (AT), which is a reliable, objective measure of pre-operative cardiorespiratory fitness, as determined by pre-operative cardiopulmonary exercise testing (CPET) is associated with poor surgical outcomes for major abdominal surgery. We aimed to assess the impact of a CPET-based risk-stratification strategy upon perioperative mortality, length of stay and non-operative costs for elective (open and endovascular) infra-renal AAA patients. Methods A retrospective cohort study was undertaken. Pre-operative CPET-based selection for elective surgical intervention was introduced in 2007. An anonymized cohort of 230 consecutive infra-renal AAA patients (2007 to 2011) was studied. A historical control group of 128 consecutive infra-renal AAA patients (2003 to 2007) was identified for comparison. Comparative analysis of demographic and outcome data for CPET-pass (AT ≥ 11 ml/kg/min), CPET-fail (AT < 11 ml/kg/min) and CPET-submaximal (no AT generated) subgroups with control subjects was performed. Primary outcomes included 30-day mortality, survival and length of stay (LOS); secondary outcomes were non-operative inpatient costs. Results Of 230 subjects, 188 underwent CPET: CPET-pass n = 131, CPET-fail n = 35 and CPET-submaximal n = 22. When compared to the controls, CPET-pass patients exhibited reduced median total LOS (10 vs 13 days for open surgery, n = 74, P < 0.01 and 4 vs 6 days for EVAR, n = 29, P < 0.05), intensive therapy unit requirement (3 vs 4 days for open repair only, P < 0.001), non-operative costs (£5,387 vs £9,634 for open repair, P < 0.001) and perioperative mortality (2.7% vs 12.6% (odds ratio: 0.19) for open repair only, P < 0.05). CPET-stratified (open/endovascular) patients exhibited a mid-term survival benefit (P < 0.05). Conclusion In this retrospective cohort study, a pre-operative AT > 11 ml/kg/min was associated with reduced perioperative mortality (open cases only), LOS, survival and inpatient costs (open and endovascular repair) for elective infra-renal AAA surgery. PMID:24472159

Trends in Hospital Volume and Operative Mortality for High-Risk Surgery

PubMed Central

Finks, Jonathan F.; Osborne, Nicholas H.; Birkmeyer, John D.

2011-01-01

BACKGROUND There were numerous efforts in the United States during the previous decade to concentrate selected surgical procedures in high-volume hospitals. It remains unknown whether referral patterns for high-risk surgery have changed as a result and how operative mortality has been affected. METHODS We used national Medicare data to study patients undergoing one of eight different cancer and cardiovascular operations from 1999 through 2008. For each procedure, we examined trends in hospital volume and market concentration, defined as the proportion of Medicare patients undergoing surgery in the top decile of hospitals by volume per year. We used regression-based techniques to assess the effects of volume and market concentration on mortality over time, adjusting for case mix. RESULTS Median hospital volumes of four cancer resections (lung, esophagus, pancreas, and bladder) and of repair of abdominal aortic aneurysm (AAA) rose substantially. Depending on the procedure, higher hospital volumes were attributable to an increasing number of cases nationwide, an increasing market concentration, or both. Hospital volumes rose slightly for aortic-valve replacement but fell for coronary-artery bypass grafting and carotid endarterectomy. Operative mortality declined for all eight procedures, ranging from a relative decline of 8% for carotid endarterectomy (1.3% mortality in 1999 and 1.2% in 2008) to 36% for AAA repair (4.4% in 1999 and 2.8% in 2008). Higher hospital volumes explained a large portion of the decline in mortality for pancreatectomy (67% of the decline), cystectomy (37%), and esophagectomy (32%), but not for the other procedures. CONCLUSIONS Operative mortality with high-risk surgery fell substantially during the previous decade. Although increased market concentration and hospital volume have contributed to declining mortality with some high-risk cancer operations, declines in mortality with other procedures are largely attributable to other factors. (Funded by the National Institute on Aging.) PMID:21631325

Expression in Whole Blood Samples of miRNA-191 and miRNA-455-3p in Patients with AAA and Their Relationship to Clinical Outcomes after Endovascular Repair.

PubMed

Tenorio, Emanuel Junio Ramos; Braga, Andre Felipe Farias; Tirapelli, Daniela Pretti Da Cunha; Ribeiro, Mauricio Serra; Piccinato, Carlos Eli; Joviliano, Edwaldo Edner

2018-03-05

The purpose of this study was to quantify and evaluate the expression response of miRNA-191 and miRNA-455-3p endovascular repair of abdominal aortic aneurysm (AAA) based in whole blood samples. This report describes a prospective study of a single center of 30 patients with AAA who underwent endovascular repair. Blood samples were collected preoperatively and 6 months postoperatively. The differential expression of the miRNAs was performed by the real-time polymerase chain reaction method, after extraction of the RNA from the blood samples at the 2 moments. In addition, bioinformatic tools were used to determine pathophysiological pathways related to AAA. The miR-191 and miR-455-3p were overexpressed preoperatively. After 6 months postoperatively, miR-191 (median 0.98, IQR 0.5-2.1, P < 0.0001) and miR-455-3p (median 1.4, IQR 0.6-3.1, P = 0.0003) presented a significant reduction in their expressions. There was no correlation between the diameter of the aneurysm and the expression of the miRNAs studied. In addition, analysis of the influence of the various types of devices used for the endovascular treatment of AAA showed no significant differences in the expression of miR-191 and miR-455-3p. Exclusion of the aneurysmal sac after endovascular treatment induces a decrease in the expression of the studied miRNAs in whole blood samples, which suggests a possible use of them as biomarkers of therapeutic success. Copyright © 2018 Elsevier Inc. All rights reserved.

Abdominal aortic aneurysm with periaortic malignant lymphoma differentiated from aneurysmal rupture by clinical presentation and magnetic resonance imaging.

PubMed

Kamata, Sokichi; Itou, Yoshito; Idoguchi, Koji; Imakita, Masami; Funatsu, Toshihiro; Yagihara, Toshikatsu

2018-06-01

Abdominal aortic aneurysm (AAA) associated with periaortic malignant lymphoma is difficult to differentiate from aneurysmal rupture because of similarities in their clinical presentation and appearance on computed tomography images. We here report a case of AAA associated with periaortic malignant lymphoma diagnosed preoperatively with an absence of typical symptoms, showing that AAA in periaortic malignant lymphoma can present without any clinical correlates. Magnetic resonance imaging was used to confirm the diagnosis. The patient was treated by endovascular repair, which may be safer and more effective than open surgery for AAA associated with malignant lymphoma because of the tight adhesion between the aneurysm and the lymphoid tissue.

Endovascular repair vs open surgical repair of abdominal aortic aneurysms: comparative utilization trends from 2001 to 2006.

PubMed

Levin, David C; Rao, Vijay M; Parker, Laurence; Frangos, Andrea J; Sunshine, Jonathan H

2009-07-01

Within the past few years, endovascular aneurysm repair (EVAR) has come into use for the treatment of abdominal aortic aneurysms (AAAs). In many cases, EVAR has the potential to replace traditional open surgical repair (OSR), which is more invasive, risky, and expensive. The aim of this study was to determine to what extent EVAR is replacing OSR, whether the frequency of treatment is increasing with the advent of the less invasive approach, and which specialties are performing the procedures. The Medicare Part B data sets for 2001 through 2006 were studied. Procedure volume and utilization rates per 100,000 Medicare beneficiaries were determined for the 7 Current Procedural Terminology, fourth edition, procedure codes that describe EVAR and the 4 codes that describe OSR for AAA. Medicare's physician specialty codes were used to ascertain the specialties of the physician providers. A total of 31,965 OSRs for AAA were performed in Medicare beneficiaries in 2001, dropping to 15,665 by 2006 (-51%). In contrast, EVAR was carried out in 11,028 instances in 2001, increasing to 28,937 by 2006 (+162%). The utilization rate per 100,000 for OSR dropped from 90 to 42 (a rate decrease of 48) during the study period, while the rate for EVAR increased from 31 to 77 (a rate increase of 46). The combined utilization rate per 100,000 of the two types of interventions for AAA (EVAR and OSR) decreased from 121 in 2001 to 119 in 2006. In performing EVAR, procedure volume and market share in 2006 by specialty were 1) 22,003 procedures by surgeons, a 76% share; 2) 3,287 procedures by radiologists, an 11% share; 3) 1,915 procedures by cardiologists, a 7% share; and 4) 1,732 procedures by all other physicians, a 6% share. Treatment for AAA seems to be an example of the responsible use of new technology by physicians. The newer, less invasive, and less risky procedure (EVAR) is replacing the older and more invasive procedure (OSR) to a considerable degree. However, the overall combined utilization rate of both types of AAA treatment has remained stable in the Medicare population. There is thus no evidence to suggest that the introduction of the newer approach has led to the overtreatment of patients. Although radiologists do have a role in EVAR, surgeons strongly predominate.

Prophylactic Mesh Reinforcement versus Sutured Closure to Prevent Incisional Hernias after Open Abdominal Aortic Aneurysm Repair via Midline Laparotomy: A Systematic Review and Meta-Analysis.

PubMed

Indrakusuma, Reza; Jalalzadeh, Hamid; van der Meij, Jessica E; Balm, Ron; Koelemay, Mark J W

2018-04-20

Incisional hernia is a frequent late complication after open abdominal aortic aneurysm (AAA) repair. We aimed to determine whether prophylactic mesh reinforcement of the abdominal wall at open AAA repair via midline laparotomy reduces the rate of incisional hernia compared to standard sutured closure. A systematic review and meta-analysis was carried out in accordance with the PRISMA statement (PROSPERO registration CRD42017072508). Randomised controlled trials (RCTs) comparing prophylactic mesh reinforcement with standard sutured closure were eligible for inclusion. MEDLINE, Embase, and the Cochrane Library were searched. A meta-analysis with a random effects model was carried out to estimate pooled risk ratios (RR) with 95% confidence intervals (CIs) for the incidence of, and re-operation rate for, incisional hernias. Assessments of methodological quality, quality of evidence, and strength of recommendations were done with the Cochrane Collaboration's tool for assessing risk of bias and the GRADE approach. Four RCTs with a total of 388 patients were included in the meta-analysis. Pooled analysis showed that mesh reinforcement significantly reduced the risk of incisional hernia after AAA repair compared with standard sutured closure (RR 0.27, 95% CI 0.11-0.66). The pooled rate of re-operations was not different between groups (RR 0.23, 95% CI 0.11-1.05). Mesh reinforcement did not cause more intra-operative or post-operative complications than sutured closure. The risk of bias in studies was low and the quality of evidence was rated as moderate. Prophylactic mesh reinforcement of the abdominal wall after open AAA repair via midline laparotomy significantly reduces the risk of incisional hernia. However, no significant difference in re-operation for incisional hernia was found. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Reporting individual surgeon outcomes does not lead to risk aversion in abdominal aortic aneurysm surgery.

PubMed

Saratzis, A; Thatcher, A; Bath, M F; Sidloff, D A; Bown, M J; Shakespeare, J; Sayers, R D; Imray, C

2017-02-01

INTRODUCTION Reporting surgeons' outcomes has recently been introduced in the UK. This has the potential to result in surgeons becoming risk averse. The aim of this study was to investigate whether reporting outcomes for abdominal aortic aneurysm (AAA) surgery impacts on the number and risk profile (level of fitness) of patients offered elective treatment. METHODS Publically available National Vascular Registry data were used to compare the number of AAAs treated in those centres across the UK that reported outcomes for the periods 2008-2012, 2009-2013 and 2010-2014. Furthermore, the number and characteristics of patients referred for consideration of elective AAA repair at a single tertiary unit were analysed yearly between 2010 and 2014. Clinic, casualty and theatre event codes were searched to obtain all AAAs treated. The results of cardiopulmonary exercise testing (CPET) were assessed. RESULTS For the 85 centres that reported outcomes in all three five-year periods, the median number of AAAs treated per unit increased between the periods 2008-2012 and 2010-2014 from 192 to 214 per year (p=0.006). In the single centre cohort study, the proportion of patients offered elective AAA repair increased from 74% in 2009-2010 to 81% in 2013-2014, with a maximum of 84% in 2012-2013. The age, aneurysm size and CPET results (anaerobic threshold levels) for those eventually offered elective treatment did not differ significantly between 2010 and 2014. CONCLUSIONS The results do not support the assumption that reporting individual surgeon outcomes is associated with a risk averse strategy regarding patient selection in aneurysm surgery at present.

Prevalence of abdominal aortic aneurysm (AAA) in a population undergoing computed tomography colonography in Canterbury, New Zealand.

PubMed

Khashram, M; Jones, G T; Roake, J A

2015-08-01

There is compelling level 1 evidence in support of screening men for abdominal aortic aneurysm (AAA) to reduce AAA mortality. However, New Zealand (NZ) lacks data on AAA prevalence, and national screening has not been implemented. The aim of this study was to determine the prevalence of AAA in a population undergoing a computed tomography colonography (CTC) for gastrointestinal symptoms. This was an observational study; all consecutive CTCs performed in three regions of the South Island of NZ over a 4 year period were reviewed. Data on abdominal and thoracic aorta diameters ≥30 mm, and iliac and femoral aneurysms ≥20 mm were recorded. Previous aortic surgical grafts or endovascular stents were also documented. Demographics, survival, and AAA related outcomes were collected and used for analysis. Included were 4,893 scans on 4,644 patients (1,933 men [41.6%], 2,711 women [58.4%]) with a median age of 69.3 years (range 17.0-97.0 years). There were 309 scans on 289 patients (75.4% men) who had either an aneurysm or a previous aortic graft with a median age of 79.6 years (range 57.0-96.0 years). Of these, 223 had a native AAA ≥30 mm. The prevalence of AAA rose with age from 1.3% in men aged 55-64 years, to 9.1% in 65-74 year olds, 16.8% in 75-84 year olds, and 22.0% in ≥85 year olds. The corresponding figures in women were 0.4%, 2%, 3.9%, and 6.2%, respectively. In this observational study, the prevalence of AAA was high and warrants further evaluation. The results acquired help to define a population that may benefit from a national AAA screening programme. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Spatial Analysis of Hospital Incidence and in Hospital Mortality of Abdominal Aortic Aneurysms in Germany: Secondary Data Analysis of Nationwide Hospital Episode (DRG) Data.

PubMed

Kuehnl, Andreas; Salvermoser, Michael; Erk, Alexander; Trenner, Matthias; Schmid, Volker; Eckstein, Hans-Henning

2018-06-01

This study aimed to analyze the spatial distribution and regional variation of the hospital incidence and in hospital mortality of abdominal aortic aneurysms (AAA) in Germany. German DRG statistics (2011-2014) were analysed. Patients with ruptured AAA (rAAA, I71.3, treated or not) and patients with non-ruptured AAA (nrAAA, I71.4, treated by open or endovascular aneurysm repair) were included. Age, sex, and risk standardisation was done using standard statistical procedures. Regional variation was quantified using systematic component of variation. To analyse spatial auto-correlation and spatial pattern, global Moran's I and Getis-Ord Gi* were calculated. A total of 50,702 cases were included. Raw hospital incidence of AAA was 15.7 per 100,000 inhabitants (nrAAA 13.1; all rAAA 2.7; treated rAAA 1.6). The standardised hospital incidence of AAA ranged from 6.3 to 30.3 per 100,000. Systematic component of variation proportion was 96% in nrAAA and 55% in treated rAAA. Incidence rates of all AAA were significantly clustered with above average values in the northwestern parts of Germany and below average values in the south and eastern regions. Standardised mortality of nrAAA ranged from 1.7% to 4.3%, with that of treated rAAA ranging from 28% to 52%. Regional variation and spatial distribution of standardised mortality was not different from random. There was significant regional variation and clustering of the hospital incidence of AAA in Germany, with higher rates in the northwest and lower rates in the southeast. There was no significant variation in standardised (age/sex/risk) mortality between counties. Copyright © 2018. Published by Elsevier B.V.

Novel Molecular Imaging Approaches to Abdominal Aortic Aneurysm Risk Stratification

PubMed Central

Toczek, Jakub; Meadows, Judith L.; Sadeghi, Mehran M.

2015-01-01

Selection of patients for abdominal aortic aneurysm (AAA) repair is currently based on aneurysm size, growth rate and symptoms. Molecular imaging of biological processes associated with aneurysm growth and rupture, e.g., inflammation and matrix remodeling, could improve patient risk stratification and lead to a reduction in AAA morbidity and mortality. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and ultrasmall superparamagnetic particles of iron oxide (USPIO) magnetic resonance imaging are two novel approaches to AAA imaging evaluated in clinical trials. A variety of other tracers, including those that target inflammatory cells and proteolytic enzymes (e.g., integrin αvβ3 and matrix metalloproteinases), have proven effective in preclinical models of AAA and show great potential for clinical translation. PMID:26763279

Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm

PubMed Central

Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan

2018-01-01

Abdominal aortic aneurysm (AAA) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of AAA, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for AAAs. However, these treatments are not appropriate for the majority of AAAs, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of AAA. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as AAA. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of AAA. Mechanisms of action underlying the effects of CHMs on AAA are also discussed. PMID:29732374

Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm.

PubMed

Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan

2018-01-01

Abdominal aortic aneurysm (AAA) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of AAA, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for AAAs. However, these treatments are not appropriate for the majority of AAAs, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of AAA. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as AAA. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of AAA. Mechanisms of action underlying the effects of CHMs on AAA are also discussed.

Outcomes over Time in Patients with Hostile Neck Anatomy Undergoing Endovascular Repair of Abdominal Aortic Aneurysm.

PubMed

Bryce, Yolanda; Kim, Wonho; Katzen, Barry; Benenati, James; Samuels, Shaun

2018-07-01

To assess differences in outcome in an early and later time period in patients with hostile neck anatomy who underwent endovascular aneurysm repair (EVAR). This single-center, institutional review board-approved retrospective study assessed patients who underwent EVAR between 2004 and 2013, divided into 2 time periods: 2004-2008 and 2009-2013. One hundred twenty-five patients had at least 1 hostile neck parameter that met inclusion criteria: 61 of 216 (28%) patients in the early period and 64 of 144 (44%) patients in the late period. Patients in the late group were younger compared to patients in the early group (late group, 74.5 ± 8.8 years vs early group, 77.5 ± 7.5 years; P = .046). No significant differences were observed in hostile neck anatomic factors between the early and late periods. No statistical difference was observed in periprocedural factors or outcome measures, except for abdominal aortic aneurysm (AAA) sac regression in the late period compared to the early period (late period, 73.5% vs early period, 55.7%; P = .038). A statistically significant increase was observed in type 1a endoleaks in patients in the late group with suprarenal fixation compared to patients with infrarenal fixation (suprarenal, 27.0% vs infrarenal, 7.9%; P = .025) and in the overall time studied (suprarenal, 20.3% vs infrarenal, 7.6%; P = .045). Except for AAA sac regression, no changes were observed in periprocedural factors and outcome measures over time in patients with hostile neck who underwent EVAR. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.

A 5-year evaluation using the talent endovascular graft for endovascular aneurysm repair in short aortic necks.

PubMed

Jim, Jeffrey; Sanchez, Luis A; Rubin, Brian G; Criado, Frank J; Fajardo, Andres; Geraghty, Patrick J; Sicard, Gregorio A

2010-10-01

Although endovascular aneurysm repair has been shown to be an effective way to treat abdominal aortic aneurysm (AAA), certain anatomic characteristics such as a short aortic neck, limit its applicability. Initially, commercially available devices were approved only for the treatment of AAA with an aortic neck length ≥ 15 mm. The purpose of this study was to evaluate the outcomes of the recently approved Talent endograft for AAAs with a short aortic neck length (10-15 mm). Data were obtained from the prospective, nonrandomized, multicenter Talent enhanced Low Profile Stent Graft System trial which enrolled patients between February 2002 and April 2003. A total of 154 patients with adequate preoperative imaging were identified for this study. Subgroup analyses were performed for AAA with 10-15 mm aortic neck and those with >15 mm neck. Safety and effectiveness endpoints were evaluated at 30 days, 1 year, and 5 years postprocedure. Patients treated with aortic neck lengths of 10-15 mm (n = 35) and those with >15 mm (n = 102) had similar age, gender, and risk factor profile. Both groups had similar preoperative aneurysm morphology in terms of maximum aneurysm size, degree of neck angulation, or proximal neck diameter. There were no statistically significant differences in freedom from major adverse events and mortality rates at 30 and 365 days. Similarly, there was no difference in the effectiveness endpoints at 12 months. At 5 years, there was no difference in migration rate, endoleaks, or change in aneurysm diameter from baseline. In addition, there is no difference in freedom from aneurysm-related mortality (94% vs. 99%). AAAs with short aortic necks (10-15 mm) and otherwise suitable anatomy for endovascular repair can be safely and effectively treated with the Talent endograft with excellent 1 and 5 year outcomes. Copyright © 2010. Published by Elsevier Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Lik Fai, E-mail: rickieclf@yahoo.com.hk; Cheung, Kwok Fai; Chan, Kwong Man

Nellix Endovascular Aneurysm Sealing (EVAS) system is a new concept and technology of abdominal aortic aneurysm (AAA) repair. Elective EVAS using Nellix device was performed for a 83-year-old man with AAA. 2-month post-EVAS CTA surveillance demonstrated mild enlargement of aneurysmal sac and separation of the EndoBags, but without detectable endoleak. The patient developed sudden AAA rupture with retroperitoneal hematoma at about 4 months after EVAS. We postulated that early enlargement of aneurysmal sac and separation of EndoBags of Nellix devices after EVAS, even without detectable endoleak, might indicate significant aneurysmal wall weakening with increased risk of later AAA rupture. To themore » best of the authors’ knowledge, this was the first reported case of aortic rupture after EVAS without detectable endoleak during and after the procedure.« less

Genetic variation within the Y chromosome is not associated with histological characteristics of the atherosclerotic carotid artery or aneurysmal wall.

PubMed

Haitjema, Saskia; van Setten, Jessica; Eales, James; van der Laan, Sander W; Gandin, Ilaria; de Vries, Jean-Paul P M; de Borst, Gert J; Pasterkamp, Gerard; Asselbergs, Folkert W; Charchar, Fadi J; Wilson, James F; de Jager, Saskia C A; Tomaszewski, Maciej; den Ruijter, Hester M

2017-04-01

Haplogroup I, a common European paternal lineage of the Y chromosome, is associated with increased risk of coronary artery disease in British men. It is unclear whether this haplogroup or any other haplogroup on the Y chromosome is associated with histological characteristics of the diseased vessel wall in other vascular manifestations of cardiovascular diseases showing a male preponderance. We examined Dutch men undergoing either carotid endarterectomy from the Athero-Express biobank (AE, n = 1217) or open aneurysm repair from the Aneurysm-Express biobank (AAA, n = 393). Upon resolving the Y chromosome phylogeny, each man was assigned to one of the paternal lineages based on combinations of single nucleotide polymorphisms of the male-specific region of the Y chromosome. We examined the associations between the Y chromosome and the histological characteristics of the carotid plaque and aneurysm wall, including lipid content, leukocyte infiltration and intraplaque haemorrhage, in all men. A majority of men were carriers of either haplogroup I (AE: 28% AAA: 24%) or haplogroup R (AE: 59% AAA: 61%). We found no association between Y chromosomal haplogroups and histological characteristics of plaque collected from carotid arteries or tissue specimens of aneurysms. Moreover, the distribution of frequency for all Y chromosomal haplogroups in both cohorts was similar to that of a general population of Dutch men. Our data show that genetic variation on the Y chromosome is not associated with histological characteristics of the plaques from carotid arteries or specimens of aneurysms in men of Dutch origin. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel strategy to translate the biomechanical rupture risk of abdominal aortic aneurysms to their equivalent diameter risk: method and retrospective validation.

PubMed

Gasser, T C; Nchimi, A; Swedenborg, J; Roy, J; Sakalihasan, N; Böckler, D; Hyhlik-Dürr, A

2014-03-01

To translate the individual abdominal aortic aneurysm (AAA) patient's biomechanical rupture risk profile to risk-equivalent diameters, and to retrospectively test their predictability in ruptured and non-ruptured aneurysms. Biomechanical parameters of ruptured and non-ruptured AAAs were retrospectively evaluated in a multicenter study. General patient data and high resolution computer tomography angiography (CTA) images from 203 non-ruptured and 40 ruptured aneurysmal infrarenal aortas. Three-dimensional AAA geometries were semi-automatically derived from CTA images. Finite element (FE) models were used to predict peak wall stress (PWS) and peak wall rupture index (PWRI) according to the individual anatomy, gender, blood pressure, intra-luminal thrombus (ILT) morphology, and relative aneurysm expansion. Average PWS diameter and PWRI diameter responses were evaluated, which allowed for the PWS equivalent and PWRI equivalent diameters for any individual aneurysm to be defined. PWS increased linearly and PWRI exponentially with respect to maximum AAA diameter. A size-adjusted analysis showed that PWS equivalent and PWRI equivalent diameters were increased by 7.5 mm (p = .013) and 14.0 mm (p < .001) in ruptured cases when compared to non-ruptured controls, respectively. In non-ruptured cases the PWRI equivalent diameters were increased by 13.2 mm (p < .001) in females when compared with males. Biomechanical parameters like PWS and PWRI allow for a highly individualized analysis by integrating factors that influence the risk of AAA rupture like geometry (degree of asymmetry, ILT morphology, etc.) and patient characteristics (gender, family history, blood pressure, etc.). PWRI and the reported annual risk of rupture increase similarly with the diameter. PWRI equivalent diameter expresses the PWRI through the diameter of the average AAA that has the same PWRI, i.e. is at the same biomechanical risk of rupture. Consequently, PWRI equivalent diameter facilitates a straightforward interpretation of biomechanical analysis and connects to diameter-based guidelines for AAA repair indication. PWRI equivalent diameter reflects an additional diagnostic parameter that may provide more accurate clinical data for AAA repair indication. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Aortic aneurysm in a 74-year-old man with coronary disease and obstructive lung disease: is double jeopardy enough?

PubMed

Hagen, M D; Eckman, M H; Pauker, S G

1989-01-01

A previous decision analysis examined a patient with severe CAD, diminished ventricular function, and an abdominal aortic aneurysm and also concluded that CABG followed by aneurysm repair was optimal. This patient, who had well-preserved cardiac function but severely compromised pulmonary status, stood to gain less from CABG than would a patient with more severe coronary disease, thus accounting for the "close-call" between the CABG-AAA and AAA only strategies. Nevertheless, the analysis did emphasize the benefit of aneurysm repair, whether done alone or after CABG. The analysis also highlighted the significant risk of aneurysm rupture the patient is exposed to while recovering from CABG surgery. The operative mortality risks of the two procedures are similar; thus, the patient's total operative risk is approximately doubled if he undergoes both procedures rather than aneurysm repair alone. The key question raised by the analysis is whether this double jeopardy is more than compensated by the degree to which prior CABG reduces both short-term cardiac risk at subsequent aneurysm repair and long-term cardiac mortality. For this patient, who had good cardiac function, the gains appeared sufficient to offset the interval risk of aneurysm rupture and the additional risk associated with a surgical procedures. THE REAL WORLD The patient indeed underwent and tolerated CABG, although he had a stormy prolonged postoperative course due to pulmonary failure. After discharge from the hospital, he declined readmission for repair of the aneurysm. We did not model that possibility, clearly an inadequacy in our tree. Some six months later, the patient was still alive and was, reluctantly, readmitted for aneurysmorrhaphy. At that time, however, his pulmonary function had deteriorated and both the anesthesiologist and the pulmonary consultant stated unequivocally that further surgery was now impossible. In retrospect, the expected utility of CABG without aneurysm repair (thus providing only a decrease in the long-term mortality risk from his CAD) would have been 1.95 (DEALE) or 2.06 (Markov) years. Sensitivity analysis revealed that, even if long-term cardiac risk were completely eliminated by CABG, immediate aneurysm repair would have been a better approach had the patient's physicians known he would be likely to refuse or not be a candidate for the second operation. In summary, although the patient's comorbidities did indeed place him at significant operative risk for either aneurysmorrhaphy alone or two sequential procedures, the benefits to be gained were shown to far outweigh the risks when compared with expectant observation.(ABSTRACT TRUNCATED AT 400 WORDS)

Anatomic characteristics of ruptured abdominal aortic aneurysm on conventional CT scans: Implications for rupture risk.

PubMed

Fillinger, Mark F; Racusin, Jessica; Baker, Robert K; Cronenwett, Jack L; Teutelink, Arno; Schermerhorn, Marc L; Zwolak, Robert M; Powell, Richard J; Walsh, Daniel B; Rzucidlo, Eva M

2004-06-01

The purpose of this study was to analyze anatomic characteristics of patients with ruptured abdominal aortic aneurysms (AAAs), with conventional two-dimensional computed tomography (CT), including comparison with control subjects matched for age, gender, and size. Records were reviewed to identify all CT scans obtained at Dartmouth-Hitchcock Medical Center or referring hospitals before emergency AAA repair performed because of rupture or acute severe pain (RUP group). CT scans obtained before elective AAA repair (ELEC group) were reviewed for age and gender match with patients in the RUP group. More than 40 variables were measured on each CT scan. Aneurysm diameter matching was achieved by consecutively deleting the largest RUP scan and the smallest ELEC scan to prevent bias. CT scans were analyzed for 259 patients with AAAs: 122 RUP and 137 ELEC. Patients were well matched for age, gender, and other demographic variables or risk factors. Maximum AAA diameter was significantly different in comparisons of all patients (RUP, 6.5 +/- 2 cm vs ELEC, 5.6 +/- 1 cm; P <.0001), and mean diameter of ruptured AAAs was 5 mm smaller in female patients (6.1 +/- 2 cm vs 6.6 +/- 2 cm; P =.007). Two hundred patients were matched for diameter, gender, and age (100 from each group; maximum AAA diameter, 6.0 +/- 1 cm vs 6.0 +/- 1 cm). Analysis of diameter-matched AAAs indicated that most variables were statistically similar in the two groups, including infrarenal neck length (17 +/- 1 mm vs 19 +/- 1 mm; P =.3), maximum thrombus thickness (25 +/- 1 mm vs 23 +/- 1 mm, P =.4), and indices of body habitus, such as [(maximum AAA diameter)/(normal suprarenal aorta diameter)] or [(maximum AAA diameter)/(L3 transverse diameter)]. Multivariate analysis controlling for gender indicated that the most significant variables for rupture were aortic tortuosity (odds ratio [OR] 3.3, indicating greater risk with no or mild tortuosity), diameter asymmetry (OR, 3.2 for a 1-cm difference in major-minor axis), and current smoking (OR, 2.7, with the greater risk in current smokers). When matched for age, gender, and diameter, ruptured AAAs tend to be less tortuous, yet have greater cross-sectional diameter asymmetry. On conventional two-dimensional CT axial sections, it appears that when diameter asymmetry is associated with low aortic tortuosity, the larger diameter on axial sections more accurately reflects rupture risk, and when diameter asymmetry is associated with moderate or severe aortic tortuosity, the smaller diameter on axial sections more accurately reflects rupture risk. Current smoking is significantly associated with rupture, even when controlling for gender and AAA anatomy.

Rupture after Previous Endovascular Aneurysm Repair due to Type IA Endoleak: Complete Endograft Preservation Is Feasible with Proximal Suturing, Aortic Neck Banding, and Sac Plication.

PubMed

Karkos, Christos D; Mitka, Maria; Pliatsios, Ioannis; Xanthopoulou, Efthalia; Giagtzidis, Ioakeim T; Papadimitriou, Christina T; Papazoglou, Konstantinos O

2018-05-01

Rupture of an abdominal aortic aneurysm (AAA) after previous endovascular repair (EVAR) may require endograft explantation and replacement with a prosthetic surgical graft. Recent reports have suggested that total endograft removal during late surgical conversion in the nonruptured setting may not be necessary and that preserving functional parts of the endograft may improve results. Similar techniques may be used for ruptured cases diminishing the magnitude of an already difficult and complex procedure. We describe the successful treatment of a ruptured AAA after previous EVAR with complete endograft preservation by combining transmural endograft fixation with sutures, proximal aortic neck banding, and sac plication. Copyright © 2018 Elsevier Inc. All rights reserved.

Prevention of Kinked Stent Graft Limb Due to Severe Angulated Proximal Neck during Endovascular Repair for Abdominal Aortic Aneurysm.

PubMed

Oh, Pyung Chun; Kim, Minsu; Shin, Eak Kyun; Kang, Woong Chol

2018-04-20

Although the technology of endovascular aortic repair (EVAR) for abdominal aortic aneurysm (AAA) is evolving that make it appealing for challenging anatomy, proximal aortic neck morphology, especially severe angulation, is still one of the most determinants for a successful procedure. We describe a patient of AAA with severely angulated proximal neck, in whom kinked stent graft limb occurred against severe angulation of proximal neck. Then, we suggested how to prevent this complication in the second patient. Our case demonstrated the stent graft limb could be kinked by severe aortic neck angulation, making it challenging. However, the kinked stent graft limb could be prevented by deploying stent graft limbs below the most severely angulated aortic neck intentionally.

Abdominal aortic feminism.

PubMed

Mortimer, Alice Emily

2014-11-14

A 79-year-old woman presented to a private medical practice 2 years previously for an elective ultrasound screening scan. This imaging provided the evidence for a diagnosis of an abdominal aortic aneurysm (AAA) to be made. Despite having a number of recognised risk factors for an AAA, her general practitioner at the time did not follow the guidance set out by the private medical professional, that is, to refer the patient to a vascular specialist to be entered into a surveillance programme and surgically evaluated. The patient became symptomatic with her AAA, was admitted to hospital and found to have a tender, symptomatic, 6 cm leaking AAA. She consented for an emergency open AAA repair within a few hours of being admitted to hospital, despite the 50% perioperative mortality risk. The patient spent 4 days in intensive care where she recovered well. She was discharged after a 12 day hospital stay but unfortunately passed away shortly after her discharge from a previously undiagnosed gastric cancer. 2014 BMJ Publishing Group Ltd.

Abdominal aortic feminism

PubMed Central

Mortimer, Alice Emily

2014-01-01

A 79-year-old woman presented to a private medical practice 2 years previously for an elective ultrasound screening scan. This imaging provided the evidence for a diagnosis of an abdominal aortic aneurysm (AAA) to be made. Despite having a number of recognised risk factors for an AAA, her general practitioner at the time did not follow the guidance set out by the private medical professional, that is, to refer the patient to a vascular specialist to be entered into a surveillance programme and surgically evaluated. The patient became symptomatic with her AAA, was admitted to hospital and found to have a tender, symptomatic, 6 cm leaking AAA. She consented for an emergency open AAA repair within a few hours of being admitted to hospital, despite the 50% perioperative mortality risk. The patient spent 4 days in intensive care where she recovered well. She was discharged after a 12 day hospital stay but unfortunately passed away shortly after her discharge from a previously undiagnosed gastric cancer. PMID:25398912

Disparities in the treatment and outcomes of vascular disease in Hispanic patients

PubMed Central

Morrissey, Nicholas J.; Giacovelli, Jeannine; Egorova, Natalia; Gelijns, Annetine; Moskowitz, Alan; McKinsey, James; Kent, Kenneth Craig; Greco, Giampaolo

2008-01-01

Background The Hispanic population represents the fastest growing minority in the United States. As the population grows and ages, the vascular surgery community will be providing increasing amounts of care to this diverse group. To appropriately administer preventive and therapeutic care, it is important to understand the incidence, risk factors, and natural history of vascular disease in Hispanic patients. Methods We analyzed hospital discharge databases from New York and Florida to determine the rate of lower extremity revascularization (LER), carotid revascularization (CR), and abdominal aortic aneurysm (AAA) repair in Hispanics relative to the general population. The rates of common comorbidities, the indications for the procedures, and outcomes during the same hospitalization as the index procedure were determined. Multivariate logistic regression analysis was used to determine the differences between Hispanics and white non-Hispanics with respect to rate of procedure, symptoms at presentation, and outcome after procedure. Demographic variables and length of stay were also analyzed. Results The rate of LER, CR, and AAA repair was significantly lower in Hispanic patients than in white non-Hispanics. Despite this lower rate of intervention, Hispanics were significantly more likely than whites to present with limb-threatening lower extremity ischemia (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.91 to 2.29), symptomatic carotid artery disease (OR, 1.57; 95% CI, 1.4 to 1.75), and ruptured AAA (OR, 1.26; 95% CI, 1.04-1.52) than white non-Hispanics These differences were maintained after controlling for the presence of diabetes mellitus and other comorbidities. Hispanic patients had higher rates of amputation during the same hospitalization after LER (6.2% vs 3.4%, P < .0001) and higher mortality after elective AAA repair (5% vs 3.4%, P = .0032). Length of stay after LER, CR, and AAA repair was longer for Hispanic patients than white non-Hispanics. Conclusion Significant disparities in the rate of utilization of three common vascular surgical procedures exist between Hispanic patients and the general population. In addition, Hispanics appear to present with more advanced disease and have worse outcomes in some cases. Reasons for these disparities must be determined to improve these results in the fastest growing segment of our society. PMID:17980283

Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development.

PubMed

Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel; Martinez-Lopez, Diego; Torres-Fonseca, Monica; Lindhot, Jes S; Vega de Ceniga, Melina; Egido, Jesus; Lopez-Andres, Natalia; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

2017-11-15

Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients ( n =225) compared with the control group ( n =100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

[Early inflammatory response following elective abdominal aortic aneurysm repair: a comparison between endovascular procedure and conventional, open surgery].

PubMed

Marjanović, Ivan; Jevtić, Miodrag; Misović, Sidor; Vojvodić, Danilo; Zoranović, Uros; Rusović, Sinisa; Sarac, Momir; Stanojević, Ivan

2011-11-01

Abdominal aorta aneurysm (AAA) represents a pathological enlargment of infrarenal portion of aorta for over 50% of its lumen. The only treatment of AAA is a surgical reconstruction of the affected segment. Until the late XX century, surgical reconstruction implied explicit, open repair (OR) of AAA, which was accompanied by a significant morbidity and mortality of the treated patients. Development of endovascular repair of (EVAR) AAA, especially in the last decade, offered another possibility of surgical reconstruction of AAA. The preliminary results of world studies show that complications of such a procedure, as well as morbidity and mortality of patients, are significantly lower than with OR of AAA. The aim of this paper was to present results of comparative clinical prospective study of early inflammatory response after reconstruction of AAA be tween endovascular and open, conventional surgical technique. A comparative clinical prospective study included 39 patients, electively operated on for AAA within the period of December 2008 - February 2010, divided into two groups. The group I counted 21 (54%) of the patients, 58-87 years old (mean 74.3 years), who had been submited to EVAR by the use of excluder stent graft. The group II consisted of 18 (46%) of the patients, 49-82 (mean 66.8) years, operated on using OR technique. All of the treated patients in both groups had AAA larger than 50 mm. The study did not include patients who have been treated as urgent cases, due to the rupture or with simptomatic AAA. Clinical, biochemical and inflamatory parameters in early postoperative period were analyzed, in direct postoperative course (number of leucocytes, thrombocytes, serum circulating levels of cytokine--interleukine (IL)-2, IL-4, IL-6 and IL-10). Parameters were monitored on the zero, first, second, third and seventh postoperative days. The study was approved by the Ethics Commitee of the Military Medical Academy. The study showed a statistically significantly shorter time of treatment in the EVAR group (average 90 min) compared to the OR group (average 136 min). Also, there was a statistically significantly less blood loss in the patients operated on by the use of EVAR surgery (average 60 mL) as compared to the patients treated with OR techinique (average 495 mL), as well as a shorter postoperative hospitalization of patients in the EVAR group (average 4 days) compared to the OR group (average 8 days). The OR group was detected with a statistically significant increase of leucocytes and statistically significant fall of the number of thrombocytes in comparison with the EVAR group in all the investigated terms. A significant concentration rise of IL-2 in the OR group and concentration rise of IL-6 in the EVAR group was shown 24 hours after the procedure, whereas on the second postoperative day there was detected a significant fall of IL-6 in the EVAR group. IL-4 concentration in the OR group was significantly higher as of the third postoperative day in comparison to the EVAR group. There was no significant difference in IL-10 concentration between the groups. The EVAR techinique is a safer and less invasive and less traumatic procedure for patients than the OR of AAA. Following the EVAR, there are less inflammatory reactions in the early postoperative period as compared to the OR and therefore less possibility of the development of systemic inflammatory respons syndrome in patients treated.

Risk models for mortality following elective open and endovascular abdominal aortic aneurysm repair: a single institution experience.

PubMed

Choke, E; Lee, K; McCarthy, M; Nasim, A; Naylor, A R; Bown, M; Sayers, R

2012-12-01

To develop and validate an "in house" risk model for predicting perioperative mortality following elective AAA repair and to compare this with other models. Multivariate logistics regression analysis was used to identify risk factors for perioperative-day mortality from one tertiary institution's prospectively maintained database. Consecutive elective open (564) and endovascular (589) AAA repairs (2000-2010) were split randomly into development (810) and validation (343) data sets. The resultant model was compared to Glasgow Aneurysm Score (GAS), Modified Customised Probability Index (m-CPI), CPI, the Vascular Governance North West (VGNW) model and the Medicare model. Variables associated with perioperative mortality included: increasing age (P = 0.034), myocardial infarct within last 10 years (P = 0.0008), raised serum creatinine (P = 0.005) and open surgery (P = 0.0001). The areas under the receiver operating characteristic curve (AUC) for predicted probability of 30-day mortality in development and validation data sets were 0.79 and 0.82 respectively. AUCs for GAS, m-CPI and CPI were poor (0.63, 0.58 and 0.58 respectively), whilst VGNW and Medicare model were fair (0.73 and 0.79 respectively). In this study, an "in-house" developed and validated risk model has the most accurate discriminative value in predicting perioperative mortality after elective AAA repair. For purposes of comparative audit with case mix adjustments, national models such as the VGNW or Medicare models should be used. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Beneficial Effects of Pre-operative Exercise Therapy in Patients with an Abdominal Aortic Aneurysm: A Systematic Review.

PubMed

Pouwels, S; Willigendael, E M; van Sambeek, M R H M; Nienhuijs, S W; Cuypers, P W M; Teijink, J A W

2015-01-01

The impact of post-operative complications in abdominal aortic aneurysm (AAA) surgery is substantial, and increases with age and concomitant co-morbidities. This systematic review focuses on the possible effects of pre-operative exercise therapy (PET) in patients with AAA on post-operative complications,aerobic capacity, physical fitness, and recovery. A systematic search on PET prior to AAA surgery was conducted. The methodological quality of the included studies was rated using the Physiotherapy Evidence Database scale. The agreement between the reviewers was assessed with Cohen's kappa. Five studies were included, with a methodological quality ranging from moderate to good. Cohen's kappa was 0.79. Three studies focused on patients with an AAA (without indication for surgical repair) with physical fitness as the outcome measure. One study focused on PET in patients awaiting AAA surgery and one study focused on the effects of PET on post-operative complications, length of stay, and recovery. PET has beneficial effects on various physical fitness variables of patients with an AAA. Whether this leads to less complications or faster recovery remains unclear. In view of the large impact of post-operative complications, it is valuable to explore the possible benefits of a PET program in AAA surgery.

Endovascular Aneurysm Repair of Acute Occlusion of Abdominal Aortic Aneurysm with Intra-Aneurysmal Dissection.

PubMed

Terai, Yasuhiko; Mitsuoka, Hiroshi; Nakai, Masanao; Goto, Shinnosuke; Miyano, Yuta; Tsuchiya, Hirokazu; Yamazaki, Fumio

2015-11-01

To report a rare case of acute abdominal aortic aneurysm (AAA) occlusion successfully treated by endovascular aneurysm repair (EVAR). An 89-year-old man complained of severe back pain and weakness in the bilateral lower extremities. Although there were neither acute ischemic signs on the brain computed tomography (CT) nor critical leg ischemia, the patient presented progressing weakness in the bilateral lower extremities and decreased sensation in the perianal and saddle area. Contrast-enhanced CT demonstrated an infrarenal AAA, the formation of an ulcer-like lesion in the aneurysmal wall, and the complete occlusion of distal AAA because of the caudal extension of intramural hematoma. Both common iliac arteries were patent because of the development of collateral vessels. The neurologic symptoms were considered to be caused by the occlusion of lumbar radicular arteries. EVAR seemed anatomically feasible, if the occlusion could be crossed by guidewires from both side of the common femoral artery. Wires easily traversed the occlusion, and the stent graft could be smoothly unwrapped and opened. The patient could recover decent iliac arterial flow. The neurovascular deficits recovered within 4 days after the procedure. Although our experience may not be reproduced in all case of AAA occlusion, EVAR warrants consideration to reduce the high mortality rate associated with the classical treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm

PubMed Central

Sun, Jingyuan; Deng, Hongping; Zhou, Zhen

2018-01-01

Abdominal aortic aneurysm (AAA) was previously ascribed to weaken defective medial arterial/adventitial layers, for example, smooth muscle/fibroblast cells. Therefore, besides surgical repair, medications targeting the medial layer to strengthen the aortic wall are the most feasible treatment strategy for AAA. However, so far, it is unclear whether such drugs have any beneficial effect on AAA prognosis, rate of aneurysm growth, rupture, or survival. Notably, clinical studies have shown that AAA is highly associated with endothelial dysfunction in the aged population. Additionally, animal models of endothelial dysfunction and endothelial nitric oxide synthase (eNOS) uncoupling had a very high rate of AAA formation, indicating there is crucial involvement of the endothelium and a possible pharmacological solution targeting the endothelium in AAA treatment. Endothelial cells have been found to trigger vascular wall remodeling by releasing proteases, or recruiting macrophages along with other neutrophils, into the medial layer. Moreover, inflammation and oxidative stress of the arterial wall were induced by endothelial dysfunction. Interestingly, there is a paradoxical differential correlation between diabetes and aneurysm formation in retinal capillaries and the aorta. Deciphering the significance of such a difference may explain current unsuccessful AAA medications and offer a solution to this treatment challenge. It is now believed that AAA and atherosclerosis are two separate but related diseases, based on their different clinical patterns which have further complicated the puzzle. Therefore, a thorough investigation of the interaction between endothelium and medial/adventitial layer may provide us a better understanding and new perspective on AAA formation, especially after taking into account the importance of endothelium in the development of AAA. Moreover, a novel medication strategy replacing the currently used, but suboptimal treatments for AAA, could be informed with this analysis. PMID:29849906

Early Enlargement of Aneurysmal Sac and Separation of EndoBags of Nellix Endovascular Aneurysm Sealing System as Signs of Increased Risk of Later Aneurysm Rupture.

PubMed

Cheng, Lik Fai; Cheung, Kwok Fai; Chan, Kwong Man; Ma, Johnny Ka Fai; Luk, Wing Hang; Chan, Micah Chi King; Ng, Carol Wing Kei; Mahboobani, Neeraj Ramesh; Ng, Wai Kin; Wong, Ting

2016-11-01

Nellix Endovascular Aneurysm Sealing (EVAS) system is a new concept and technology of abdominal aortic aneurysm (AAA) repair. Elective EVAS using Nellix device was performed for a 83-year-old man with AAA. 2-month post-EVAS CTA surveillance demonstrated mild enlargement of aneurysmal sac and separation of the EndoBags, but without detectable endoleak. The patient developed sudden AAA rupture with retroperitoneal hematoma at about 4 months after EVAS. We postulated that early enlargement of aneurysmal sac and separation of EndoBags of Nellix devices after EVAS, even without detectable endoleak, might indicate significant aneurysmal wall weakening with increased risk of later AAA rupture. To the best of the authors' knowledge, this was the first reported case of aortic rupture after EVAS without detectable endoleak during and after the procedure.

Update on the status of infrarenal AAA devices.

PubMed

Hart, Theodore; Milner, Ross

2018-06-01

There are a variety of endografts currently available for endovascular repair of abdominal aortic aneurysms. Aneurysms of increasing anatomic complexity are being repaired with devices that are either newly approved or redesigned relative to the initial published experience with infrarenal endovascular aortic aneurysm repair (EVAR). This article describes the contemporary devices approved for infrarenal EVAR in the United States and includes an up-to-date compilation of the data addressing outcomes specific to each device.

Explanting the Nellix Endovascular Aortic Sealing Endoprosthesis for Proximal Aortic Neck Failure.

PubMed

Lee, Cheong Jun; Cuff, Robert

2018-05-17

Open conversion following endovascular aortic repair (EVAR) has inherent challenges particular to the device being explanted. The Nellix endograft is unlike any other device as it utilizes polymer filling of endobags within the aorto-iliac lumen to seal the AAA sac; a developing concept known as endovascular aortic sealing (EVAS). Conversion to open repair of AAA treated with the Nellix endograft have rarely been discussed. Explants that have been previously reported were for graft infection. We present two Nellix graft explants that were required for device migration and subsequent development of a type IA endoleak. The technique and nuances observed during open conversion of this novel endograft for proximal aortic neck failure is described in this report. Copyright © 2018. Published by Elsevier Inc.

Prevalence of Synchronous and Metachronous Aneurysms in Women With Abdominal Aortic Aneurysm.

PubMed

Wallinder, Jonas; Georgiou, Anna; Wanhainen, Anders; Björck, Martin

2018-06-20

Abdominal aortic aneurysm (AAA) is three to five times more common among men compared with women, yet up to 38% of all aneurysm related deaths affect women. The aim of this study was to estimate the prevalence of synchronous or metachronous aneurysms among women with AAA, as diagnosis and treatment could improve survival. This is a retrospective study of prospectively registered patients. All women operated on, or under surveillance for, AAA were identified at two Swedish hospitals. Aneurysms in different locations were identified using available imaging studies. Aneurysms were defined according to location: thoracic ascending aorta ≥42 mm, descending ≥33 mm, abdominal aorta ≥30 mm, common iliac artery ≥20 mm or 50% wider than the contralateral artery, common femoral artery ≥12 mm, popliteal artery ≥10 mm. A total of 339 women with an AAA were included. The median follow up was 2.8 (range 0-15.7) years. Thirty-one per cent had an aneurysm in the thoracic aorta (67 of 217 investigated, 84% were located in the descending aorta), 13 (19%) underwent repair. Twelve per cent had a common iliac artery aneurysm (24/259, 76% were investigated). Common femoral artery aneurysms were identified in 4.3% (8/184, 54% investigated). Popliteal artery aneurysms were identified in 4.0% (6/149, 44% investigated). The prevalence of infrainguinal aneurysms was higher among patients with synchronous iliac aneurysms (40% vs. 1.6%, OR 42, 95% CI 6.4-279, p < .001). Thoracic aortic aneurysms are common among women with AAA, most commonly affecting the descending aorta, and detection frequently results in repair. Popliteal and femoral aneurysms are not rare among women with AAA, and even common if there is a synchronous iliac aneurysm. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Long-term results of Talent endografts for endovascular abdominal aortic aneurysm repair.

PubMed

Verhoeven, Bart A N; Waasdorp, Evert J; Gorrepati, Madhu L; van Herwaarden, Joost A; Vos, Jan Albert; Wille, Jan; Moll, Frans L; Zarins, Christopher K; de Vries, Jean Paul P M

2011-02-01

Since the introduction of endovascular aneurysm repair (EVAR), long-term follow-up studies reporting single-device results are scarce. In this study, we focus on EVAR repair with the Talent stent graft (Medtronic, Santa Rosa, Calif). Between July 2000 and December 2007, 365 patients underwent elective EVAR with a Talent device. Patient data were gathered prospectively and evaluated retrospectively. By American Society of Anesthesiologists category, 74% were categories III and IV. Postoperative computed tomography (CT) scanning was performed before discharge, at 3, 12 months, and yearly thereafter. Data are presented according to reporting standards for EVAR. The mean proximal aortic neck diameter was 27 mm (range, 16-36 mm), with a neck length <15 mm in 31% (data available for 193 patients). Deployment of endografts was successful in 361 of 365 patients (99%). Initially, conversion to laparotomy was necessary in four patients. Primary technical success determined by results from computed tomography (CT) scans before discharge was achieved in 333 patients (91%). Proximal type I endoleaks were present in 28 patients (8%) during follow-up, and 14 of these patients needed additional treatment for type I endoleak. The 30-day mortality for the whole Talent group was 1.1% (4 of 365). Follow-up to 84 months is reported for 24 patients. During follow-up, 122 (33%) patients died; in nine, death was abdominal aortic aneurysm (AAA)-related (including 30-day mortality). Kaplan-Meier estimates revealed primary clinical success rates of 98% at 1 year, 93% at 2 years, 88% at 3 years, 79% at 4 years, 64% at 5 years, 51% at 6 years, and 48% at 7 years. Secondary interventions were performed in 73 of 365 patients (20%). Ten conversions for failed endografts were performed. Life-table yearly risk for AAA-related reintervention was 6%, yearly risk for conversion to open repair was 1.1%, yearly risk for total mortality was 8.9%, and yearly risk for AAA-related mortality was 0.8%. Initially, technical success of endovascular aneurysm repair (EVAR) using the Talent endograft is high, with acceptable yearly risk for AAA-related mortality and conversion. However, a substantial amount of mainly endovascular reinterventions is necessary during long-term follow-up to achieve these results. Copyright © 2011 Society for Vascular Surgery. All rights reserved.

Measurement of free radicals using electron paramagnetic resonance spectroscopy during open aorto-iliac arterial reconstruction.

PubMed

Majewski, Wacław; Krzyminiewski, Ryszard; Stanisić, Michał; Iskra, Maria; Krasiński, Zbigniew; Nowak, Marek; Dobosz, Bernadeta

2014-11-27

Aortic cross-clamping during abdominal aortic aneurysm (AAA) open repair leads to development of ischemia-reperfusion injury. Electron paramagnetic resonance spectroscopy (EPR) spin-trapping is a valuable method of direct measurement of free radicals. The objective of the study was to evaluate the results of EPR as a direct method of free radical measurement and degree of inflammatory response in open operative treatment of patients with AAA and aorto-iliac occlusive disease (AIOD). The study was performed on a group of 32 patients with AAA and 25 patients with AIOD scheduled for open repair. Peripheral venous blood for EPR spectroscopy and for SOD, GPx, ox-LDL, Il-6, TNF-alfa, CRP, and HO-1 were harvested. Selected parameters were established accordingly to specified EPR and immunohistochemical methods and analyzed between groups by Mann-Whitney U test and Wilcoxon matched-pairs signed-ranks test with Bonferroni correction. Free radicals level was correlated with the time of the aortic cross-clamping after the reperfusion of he first and second leg in AAA (r=0.7; r=0.47). ox-LDL in AAA decreased 5 min after reperfusion of the first leg (32.99 U/L, range: 14.09-77.12) and 5 min after reperfusion of the second leg (26.75 U/L, range: 11.56-82.12) and 24 h after the operation (25.85 U/L, range: 14.29-49.70). HO-1 concentration increased to above the level before intervention 24 h after surgery. The activities of GPx and SOD decreased 5 min after the first-leg reperfusion in AAA. Twenty-four hours after surgery, inflammatory markers increased in AAA to CRP was 14.76 ml/l (0.23-38.55), IL-6 was 141.22 pg/ml (84.3-591.03), TNF-alfa was 6.82 pg/ml (1.76-80.01) and AIOD: CRP was 18.44 mg/l (2.56-33.14), IL-6: 184.1 pg/ml (128.46-448.03), TNF-alfa was 7.74 pg/ml (1.74-74.74). EPR spin-trapping demonstrates temporarily elevated level of free radicals in early phase of reperfusion, leading to decrease antioxidants in AAA. Elevated free radical levels decreased 24 h after surgery due to various endogenous antioxidants and therapies.

Association of statin prescription with small abdominal aortic aneurysm progression

PubMed Central

Ferguson, Craig D.; Clancy, Paula; Bourke, Bernard; Walker, Philip J.; Dear, Anthony; Buckenham, Tim; Norman, Paul; Golledge, Jonathan

2009-01-01

Background Statins have been suggested to reduce expansion of abdominal aortic aneurysms (AAA) independent of lipid lowering effects. Methods We assessed the association of statin treatment and serum low density lipoprotein (LDL) concentrations with small AAA expansion. 652 patients undergoing surveillance of small AAAs were entered into the study from five vascular centers. In a subset fasting lipids (n=451) and other biomarkers (n=216) were measured. AAA diameter was followed by ultrasound surveillance for a median of 5 years. Results 349 (54%) of the patients were prescribed statins. Adjusting for other risk factors statin prescription was not associated with AAA growth (odds ratio, OR, 1.23, 95% confidence interval, CI, 0.86–1.76). Above median AAA growth was positively associated with initial diameter (OR 1.78 per 4.35mm larger initial aortic diameter, 95% CI 1.49–2.14) and negatively associated with diabetes (OR 0.37, 95% CI 0.22–0.62). Above median serum LDL concentration was not associated with AAA growth. Patients receiving statins had lower serum C-reactive protein concentrations but similar matrix metalloproteinase-9 and interleukin-6 concentrations to those not prescribed these medications. Conclusions We found no association between statin prescription or LDL concentration with AAA expansion. The results do not support the findings of smaller studies and suggest that statins may have no benefit in reducing AAA progression. PMID:20152231

Geometric analysis of ruptured and nonruptured abdominal aortic aneurysms.

PubMed

Kimura, Masaru; Hoshina, Katsuyuki; Miyahara, Kazuhiro; Nitta, Jun; Kobayashi, Masaharu; Yamamoto, Sota; Ohshima, Marie

2018-06-15

The objective of this study was to use parameters to determine the geometric differences between ruptured abdominal aortic aneurysms (AAAs) and nonruptured AAAs. Computed tomography data of 38 ruptured AAAs and 215 electively repaired (nonruptured) AAAs were collected from multiple institutes. We compared the ruptured AAA group and nonruptured AAA group with 1:1 matching by using the Mahalanobis distance, which was calculated using the patient's age, sex, and AAA diameter. We selected the longitudinal AAA image in multiplanar reconstruction view, placed a hypothetical ellipse on the aneurysm's protruded curve, and placed a circle on the portion connecting the aneurysm and the aorta. We then measured the aspect ratio (the vertical diameter divided by the horizontal diameter) and fillet radius (the radius of arc). The aspect ratio was significantly lower in the ruptured group than in the nonruptured group (2.02 ± 0.53 vs 2.60 ± 1.02; P = .002), as was the fillet radius (0.28 ± 0.18 vs 0.81 ± 0.44; P < .001). Receiver operating characteristic analysis revealed that the area under the curve of the aspect ratio was 0.688, and the optimal cutoff point was 2.23, with sensitivity and specificity of 0.55 and 0.76, respectively. The area under the curve of the fillet radius was 0.933, and the optimal cutoff was 0.347, with sensitivity and specificity of 0.97 and 0.87, respectively. The geometric analysis performed in this study revealed that ruptured AAAs had a smaller fillet radius and smaller aspect ratio than nonruptured AAAs did. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Short- and long-term survival after open versus endovascular repair of abdominal aortic aneurysm-Polish population analysis.

PubMed

Symonides, Bartosz; Śliwczyński, Andrzej; Gałązka, Zbigniew; Pinkas, Jarosław; Gaciong, Zbigniew

2018-01-01

The aim of the study was to compare short and long-term mortality and readmissions in patients with non-ruptured abdominal aortic aneurysm (AAA) treated with endovascular aortic repair (EVAR) or open aneurysm repair (OAR). Retrospective survival analysis based on prospectively collected medical records of the national Polish public health insurer. In the National Health Fund database we identified all patients who underwent elective open or endovascular treatment of AAA between January 1st 2011 and March 22nd 2016. The data on mortality, selected concomitant diseases and readmissions were collected. A total of 7805 patients (mean age 70.9±8.1 yrs, 85.8% males) underwent OAR (n = 2336) or EVAR (n = 5469). A median follow up was 27.5 months (IQR range 10.0-38.4 months). The primary outcome variable was all-cause mortality, secondary outcomes included 30-day mortality and readmissions. Kaplan-Meier (K-M), Cox proportional-hazards and propensity score analyses were performed for primary and secondary outcomes adjusting for repair type of AAA (OAR vs. EVAR), age, sex and concomitant diseases. EVAR patients had higher all-cause mortality (6.4% vs. 4.6% P = 0.002, adjHR 1.34, 95%CI 1.07-1.67, P = 0.010) compared with OAR. The mortality risks for OAR patients decreased below those for EVAR patients after 9.9 months. Of all the tested confounding factors only age independently and significantly influenced long-term mortality. Readmissions occurred more often in EVAR than in OAR (16.5% vs. 8.4% P<0.001, adjHR 2.15, 95%CI 1.84-2.52, P<0.001) independently from other covariants. Survival and readmissions Kaplan-Meier curves remained statistically different between OAR and EVAR patients after propensity score matching. Survival benefit of EVAR over OAR disappeared early during the first year after procedure, particularly in patients below 70 years of age, accompanied by an increased frequency of readmissions of EVAR patients. Our data suggest re-evaluation of the strategy for AAA management in vascular units in the country.

m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

PubMed

Consolato, Francesco; Maltecca, Francesca; Tulli, Susanna; Sambri, Irene; Casari, Giorgio

2018-04-09

The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m) - AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m - AAA and i - AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

Early and Late Outcomes of Endovascular Aortic Aneurysm Repair versus Open Surgical Repair of an Abdominal Aortic Aneurysm: A Single-Center Study.

PubMed

Choi, Kyunghak; Han, Youngjin; Ko, Gi-Young; Cho, Yong-Pil; Kwon, Tae-Won

2018-06-09

The objective of the study was to compare the treatment outcomes and cost of endovascular aortic aneurysm repair (EVAR) and open surgical repair (OSR) in patients with an abdominal aortic aneurysm (AAA) at a single center. Patients treated for an AAA at a single center between January 2007 and December 2012 were retrospectively identified and classified based on the treatment they received (EVAR or OSR). Patient demographics and in-hospital costs were recorded. Long-term survival was calculated using the Kaplan-Meier method. During the study period, 401 patients with AAA were treated at Asan Medical Center. Among these cases, 226 were treated with EVAR (56%) and 175 received OSR (44%). The mean age of the EVAR group was higher than that of the OSR group (71.25 ± 7.026 vs. 61.26 ± 8.175, P < 0.001). The need for intraoperative transfusion and total length of in-hospital stay were significantly lower in the EVAR group (P < 0.001). The OSR group showed significantly reduced rates of overall mortality (P = 0.003), overall reintervention (P = 0.001), and long-term survival (63.98 ± 1.86 vs. 99.54 ± 3.17, P < 0.001). The OSR group was charged significantly less than the EVAR group ($12,879.21 USD vs. $18,057.78 USD, P < 0.001). EVAR has advantages over OSR in terms of short-term mortality, in-hospital length of stay, and rates of perioperative transfusion. However, OSR is associated with better long-term survival, lower reintervention rates, and lower costs. Copyright © 2018 Elsevier Inc. All rights reserved.

Prior Radiological Investigations in 65-Year-Old Men Screened for AAA.

PubMed

Meecham, Lewis; Summerour, Virginia; Hobbs, Simon; Newman, Jeremy; Wall, Michael L

2018-05-01

The National Health Service abdominal aortic aneurysm screening programme (NAAASP) is now fully operational. Those who have previously been formally investigated for abdominal aortic aneurysm (AAA) are excluded; however, many patients undergo radiological investigation of the abdomen for other reasons. Such practices may find incidental AAA which may be eroding the performance of the NAAASP. We investigated the rates of preinvestigation before invitation to screening in our local AAA screening programme. Electronic patient records were retrospectively reviewed for all patients called between March 2013 and February 2016 in 1 local AAA screening programme. Their records were interrogated to identify any abdominal imaging within 5 years of their invitation to screening. Two thousand six hundred thirty-eight men were invited for screening; of these, 563 (21.3%) had been "prescreened". Median time between prescreening and screening was 19 months (0-60 months). Ultrasound abdomen was the most prevalent at 248 (44.0%). Two thousand two hundred forty-three (85.0%) men attended screening, and 6 (0.27%) were excluded for known AAA. Prevalence of AAA was 1.8% (n = 41). Of these, 15 (36.6%) had prior investigation with 6 (40.0%) having AAA diagnosed. Therefore, 9 (22.0%) had potential missed AAA on "prescreening" (mean diameter 35 mm [30-45], mean time lapse between investigation and screening 21.1 months [1-49]). Incidence of missed aneurysm in the "prescreened" cohort was 1.6% (9/563). Large numbers of men invited for AAA screening have undergone preinvestigation of their abdominal aorta, with 60% of the present AAA being missed. Reliance on incidental detection of AAA would leave many patients undiagnosed in the community-at risk of future rupture. Copyright © 2018 Elsevier Inc. All rights reserved.

Spinal cord ischemia following elective endovascular repair of infrarenal aortic aneurysms: A systematic review.

PubMed

Moulakakis, Konstantinos G; Alexiou, Vangelis G; Karaolanis, Georgios; Sfyroeras, George S; Theoharopoulos, George; Lazaris, Andreas; Kakisis, John; Geroulakos, George

2018-06-06

Spinal cord ischemia (SCI) following endovascular abdominal aortic aneurysm (AAA) repair (EVAR) is a rare but devastating complication. The mechanism underlying the occurrence of SCI following EVAR seems to be multifactorial and is underreported and not fully elucidated. The aim of the study was to investigate the clinical outcomes in patients with this serious complication. A systematic review of the current literature, as per PRISMA statement guidelines, to evaluate the incidence of SCI following elective EVAR was performed. PubMed and Scopus databases were systematically searched. Studies reporting on thoracic endovascular aneurysm repair, open repair of AAAs, and symptomatic or ruptured AAAs were excluded. In total, 18 articles reporting 25 cases were included. The mean age was 74.6 ± 7.6 (range: 60-90) years. The mean diameter of AAAs was 5.96 ± 1.0 cm (range: 4.7-8.3). Six cases also had aneurysms in the common iliac arteries. Seventy-one percent of AAAs had characteristics that made EVAR difficult and technically demanding. The mean operative time was prolonged, 254 ± 104.6 minutes, and associated with extensive intravascular handling. In 41.6% of cases, additional procedures were performed because of the difficult anatomy. Thirty-two percent of the cases had 1 internal iliac artery (IIA) embolized with coils or covered with the stent graft and 14% had both IIAs compromised. In most of the cases, SCI symptoms presented immediately after the operation, and in 14.8% of patients the symptoms had late presentation. Almost all cases had motor loss in the form of paraparesis or paraplegia, 54% of the cases also had diminished sensation, and 29.1% of the cases had urinary and/or fecal incontinence. Heterogeneity was observed regarding the management of the disease; in 6 of the cases cerebrospinal fluid (CSF) drainage was performed, steroids were administered in 5, and in the other cases an expectant strategy was selected. In 50% of the cases, only small improvement was seen at follow-up. In 25% of the cases no improvement was seen, and 25% had almost complete recovery. Our study identified a common pattern among patients who present SCI following EVAR: difficult anatomy, prolonged operative time, additional procedures, and extensive intravascular handling that may have led to embolization. Patency of pelvic circulation preoperatively is also of importance. Regarding outcomes, only 25% of patients recovered, and in certain cases CSF drainage may have significantly improved chances for recovery. Copyright © 2018. Published by Elsevier Inc.

Adventitial adipogenic degeneration is an unidentified contributor to aortic wall weakening in the abdominal aortic aneurysm.

PubMed

Doderer, Stefan A; Gäbel, Gabor; Kokje, Vivianne B C; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

2018-06-01

The processes driving human abdominal aortic aneurysm (AAA) progression are not fully understood. Although antiinflammatory and proteolytic strategies effectively quench aneurysm progression in preclinical models, so far all clinical interventions failed. These observations hint at an incomplete understanding of the processes involved in AAA progression and rupture. Interestingly, strong clinical and molecular associations exist between popliteal artery aneurysms (PAAs) and AAAs; however, PAAs have an extremely low propensity to rupture. We thus reasoned that differences between these aneurysms may provide clues toward (auxiliary) processes involved in AAA-related wall debilitation. A better understanding of the pathophysiologic processes driving AAA growth can contribute to pharmaceutical treatments in the future. Aneurysmal wall samples were collected during open elective and emergency repair. Control perirenal aorta was obtained during kidney transplantation, and reference popliteal tissue obtained from the anatomy department. This study incorporates various techniques including (immuno)histochemistry, Western Blot, quantitative polymerase chain reaction, microarray, and cell culture. Histologic evaluation of AAAs, PAAs, and control aorta shows extensive medial (PAA) and transmural fibrosis (AAA), and reveals abundant adventitial adipocytes aggregates as an exclusive phenomenon of AAAs (P < .001). Quantitative polymerase chain reaction, immunohistochemistry, Western blotting, and microarray analysis showed enrichment of adipogenic mediators (C/EBP family P = .027; KLF5 P < .000; and peroxisome proliferator activated receptor-γ, P = .032) in AAA tissue. In vitro differentiation tests indicated a sharply increased adipogenic potential of AAA adventitial mesenchymal cells (P < .0001). Observed enrichment of adipocyte-related genes and pathways in ruptured AAA (P < .0003) supports an association between the extent of fatty degeneration and rupture. This translational study identifies extensive adventitial fatty degeneration as an ignored and distinctive feature of AAA disease. Enrichment of adipocyte genesis and adipocyte-related genes in ruptured AAA point to an association between the extent of fatty degeneration and rupture. This observation may (partly) explain the failure of medical therapy and could provide a lead for pharmaceutical alleviation of AAA progression. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Use of an Assistant Surgeon Does not Mitigate the Effect of Lead Surgeon Volume on Outcomes Following Open Repair of Intact Abdominal Aortic Aneurysms.

PubMed

Deery, Sarah E; O'Donnell, Thomas F X; Zettervall, Sara L; Darling, Jeremy D; Shean, Katie E; O'Malley, A James; Landon, Bruce E; Schermerhorn, Marc L

2018-05-01

While higher lead surgeon volume has been associated with lower mortality following open abdominal aortic aneurysm (AAA) repair, little is known about the impact of using an attending surgeon as assistant surgeon. The aim of this study was to determine whether the presence of an assistant surgeon, particularly a high volume assistant, mitigates the relationship between lead surgeon volume and outcomes. All Medicare beneficiaries who underwent intact, open AAA repair between 2003 and 2008 were evaluated and nested regression models were constructed to evaluate the relationship between surgeon and assistant volume and peri-operative mortality, adjusting for comorbid conditions and hospital volume. In total 28,590 repairs were studied, of which 19,284 (67.5%) were performed by a single surgeon and 9306 (32.5%) included an assistant surgeon. Of cases with an assistant, 12.3% included a high volume assistant surgeon. Lower volume surgeons more frequently used an assistant (lead surgeon Q1 volume: 40%; Q2: 36%; Q3: 34%; Q4: 29%; Q5: 27% [p < .01]). In cases with no assistant, adjusted peri-operative mortality varied monotonically with surgeon volume (Q1: 4.7%; Q2: 4.4%; Q3: 4.1%; Q4: 3.3%; Q5: 3.2%). However, the use of a high or a low volume assistant surgeon, compared with no attending surgeon as assistant, was not associated with lower peri-operative mortality in any lead surgeon volume quintile, even among those operations performed by the lowest volume lead surgeons. Employing an assistant surgeon does not improve outcomes amongst any quintile of volume of the lead surgeon. As surgeons perform fewer open AAA repairs in the modern era, these data imply that even the help of a high volume assistant surgeon may not mitigate the detrimental effect of a lower volume surgeon. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Understanding administrative abdominal aortic aneurysm mortality data.

PubMed

Hussey, K; Siddiqui, T; Burton, P; Welch, G H; Stuart, W P

2015-03-01

Administrative data in the form of Hospital Episode Statistics (HES) and the Scottish Morbidity Record (SMR) have been used to describe surgical activity. These data have also been used to compare outcomes from different hospitals and regions, and to corroborate data submitted to national audits and registries. The aim of this observational study was to examine the completeness and accuracy of administrative data relating to abdominal aortic aneurysm (AAA) repair. Administrative data (SMR-01 returns) from a single health board relating to AAA repair were requested (September 2007 to August 2012). A complete list of validated procedures; termed the reference data set was compiled from all available sources (clinical and administrative). For each patient episode electronic health records were scrutinised to confirm urgency of admission, diagnosis, and operative repair. The 30-day mortality was recorded. The reference data set was used to systematically validate the SMR-01 returns. The reference data set contained 608 verified procedures. SMR-01 returns identified 2433 episodes of care (1724 patients) in which a discharge diagnosis included AAA. This included 574 operative repairs. There were 34 missing cases (5.6%) from SMR-01 returns; nine of these patients died within 30 days of the index procedure. Omission of these cases made a statistically significant improvement to perceived 30-day mortality (p < .05, chi-square test). If inconsistent SMR-01 data (in terms of ICD-10 and OPCS-4 codes) were excluded only 81.9% of operative repairs were correctly identified and only 30.9% of deaths were captured. The SMR-01 returns contain multiple errors. There also appears to be a systematic bias that reduces apparent 30-day mortality. Using these data alone to describe or compare activity or outcomes must be done with caution. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Wall stress reduction in abdominal aortic aneurysms as a result of polymeric endoaortic paving.

PubMed

Ashton, John H; Ayyalasomayajula, Avinash; Simon, Bruce R; Vande Geest, Jonathan P

2011-06-01

Polymeric endoaortic paving (PEAP) may improve endovascular repair of abdominal aortic aneurysms (AAA) since it has the potential to treat patients with complex AAA geometries while reducing the incidence of migration and endoleak. Polycaprolactone (PCL)/polyurethane (PU) blends are proposed as PEAP materials due to their range of mechanical properties, thermoformability, and resistance to biodegradation. In this study, the reduction in AAA wall stress that can be achieved using PEAP was estimated and compared to that resulting from stent-grafts. This was accomplished by mechanically modeling the anisotropic response of PCL/PU blends and implementing these results into finite element model (FEM) simulations. We found that at the maximum diameter of the AAA, the 50/50 and 10/90 PCL/PU blends reduced wall stress by 99 and 98%, respectively, while a stent-graft reduced wall stress by 99%. Our results also show that wall stress reduction increases with increasing PEAP thickness and PCL content in the blend ratio. These results indicate that PEAP can reduce AAA wall stress as effectively as a stent-graft. As such, we propose that PEAP may provide an improved treatment alternative for AAA, since many of the limitations of stent-grafts have the potential to be solved using this approach.

Intervisceral artery origins in patients with abdominal aortic aneurysmal disease; evidence for systemic vascular remodelling.

PubMed

Bailey, Damian M; Evans, Tom G; Thomas, Kate Gower; White, Richard D; Twine, Chistopher P; Lewis, Michael H; Williams, Ian M

2016-08-01

What is the central question of this study? To what extent focal abdominal aortic aneurysmal (AAA) disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between distances of the intervisceral artery origins and AAA location/size in patients with disease compared with healthy patients. What is the main finding and its importance? Intervisceral artery distances were shown to be consistently greater in AAA patients, highlighting the systemic nature of AAA disease that extends proximally to the abdominal aorta and its branches. The anatomical description of the natural variation in visceral artery origins has implications for the design of stent grafts and planning complex open aortic surgery. The initial histopathology of abdominal aortic aneurysmal (AAA) disease is atherosclerotic, later diverting towards a distinctive dilating rather than occlusive aortic phenotype. To what extent focal AAA disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between the intervisceral artery origins and AAA location/size in patients with AAA disease (AAA+) relative to those without (AAA-). Preoperative contrast-enhanced computerized tomograms were reviewed in 90 consecutive AAA+ patients scheduled for open repair who underwent an infrarenal (n = 45), suprarenal (n = 26) or supracoeliac clamp (n = 19). These were compared with 39 age-matched AAA- control patients. Craniocaudal measurements were recorded from the distal origin of the coeliac artery to the superior mesenteric artery and from the origin of the superior mesenteric artery to both renal artery origins. Serial blood samples were obtained for estimation of the glomerular filtration rate before and after surgery. Intervisceral artery origins were shown to be consistently greater in AAA+ patients (P < 0.05 versus AAA-), although unrelated to AAA diameter (P > 0.05). Postoperative renal function became progressively more impaired the more proximal the clamp placement (estimated glomerular filtration rate for supracoeliac < suprarenal < infrarenal clamps, P < 0.05). These findings highlight the systemic nature of AAA disease that extends proximally to the abdominal aorta and its branches. The anatomical description of the natural variation in visceral artery origins has implications for the design of stent grafts and planning complex open aortic surgery. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Morphology-related limitations of EVAR applicability in the treatment of AAA in West-Central Poland.

PubMed

Dzieciuchowicz, Łukasz; Tomczak, Jolanta; Strauss, Ewa; Oszkinis, Grzegorz

2018-05-14

To analyze the current applicability of endovascular aneurysm repair (EVAR) in patients with an infrarenal abdominal aortic aneurysm (AAAs) with indication for elective treatment in West-Central Poland. Computed tomography angiograms of 100 consecutive patients with infrarenal AAA deemed to require treatment were analyzed with an OsiriX DICOM viewer in 3D-MPR mode. Proximal neck diameter, length, angulation, shape, the presence of thrombus and calcification, distal neck diameter, and morphology of the iliac arteries were determined. Three sets of morphological criteria were established. The optimal criteria consisted of a non-conical proximal neck without moderate or severe calcification or thrombus, with a diameter of 18-28 mm, length of ≥15 mm, and β angulation of <60%; a distal neck with a diameter of ≥20 mm; a landing zone in the common iliac arteries with a length of ≥ 10 mm and diameter of ≤ 20 mm; and external iliac arteries with diameters of ≥7 mm. The suboptimal criteria included proximal neck diameters of 18-32 mm, neck lengths ≥10 mm, infrarenal neck angulations of up to 75˚, and common iliac artery diameters of up to 25 mm. Finally, the extended suboptimal criteria included proximal neck diameters of 16-34 mm and infrarenal neck angulations ≤90˚, without limits in the maximal diameter of the common iliac arteries. The median maximum aneurysm diameter was 61 mm. The optimal, suboptimal, and extended suboptimal criteria were met by 23%, 32%, and 53% of patients, respectively. The most common deviations were wide, conical, and angulated proximal necks and aneurysmal iliac arteries. The majority of patients with AAA deemed to be candidates for elective repair do not meet the most favorable criteria for EVAR. Availability of better endovascular solutions for conical, angulated, and wide necks and aneurysmal iliac arteries would likely expand EVAR applicability. Open repair remains a valid option. Copyright © 2018 Elsevier Inc. All rights reserved.

Vitamins and abdominal aortic aneurysm.

PubMed

Takagi, Hisato; Umemoto, Takuya

2017-02-01

To summarize the association of vitamins (B6, B12, C, D, and E) and abdominal aortic aneurysm (AAA), we reviewed clinical studies with a comprehensive literature research and meta-analytic estimates. To identify all clinical studies evaluating the association of vitamins B6/B12/C/D/E and AAA, databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through April 2015, using Web-based search engines (PubMed and OVID). For each case-control study, data regarding vitamin levels in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Pooled analyses of the 4 case-control studies demonstrated significantly lower circulating vitamin B6 levels (SMD, -0.33; 95% CI, -0.55 to -0.11; P=0.003) but non-significantly lower vitamin B12 levels (SMD, -0.42; 95% CI, -1.09 to 0.25; P=0.22) in patients with AAA than subjects without AAA. Pooled analyses of the 2 case-control studies demonstrated significantly lower levels of circulating vitamins C (SMD, -0.71; 95% CI, -1.23 to -0.19; P=0.007) and E (SMD, -1.76; 95% CI, -2.93 to 0.60; P=0.003) in patients with AAA than subjects without AAA. Another pooled analysis of the 3 case-control studies demonstrated significantly lower circulating vitamin D (25-hydroxyvitamin D) levels (SMD, -0.25; 95% CI, -0.50 to -0.01; P=0.04) in patients with AAA than subjects without AAA. In a double-blind controlled trial, 4.0-year treatment with a high-dose folic acid and vitamin B6/B12 multivitamin in kidney transplant recipients did not reduce a rate of AAA repair despite significant reduction in homocysteine level. In another randomized, double-blind, placebo-controlled trial, 5.8-year supplementation with α-tocopherol (vitamin E) had no preventive effect on large AAA among male smokers. In clinical setting, although low circulating vitamins B6/C/D/E (not B12) levels are associated with AAA presence, vitamins B6/B12/E supplementation may not reduce AAA incidence.

Low Serum Levels of EPA are Associated with the Size and Growth Rate of Abdominal Aortic Aneurysm.

PubMed

Aikawa, Tatsuro; Miyazaki, Tetsuro; Shimada, Kazunori; Sugita, Yurina; Shimizu, Megumi; Ouchi, Shohei; Kadoguchi, Tomoyasu; Yokoyama, Yasutaka; Shiozawa, Tomoyuki; Hiki, Masaru; Takahashi, Shuhei; Al Shahi, Hamad; Dohi, Shizuyuki; Amano, Atsushi; Daida, Hiroyuki

2017-09-01

Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to reduce the risk of cardiovascular disease. However, whether omega-3 PUFAs are involved in the pathogenesis of abdominal aortic aneurysms (AAA) remains unclear. We analyzed 67 consecutive patients admitted for the elective surgical repair of AAA. We investigated the association of serum EPA and DHA levels as well as the EPA/AA ratio with the size of AAA assessed using three-dimensional reconstructed computed tomography images. Mean patient age was 70±9 years and 60 patients were male. Serum EPA and DHA levels were 75.2±35.7 μg/mL and 146.1±48.5 μg/mL, respectively. EPA/AA ratio was 0.44±0.22, which was lower than those in healthy Japanese subject and equivalent to those in Japanese patients with coronary artery disease as previously reported. Mean of the maximum AAA diameter was 56.4±8.9 mm, and serum EPA levels and EPA/AA ratio negatively correlated with it (r=-0.32 and r=-0.32, respectively). Multiple liner regression analysis showed that EPA levels were significant independent factor contributing to the maximum AAA diameter. Furthermore, low serum EPA levels and low EPA/AA ratio were significantly associated with the growth rate of AAA diameter (r=-0.43 and r=-0.33, respectively). EPA levels in patients with AAA were relatively low. Low serum EPA levels and EPA/AA ratio were associated with the size and growth rate of AAA.

Quantitative expression and localization of cysteine and aspartic proteases in human abdominal aortic aneurysms

PubMed Central

Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Haertl, Felix; Matevossian, Edouard; Zernecke, Alma; Eckstein, Hans-Henning; Pelisek, Jaroslav

2014-01-01

Cysteine and aspartic proteases possess high elastolytic activity and might contribute to the degradation of the abdominal aortic aneurysm (AAA) wall. The aim of this study was to analyze, in detail, the proteases (cathepsins B, D, K, L and S, and inhibitor cystatin C) found in human AAA and healthy aortic tissue samples. The vessel walls from AAA patients (n=36) and nonaneurysmal aortae (n=10) were retrieved using conventional surgical repair and autopsy methods. Serum samples from the same AAA patients and 10 healthy volunteers were also collected. Quantitative expression analyses were performed at the mRNA level using real-time reverse transcriptase-PCR (RT–PCR). Furthermore, analyses at the protein level included western blot and immunoprecipitation analyses. Cellular sources of cysteine/aspartic proteases and cystatin C were identified by immunohistochemistry (IHC). All cysteine/aspartic proteases and cystatin C were detected in the AAA and control samples. Using quantitative RT–PCR, a significant increase in expression was observed for cathepsins B (P=0.021) and L (P=0.018), compared with the controls. Cathepsin B and cystatin C were also detected in the serum of AAA patients. Using IHC, smooth muscle cells (SMCs) and macrophages were positive for all of the tested cathepsins, as well as cystatin C; in addition, the lymphocytes were mainly positive for cathepsin B, followed by cathepsins D and S. All cysteine/aspartic proteases analyzed in our study were detected in the AAA and healthy aorta. The highest expression was found in macrophages and SMCs. Consequently, cysteine/aspartic proteases might play a substantial role in AAA. PMID:24833013

Endovascular abdominal aortic aneurysm repair is more profitable than open repair based on contribution margin per day.

PubMed

Rosenberg, Barry L; Comstock, Matthew C; Butz, David A; Taheri, Paul A; Williams, David M; Upchurch, Gilbert R

2005-03-01

Earlier studies have reported that endovascular abdominal aortic aneurysm (EAAA) repair yields lower total profit margins than open AAA (OAAA) repair. This study compared EAAA versus OAAA based on contribution margin per day, which may better measure profitability of new clinical technologies. Contribution margin equals revenue less variable direct costs (VDCs). VDCs capture incremental resources tied directly to individual patients' activity (eg, invoice price of endograft device, nursing labor). Overhead costs factor into total margin, but not contribution margin. The University of Michigan Health System's cost accounting system was used to extract fiscal year 2002-2003 information on revenue, total margin, contribution margin, and duration of stay for Medicare patients with principal diagnosis of AAA (ICD-9 code 441.4). OAAA had revenues of $37,137 per case versus $28,960 for EAAA, similar VDCs per case, and thus higher contribution margin per case ($24,404 for OAAA vs $13,911 for EAAA, P < .001). However, OAAA had significantly longer mean duration of stay per case (10.2 days vs 2.2 days, P < .001). Therefore, mean contribution margin per day was $2948 for OAAA, but $8569 for EAAA ( P < .001). On the basis of contribution margin per day, EAAA repair dominates OAAA repair. The shorter duration of stay with EAAA allows higher throughput, fuller overhead amortization, better use of scarce inpatient beds, and higher health system profits. Surgeons must understand overhead allocation to devices, especially when new technologies cut duration of stay markedly.

Accuracy and trending ability of the fourth-generation FloTrac/Vigileo System™ in patients undergoing abdominal aortic aneurysm surgery.

PubMed

Maeda, Takuma; Hattori, Kohshi; Sumiyoshi, Miho; Kanazawa, Hiroko; Ohnishi, Yoshihiko

2018-06-01

The fourth-generation FloTrac/Vigileo™ improved its algorithm to follow changes in systemic vascular resistance index (SVRI). This revision may improve the accuracy and trending ability of CI even in patients who undergo abdominal aortic aneurysm (AAA) surgery which cause drastic change of SVRI by aortic clamping. The purpose of this study is to elucidate the accuracy and trending ability of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery by comparing the FloTrac/Vigileo™-derived CI (CI FT ) with that measured by three-dimensional echocardiography (CI 3D ). Twenty-six patients undergoing elective AAA surgery were included in this study. CI FT and CI3 D were determined simultaneously in eight points including before and after aortic clamp. We used CI 3D as the reference method. In the Bland-Altman analysis, CI FT had a wide limit of agreement with CI 3D showing a percentage error of 46.7%. Subgroup analysis showed that the percentage error between CO 3D and CO FT was 56.3% in patients with cardiac index < 2.5 L/min/m 2 and 28.4% in patients with cardiac index ≥ 2.5 L/min/m 2 . SVRI was significantly higher in patients with cardiac index < 2.5 L/min/m 2 (1703 ± 330 vs. 2757 ± 798; p < 0.001). The tracking ability of fourth generation of FloTrac/Vigileo™ after aortic clamp was not clinically acceptable (26.9%). The degree of accuracy of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery was not acceptable. The tracking ability of the fourth-generation FloTrac/Vigileo™ after aortic clamp was below the acceptable limit.

Periprocedural and long-term outcomes of endovascular abdominal aortic aneurysm repair in cardiology practice.

PubMed

Basoor, Abhijeet; Patel, Kiritkumar C; Halabi, Abdul R; Todorov, Mina; Senthilvadivel, Prashanth; Choksi, Nishit; Phan, Thanh; LaLonde, Thomas; Yamasaki, Hiroshi; DeGregorio, Michele

2014-12-01

Endovascular repair of abdominal aortic aneurysm (AAA) has recently been made a class I indication in the treatment of AAA. In comparison to the conventional open surgical treatment, endovascular AAA repair (EVAR) is associated with equivalent long-term morbidity and mortality rates. Vascular surgeons perform majority of EVAR. There are no reports for the long-term results of this intervention performed by interventional cardiologists. We present one of the first reports of periprocedural and long-term outcomes of EVAR performed by interventional cardiologists. Retrospective chart review on patients with attempted EVAR between September 2005 and January 2011 was performed. Included cases were all consecutive patients who had attempted EVAR by interventional cardiologists. During the study period EVAR was attempted in 170 patients, with 27% being women. The mean age was 74 years (range 52-93). The endovascular graft placement was successful in 96% (163/170) of patients. Procedure failures were more common in women (6 of 46 vs 1 of 124, P = 0.003). The 30-day mortality was 1.8 % (3 of 170). In patients with successful EVAR the mean follow-up was 30 months and mean length of hospital stay was 3.5 ± 3.2 days. Major periprocedural complications were noted in 9% patients (15 of 167). During follow-up, six patients (3.5%) required re-intervention and additional 16 patients died with no aneurysm related deaths. EVAR primarily performed by interventional cardiologists demonstrates high periprocedural and long-term success rates. A higher EVAR failure rate has been observed in women. © 2014 Wiley Periodicals, Inc.

Association of Matrix Metalloproteinase Levels with Collagen Degradation in the Context of Abdominal Aortic Aneurysm.

PubMed

Klaus, V; Tanios-Schmies, F; Reeps, C; Trenner, M; Matevossian, E; Eckstein, H-H; Pelisek, J

2017-04-01

Matrix metalloproteinases (MMPs) have already been identified as key players in the pathogenesis of abdominal aortic aneurysm (AAA). However, the current data remain inconclusive. In this study, the expression of MMPs at mRNA and protein levels were investigated in relation to the degradation of collagen I and collagen III. Tissue samples were obtained from 40 patients with AAA undergoing open aortic repair, and from five healthy controls during kidney transplantation. Expression of MMPs 1, 2, 3, 7, 8, 9, and 12, and tissue inhibitor of metalloproteinase (TIMP)1, and TIMP2 were measured at the mRNA level using quantitative reverse transcription polymerase chain reaction. At the protein level, MMPs, collagen I, and collagen III, and their degradation products carboxy-terminal collagen cross-links (CTX)-I and CTX-III, were quantified via enzyme linked immunosorbent assay. In addition, immunohistochemistry and gelatine zymography were performed. In AAA, significantly enhanced mRNA expression was observed for MMPs 3, 9, and 12 compared with controls (p ≤ .001). MMPs 3, 9, and 12 correlated significantly with macrophages (p = .007, p = .018, and p = .015, respectively), and synthetic smooth muscle cells with MMPs 1, 2, and 9 (p = .020, p = .018, and p = .027, respectively). At the protein level, MMPs 8, 9, and 12 were significantly elevated in AAA (p = .006, p = .0004, and p < .001, respectively). No significant correlation between mRNA and protein was observed for any MMP. AAA contained significantly reduced intact collagen I (twofold; p = .002), whereas collagen III was increased (4.6 fold; p < .001). Regarding degraded collagen I and III relative to intact collagens, observations were inverse (1.4 fold increase for CTX-1 [p < .001]; fivefold decrease for CTX-III [p = .004]). MMPs 8, 9, and 12 correlated with collagen I (p = .019, p < .001, and p = 0.003, respectively), collagen III (p = .015, p < .001, and p < .001, respectively), and degraded collagen I (p = .012, p = .049, and p = .001, respectively). No significant relationship was found between mRNA and protein and MMP levels. MMPs 9 and 12 were overexpressed in AAA at the mRNA and protein level, and MMP-8 at the protein level. MMP-2 was detected in synthetic SMCs. Collagen I and III showed inverse behaviour in AAA. In particular, MMPs 8, 9, and 12 appear to be associated with collagen I, collagen III, and their degradation products. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Endovascular repair of abdominal aortic aneurysms in patients with congenital renal vascular anomalies.

PubMed

Kaplan, D B; Kwon, C C; Marin, M L; Hollier, L H

1999-09-01

The endovascular repair of abdominal aortic aneurysms (AAAs) has been suggested as an alternative to conventional aortic reconstruction. The presence of anomalous renal vascular anatomy frequently necessitates special planning during conventional aortic replacement and may also create unique challenges for endovascular repair. We analyzed our experience with 24 patients with variant renal vascular anatomies who underwent treatment with aortic endografts to determine the safety and efficacy of this technique in this population. During a 6-year period, 204 patients underwent aortic endograft procedures, 24 (11.8%) of whom had variations in renal vascular anatomy. There were 19 men and five women. Each of the 24 patients had variant renal vascular anatomy, which was defined by the presence of multiple renal arteries (n = 32), with or without a renal parenchymal anomaly (horseshoe or solitary pelvic kidney). Twenty patients underwent aneurysm repair with balloon expandable polytetrafluoroethylene grafts, and the remaining patients underwent endograft placement with self-expanding attachment systems. Eighteen patients underwent exclusion and presumed thrombosis of anomalous renal branches to effectively attach the aortic endograft. The decision to sacrifice a supernumerary artery was made on the basis of the vessel size (<3 mm), the absence of coexisting renal insufficiency, and the expectation for successful aneurysm exclusion. The successful exclusion of the AAAs was achieved in all the patients, with the loss of a total of 17 renal artery branches in 12 patients. Small segmental renal infarcts (<20%) were detected in only six of the 12 patients with follow-up computed tomographic scan results, despite angiographic evidence of vessel occlusion at the time of endografting. No evidence of new onset hypertension or changes in antihypertensive medication was seen in this group. No retrograde endoleaks were detected through the excluded renal branches on late follow-up computed tomographic scans. Serum creatinine levels before and after endografting were unchanged after the exclusion of the AAA in all but one patient with multiple renal branches. One patient had a transient rise in serum creatinine level presumed to be caused by contrast nephropathy. On the basis of this experience, we recommend the consideration of endovascular grafting for patients with AAAs and anomalous renal vessels when the main renal vascular anatomy can be preserved and when the loss of only small branches (<3 mm) is necessitated in patients with otherwise normal renal functions.

[Review of pre- and post-treatment multidetector computed tomography findings in abdominal aortic aneurysms].

PubMed

Casula, E; Lonjedo, E; Cerverón, M J; Ruiz, A; Gómez, J

2014-01-01

The increase in the frequency of abdominal aortic aneurysms (AAA) and the widely accepted use of endovascular aneurysm repair (EVAR) as a first-line treatment or as an alternative to conventional surgery make it necessary for radiologists to have thorough knowledge of the pre- and post-treatment findings. The high image quality provided by multidetector computed tomography (MDCT) enables CT angiography to play a fundamental role in the study of AAA and in planning treatment. The objective of this article is to review the cases of AAA in which CT angiography was the main imaging technique, so that radiologists will be able to detect the signs related to this disease, to diagnose it, to plan treatment, and to detect complications in the postoperative period. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Abdominal aortic aneurysm screening program in Poland.

PubMed

Jawien, A; Formankiewicz, B; Derezinski, T; Migdalski, A; Brazis, P; Woda, L

Screening for abdominal aortic aneurysms (AAA) is currently recommended by several vascular societies. In countries where it has been introduced the prevalence of AAAs differed greatly and was mainly related to cigarette smoking. The screening program also had an enormous impact on the decrease of AAA ruptures and reduced mortality rate. These facts have led to the introduction of the first screening program for AAAs in Poland. The aim of the study was to determine the prevalence of AAAs among men aged 60 years and older undergoing ultrasound examination of the abdominal aorta. A single ultrasonography of the abdomen was performed to assess the aorta from the renal arteries to the bifurcation and the diameter of the aorta was measured at its widest point. The cut-off value for determining an aortic aneurysm was set at a diameter of ≥ 30 mm. All ultrasonography measurements were performed by physicians in outpatient departments throughout the Kuyavian-Pomeranian Province. Additionally, each subject had to fill out a questionnaire with demographic data, smoking habits, existing comorbidities and familial occurrence of AAAs. The study was conducted from October 2009 to November 2011. The abdominal aorta ultrasound examinations were carried out in 1556 men aged 60 years and older. The prevalence of AAA in the study population was 6.0 % (94 out of 1556). The average age of the men was 69 years (SD 6 years, range 60-92 years). In the study population 55 % of the men smoked or had smoked and 3 % were aware of the presence of AAAs in family members. There were three risk factors significantly associated with the presence of AAAs: age (p < 0.05), smoking (72.3 % vs 53.9 %, p = 0.004) and family history of AAAs (9.6 % vs 2.7 %, p = 0.017). The prevalence of AAAs among men in Poland is higher than in other European countries and the USA. The screening program for AAAs is an easy and reliable method for detecting early stages of the disease and risk factors which are the driving forces for the development of AAAs.

Awake Craniotomy Anesthesia: A Comparison of the Monitored Anesthesia Care and Asleep-Awake-Asleep Techniques.

PubMed

Eseonu, Chikezie I; ReFaey, Karim; Garcia, Oscar; John, Amballur; Quiñones-Hinojosa, Alfredo; Tripathi, Punita

2017-08-01

Commonly used sedation techniques for an awake craniotomy include monitored anesthesia care (MAC), using an unprotected airway, and the asleep-awake-asleep (AAA) technique, using a partially or totally protected airway. We present a comparative analysis of the MAC and AAA techniques, evaluating anesthetic management, perioperative outcomes, and complications in a consecutive series of patients undergoing the removal of an eloquent brain lesion. Eighty-one patients underwent awake craniotomy for an intracranial lesion over a 9-year period performed by a single-surgeon and a team of anesthesiologists. Fifty patients were treated using the MAC technique, and 31 were treated using the AAA technique. A retrospective analysis evaluated anesthetic management, intraoperative complications, postoperative outcomes, pain management, and complications. The MAC and AAA groups had similar preoperative patient and tumor characteristics. Mean operative time was shorter in the MAC group (283.5 minutes vs. 313.3 minutes; P = 0.038). Hypertension was the most common intraoperative complication seen (8% in the MAC group vs. 9.7% in the AAA group; P = 0.794). Intraoperative seizure occurred at a rate of 4% in the MAC group and 3.2% in the AAA group (P = 0.858). Awake cases were converted to general anesthesia in no patients in the MAC group and in 1 patient (3.2%) in the AAA group (P = 0.201). No cases were aborted in either group. The mean hospital length of stay was 3.98 days in the MAC group and 3.84 days in the AAA group (P = 0.833). Both the MAC and AAA sedation techniques provide an efficacious and safe method for managing awake craniotomy cases and produce similar perioperative outcomes, with the MAC technique associated with shorter operative time. Copyright © 2017 Elsevier Inc. All rights reserved.

Trend, Risk Factors, and Costs of Clostridium difficile Infections in Vascular Surgery.

PubMed

Egorova, Natalia N; Siracuse, Jeffrey J; McKinsey, James F; Nowygrod, Roman

2015-01-01

Starting in December 2013, the Hospital Inpatient Quality Reporting Program included Clostridium difficile infection (CDI) rates as a new publically reported quality measure. Our goal was to review the trend, hospital variability in CDI rates, and associated risk factors and costs in vascular surgery. The rates of CDI after major vascular procedures including aortic abdominal aneurysm (AAA) repair, carotid endarterectomy or stenting, lower extremity revascularization (LER), and LE amputation were identified using Nationwide Inpatient Sample database for 2000-2011. Risk factors associated with CDI were analyzed with hierarchical multivariate logistic regression. Extra costs, length of stay (LOS), and mortality were assessed for propensity-matched hospitalizations with and without CDI. During the study period, the rates of CDI after vascular procedures had increased by 74% from 0.6 in 2000 to 1.05% in 2011, whereas the case fatality rate was stable at 9-11%. In 2011, the highest rates were after ruptured aortic abdominal aneurysm (rAAA) repair (3.3%), followed by lower extremity amputations (2.3%) and elective open AAA (1.3%). The rates of CDI increased after all vascular procedures during the 12 years. The highest increase was after endovascular LER (151.8%) and open rAAA repair (135.7%). In 2011, patients who had experienced CDI had median LOS of 15 days (interquartile range, 9-25 days) compared with 8.3 days for matched patients without CDI, in-hospital mortality 9.1% (compared with 5.0%), and $13,471 extra cost per hospitalization. The estimated cost associated with CDI in vascular surgery in the United States was ∼$98 million in 2011. Hospital rates of CDI varied from 0 to 50% with 3.5% of hospitals having infection rates ≥5%. Factors associated with CDI included multiple chronic conditions, female gender, surgery type, emergent and weekend hospitalizations, hospital transfers, and urban locations. Despite potential reduction of infection rates as evidenced by the experience of hospitals with effective interventions, CDI is increasing among vascular surgery patients. It is associated with prolonged LOS, increased mortality, and higher costs. Copyright © 2015 Elsevier Inc. All rights reserved.

Aneurysm Shrinkage Is Compatible With Massive Endoleak in the Presence of an Aortocaval Fistula: Potential Therapeutic Implications for Endoleaks and Spinal Cord Ischemia.

PubMed

Sveinsson, Magnus; Sonesson, Björn; Resch, Timothy A; Dias, Nuno V; Holst, Jan; Malina, Martin

2016-06-01

To present a patient with ruptured abdominal aortic aneurysm (AAA) and aortocaval fistula who was successfully treated with endovascular aneurysm repair in spite of developing a massive endoleak. A 70-year-old man with ruptured AAA and aortocaval fistula was treated with endovascular aneurysm repair (EVAR). During 8 years of follow-up, he had massive perfusion of the aneurysm sac by retrograde flow from the inferior mesenteric artery into the caval vein through the aortocaval fistula. The aneurysm diameter decreased continuously in spite of the type II endoleak. This observation illustrates the mechanisms of sac expansion and may have therapeutic implications for complicated type II endoleaks and prevention of spinal cord ischemia in thoracic stent-grafting. EVAR can be applied in this rare setting because the ensuing high-flow endoleak is associated with sac shrinkage owing to depressurization by the caval shunt. © The Author(s) 2016.

Sac Angiography and Glue Embolization in Emergency Endovascular Aneurysm Repair for Ruptured Abdominal Aortic Aneurysm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koike, Yuya, E-mail: r06118@hotmail.co.jp; Nishimura, Jun-ichi, E-mail: jun-ichi-n@nifty.com; Hase, Soichiro, E-mail: haseman@hotmail.co.jp

PurposeThe purpose of this study was to demonstrate a sac angiography technique and evaluate the feasibility of N-butyl cyanoacrylate (NBCA) embolization of the ruptured abdominal aortic aneurysm (AAA) sac in emergency endovascular aneurysm repair (EVAR) in hemodynamically unstable patients.MethodsA retrospective case series of three patients in whom sac angiography was performed during emergency EVAR for ruptured AAA was reviewed. After stent graft deployment, angiography within the sac of aneurysm (sac angiography) was performed by manually injecting 10 ml of contrast material through a catheter to identify the presence and site of active bleeding. In two patients, sac angiography revealed active extravasationmore » of the contrast material, and NBCA embolization with a coaxial catheter system was performed to achieve prompt sealing.ResultsSac angiography was successful in all three patients. In the two patients who underwent NBCA embolization for aneurysm sac bleeding, follow-up computed tomography (CT) images demonstrated the accumulation of NBCA consistent with the bleeding site in preprocedural CT images.ConclusionsEVAR is associated with a potential risk of ongoing bleeding from type II or IV endoleaks into the disrupted aneurysm sac in patients with severe coagulopathy. Therefore, sac angiography and NBCA embolization during emergency EVAR may represent a possible technical improvement in the treatment of ruptured AAA in hemodynamically unstable patients.« less

Multi-Centre Study on Cardiovascular Risk Management on Patients Undergoing AAA Surveillance.

PubMed

Saratzis, A; Dattani, N; Brown, A; Shalhoub, J; Bosanquet, D; Sidloff, D; Stather, P

2017-07-01

The risk of cardiovascular events and death in patients with abdominal aortic aneurysms (AAA) is high. Screening has been introduced to reduce AAA related mortality; however, after AAA diagnosis, cardiovascular modification may be as important to patient outcomes as surveillance. The aim of this study was to assess cardiovascular risk reduction in patients with small AAA. Institutional approval was granted for The Vascular and Endovascular Research Network (VERN) to retrospectively collect data pertaining to cardiovascular risk reduction from four tertiary vascular units in England. Patients with small AAA (January 2013-December 2015) were included. Demographic details, postcode, current medications, and smoking status were recorded using a bespoke electronic database and analysed. In a secondary analysis VERN contacted all AAA screening units in England and Wales to assess their current protocols relating to CV protection. In total, 1053 patients were included (mean age 74 ± 9 years, all men). Of these, 745 patients (70.8%) had been prescribed an antiplatelet agent and 787 (74.7%) a statin. Overall, only 666 patients (63.2%) were prescribed both a statin and antiplatelet. Two hundred and sixty eight patients (32.1%) were current smokers and the proportion of patients who continued to smoke decreased with age. Overall, only 401 patients (48.1%) were prescribed a statin, antiplatelet, and had stopped smoking. In the secondary analysis 38 AAA screening units (84% national coverage) replied. Thirty-one units (82%) suggest changes to the patient's prescription; however, none monitor compliance with these recommendations or assess whether the general practitioner has been made aware of the AAA diagnosis or prescription advice. Many patients with small AAA are not prescribed an antiplatelet/statin, and still smoke cigarettes, and therefore remain at high risk of cardiovascular morbidity and mortality. National guidance to ensure this high risk group of patients is adequately protected from poor cardiovascular outcomes is lacking. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Cytokines as biomarkers of inflammatory response after open versus endovascular repair of abdominal aortic aneurysms: a systematic review.

PubMed

Tsilimigras, Diamantis I; Sigala, Fragiska; Karaolanis, Georgios; Ntanasis-Stathopoulos, Ioannis; Spartalis, Eleftherios; Spartalis, Michael; Patelis, Nikolaos; Papalampros, Alexandros; Long, Chandler; Moris, Demetrios

2018-05-17

The repair of an abdominal aortic aneurysm (AAA) is a high-risk surgical procedure related to hormonal and metabolic stress-related response with an ensuing activation of the inflammatory cascade. In contrast to open repair (OR), endovascular aortic aneurysm repair (EVAR) seems to decrease the postoperative stress by offering less extensive incisions, dissection, and tissue manipulation. However, these beneficial effects may be offset by the release of cytokines and arachidonic acid metabolites during intra-luminal manipulation of the thrombus using catheters in endovascular repair, resulting in systemic inflammatory response (SIR), which is clinically called post-implantation syndrome. In this systematic review we compared OR with EVAR in terms of the post-interventional inflammatory response resulting from alterations in the circulating cytokine levels. We sought to summarize all the latest evidence regarding post-implantation syndrome after EVAR. We searched Medline (PubMed), ClinicalTrials.gov and the Cochrane library for clinical studies reporting on the release of cytokines as part of the inflammatory response after both open/conventional and endovascular repair of the AAA. We identified 17 studies examining the cytokine levels after OR versus EVAR. OR seemed to be associated with a greater SIR than EVAR, as evidenced by the increased cytokine levels, particularly IL-6 and IL-8, whereas IL-1β, IL-10 and TNF-α showed conflicting results or no difference between the two groups. Polyester endografts appear to be positively correlated with the incidence of post-implantation syndrome after EVAR. Future large prospective studies are warranted to delineate the underlying mechanisms of the cytokine interaction in the post-surgical inflammatory response setting.

High risk endovascular aneurysm repair: a case report.

PubMed

De Silva, Samanthi

2017-10-01

Mr AB is a 66-year old gentleman who presented for elective endovascular aneurysm repair (EVAR) following a routine screening scan identifying a 5.5cm abdominal aortic aneurysm (AAA). He had a past history of chronic obstructive pulmonary disease (COPD) with FEV1/FVC ratio of 48% on pre-assessment. He was hypertensive with a history of ischaemic heart disease (IHD), which has remained asymptomatic following coronary artery bypass grafting (CABG) eight years prior to this presentation. Copyright the Association for Perioperative Practice.

Heterogeneous histomorphology, yet homogeneous vascular smooth muscle cell dedifferentiation, characterize human aneurysm disease.

PubMed

Busch, Albert; Hartmann, Elena; Grimm, Caroline; Ergün, Süleyman; Kickuth, Ralph; Otto, Christoph; Kellersmann, Richard; Lorenz, Udo

2017-11-01

Abdominal aortic aneurysm (AAA) is a frequent, potentially life-threatening, disease that can only be treated by surgical means such as open surgery or endovascular repair. No alternative treatment is currently available, and despite expanding knowledge about the pathomechanism, clinical trials on medical aneurysm abrogation have led to inconclusive results. The heterogeneity of human AAA based on histologic examination is thereby generally neglected. In this study we aimed to further elucidate the role of these differences in aneurysm disease. Tissue samples from AAA and popliteal artery aneurysm patients were examined by histomorphologic analysis, immunohistochemistry, Western blot, and polymerase chain reaction. The results were correlated with clinical data such as aneurysm diameter and laboratory results. The morphology of human AAA vessel wall probes varies tremendously based on the grade of inflammation. This correlates with increasing intima/media thickness and upregulation of the vascular endothelial growth factor cascade but not with any clinical parameter or the aneurysm diameter. The phenotypic switch of vascular smooth muscle cells occurred regardless of the inflammatory state and expressional changes of the transcription factors Kruppel-like factor-4 and transforming growth factor-β lead to differential protein localization in aneurysmal compared with control arteries. These changes were in similar manner also observed in samples from popliteal artery aneurysms, which, however, showed a more homogenous phenotype. Heterogeneity of AAA vessel walls based on inflammatory morphology does not correlate with AAA diameter yet harbors specific implications for basic research and possible aneurysm detection. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Patients with abdominal aortic aneurysm have a high prevalence of popliteal artery aneurysms.

PubMed

Tuveson, Viktoria; Löfdahl, Hedvig E; Hultgren, Rebecka

2016-08-01

Patients with abdominal aortic aneurysms (AAA) are more prone to develop popliteal artery aneurysms (PAA), but the prevalence is not well known. Our aim was to investigate the prevalence of PAA in patients with AAA, and to determine whether a certain risk factor profile is more commonly found in patients with concurrent aneurysms. All AAA patients (ICD code I71.3, I71.4) attending the outpatient clinic at the Karolinska University Hospital between 2011 and 2013 were included in the study cohort (n=465); 48% (225) had been subjected to an ultrasound or computed tomography scan of their popliteal arteries. In these patients, three definitions of PAA were considered (⩾ 10.5, ⩾ 12, ⩾ 15 mm), although the overall analysis is based on PAA ⩾ 12 mm. The mean age was 70.7 years (SD 7.5), 89% were men, and the mean AAA diameter was 47 mm (SD 14). The prevalence of PAA was 19% (n=43) by definition ⩾ 12 mm, and 11% (n=25) with 15 mm. Claudication was more frequently found in AAA patients with PAA than patients without PAA. Sensitivity between clinical examination and radiology was 26%, and the specificity for clinical examination was 90%. In conclusion, owing to the high prevalence of PAA in AAA patients, described by us and others, the low cost and risks associated with ultrasound and the poor sensitivity at clinical examination, all women and men with AAA should undergo one radiological examination of their popliteal arteries. © The Author(s) 2016.

How Quickly Do Asymptomatic Infrarenal Abdominal Aortic Aneurysms Grow and What Factors Affect Aneurysm Growth Rates? Analysis of a Single Centre Surveillance Cohort Database.

PubMed

Ahmad, Mehtab; Mistry, Rakesh; Hodson, James; Bradbury, Andrew W

2017-11-01

Abdominal aortic aneurysm (AAA) maximum antero-posterior diameter (MAPD) is the parameter most commonly used to inform the timing of surgical intervention. However, other factors, such as growth rates and patient comorbidities are likely to be important considerations as they may influence AAA related complications including rupture, operative outcomes, and the clinical and cost effectiveness of continued surveillance. This was a retrospective analysis of a 20 year period of a single centre AAA surveillance database. In total, 5363 AAA measurements in 692 patients were analysed for patient demographics, including comorbidity and drug history, growth and rupture rates, and cause of death. A significant proportion of patients (n = 73; 11%) were kept under surveillance despite having a MAPD < 30 mm. Overall, mean aneurysm growth rate was 2.3 mm/year. Elective repair was undertaken in 20.1% and those who required surgical intervention had significantly faster growth rates. Only 3.9% of patients in surveillance ruptured, 40.7% of whom had a MAPD <55 mm at their last scan. Of the 214 deaths recorded, only 11.7% were related to AAA. The majority of patients who died in surveillance did so from malignancy. Patients with larger AAA (MAPD > 40 mm) on entry into surveillance were significantly more likely to receive surgical intervention, as were those whose AAA expanded >4 mm/year. Females had significantly higher growth rates, and those with diabetes had significantly smaller growth rates. Other comorbidities and drug history were not associated with AAA growth, or 5 and 10 year surgery free survival. The results highlight several areas for service improvement. Specifically, it is important not to maintain surveillance in patients who are very unlikely to ever grow to a point where AAA surgery would be contemplated on grounds or age and/or comorbidity. Similarly, patients should be discharged from surveillance when this likelihood becomes apparent. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Experience with early postoperative feeding after abdominal aortic surgery.

PubMed

Ko, Po-Jen; Hsieh, Hung-Chang; Liu, Yun-Hen; Liu, Hui-Ping

2004-03-01

Abdominal aortic surgery is a form of major vascular surgery, which traditionally involves long hospital stays and significant postoperative morbidity. Experiences with transit ileus are often encountered after the aortic surgery. Thus traditional postoperative care involves delayed oral feeding until the patients regain their normal bowel activities. This report examines the feasibility of early postoperative feeding after abdominal aortic aneurysm (AAA) open-repair. From May 2002 through May 2003, 10 consecutive patients with infrarenal AAA who underwent elective surgical open-repair by the same surgeon in our department were reviewed. All of them had been operated upon and cared for according to the early feeding postoperative care protocol, which comprised of adjuvant epidural anesthesia, postoperative patient controlled analgesia, early postoperative feeding and early rehabilitation. The postoperative recovery and length of hospital stay were reviewed and analyzed. All patients were able to sip water within 1 day postoperatively without trouble (Average; 12.4 hours postoperatively). All but one patient was put on regular diet within 3 days postoperatively (Average; 2.2 days postoperatively). The average postoperative length of stay in hospital was 5.8 days. No patient died or had major morbidity. Early postoperative feeding after open repair of abdominal aorta is safe and feasible. The postoperative recovery could be improved and the length of stay reduced by simply using adjuvant epidural anesthesia during surgery, postoperative epidural patient-controlled analgesia, early feeding, early ambulation, and early rehabilitation. The initial success of our postoperative recovery program of aortic repair was demonstrated.

Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

PubMed

Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

2015-08-01

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

Mini-invasive treatment of abdominal aortic aneurysms: current roles of endovascular, laparoscopic, and open techniques.

PubMed

Coscas, Raphaël; Maumias, Thibault; Capdevila, Clément; Javerliat, Isabelle; Goëau-Brissonnière, Olivier; Coggia, Marc

2014-01-01

Endovascular aortic repair (EVAR), laparoscopic aortic surgery (LAS), and open surgery (OS) are three established treatment methods of abdominal aortic aneurysms (AAA). While these techniques are often percieved as competitive between them, they are complementary for the vascular surgeon, whose goal is to provide a treatment adapted to each case that is noninvasive and durable. The objective of this study was to report our results of AAA repair to better define the roles of the three techniques. From January 2009 to December 2011, we operated on 235 patients for AAAs. Patients for whom the three technical methods were discussed preoperatively were selected. Cases where the three techniques were not discussed were excluded (ruptured AAA, technique not available). One hundred seventy-five (75%) patients were included. Four groups were established based on the surgical risk and the anatomic EVAR criteria of the French Health Authority (Haute Autorité de Santé [HAS]), including: (1) good risk and favorable anatomy (GR-FA); (2) good risk and unfavorable anatomy (GR-UA); (3) high-risk and favorable anatomy (HR-FA); and (4) high-risk and unfavorable anatomy (HR-UA). Data collection was prospective. The numerical data were expressed as median and range. There were 166 (95%) men, aged 74 years (range 38-97 years). AAA diameter was 51 mm (range 30-81 mm). Mini-invasive treatment (EVAR or LAS) was chosen in 156 (89%) cases. Mortality at 30 days was 3.4% (6 patients, 1 EVAR, 1 LAS, and 4 OS), including 3 patients presenting with a "shaggy aorta." There were 58, 19, 65, and 33 patients in groups GR-FA (33%), GR-UA (11%), HR-FA (37%), and HR-UA (19%), respectively. The distribution of the three techniques (EVAR, LAS, OS) according to the groups was as follows: GR-FA (9, 46, 3); GR-UA (0, 13, 6); HR-FA (50, 13, 2); and HR-UA (12, 13, 8), respectively. The results by subgroups are presented. Based on our results, we present a new algorithm for AAA treatment. Among GR-FA patients, EVAR and LAS should be discussed according to life expectancy and wish of the patient. In GR-UA patients, LAS and OS can be proposed. For HR-FA patients, EVAR remains the first choice, but LAS can be used in cases with good life expectancy. In the HR-UA patients, LAS is the best choice because of the late complications of EVAR, but a broader use of fenestrated stent grafts or the chimney technique may be beneficial. Last, the surgical threshold should be pushed back among AAA patients presenting with a shaggy aorta. Copyright © 2014 Elsevier Inc. All rights reserved.

Surgical Treatment of Synchronous Type B Acute Aortic Dissection and Abdominal Aortic Aneurysm.

PubMed

Bellosta, Raffaello; Gelpi, Guido; Lomazzi, Chiara; Romagnoni, Claudia; Castelli, Patrizio; Trimarchi, Santi; Piffaretti, Gabriele

2018-05-01

We report the results of the operative treatment of synchronous type B acute aortic dissection (TBAAD) and infrarenal abdominal aortic aneurysm (AAA). It is an observational, descriptive multicenter case series. Inclusion criterion was patients with diagnosis of TBAAD and AAA detected synchronously for the first time at clinical onset of dissection. Follow-up imaging protocol included triple-phase spiral/computed tomography angiography performed at 1, 6, and 12 months after thoracic endovascular aortic repair (TEVAR), and annually thereafter. Major end points were perioperative mortality and long-term survival, freedom from aortic events, and freedom from reintervention. We identified and treated 15 cases. All TBAADs were treated by TEVAR in the acute phase: infrarenal aortic repair was performed with stent graft (SG) in 10 (66.7%) patients, with open repair in 5 (33.3%). Overall, staged repair was used in 11 (73.3%) patients. Mean descending aortic endovascular length coverage was 21 cm ± 7 (range, 10-35; interquartile range [IQR], 150-265). Overall, early perioperative mortality occurred in 1 (6.7%) patient. Median radiologic follow-up was 48 months (range, 6-120; IQR, 36-67). During the follow-up, TEVAR-related mortality was not observed. Aortic remodeling after TEVAR was obtained in 12 (85.7%) patients; abdominal sac shrinkage after SG was obtained in 8 (80.0%) patients. Freedom from aortic event rate was 79% ± 10 (95% confidence interval [CI]: 53.1-92.6) at 1 year and 64% ± 13 (95% CI: 38.1-83.5) at 5 year. Freedom from reintervention rate at 1 and 5 year was 85% ± 10 (95% CI: 57.8-95.7). In our experience, the association of TBAAD and AAA was a rare finding. Because of the lack of available evidence to opt for a single intervention or a staged approach, selective approach with TEVAR and endovascular/open conventional treatment of the abdominal aorta yielded satisfactory results at midterm follow-up. Copyright © 2018 Elsevier Inc. All rights reserved.

Three-year audit and cost assessment of open abdominal aortic aneurysm repair in a district general hospital.

PubMed

El Kafsi, J; Wake, J; Lintott, P; Northeast, A; McLaren, A

2009-11-01

The aims of this study were to audit the outcome of elective open abdominal aortic aneurysm (AAA) repair in a district general hospital, as well as investigate the true costs for this procedure in relation to the national tariff. A database is maintained on AAA surgery in the trust. Data were supplemented by drawing information from blood bank and clinical notes. Patients with symptomatic or emergency aneurysms were excluded. Data from January 2005 to December 2007 were obtained on demographics, morbidity, 30-day mortality and blood usage. Costs were obtained from the trust finance department. Between January 2005 and December 2007, 79 elective AAA procedures were undertaken. Median age was 75 years (range, 52-85 years), median aneurysm size was 63 mm (range, 42-105 mm) and median ITU stay was 3 days (range, 1-41 days). Major morbidity rate was 20.3% (16 of 79 patients) and 30-day mortality overall was 5.1% (4 of 79 patients). Average cost per case was pound15,012.91 (range, pound4,040.03- pound82,158.00), when National Tariff is pound6,722.00 ( pound5,649.00 x local Market Forces Factor of 1.19). Loss per case for our trust was pound8,290.91 with a total annual loss of pound218,299.56. Morbidity and mortality in this district general hospital compare well with national studies; however, the total cost is far in excess of the national tariff.

The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors

PubMed Central

Matias, Pedro M.; Baek, Sung Hee; Bandeiras, Tiago M.; Dutta, Anindya; Houry, Walid A.; Llorca, Oscar; Rosenbaum, Jean

2015-01-01

Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10–12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models. PMID:25988184

The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors.

PubMed

Matias, Pedro M; Baek, Sung Hee; Bandeiras, Tiago M; Dutta, Anindya; Houry, Walid A; Llorca, Oscar; Rosenbaum, Jean

2015-01-01

Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10-12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models.

Health-related quality of life prospectively evaluated by the 8-item short form after endovascular repair versus open surgery for abdominal aortic aneurysms.

PubMed

Kato, Takayoshi; Tamaki, Mototsugu; Tsunekawa, Tomohiro; Motoji, Yusuke; Hirakawa, Akihiro; Okawa, Yasuhide; Tomita, Shinji

2017-08-01

Open repair for infra-renal abdominal aortic and iliac artery aneurysms (AAAs) is a robust treatment. On the other hand, endovascular aneurysm repair (EVAR) has been widespread because of its less invasiveness. However, patients after EVAR frequently require postoperative radiographic examinations and may feel anxiety for their endoleaks. We prospectively evaluated Health-related Quality of Life of the patients with these two fashions using the 8-item Short Form (SF-8). From 2011 to 2013, 89 consecutive elective cases of AAAs were treated. They were prospectively divided into EVAR and open repair groups but not randomly. The exclusion criteria were as follows: perioperative status for other surgeries, infectious aneurysm, severely deteriorated conditions, and patients who cannot answer for these questionnaire or show their consent. The SF-8 questionnaire was completed through interviews preoperatively, and at 1, 3, 6, and 12 months after treatment. The SF-8 questionnaire was completed for 55 cases [EVAR group (ER): 25, open repair group (OR): 30]. There was no significant difference between these groups regarding patients' characteristics except congestive heart disease. The preoperative scores of the SF-8 were similar in both groups except physical function and social function, which were lower in ER (p < 0.05). There was no operative death in both groups. Operative duration and hospital stay in EVAR were significantly shorter than those in OR (p < 0.05). Follow-up rate at 1, 3, 6, and 12 months was 100, 100, 68.0, and 64.0% in ER, and 100, 90.0, 80.0, and 66.6% in OR, respectively. During follow-up, both groups had no AAAs associated death. Regarding changes of the SF-8 scales, there were some trends at physical component summary score (PCS) and mental component summary score (MCS) in ER. The PCS decreased at 1 month, gradually increased at 3 months, and levelled off until 12 months. The MCS increased at 1 and 3 months, but gradually went down and almost stayed at the same level as preoperative one at 12 months. In OR, PCS and MCS decreased at 1 month and after that increased gradually at 3 and 6 months, and stayed the same at 12 months. The MCS recovered to preoperative score earlier than the PCS. In this study, EVAR did not show any significant mental disturbance based on the SF-8 for 1-year comparing to open repair.

Persistent type II endoleak after EVAR: the predictive value of the AAA thrombus volume.

PubMed

Gallitto, Enrico; Gargiulo, Mauro; Mascoli, Chiara; Freyrie, Antonio; DE Matteis, Massimo; Serra, Carla; Bianchini Massoni, Claudio; Faggioli, Gianluca; Stella, Andrea

2018-02-01

Persistent type II endoleaks (ELIIp, ≥6 months) after an endovascular aneurysm repair (EVAR) can be associated with adverse outcomes. The aims of this study are the evaluation of the incidence of ELIIp, their preoperative morphological predictive features (PMF) and the post-EVAR abdominal aortic aneurysm (AAA) evolution in the presence of ELIIp. Patients underwent EVAR between 2008 and 2010 were prospectively collected. Cases with ELIIp (group A: AG) were identified. A control group without ELIIp (group B: BG), homogeneous for clinical characteristics, follow-up timing and methods (CTA and/or CEUS at 6.12 months and yearly thereafter) was retrospectively selected. The PMF evaluated by computed-tomography-angiography (CTA) were: AAA-diameter, number and diameter of AAA efferent patent vessels (EPV), AAA-total volume (TV), AAA-thrombus volume (THV) and TV/THV rate (%VR). Volumes were calculated by the dedicated vessels analysis software. AG and BG were compared. The primary endpoint was to evaluate the incidence of ELIIp. Secondary endpoints were to analyze the relation between PMF and ELIIp and to assess the post-EVAR AAA-evolution in the presence of ELIIp. Between 2008 and 2010, 200 patients underwent EVAR to treat AAA electively. An ELIIp was detected in 35cases (17.5%) (AG). Twenty-seven patients (13.5%) were included in BG. An overall of 62 patients (GA+GB) were analyzed. The mean pre-operative AAA diameter and EPV were 58±11.6 mm and 5.5±1.8 mm, respectively. The mean TV and THV were 187±111.5 cc and 82±75 cc, respectively. The median %VR was 42.3%. ELIIp was correlated to EPV≥6 (χ2, p=.015) and %VR <40% (logistic regression, P=0.032). The mean follow-up was 22±9 months. Seven (20%) ELIIp spontaneously sealed and 6 (17%) required reinterventions (2 conversions to OR). There were not PMF associated to ELIIp evolution and AAA growth post-EVAR. ELIIp is a not rare complication and it could require re-interventions. Our data suggest that VEP≥6 or %VT<40% are risk factors for ELIIp. No PMF was able to predict the ELIIp evolution. The relative high rate of re-interventions, could suggest the need of adjunctive/preventing primary procedures in patients at high-risk for ELIIp.

Surgical internal iliac artery preservation associated with endovascular repair of infrarenal aortoiliac aneurysms to avoid buttock claudication and distal type I endoleaks.

PubMed

Gaudric, Julien; Tresson, Philippe; Derycke, Lucie; Tezenas Du Montcel, Sophie; Couture, Thibault; Davaine, Jean-Michel; Kashi, Mahine; Lawton, James; Chiche, Laurent; Koskas, Fabien

2018-06-21

The objective of this study was to assess outcomes of a hybrid technique for treatment of abdominal aortic aneurysm (AAA) associated with iliac aneurysm without distal neck by combining an AAA endovascular repair approach with open surgery for preservation of the internal iliac artery (IIA). The files of 51 patients operated on between 1998 and 2017 in a single vascular surgery department were retrospectively analyzed. Inclusion criteria were patients with AAA associated with uni-iliac or bi-iliac aneurysm without suitable distal sealing zone. Surgery consisted of deployment of an aortouni-iliac stent graft combined with an extra-anatomic crossover prosthetic bypass. With use of a limited retroperitoneal approach, the contralateral proximal common iliac aneurysm was surgically excluded and the IIA revascularized by direct ilioiliac anastomosis or terminal common iliac suture, preserving the iliac bifurcation. The patients' mean age was 74 years (58-88 years), and 92% were men. The mean follow-up was 5.8 years (0.1-18 years). Twenty-nine patients (57%) had one or more high-risk criteria for open surgery. Nineteen patients (37.3%) had aortouni-iliac aneurysms, 19 (37.3%) aortobi-iliac aneurysms, 5 (10%) isolated iliac aneurysms, and 8 (15.7%) bi-iliac aneurysms without aortic location. Four patients (7.8%) also had IIA aneurysms. Surgery was successful in all cases. Two patients (4%) died during the 30 days after surgery. One surgically preserved IIA occluded within the first month, resulting in buttock claudication. The 5-year IIA primary patency rate was 96%. Type I proximal endoleaks occurred in two patients, requiring additional surgery 3 years and 13 years after the initial surgery, respectively. This hybrid technique, consisting of AAA endovascular exclusion combined with open IIA revascularization, is safe and effective for preservation of pelvic vascularization. It is associated with long-term patency and low morbidity rates. We have been using this technique since before the advent of branched dedicated devices, allowing preservation of the IIA with good results. This technique should continue to be proposed, especially in patients not eligible for endovascular iliac branch repair because of anatomic contraindications, to avoid pelvic ischemia if the IIA has to be sacrificed. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

In vivo assessment of aortic aneurysm wall integrity using elastin-specific molecular magnetic resonance imaging.

PubMed

Botnar, René M; Wiethoff, Andrea J; Ebersberger, Ullrich; Lacerda, Sara; Blume, Ulrike; Warley, Alice; Jansen, Christian H P; Onthank, David C; Cesati, Richard R; Razavi, Reza; Marber, Michael S; Hamm, Bernd; Schaeffter, Tobias; Robinson, Simon P; Makowski, Marcus R

2014-07-01

The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs. To induce AAAs, ApoE(-/-) mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers. Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular magnetic resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs. © 2014 American Heart Association, Inc.

Fourier Transform Infrared Spectroscopic Imaging-Derived Collagen Content and Maturity Correlates with Stress in the Aortic Wall of Abdominal Aortic Aneurysm Patients.

PubMed

Cheheltani, Rabee; Pichamuthu, Joseph E; Rao, Jayashree; Weinbaum, Justin S; Kiani, Mohammad F; Vorp, David A; Pleshko, Nancy

2017-03-01

Abdominal aortic aneurysm (AAA) is a degenerative disease of the aorta characterized by severe disruption of the structural integrity of the aortic wall and its major molecular constituents. From the early stages of disease, elastin in the aorta becomes highly degraded and is replaced by collagen. Questions persist as to the contribution of collagen content, quality and maturity to the potential for rupture. Here, using our recently developed Fourier transform infrared imaging spectroscopy (FT-IRIS) method, we quantified collagen content and maturity in the wall of AAA tissues in pairs of specimens with different wall stresses. CT scans of AAAs from 12 patients were used to create finite element models to estimate stress in different regions of tissue. Each patient underwent elective repair of the AAA, and two segments of the AAA tissues from anatomic regions more proximal or distal with different wall stresses were evaluated by histology and FT-IRIS after excision. For each patient, collagen content was generally greater in the tissue location with lower wall stress, which corresponded to the more distal anatomic regions. The wall stress/collagen ratio was greater in the higher stress region compared to the lower stress region (1.01 ± 1.09 vs. 0.55 ± 0.084, p = 0.02). The higher stress region also corresponded to the location with reduced intraluminal thrombus thickness. Further, collagen maturity tended to decrease with increased collagen content (p = 0.068, R = 0.38). Together, these results suggest that an increase in less mature collagen content in AAA patients does not effectively compensate for the loss of elastin in the aortic wall, and results in a reduced capability to endure wall stresses.

Survival following ruptured abdominal aortic aneurysm before and during the IMPROVE Trial: a single-centre series.

PubMed

Ambler, G K; Twine, C P; Shak, J; Rollins, K E; Varty, K; Coughlin, P A; Hayes, P D; Boyle, J R

2014-04-01

The first large-scale randomised trial (Immediate Management of the Patient with Rupture: Open Versus Endovascular repair [IMPROVE]) for endovascular repair of ruptured abdominal aortic aneurysm (rEVAR) has recently finished recruiting patients. The aim of this study was to examine the impact on survival after rEVAR when the IMPROVE protocol was initiated in a high volume abdominal aortic aneurysm (AAA) centre previously performing rEVAR. One hundred and sixty-nine patients requiring emergency infrarenal AAA repair from January 2006 to April 2013 were included. Eighty-four patients were treated before (38 rEVAR, 46 open) and 85 (31 rEVAR, 54 open) were treated during the trial period. A retrospective analysis was performed. Before the trial, there was a significant survival benefit for rEVAR over open repair (90-day mortality 13% vs. 30%, p = .04, difference remained significant up to 2 years postoperatively). This survival benefit was lost after starting randomisation (90-day mortality 35% vs. 33%, p = .93). There was an increase in overall 30-day mortality from 15% to 31% (p = .02), while there was no change for open repair (p = .438). There was a significant decrease in general anaesthetic use (p = .002) for patients treated during the trial. Randomised patients had shorter hospital and intensive treatment unit stays (p = .006 and p = .03 respectively). The change in survival seen during the IMROVE trial highlights the need for randomised rather than cohort data to eliminate selection bias. These results from a single centre reinforce those recently reported in IMPROVE. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Engineering Silicone Rubbers for In vitro Studies: Creating AAA Models and ILT Analogues with Physiological Properties

PubMed Central

Corbett, T.J.; Doyle, B.J.; Callanan, A.; Walsh, M.T.; McGloughlin, T.M

2010-01-01

Background In vitro studies of abdominal aortic aneurysm (AAA) have been widely reported. Frequently mock artery models with intraluminal thrombus (ILT) analogues are used to mimic the AAA in vivo. While the models used may be physiological, their properties are frequently either not reported or investigated. Method of Approach This study is concerned with the testing and characterisation of previously used vessel analogue materials and the development of new materials for the manufacture of AAA models. These materials were used in conjunction with a previously validated injection moulding technique to manufacture AAA models of ideal geometry. To determine the model properties (stiffness (β) and compliance) the diameter change of each AAA model was investigated under incrementally increasing internal pressures and compared to published in vivo studies to determine if the models behaved physiologically. A FEA study was implemented to determine if the pressure – diameter change behaviour of the models could be predicted numerically. ILT analogues were also manufactured and characterised. Ideal models were manufactured with ILT analogue internal to the aneurysm region and the effect of the ILT analogue on the model compliance and stiffness was investigated. Results The wall materials had similar properties to aortic tissue at physiological pressures (Einit 2.22MPa and 1.57MPa (aortic tissue: 1.8MPa)). ILT analogues had similar Young’s modulus to the medial layer of ILT (0.24 and 0.33MPa (ILT: 0.28MPa)). All models had aneurysm sac compliance in the physiological range (2.62 – 8.01×10-4/mmHg (AAA in vivo: 1.8 – 9.4×10-4/mmHg)). The necks of our AAA models had similar stiffness to healthy aortas (20.44 – 29.83 (healthy aortas in vivo: 17.5±5.5)). Good agreement was seen between the diameter changes due to pressurisation in the experimental and FEA wall models with a maximum error of 7.3% at 120mmHg. It was also determined that the inclusion of ILT analogue in the sac of our models could have an effect on the compliance of the model neck. Conclusions Ideal AAA models with physiological properties were manufactured. The behaviour of these models due to pressurisation was predicted using FEA, validating this technique for the future design of realistic, physiological AAA models. Addition of ILT analogues in the aneurysm sac was shown to affect neck behaviour. This could have implications for endovascular AAA repair due to the importance of the neck for stent-graft fixation. PMID:20524746

Initial Clinical Experience Using the Low-Profile Altura Endograft System With Double D-Shaped Proximal Stents for Endovascular Aneurysm Repair.

PubMed

Krievins, Dainis; Krämer, Albrecht; Savlovskis, Janis; Oszkinis, Georgij; Debus, E Sebastian; Oberhuber, Alexander; Zarins, Christopher K

2018-06-01

To report the initial clinical results of endovascular aneurysm repair (EVAR) using the low-profile (14-F) Altura Endograft System, which features a double "D-shaped" stent design with suprarenal fixation and modular iliac components that are deployed from distal to proximal. From 2011 to 2015, 90 patients (mean age 72.8±8.3 years; 79 men) with abdominal aortic aneurysm (AAA; mean diameter 53.8±5.7 mm) were treated at 10 clinical sites in 2 prospective, controlled clinical studies using the Altura endograft. Outcomes evaluated included mortality, major adverse events (MAEs: all-cause death, stroke, paraplegia, myocardial infarction, respiratory failure, bowel ischemia, and blood loss ≥1000 mL), and clinical success (freedom from procedure-related death, type I/III endoleak, migration, thrombosis, and reintervention). Endografts were successfully implanted in 89 (99%) patients; the single failure was due to delivery system malfunction before insertion in the early-generation device. One (1%) patient died and 4 patients underwent reinterventions (1 type I endoleak, 2 iliac limb stenoses, and 1 endograft occlusion) within the first 30 days. During a median follow-up of 12.5 months (range 11.5-50.9), there were no aneurysm ruptures, surgical conversions, or AAA-related deaths. The cumulative MAE rates were 3% (3/89) at 6 months and 7% (6/89) at 1 year. Two patients underwent coil embolization of type II endoleaks at 6.5 months and 2.2 years, respectively. Clinical success was 94% (84/89) at 30 days, 98% (85/87) at 6 months, and 99% (82/83) at 1 year. Early results suggest that properly selected AAA patients can be safely treated using the Altura Endograft System with favorable midterm outcome. Thus, further clinical investigation is warranted to evaluate the role of this device in the treatment of AAA.

ACE DD genotype: a predisposing factor for abdominal aortic aneurysm.

PubMed

Fatini, C; Pratesi, G; Sofi, F; Gensini, F; Sticchi, E; Lari, B; Pulli, R; Dorigo, W; Azas, L; Pratesi, C; Gensini, G F; Abbate, R

2005-03-01

To examine the role of polymorphisms in angiotensin converting enzyme (ACE, I/D) and angiotensin II receptor (AT1R, A1166C) in the development of abdominal aortic aneurysm (AAA). We investigated 250 consecutive patients, 217 males and 33 females (median age 72, range 50-83), undergone AAA elective repair and 250 healthy controls, comparable for sex and age. ACE and AT1R polymorphisms were studied by PCR-RFLP analysis. The genotype distribution was in Hardy-Weinberg equilibrium for all polymorphisms. The genotype distribution and allele frequency of ACE I/D, but not AT1R A1166C polymorphism were significantly different between patients and controls (ACE I/D: p=0.0002 and p<0.0001, respectively, and AT1R A1166C: p=0.6 and p=0.4, respectively). An association between the ACE DD genotype and the predisposition to AAA was found (OR DD vs. ID+II=1.9 95% CI 1.3-2.9, p<0.0001). Multivariate analysis adjusted for age, sex, traditional vascular risk factors and other atherosclerotic localizations, showed ACE DD genotype to be independently related to the disease (OR DD vs. ID+II=2.4, 95% CI 1.3-4.2 p=0.003). Our findings document that ACE DD genotype represents a susceptibility factor for AAA.

Ruptured Abdominal Aortic Aneurysm: Prediction of Mortality From Clinical Presentation and Glasgow Aneurysm Score.

PubMed

Weingarten, Toby N; Thompson, Lauren T; Licatino, Lauren K; Bailey, Christopher H; Schroeder, Darrell R; Sprung, Juraj

2016-04-01

To examine association of presenting clinical acuity and Glasgow Aneurysm Score (GAS) with perioperative and 1-year mortality. Retrospective chart review. Major tertiary care facility. Patients with ruptured abdominal aortic aneurysm (rAAA) from 2003 through 2013. Emergency repair of rAAA. The authors reviewed outcomes after stable versus unstable presentation and by GAS. Unstable presentation included hypotension, cardiac arrest, loss of consciousness, and preoperative tracheal intubation. In total, 125 patients (40 stable) underwent repair. Perioperative mortality rates were 41% and 12% in unstable and stable patients, respectively (p<0.001). Unstable status had 88% sensitivity and 41% specificity for predicting perioperative mortality. Using logistic regression, higher GAS was associated with perioperative mortality (p<0.001). Using receiver operating characteristic analysis, the area under the curve was 0.72 (95% CI, 0.62-0.82) and cutoff GAS≥96 had 63% and 72% sensitivity and specificity, respectively. Perioperative mortality for GAS≥96 was 51% (25/49), whereas it was 20% (15/76) for GAS≤95. The estimated 1-year survival (95% CI) was 75% (62%-91%) for stable patients and 48% (38%-60%) for unstable patients. Estimated 1-year survival (95% CI) was 23% (13%-40%) for GAS≥96 and 77% (67%-87%) for GAS≤95. Clinical presentation and GAS identified patients with rAAA who were likely to have a poor surgical outcome. GAS≥96 was associated with poor long-term survival, but>20% of these patients survived 1 year. Thus, neither clinical presentation nor GAS provided reliable guidance for decisions regarding futility of surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

The incidence and effect of noncylindrical neck morphology on outcomes after endovascular aortic aneurysm repair in the Global Registry for Endovascular Aortic Treatment.

PubMed

Shutze, William; Suominem, Velipekka; Jordan, William; Cao, Piergiorgio; Oweida, Steven; Milner, Ross

2018-05-23

The Gore Global Registry for Endovascular Aortic Treatment (GREAT) was designed to evaluate real-world outcomes after treatment with Gore aortic endografts used in a real-world, global setting. We retrospectively analyzed the GREAT data to evaluate the incidence and effects of noncylindrical neck anatomy in patients undergoing endovascular aortic aneurysm repair. The present analysis included patients with data in the GREAT who had been treated with the EXCLUDER endograft from August 2010 to October 2016. A noncylindrical neck was defined when the proximal aortic landing zone diameter had changed ≥2 mm over the first 15 mm of the proximal landing zone, indicating a tapered, conical, or hourglass morphology. Cox multivariate regression analyses were performed for any reintervention (including reinterventions on aortic branch vessels), device-related reinterventions, and reintervention specifically for endoleak. Independent binary (cylindrical vs noncylindrical necks) and continuous (percentage of neck diameter change) variables were assessed. The abdominal aortic aneurysm (AAA) diameter, proximal neck length, maximal infrarenal neck angle, gender, and use of aortic extender cuffs were also assessed. Of 3077 GREAT patients with available proximal aortic landing zone diameter measurements available, 1765 were found to have cylindrical necks and 1312 had noncylindrical necks. The noncylindrical neck cohort had a significantly greater proportion of women (17.4% vs 12.6%; P < .001) and more severe infrarenal angulation (33.8° vs 28.4°; P < .001). A total 14.7% of noncylindrical neck patients and 11.2% cylindrical neck patients underwent implantation outside of the EXCLUDER instructions for use regarding the anatomic inclusion criteria (P = .004). The procedural characteristics were similar between the two cohorts; however, noncylindrical neck patients required significantly more aortic extender cuffs (P = .004). The average follow-up was 21.2 ± 17.5 months and 17.8 ± 15.8 months for the cylindrical and noncylindrical cohorts, respectively (P < .001). The Cox multivariate regression models demonstrated female gender and maximum AAA diameter were significant risk factors for subsequent reintervention (overall, device-related, and endoleak-specific). Women were 2.2 times as likely to require device-related intervention during the follow-up period compared with men (P < .001). Neck shape morphology was not a significant predictor, except for device-related intervention, for which cylindrical necks (binary definition) resulted in a slightly elevated risk (1.5 times; P = .03). Noncylindrical neck morphology was more common in women and was associated with an increased use of aortic extender cuffs but did not increase the risk of intervention. Female gender and AAA diameter were associated with an increased need for reintervention. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Assessment of subclinical acute kidney injury after abdominal aortic aneurysm surgery using novel markers: L-FABP and H-FABP.

PubMed

Kokot, Michał; Biolik, Grzegorz; Ziaja, Damian; Fojt, Tadeusz; Kędzierski, Leszek; Antoniak, Katarzyna; Janowska, Mirosława; Pawlicki, Krzysztof; Ziaja, Krzysztof; Duława, Jan

2014-01-01

One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Even small rises in serum creatinine are associated with increased mortality. The aim of this study was to assess the dynamics of AKI after elective AAA surgery using novel markers. The study group consisted of 22 patients with AAA. We measured urinary liver- (u-L-FABP) and heart-type fatty acid-binding proteins (u-H-FABP) before, during and within 3 days after surgery. We found an abrupt and significant elevation of both urine FABPs normalized to urinary creatinine; u-L-FABP reached its peak value 2 hours after aortic clamp release {137.79 (38.57-451.79) vs. 9.94 (6.82-12.42) ng/mg baseline value, p<0.05; values are medians (lower-upper quartile)}. The peak value of u-H-FABP was reported 72 hours after aortic clamp release {16.462 (4.182-37.595) vs. 0.141 (0.014-0.927) ng/mg baseline value, p<0.05}. The serum creatinine level did not changed significantly during the investigation period. The significant rise of both u-L-FABP and u-H-FABP after AAA surgery indicates renal proximal and distal tubule injury in this population. Our results suggest that, after AAA surgery, the distal tubules could be more affected than the proximal ones. u-FABPs could serve as sensitive biomarkers of kidney tubular injury and may allow to detect the very early phases of AKI.

Three-dimensional finite volume modelling of blood flow in simulated angular neck abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Algabri, Y. A.; Rookkapan, S.; Chatpun, S.

2017-09-01

An abdominal aortic aneurysm (AAA) is considered a deadly cardiovascular disease that defined as a focal dilation of blood artery. The healthy aorta size is between 15 and 24 mm based on gender, bodyweight, and age. When the diameter increased to 30 mm or more, the rupture can occur if it is kept growing or untreated. Moreover, the proximal angular neck of aneurysm is categorized as a significant morphological feature with prime harmful effects on endovascular aneurysm repair (EVAR). Flow pattern in pathological vessel can influence the vascular intervention. The aim of this study is to investigate the blood flow behaviours in angular neck abdominal aortic aneurysm with simulated geometry based on patient’s information using computational fluid dynamics (CFD). The 3D angular neck AAA models have been designed by using SolidWorks Software. Consequently, CFD tools are used for simulating these 3D models of angular neck AAA in ANSYS FLUENT Software. Eventually, based on the results, we summarized that the CFD techniques have shown high performance in explaining and investigating the flow patterns for angular neck abdominal aortic aneurysm.

Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs.

PubMed

Machado-Pinilla, Rosario; Liger, Dominique; Leulliot, Nicolas; Meier, U Thomas

2012-10-01

The AAA+ ATPases pontin and reptin function in a staggering array of cellular processes including chromatin remodeling, transcriptional regulation, DNA damage repair, and assembly of macromolecular complexes, such as RNA polymerase II and small nucleolar (sno) RNPs. However, the molecular mechanism for all of these AAA+ ATPase associated activities is unknown. Here we document that, during the biogenesis of H/ACA RNPs (including telomerase), the assembly factor SHQ1 holds the pseudouridine synthase NAP57/dyskerin in a viselike grip, and that pontin and reptin (as components of the R2TP complex) are required to pry NAP57 from SHQ1. Significantly, the NAP57 domain captured by SHQ1 harbors most mutations underlying X-linked dyskeratosis congenita (X-DC) implicating the interface between the two proteins as a target of this bone marrow failure syndrome. Homing in on the essential first steps of H/ACA RNP biogenesis, our findings provide the first insight into the mechanism of action of pontin and reptin in the assembly of macromolecular complexes.

Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs

PubMed Central

Machado-Pinilla, Rosario; Liger, Dominique; Leulliot, Nicolas; Meier, U. Thomas

2012-01-01

The AAA+ ATPases pontin and reptin function in a staggering array of cellular processes including chromatin remodeling, transcriptional regulation, DNA damage repair, and assembly of macromolecular complexes, such as RNA polymerase II and small nucleolar (sno) RNPs. However, the molecular mechanism for all of these AAA+ ATPase associated activities is unknown. Here we document that, during the biogenesis of H/ACA RNPs (including telomerase), the assembly factor SHQ1 holds the pseudouridine synthase NAP57/dyskerin in a viselike grip, and that pontin and reptin (as components of the R2TP complex) are required to pry NAP57 from SHQ1. Significantly, the NAP57 domain captured by SHQ1 harbors most mutations underlying X-linked dyskeratosis congenita (X-DC) implicating the interface between the two proteins as a target of this bone marrow failure syndrome. Homing in on the essential first steps of H/ACA RNP biogenesis, our findings provide the first insight into the mechanism of action of pontin and reptin in the assembly of macromolecular complexes. PMID:22923768

Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair

PubMed Central

Subramanian, Vijayalakshmi V.; MacQueen, Amy J.; Vader, Gerben; Shinohara, Miki; Sanchez, Aurore; Borde, Valérie; Shinohara, Akira; Hochwagen, Andreas

2016-01-01

Faithful meiotic chromosome segregation and fertility require meiotic recombination between homologous chromosomes rather than the equally available sister chromatid, a bias that in Saccharomyces cerevisiae depends on the meiotic kinase, Mek1. Mek1 is thought to mediate repair template bias by specifically suppressing sister-directed repair. Instead, we found that when Mek1 persists on closely paired (synapsed) homologues, DNA repair is severely delayed, suggesting that Mek1 suppresses any proximal repair template. Accordingly, Mek1 is excluded from synapsed homologues in wild-type cells. Exclusion requires the AAA+-ATPase Pch2 and is directly coupled to synaptonemal complex assembly. Stage-specific depletion experiments further demonstrate that DNA repair in the context of synapsed homologues requires Rad54, a repair factor inhibited by Mek1. These data indicate that the sister template is distinguished from the homologue primarily by its closer proximity to inhibitory Mek1 activity. We propose that once pairing or synapsis juxtaposes homologues, exclusion of Mek1 is necessary to avoid suppression of all templates and accelerate repair progression. PMID:26870961

Minimally invasive retrieval of a dislodged Wallstent endoprosthesis after an endovascular abdominal aortic aneurysm repair.

PubMed

Lam, Russell C; Rhee, Soo J; Morrissey, Nicholas J; McKinsey, James F; Faries, Peter L; Kent, K Craig

2008-02-01

Endovascular abdominal aortic aneurysm repair (EVAR) is being performed more frequently in patients with concomitant iliac artery occlusive disease. We report a case of a 70-year-old male status post angioplasty and stenting of bilateral iliac arteries for occlusive disease who subsequently underwent EVAR for a rapidly expanding abdominal aortic aneurysm (AAA). One month after the placement of the endograft, it was discovered that the previously placed Wallstent had been dislodged during the endovascular abdominal aortic aneurysm repair. Minimally invasive retrieval using an Amplatz Goose Neck Snare was successful in recovering the stent. This case underscores the danger of performing EVAR in the setting of prior iliac artery stenting and the potential complications that may ensue.

Preliminary results of endovascular aneurysm sealing from the multicenter Italian Research on Nellix Endoprosthesis (IRENE) study.

PubMed

Gossetti, Bruno; Martinelli, Ombretta; Ferri, Michelangelo; Silingardi, Roberto; Verzini, Fabio

2018-05-01

Because of advances in technology and experience of the operator, endovascular aneurysm repair (EVAR) has supplanted open repair to treat abdominal aortic aneurysm (AAA). The low 30-day mortality and morbidity of EVAR make the endovascular approach particularly suitable for patients at high surgical risk. However, endoleak or endograft migration requiring secondary intervention or open surgical conversion is a limitation of EVAR. The Nellix system (Endologix, Inc, Irvine, Calif) has been designed to seal the entire AAA to overcome these limitations with EVAR. We report the results of a retrospective, multicenter study with endovascular aneurysm sealing (EVAS) aimed to assess technical success, procedure-related mortality, complications, and reinterventions. This study included patients selected for elective treatment with the Nellix device per the endovascular repair protocol at 16 Italian vascular centers. All patients were enrolled in a postoperative surveillance imaging program including duplex ultrasound investigations, computed tomography, and magnetic resonance controls following local standards of care. From 2013 to 2015, there were 335 patients (age, 75.5 ± 7.4 years; 316 men) who underwent elective EVAS. In 295 cases (88.0%), EVAS was performed under standard instructions for use of the Nellix system. Preoperative aneurysm diameter was 55.5 ± 9.4 mm (range, 46-65 mm). The inferior mesenteric artery and lumbar arteries emerging from the AAA were patent in 61.8% and 81.3% of cases, respectively. Chimney grafts were electively carried out in eight cases (2.4%). One (0.3%) intraprocedural type IB endoleak was observed and promptly corrected. Device deployment was successful in all patients, with no perioperative mortality. Early (≤30 days) complications included 1 (0.3%) type IA endoleak, 2 (0.6%) type II endoleaks (0.6%), 2 (0.6%) stent occlusions (0.6%), 3 (0.9%) distal embolizations, and 2 (0.2%) femoral artery dissections. Six (2.9%) patients underwent reinterventions. At 1-year follow-up, complications included 3 (1.1%) type II endoleaks, 4 (1.4%) type IA endoleaks, 1 (0.3%) type IB endoleak, 2 (0.7%) distal stent migrations, 5 (1.8%) distal embolizations, and 1 (0.3%) stent occlusion. Twelve patients (3.7%) underwent reinterventions, including four (1.4%) surgical conversions due to aortoduodenal fistula (1), endograft infection (1), and type IA endoleak that was unsuccessfully treated percutaneously (2). Two AAA-related deaths occurred. Freedom from aneurysm-related reintervention was 98.3% at 1-month and 94.7% at 12-month follow-up. The preliminary results of this real-world multicenter study showed that EVAS with Nellix for the management of AAAs appears feasible. This device platform is associated with acceptable procedure-related mortality and low overall complication and reintervention rates. Definitive conclusions on the value of this novel device await long-term follow-up data. Published by Elsevier Inc.

Intra-Abdominal Hypertension and Abdominal Compartment Syndrome in Association with Ruptured Abdominal Aortic Aneurysm in the Endovascular Era: Vigilance Remains Critical

PubMed Central

Bozeman, Matthew C.; Ross, Charles B.

2012-01-01

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are common complications of ruptured abdominal aortoiliac aneurysms (rAAAs) and other abdominal vascular catastrophes even in the age of endovascular therapy. Morbidity and mortality due to systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) are significant. Recognition and management of IAH are key critical care measures which may decrease morbidity and improve survival in these vascular patients. Two strategies have been utilized: expectant management with prompt decompressive laparotomy upon diagnosis of threshold levels of IAH versus prophylactic, delayed abdominal closure based upon clinical parameters at the time of initial repair. Competent management of the abdominal wound with preservation of abdominal domain is also an important component of the care of these patients. In this review, we describe published experience with IAH and ACS complicating abdominal vascular catastrophes, experience with ACS complicating endovascular repair of rAAAs, and techniques for management of the abdominal wound. Vigilance and appropriate management of IAH and ACS remains critically important in decreasing morbidity and optimizing survival following catastrophic intra-abdominal vascular events. PMID:22454763

Intra-abdominal hypertension and abdominal compartment syndrome in association with ruptured abdominal aortic aneurysm in the endovascular era: vigilance remains critical.

PubMed

Bozeman, Matthew C; Ross, Charles B

2012-01-01

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are common complications of ruptured abdominal aortoiliac aneurysms (rAAAs) and other abdominal vascular catastrophes even in the age of endovascular therapy. Morbidity and mortality due to systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) are significant. Recognition and management of IAH are key critical care measures which may decrease morbidity and improve survival in these vascular patients. Two strategies have been utilized: expectant management with prompt decompressive laparotomy upon diagnosis of threshold levels of IAH versus prophylactic, delayed abdominal closure based upon clinical parameters at the time of initial repair. Competent management of the abdominal wound with preservation of abdominal domain is also an important component of the care of these patients. In this review, we describe published experience with IAH and ACS complicating abdominal vascular catastrophes, experience with ACS complicating endovascular repair of rAAAs, and techniques for management of the abdominal wound. Vigilance and appropriate management of IAH and ACS remains critically important in decreasing morbidity and optimizing survival following catastrophic intra-abdominal vascular events.

Controlled hypotension versus normotensive resuscitation strategy for people with ruptured abdominal aortic aneurysm.

PubMed

Moreno, Daniel H; Cacione, Daniel G; Baptista-Silva, Jose C C

2016-05-13

An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mm Hg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 to 100 mm Hg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function. To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA. The Cochrane Vascular Information Specialist searched the Specialised Register (April 2016) and the Cochrane Register of Studies (CENTRAL (2016, Issue 3)). Clinical trials databases were searched (April 2016) for details of ongoing or unpublished studies. We sought all published and unpublished randomised controlled trial (RCTs) that compared controlled hypotension and normotensive resuscitation strategies for the management of shock in patients with ruptured abdominal aortic aneurysms. Two review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions. We identified no RCTs that met the inclusion criteria. We found no RCTs that compared controlled hypotension and normotensive resuscitation strategies in the management of haemorrhagic shock in patients with ruptured abdominal aortic aneurysm that assessed mortality, presence of coagulopathy, intensive care unit length of stay, and the presence of myocardial infarct and renal failure. High quality studies that evaluate the best strategy for managing haemorrhagic shock in ruptured abdominal aortic aneurysms are required.

Controlled hypotension versus normotensive resuscitation strategy for people with ruptured abdominal aortic aneurysm.

PubMed

Moreno, Daniel H; Cacione, Daniel G; Baptista-Silva, Jose Cc

2018-06-13

An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mmHg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 mmHg to 100 mmHg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function. This is an update of a review first published in 2016. To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA. The Cochrane Vascular Information Specialist searched the Specialised Register (August 2017), the Cochrane Register of Studies (CENTRAL (2017, Issue 7)) and EMBASE (August 2017). The Cochrane Vascular Information Specialist also searched clinical trials databases (August 2017) for details of ongoing or unpublished studies. We sought all published and unpublished randomised controlled trial (RCTs) that compared controlled hypotension and normotensive resuscitation strategies for the management of shock in patients with ruptured abdominal aortic aneurysms. Two review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions. We identified no RCTs that met the inclusion criteria. We found no RCTs that compared controlled hypotension and normotensive resuscitation strategies in the management of haemorrhagic shock in patients with ruptured abdominal aortic aneurysm that assessed mortality, presence of coagulopathy, intensive care unit length of stay, and the presence of myocardial infarct and renal failure. High quality studies that evaluate the best strategy for managing haemorrhagic shock in ruptured abdominal aortic aneurysms are required.

Rapid reversal of colonic pneumatosis with restoration of mesenteric arterial supply.

PubMed

Abidali, Hussein; Cole, Lauren; Seetharam, Anil Bellur

2018-06-07

Pneumatosis cystoides intestinalis (PCI) is characterized by gas-filled cystic lesions within the wall of the large intestine and presents along a spectrum of clinical severity ranging from benign to life threatening. Etiopathogenesis is multifactorial and postulated to result from either mechanical or bacterial causes. In this report, we present a patient with chronic abdominal pain evaluated with colonoscopy revealing segmental PCI isolated to the distal colon. Further investigation revealed an abdominal aortic aneurysm (AAA) compromising the inferior mesenteric artery takeoff. Endovascular repair of the AAA resulted in clinical resolution of abdominal pain and endoscopic resolution of PCI. To our knowledge, this is the first report to document endoscopic resolution of PCI with restoration of mesenteric arterial supply, highlighting vascular insufficiency as a predisposing and reversible pathogenic mechanism.

Impact of preoperative regular physical activity on postoperative course after open abdominal aortic aneurysm surgery.

PubMed

Hayashi, Kazuhiro; Hirashiki, Akihiro; Kodama, Akio; Kobayashi, Kiyonori; Yasukawa, Yuto; Shimizu, Miho; Kondo, Takahisa; Komori, Kimihiro; Murohara, Toyoaki

2016-04-01

Early ambulation after open abdominal aortic aneurysm (AAA) surgery is assumed to play a key role in preventing postoperative complications and reducing hospital length of stay. However, the factors predicting early ambulation after open AAA surgery have not yet been sufficiently investigated. Here, we investigated which preoperative and intraoperative variables are associated with start time for ambulation in patients after open AAA surgery. A total of 67 consecutive patients undergoing open AAA surgery were included in the study [male, 62 (92 %); mean age, 68 years (range, 47-82 years), mean AAA diameter, 53 mm (range, 28-80 mm)]. Preoperative physical activity was examined by means of 6-min walk distance (6MWD) and a medical interview. Patients were divided into two groups, according to when independence in walking was attained: early group <3 days (n = 36) and late group ≥3 days (n = 31), and the pre-, intra-, and postoperative recovery data were compared. There were no significant differences in patient baseline characteristics or intraoperative data between the two groups. The number of patients engaging in preoperative regular physical activity and 6MWD were significantly greater (p = 0.042 and p = 0.034, respectively) in the early group than in the late group. In addition, time to hospital discharge was significantly shorter in the early group than in the late group (p = 0.031). Binary logistic regression analysis showed that preoperative regular physical activity was the only independent factor for identifying patients in the early group (odds ratio 2.769, 95 % confidence interval 1.024-7.487, p = 0.045). These results suggest that engaging in regular physical activity is an effective predictor of early ambulation after open AAA surgery.

Asymmetric processing of a substrate protein in sequential allosteric cycles of AAA+ nanomachines

NASA Astrophysics Data System (ADS)

Kravats, Andrea N.; Tonddast-Navaei, Sam; Bucher, Ryan J.; Stan, George

2013-09-01

Essential protein quality control includes mechanisms of substrate protein (SP) unfolding and translocation performed by powerful ring-shaped AAA+ (ATPases associated with various cellular activities) nanomachines. These SP remodeling actions are effected by mechanical forces imparted by AAA+ loops that protrude into the central channel. Sequential intra-ring allosteric motions, which underlie repetitive SP-loop interactions, have been proposed to comprise clockwise (CW), counterclockwise (CCW), or random (R) conformational transitions of individual AAA+ subunits. To probe the effect of these allosteric mechanisms on unfoldase and translocase functions, we perform Langevin dynamics simulations of a coarse-grained model of an all-alpha SP processed by the single-ring ClpY ATPase or by the double-ring p97 ATPase. We find that, in all three allosteric mechanisms, the SP undergoes conformational transitions along a common set of pathways, which reveals that the active work provided by the ClpY machine involves single loop-SP interactions. Nevertheless, the rates and yields of SP unfolding and translocation are controlled by mechanism-dependent loop-SP binding events, as illustrated by faster timescales of SP processing in CW allostery compared with CCW and R allostery. The distinct efficacy of allosteric mechanisms is due to the asymmetric collaboration of adjacent subunits, which involves CW-biased structural motions of AAA+ loops and results in CW-compatible torque applied onto the SP. Additional simulations of mutant ClpY rings, which render a subset of subunits catalytically-defective or reduce their SP binding affinity, reveal that subunit-based conformational transitions play the major role in SP remodeling. Based on these results we predict that the minimally functional AAA+ ring includes three active subunits, only two of which are adjacent.

Selective Intra-procedural AAA sac Embolization During EVAR Reduces the Rate of Type II Endoleak.

PubMed

Mascoli, C; Freyrie, A; Gargiulo, M; Gallitto, E; Pini, R; Faggioli, G; Serra, C; De Molo, C; Stella, A

2016-05-01

The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) <40% are considered to be positive predictive factors for persistent type II endoleak (ELIIp). The aim of the present study was to evaluate the effectiveness of sac embolization during EVAR in patients with pre-operative morphological risk factors (p-MRF) for ELIIp. Patients undergoing EVAR and intra-procedural AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra-procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months. Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p < .001) at discharge, and this was confirmed at 6-12 months (7/26 vs. 30/44 respectively, p = .001, and 5/25 vs. 32/44, respectively, p < .001). On multivariate analysis, intra-procedural AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p = .007) and 12 months (OR 0.098, 95% CI 0.02-0.35; p < .001). No differences in median AAA sac diameter shrinkage were detected between the two groups at 6-12 months (p = .42 and p = .58, respectively). Freedom from ELIIp related and embolization related re-interventions was 100% in both groups, at 6 and 12 months. Selective intra-procedural AAA sac embolization in patients with p-MRF is safe and could be an effective method to reduce ELIIp. Further studies are mandatory to support these results at long-term follow up. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosarge, Christina L., E-mail: cbosarge@umail.iu.edu; Ewing, Marvene M.; DesRosiers, Colleen M.

To demonstrate the dosimetric advantages and disadvantages of standard anteroposterior-posteroanterior (S-AP/PA{sub AAA}), inverse-planned AP/PA (IP-AP/PA) and volumetry-modulated arc (VMAT) radiotherapies in the treatment of children undergoing whole-lung irradiation. Each technique was evaluated by means of target coverage and normal tissue sparing, including data regarding low doses. A historical approach with and without tissue heterogeneity corrections is also demonstrated. Computed tomography (CT) scans of 10 children scanned from the neck to the reproductive organs were used. For each scan, 6 plans were created: (1) S-AP/PA{sub AAA} using the anisotropic analytical algorithm (AAA), (2) IP-AP/PA, (3) VMAT, (4) S-AP/PA{sub NONE} without heterogeneitymore » corrections, (5) S-AP/PA{sub PB} using the Pencil-Beam algorithm and enforcing monitor units from technique 4, and (6) S-AP/PA{sub AAA[FM]} using AAA and forcing fixed monitor units. The first 3 plans compare modern methods and were evaluated based on target coverage and normal tissue sparing. Body maximum and lower body doses (50% and 30%) were also analyzed. Plans 4 to 6 provide a historic view on the progression of heterogeneity algorithms and elucidate what was actually delivered in the past. Averages of each comparison parameter were calculated for all techniques. The S-AP/PA{sub AAA} technique resulted in superior target coverage but had the highest maximum dose to every normal tissue structure. The IP-AP/PA technique provided the lowest dose to the esophagus, stomach, and lower body doses. VMAT excelled at body maximum dose and maximum doses to the heart, spine, and spleen, but resulted in the highest dose in the 30% body range. It was, however, superior to the S-AP/PA{sub AAA} approach in the 50% range. Each approach has strengths and weaknesses thus associated. Techniques may be selected on a case-by-case basis and by physician preference of target coverage vs normal tissue sparing.« less

Is Conventional Open Repair for Abdominal Aortic Aneurysm Feasible in Nonagenarians?

PubMed

Uehara, Kyokun; Matsuda, Hitoshi; Inoue, Yosuke; Omura, Atsushi; Seike, Yoshimasa; Sasaki, Hiroaki; Kobayashi, Junjiro

2017-09-25

Background : Although endovascular repair for abdominal aortic aneurysm has been found to be beneficial in very elderly patients, some patients have contraindications to this procedure. For nonagenarians, the results of open repair remain unclear. The purpose of this study was to compare the outcomes of open vs. endovascular repair for abdominal aortic aneurysm in nonagenarian patients. Methods and Results : Fourteen patients undergoing open surgical repair and 24 undergoing endovascular repair for abdominal aortic aneurysm were evaluated. There was no significant difference in early mortality between the open and endovascular groups (0% vs. 4.1%, p=0.16). The open repair group required much longer hospital stays (26.4 vs. 10.6 days, respectively, p=0.003). Finally, 12 patients (86%) undergoing open repair vs. 21 (88%) undergoing endovascular repair returned home (p=0.49). During a mean follow-up period of 23.4±23.5 months, cumulative estimated 1- and 3-year survival rates were 90.0% and 48.0%, respectively in the open repair group and 90.6% and 54.9%, respectively in the endovascular repair group (p=0.51). Conclusion : Although endovascular repair for abdominal aortic aneurysm was superior in terms of recovery, the results of conventional open repair were acceptable even in nonagenarian patients. Open repair remains an alternative for patients with contraindications to endovascular repair.

Reinterventions after open and endovascular AAA repair.

PubMed

Malina, M

2015-04-01

Reinterventions seem to occur more frequently after endovascular aneurysm repair than after open surgical repair and are encountered in about 20% versus 10% of the cases, respectively. However, reinterventions following endovascular repair are predominantly endoluminal and early reinterventions are more frequent after open repair. The indications for reintervention after EVAR have changed over time. The incidence and type of reintervention depends on the complexity of the primary procedure, irrespective of whether it was open or endovascular. The use of a device outside instructions for use is associated with a higher complication rate but it may nevertheless be fully justified. Advanced stent-grafts such as fenestrated and branched devices require secondary procedures more often than a standard stent-graft. Similarly, more complex open repair, e.g. a bifurcated bypass, reimplantation of visceral arteries or a redo procedure, is also associated with more reinterventions than a simple tube graft. This manuscript presents some of the most common complications of open and endovascular aortic aneurysm repair and the reinterventions they require. Many of the complications are similar with both open and endovascular techniques. Limb thrombosis, infections and endoleaks are the most frequent indications for reintervention.

Endovascular Repair of Abdominal Aortic Aneurysms in the Presence of a Transplanted Kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silverberg, Daniel, E-mail: silverberg-d@msn.com; Yalon, Tal; Halak, Moshe

PurposeTo present our experience performing endovascular repair of abdominal aortic aneurysms in kidney transplanted patients.MethodsA retrospective review of all patients who underwent endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA) performed at our institution from 2007 to 2014. We identified all patients who had previously undergone a kidney transplant. Data collected included: comorbidities, preoperative imaging modalities, indication for surgery, stent graft configurations, pre- and postoperative renal function, perioperative complications, and survival rates.ResultsA total of 267 EVARs were performed. Six (2 %) had a transplanted kidney. Mean age was 74 (range, 64–82) years; five were males. Mean time from transplantation tomore » EVAR was 7.5 (range, 2–12) years. Five underwent preoperative planning with noncontrast modalities only. Devices used included bifurcated (n = 3), aortouniiliac (n = 2), and tube (n = 1) stent grafts. Technical success was achieved in all patients. None experienced deterioration in renal function. Median follow-up was 39 (range, 6–51) months. Four patients were alive at the time of the study. Two patients expired during the period of follow-up from unrelated causes.ConclusionsEVAR is an effective modality for the management of AAAs in the coexistence of a transplanted kidney. It can be performed with minimal morbidity and mortality without harming the transplanted kidney. Special consideration should be given to device configuration to minimize damage to the renal graft.« less

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

PubMed

Dijkstra, Martijn L; Tielliu, Ignace F J; Meerwaldt, Robbert; Pierie, Maurice; van Brussel, Jerome; Schurink, Geert Willem H; Lardenoye, Jan-Willem; Zeebregts, Clark J

2014-08-01

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. 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. 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%. 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. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Carbon dioxide (CO2) angiography as an option for endovascular abdominal aortic aneurysm repair (EVAR) in patients with chronic kidney disease (CKD).

PubMed

De Angelis, Chiara; Sardanelli, Francesco; Perego, Matteo; Alì, Marco; Casilli, Francesco; Inglese, Luigi; Mauri, Giovanni

2017-11-01

To assess feasibility, efficacy and safety of carbon dioxide (CO 2 ) digital subtraction angiography (DSA) to guide endovascular aneurysm repair (EVAR) in a cohort of patients with chronic kidney disease (CKD). After Ethical Committee approval, the records of 13 patients (all male, mean age 74.6 ± 8.0 years) with CKD, who underwent EVAR to exclude an abdominal aortic aneurysm (AAA) under CO 2 angiography guidance, were reviewed. The AAA to be excluded had a mean diameter of 52.0 ± 8.0 mm. CO 2 angiography was performed by automatic (n = 7) or hand (n = 6) injection. The endograft was correctly placed and the AAA was excluded in all cases, without any surgical conversions. Two patients (15.4%) had an endoleak: one type-Ia, detected by CO 2 -DSA and effectively treated with prosthesis dilatation; one type-III, detected by CO 2 -DSA, confirmed using 10 ml of ICM, and conservatively managed. In one patient, CO 2 angiograms were considered of too low quality for guiding the procedure and 200 ml of ICM were administered. Overall, 11 patients (84.6%) underwent a successful EVAR under the guidance of the sole CO 2 angiography. No patients suffered from major complications, including those typically CO 2 -related. Two patients suffered from abdominal pain during the procedure secondary to a transient splanchnic perfusion's reduction due to CO 2 , and one patient had a worsening of renal function probably caused by a cholesterol embolization during the procedure. In patients with CKD, EVAR under CO 2 angiography guidance is feasible, effective, and safe.

Midterm outcomes of the Zenith Renu AAA Ancillary Graft.

PubMed

Jim, Jeffrey; Rubin, Brian G; Geraghty, Patrick J; Money, Samuel R; Sanchez, Luis A

2011-08-01

The Zenith Renu abdominal aortic aneurysm (AAA) Ancillary Graft (Cook Medical Inc, Bloomington, Ind) provides active proximal fixation for treatment of pre-existing endografts with failed or failing proximal fixation or seal. The purpose of this study was to evaluate the midterm outcomes of treatment with this device. From September 2005 to November 2006, a prospective, nonrandomized, multicenter, postmarket registry was utilized to collect physician experiences from 151 cases (89 converters and 62 main body extensions) at 95 institutions. Preoperative indications and procedural and postimplantation outcomes were collected and analyzed. Technical success and clinical success were determined as defined by the Society of Vascular Surgery reporting standards. Patients were predominantly male (87%) with a mean age of 77 years. The interval between the original endograft implantation to Renu treatment was 43.4 ± 18.7 months. The indications for treatment were endoleak (n = 111), migration (n = 136), or both (n = 94). Technical success was 98.0% with two cases of intraoperative conversion and one case of persistent type IA endoleak. The median follow-up for the cohort was 45.0 months (range, 0-56 months; interquartile range, 25.0 months). Overall, 32 cases had treatment failures that included at least one of the following: death (n = 5), type I/III endoleak (n = 18), graft infection (n = 1), thrombosis (n = 1), aneurysm enlargement >5 mm (n = 9), rupture (n = 4), conversion (n = 9, with 7 after 30 days), and migration (n = 1). Overall, the clinical success for the entire cohort during the follow-up period was 78.8% (119/151). The postmarket registry data confirm that the Zenith Renu AAA Ancillary Graft can be used to treat endovascular repairs that failed due to proximal attachment failures. The salvage treatment with the Renu device had high technical success rate and resulted in clinical success in a majority of patients (78.8%). While failed endovascular repairs can be salvaged, a clinical failure in one of five patients still emphasizes the importance of patient and device selection during initial endovascular aneurysm repair to ensure durable success. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Concurrent renal artery stent during endovascular infrarenal aortic aneurysm repair confers higher risk for 30-day acute renal failure

PubMed Central

Nejim, Besma; Arhuidese, Isibor; Rizwan, Muhammmad; Khalil, Lana; Locham, Satinderjit; Zarkowsky, Devin; Goodney, Philip; Malas, Mahmoud B.

2018-01-01

Objective Concurrent renal artery angioplasty and stenting (RAAS) during endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysm (AAA) has been practiced in an attempt to maintain renal perfusion. The aim of this study was to identify the current practice of RAAS during EVAR and its effect on perioperative renal outcome. Methods Patients with infrarenal AAA were identified from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP, 2011-2014) database. Baseline characteristics of patients with concurrent RAAS during EVAR were compared with those of patients who underwent EVAR only. Bivariate and multivariable logistic regression analyses controlling for patients’ demographics, comorbidities, and operative factors were used to evaluate the predictors of 30-day acute renal failure (ARF). Sensitivity analysis was done to evaluate the role of RAAS in patients with prior kidney disease. Results Overall, 6183 patients underwent EVAR for infrarenal AAA during the study period. Of them, 281 patients had RAAS during EVAR (4.5%). The median age of the patients was 74 years; 81.7% of the cohort was male, but a higher proportion of female patients received EVAR + RAAS compared with patients who underwent EVAR only (26.3% vs 17.9%; P < .001). There was no difference between groups in terms of comorbidities, being on dialysis, or functional status, yet the EVAR + RAAS group had a higher proportion of patients with glomerular filtration rate <60 mL/min/1.73 m2 (45.2% vs 37.2%; P = .011). RAAS was associated with significantly higher odds for development of ARF (adjusted odds ratio [aOR], 4.27; 95% confidence interval [CI], 2.06-8.84; P < .001). Other highly predictive factors of 30-day ARF were glomerular filtration rate <60 (aOR, 2.92; 95% CI, 1.47-5.78; P = .002), emergency status (aOR, 2.97; 95% CI, 1.21-7.27; P = .017), and ruptured AAA as the indication for EVAR (aOR, 4.74; 95% CI, 1.80-12.50; P = .002). Patients with prior kidney disease who had EVAR + RAAS demonstrated a 12-fold higher odds for 30-day ARF (aOR, 12.37; 95% CI, 4.66-32.89; P < .001). Conclusions Concurrent RAAS was found to be a significant determinant of adverse renal outcomes after EVAR for infrarenal AAA. This effect was present even after controlling for patients’ risk factors that might contribute to postoperative ARF. PMID:28222985

Does lower limb exercise worsen renal artery hemodynamics in patients with abdominal aortic aneurysm?

PubMed

Sun, Anqiang; Tian, Xiaopeng; Zhang, Nan; Xu, Zaipin; Deng, Xiaoyan; Liu, Ming; Liu, Xiao

2015-01-01

Renal artery stenosis (RAS) and renal complications emerge in some patients after endovascular aneurysm repair (EVAR) to treat abdominal aorta aneurysm (AAA). The mechanisms for the causes of these problems are not clear. We hypothesized that for EVAR patients, lower limb exercise could negatively influence the physiology of the renal artery and the renal function, by decreasing the blood flow velocity and changing the hemodynamics in the renal arteries. To evaluate this hypothesis, pre- and post-operative models of the abdominal aorta were reconstructed based on CT images. The hemodynamic environment was numerically simulated under rest and lower limb exercise conditions. The results revealed that in the renal arteries, lower limb exercise decreased the wall shear stress (WSS), increased the oscillatory shear index (OSI) and increased the relative residence time (RRT). EVAR further enhanced these effects. Because these parameters are related to artery stenosis and atherosclerosis, this preliminary study concluded that lower limb exercise may increase the potential risk of inducing renal artery stenosis and renal complications for AAA patients. This finding could help elucidate the mechanism of renal artery stenosis and renal complications after EVAR and warn us to reconsider the management and nursing care of AAA patients.

Primary aortoduodenal fistula associated with abdominal aortic aneurysm with presentation of gastrointestinal bleeding: a case report.

PubMed

Lin, Tzu-Chieh; Tsai, Chung-Lin; Chang, Yao-Tien; Hu, Sung-Yuan

2018-06-07

Primary aortoduodenal fistula (ADF) is a rare cause of gastrointestinal (GI) bleeding and is difficult to diagnose as the clinical presentation is subtle. Clinicians should keep a high level of suspicion for an unknown etiology of GI bleeding, especially in older patients with or without abdominal aortic aneurysm (AAA). Computed tomographic angiography (CTA) can be used to detect primary ADF. Open surgery or endovascular aortic repair (EVAR) for ADF with bleeding will improve the survival rate. We report a rare case of AAA complicating ADF with massive GI bleeding in a 73-year-old Taiwanese man. He presented with abdominal pain and tarry stool for 5 days and an initial upper GI endoscopy at a rural hospital showed gastric ulcer only, but hypotension with tachycardia and a drop in hemoglobin of 9 g/dl from 12 g/dl occurred the next day. He was referred to our hospital for EVAR and primary closure of fistula defect due to massive GI bleeding with shock from ADF caused by AAA. Diagnosis was made by CTA of aorta. A timely and accurate diagnosis of primary ADF may be challenging due to insidious episodes of GI bleeding, which are frequently under-diagnosed until the occurrence of massive hemorrhage. Clinical physicians should keep a high index of awareness for primary ADF, especially in elderly patients with unknown etiology of upper GI bleeding with or without a known AAA.

Unfolding the mechanism of the AAA+ unfoldase VAT by a combined cryo-EM, solution NMR study.

PubMed

Huang, Rui; Ripstein, Zev A; Augustyniak, Rafal; Lazniewski, Michal; Ginalski, Krzysztof; Kay, Lewis E; Rubinstein, John L

2016-07-19

The AAA+ (ATPases associated with a variety of cellular activities) enzymes play critical roles in a variety of homeostatic processes in all kingdoms of life. Valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT), the archaeal homolog of the ubiquitous AAA+ protein Cdc48/p97, functions in concert with the 20S proteasome by unfolding substrates and passing them on for degradation. Here, we present electron cryomicroscopy (cryo-EM) maps showing that VAT undergoes large conformational rearrangements during its ATP hydrolysis cycle that differ dramatically from the conformational states observed for Cdc48/p97. We validate key features of the model with biochemical and solution methyl-transverse relaxation optimized spectroscopY (TROSY) NMR experiments and suggest a mechanism for coupling the energy of nucleotide hydrolysis to substrate unfolding. These findings illustrate the unique complementarity between cryo-EM and solution NMR for studies of molecular machines, showing that the structural properties of VAT, as well as the population distributions of conformers, are similar in the frozen specimens used for cryo-EM and in the solution phase where NMR spectra are recorded.

Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

PubMed Central

Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

2015-01-01

Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

Biological and Pathological Implications of an Alternative ATP-Powered Proteasomal Assembly With Cdc48 and the 20S Peptidase.

PubMed

Esaki, Masatoshi; Johjima-Murata, Ai; Islam, Md Tanvir; Ogura, Teru

2018-01-01

The ATP-powered protein degradation machinery plays essential roles in maintaining protein homeostasis in all organisms. Robust proteolytic activities are typically sequestered within protein complexes to avoid the fatal removal of essential proteins. Because the openings of proteolytic chambers are narrow, substrate proteins must undergo unfolding. AAA superfamily proteins (ATPases associated with diverse cellular activities) are mostly located at these openings and regulate protein degradation appropriately. The 26S proteasome, comprising 20S peptidase and 19S regulatory particles, is the major ATP-powered protein degradation machinery in eukaryotes. The 19S particles are composed of six AAA proteins and 13 regulatory proteins, and bind to both ends of a barrel-shaped proteolytic chamber formed by the 20S peptidase. Several recent studies have reported that another AAA protein, Cdc48, can replace the 19S particles to form an alternative ATP-powered proteasomal complex, i.e., the Cdc48-20S proteasome. This review focuses on our current knowledge of this alternative proteasome and its possible linkage to amyotrophic lateral sclerosis.

Carotid and coronary disease management prior to open and endovascular aortic surgery. What are the current guidelines?

PubMed

Thompson, J P

2014-04-01

Several bodies produce broadly concurring and updated guidelines for the evaluation and treatment of cardiovascular disease in both surgical and non-surgical patients. Recent developments include revised recommendations on preoperative stress testing, referral for possible coronary revascularization and medical management. It is recognized that non-invasive cardiac tests are relatively poor at predicting perioperative risk, and "prophylactic" coronary revascularization has a limited role. The planned aortic intervention (open or endovascular repair) also influences preoperative management. Patients presenting for elective abdominal aortic aneurysm (AAA) repair should only be referred for cardiological testing if they have active symptoms of coronary artery disease (CAD), known CAD and poor functional exercise capacity, or multiple risk factors for CAD. Coronary revascularization before AAA surgery should be limited to patients with established indications, so cardiac stress testing should only be performed if it would change management i.e. the patient is a candidate for and would benefit from coronary revascularization. When endovascular aortic repair is planned, it is reasonable to proceed to surgery without further cardiac stress testing or evaluation unless otherwise indicated. All non-emergency patients require medical optimization, but perioperative beta blockade benefits only certain patients. Some of the data informing recent guidelines have been questioned and some guidelines are being revised. Current guidelines do not specifically address the management of patients with known or suspected carotid artery disease who may require aortic surgery. For these patients, an individualized approach is required. This review considers recent guidelines. Algorithms for investigation and management based on their recommendations are included.

French Women From Multiplex Abdominal Aortic Aneurysm Families Should Be Screened

PubMed Central

Le Hello, Claire; Koskas, Fabien; Cluzel, Philippe; Tazi, Zoubida; Gallos, Corina; Piette, Jean Charles; Lasserve, Elisabeth Tournier; Kieffer, Edouard; Cacoub, Patrice

2005-01-01

Background: Multiplex abdominal aortic aneurysm families (MAAAFs) (≥1 subject plus the proband) represent 1% to 34% of abdominal aortic aneurysm (AAA), but the percentage in France is unknown. Method: The MAAAF rate was retrospectively defined by analysis of 3 groups: 72 of 104 consecutive individuals undergoing AAA surgery during 1994, 24 of 53 women and 35 of 76 men with giant (≥9 cm) AAA operated on during 1986 to 1994. MAAAF characteristics were determined based on 10 families issued from these 3 groups and 34 others identified nationwide. Data were obtained from a standardized questionnaire for probands and relatives, detailed pedigrees of each family, and computed tomography (CT) scans without contrast medium of the aorta and lower limb arteries for first-degree relatives ≥40-year-of age. Results: The MAAAF rate was 4.2% for the consecutive-surgery patients (proband M/F ratio, 17:1; mean age at surgery, 68.5 ± 8.5 years). CT detected no additional AAA among them (screened individuals M/F ratio, 0.63; mean age, 54.0 ± 11.2 years). MAAAF rates were 8.3% and 14.3% for the women's and giant-AAA groups with CT screening, respectively. Characteristics were investigated in 104 affected subjects from 44 MAAAFs: female relatives were more often affected than probands (P < 0.025). Compared with men, affected female relatives were significantly older at diagnosis and surgery (P < 0.05 and P < 0.02, respectively), as were affected women (P < 0.02 and P < 0.01, respectively). CT scan screening identified significantly more AAA and abdominal aortic dilatations among the 44 MAAAFs than the consecutive-surgery group (5 and 4, respectively; P < 0.001). Conclusion: Although the MAAAF rate seems low in France, women from MAAAF were affected more often and later, suggesting that they should be screened. PMID:16244549

Stabilization of the Abdominal Aorta During the Cardiac Cycle with the Sac-Anchoring Nellix Device.

PubMed

Itoga, Nathan K; Suh, Ga-Young; Cheng, Christopher P

2018-06-09

The Nellix device uses polymer-filled endobags to stabilize the abdominal aortic aneurysm (AAA) sac which is described as endovascular aneurysm sealing (EVAS). We analyzed cardiac-gated computed tomography angiography scans of repaired AAA with EVAS in 4 patients to evaluate the geometry and cardiac pulsatility-induced deformation. Graft translation and aortic curvature changes were found to be minimal during the cardiac cycle. The mean ± standard deviation changes in renal-aorta angles (1.0 ± 0.9°) were less than the changes in the superior mesenteric artery-aorta angle (4.0 ± 2.1°) (P < 0.01), during the cardiac cycle, demonstrating greater stabilization of the visceral branches closer to the device. These findings confirm stabilization of the abdominal aorta during the cardiac cycle using EVAS. Copyright © 2018 Elsevier Inc. All rights reserved.

Cathepsin S is associated with degradation of collagen I in abdominal aortic aneurysm.

PubMed

Klaus, Veronika; Schmies, Fadwa; Reeps, Christian; Trenner, Matthias; Geisbüsch, Sarah; Lohoefer, Fabian; Eckstein, Hans-Henning; Pelisek, Jaroslav

2018-06-01

Cathepsins have been described in the pathogenesis of abdominal aortic aneurysm (AAA), their exact role, especially in collagen degradation, is still unclear. The aim of the present study was therefore to analyse relevant cathepsins in human AAA tissue samples in relation to collagen I, III, and their degradation products. Samples from 37 AAA patients obtained from elective open surgical repair and eight healthy non-aneurysmatic aortas from kidney donors were included. Expression of cathepsins B, D, K, L, S, cystatin C, collagen I and III, their degraded products C-Telopeptide of type 1 and 3 collagen (CTX-I, CTX-III), cellular markers for leukocytes (CD45), T cells (CD3), macrophage scavenger receptor-1 (MSR-1), synthetic, and contractile smooth muscle cells (SMCs) (smoothelin: SMTH, collagen I and III, myosin heavy chain: MHC, embryonic smooth muscle myosin heavy chain: SMemb) were determined at messenger RNA (mRNA) level, using SYBRGreen-based quantitative PCR and at protein level using enzyme-linked immunosorbent assay (ELISA). Expression of cathepsins B, D, L, and S at mRNA level was significantly elevated in AAA compared to control aorta (1.7-fold, p = 0.025; 2.5-fold, p = 0.002; 2.6-fold, p = 0.034; and 7.0-fold, p = 0.003). Expression of cathepsin S correlated significantly with leukocytes and macrophages (ρ = 0.398, p = 0.033 and ρ = 0.422, p = 0.020), synthetic SMCs were significantly associated with cathepsins B, D, and L (ρ = 0.522, p = 0.003; ρ = 0.431, p = 0.015 and ρ = 0.467, p = 0.008). At protein level, cathepsins B and S were elevated in AAA compared to controls (5.4-fold, p = 0.001 and 7.3-fold, p < 0.001). Significant correlations were observed between collagen I, its degraded product, and cathepsin S (r = -0.350, p = 0.034 and r = +0.504, p < 0.001). Expression of cathepsin B was associated with SMCs, expression of cathepsin S with inflammatory cells. Particularly cathepsin S was associated with the degradation product of collagen I and thus might be involved in the progression of AAA. Furthermore, cathepsin S correlated with inflammatory cells.

Developing and Evaluating an Eighth Grade Curriculum Unit That Links Foundational Chemistry to Biological Growth. Paper #1: Selecting Core Ideas and Practices -- An Iterative Process

ERIC Educational Resources Information Center

Roseman, Jo Ellen; Herrmann-Abell, Cari; Flanagan, Jean; Kruse, Rebecca; Howes, Elaine; Carlson, Janet; Roth, Kathy; Bourdelat-Parks, Brooke

2013-01-01

Researchers at AAAS and BSCS have developed a six-week unit that aims to help middle school students learn important chemistry ideas that can be used to explain growth and repair in animals and plants. By integrating core physical and life science ideas and engaging students in the science practices of modeling and constructing explanations, the…

Acetyl aspartic acid, a novel active ingredient, demonstrates potential to improve signs of skin ageing: from consumer need to clinical proof.

PubMed

Mavon, A

2015-10-01

The megatrend of population ageing is leading to a growing demand for "anti-ageing" treatments, especially to prevent or treat skin ageing. Facing an increasing offer, consumers are choosing more and more skin care products supported by a scientific rationale, active ingredients and clinical proof of efficacy. Considering consumer expectations, this research led to the discovery of acetyl aspartic acid (A-A-A), a novel active ingredient to improve sagging skin and loss of skin firmness. This supplement is featuring seven manuscripts aiming at presenting the research and investigations from consumer insights, discovery of A-A-A, its in vitro activity confirmation, safety assessment, formulation and its dermal absorption to the clinical proof of efficacy, investigated through two pilots' double bind randomized and placebo controlled studies on photo-aged skin. This extensive research enabled us to discover A-A-A, as an active ingredient with potential to repair sign of skin ageing and supported by clinical proof of efficacy. This active ingredient will be soon launched in a commercial innovative skin care range, delivering desirable anti-wrinkle and skin lifting benefits. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Adjusted Hospital Outcomes of Abdominal Aortic Aneurysm Surgery Reported in the Dutch Surgical Aneurysm Audit.

PubMed

Lijftogt, N; Vahl, A C; Wilschut, E D; Elsman, B H P; Amodio, S; van Zwet, E W; Leijdekkers, V J; Wouters, M W J M; Hamming, J F

2017-04-01

The Dutch Surgical Aneurysm Audit (DSAA) is mandatory for all patients with primary abdominal aortic aneurysms (AAAs) in the Netherlands. The aims are to present the observed outcomes of AAA surgery against the predicted outcomes by means of V-POSSUM (Vascular-Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity). Adjusted mortality was calculated by the original and re-estimated V(physiology)-POSSUM for hospital comparisons. All patients operated on from January 2013 to December 2014 were included for analysis. Calibration and discrimination of V-POSSUM and V(p)-POSSUM was analysed. Mortality was benchmarked by means of the original V(p)-POSSUM formula and risk-adjusted by the re-estimated V(p)-POSSUM on the DSAA. In total, 5898 patients were included for analysis: 4579 with elective AAA (EAAA) and 1319 with acute abdominal aortic aneurysm (AAAA), acute symptomatic (SAAA; n = 371) or ruptured (RAAA; n = 948). The percentage of endovascular aneurysm repair (EVAR) varied between hospitals but showed no relation to hospital volume (EAAA: p = .12; AAAA: p = .07). EAAA, SAAA, and RAAA mortality was, respectively, 1.9%, 7.5%, and 28.7%. Elective mortality was 0.9% after EVAR and 5.0% after open surgical repair versus 15.6% and 27.4%, respectively, after AAAA. V-POSSUM overestimated mortality in most EAAA risk groups (p < .01). The discriminative ability of V-POSSUM in EAAA was moderate (C-statistic: .719) and poor for V(p)-POSSUM (C-statistic: .665). V-POSSUM in AAAA repair overestimated in high risk groups, and underestimated in low risk groups (p < .01). The discriminative ability in AAAA of V-POSSUM was moderate (.713) and of V(p)-POSSUM poor (.688). Risk adjustment by the re-estimated V(p)-POSSUM did not have any effect on hospital variation in EAAA but did in AAAA. Mortality in the DSAA was in line with the literature but is not discriminative for hospital comparisons in EAAA. Adjusting for V(p)-POSSUM, revealed no association between hospital volume and treatment or outcome. Risk adjustment for case mix by V(p)-POSSUM in patients with AAAA has been shown to be important. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

The Hardman index in patients operated on for ruptured abdominal aortic aneurysm: A systematic review.

PubMed

Acosta, Stefan; Ogren, Mats; Bergqvist, David; Lindblad, Bengt; Dencker, Magnus; Zdanowski, Zbigniew

2006-11-01

The aims of the present study were to (1) analyze preoperative predictors for outcome suggested by Hardman and surgical mortality after open repair and endovascular repair (EVAR) of ruptured abdominal aortic aneurysms (rAAA), and (2) further evaluate the Hardman index in a systematic review. Patients operated on for rAAA during a 5-year period between 2000 and 2004 were scored according to Hardman-1 point for either age >76 years, loss of consciousness after presentation, hemoglobin <90 g/L, serum creatinine >190 micromol/L or electrocardiographic (ECG) signs of ischemia-with blinded evaluation of ECGs by a specialist in clinical physiology. The results were included in a systematic review of studies evaluating the Hardman index. In-hospital mortality after operation was 41% (67/162). There was no difference in in-hospital mortality between open repair (n = 106) and EVAR (n = 56), whereas the Hardman index was associated with operative mortality in our institution and in the systematic review of 970 patients (P < .001). Mortality rate in patients with Hardman index > or =3 was 77% in the pooled analysis. A full data set of all five scoring variables was obtained in 94 (58%) of 162 patients in our study, and potential underscoring was thus possible in 68 patients. Of the available ECGs, 12 (8.7%) of 138 were judged nondiagnostic. Five studies did not state their missing data on ECG and hemoglobin and serum creatinine concentrations, nor did they specify the criteria for ECG ischemia. A strong correlation between the Hardman index and mortality was found. A Hardman index > or =3 cannot be used as an absolute limit for denial of surgery. The utility of the Hardman index seems to be impeded by variability in scoring resulting from missing or nondiagnostic data.

A Custom-Made Treovance® Abdominal Aortic Aneurysm Endograft to Correct Late Failure of Trombone Technique with a Tube Endograft.

PubMed

Georgiadis, George S; Argyriou, Christos; Valsamidou, Christina D; Nikova, Alexandrina S; Lazarides, Miltos K

2018-05-01

Unfavorable anatomy is one of the major limitations of endovascular aortic aneurysm repair (EVAR) with specifically adverse proximal neck morphology excluding many patients from receiving the standard endograft devices. Thoracic tube endografts have been used to overcome the issue of wide infrarenal necks, either as a sole device (single tubes or double tubes using the trombone technique) or as the proximal part of a bifurcated device fixed to the aortic bifurcation or infrarenally oriented. However, custom-made large proximal diameter bifurcated endograft designs have never been used. We present the case of a 56-year-old man with Marfan syndrome, suffering abdominal aortic aneurysm (AAA) enlargement from a type Ib endoleak after previous EVAR with 2 Endofit tube endografts (trombone technique). He was considered unfit for open surgery while possible alternatives such as fenestrated endovascular AAA repair and chimney technique were excluded. The patient was treated with a custom-made 44-mm proximal diameter, bifurcated Bolton Medical Treovance device with technical and clinical success. No immediate or perioperative complications were noted. Follow-up after 6 months showed graft patency and no endoleak of any type. This alternative technique for hostile proximal neck management is promising and needs long-term follow-up; an issue which is discussed within the broader context of custom-made device regulations. Copyright © 2018 Elsevier Inc. All rights reserved.

Anatomical Features and Early Outcomes of Endovascular Repair of Abdominal Aortic Aneurysm from a Korean Multicenter Registry.

PubMed

Kwon, Hyunwook; Lee, Do Yun; Choi, Soo Jin Na; Park, Ki Hyuk; Min, Seung-Kee; Chang, Jeong-Hwan; Huh, Seung; Jeon, Yong Sun; Won, Jehwan; Byun, Seung Jae; Park, Sang Jun; Jang, Lee Chan; Kwon, Tae-Won

2015-09-01

To introduce a nation-based endovascular aneurysm repair (EVAR) registry in South Korea and to analyze the anatomical features and early clinical outcomes of abdominal aortic aneurysms (AAA) in patients who underwent EVAR. The Korean EVAR registry (KER) was a template-based online registry developed and established in 2009. The KER recruited 389 patients who underwent EVAR from 13 medical centers in South Korea from January 2010 to June 2010. We retrospectively reviewed the anatomic features and 30-day clinical outcomes. Initial deployment without open conversion was achieved in all cases and procedure-related 30-day mortality rate was 1.9%. Anatomic features showed the following variables: proximal aortic neck angle 48.8±25.7° (mean±standard deviation), vertical neck length 35.0±17.2 mm, aneurysmal sac diameter 57.2±14.2 mm, common iliac artery (CIA) involvement in 218 (56.3%) patients, and median right CIA length 34.9 mm. Two hundred and nineteen (56.3%) patients showed neck calcification, 98 patients (25.2%) had neck thrombus, and the inferior mesenteric arteries of 91 patients (23.4%) were occluded. Anatomical features of AAA in patients from the KER were characterized as having angulated proximal neck, tortuous iliac artery, and a higher rate of CIA involvement. Long-term follow-up and ongoing studies are required.

Unfolding the mechanism of the AAA+ unfoldase VAT by a combined cryo-EM, solution NMR study

PubMed Central

Huang, Rui; Ripstein, Zev A.; Augustyniak, Rafal; Lazniewski, Michal; Ginalski, Krzysztof; Kay, Lewis E.; Rubinstein, John L.

2016-01-01

The AAA+ (ATPases associated with a variety of cellular activities) enzymes play critical roles in a variety of homeostatic processes in all kingdoms of life. Valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT), the archaeal homolog of the ubiquitous AAA+ protein Cdc48/p97, functions in concert with the 20S proteasome by unfolding substrates and passing them on for degradation. Here, we present electron cryomicroscopy (cryo-EM) maps showing that VAT undergoes large conformational rearrangements during its ATP hydrolysis cycle that differ dramatically from the conformational states observed for Cdc48/p97. We validate key features of the model with biochemical and solution methyl-transverse relaxation optimized spectroscopY (TROSY) NMR experiments and suggest a mechanism for coupling the energy of nucleotide hydrolysis to substrate unfolding. These findings illustrate the unique complementarity between cryo-EM and solution NMR for studies of molecular machines, showing that the structural properties of VAT, as well as the population distributions of conformers, are similar in the frozen specimens used for cryo-EM and in the solution phase where NMR spectra are recorded. PMID:27402735

[Effect of thermal cycling on the composite- composite repair bond strength].

PubMed

Liu, Chang; Lin, Fei; Yue, Lin

2015-08-01

To evaluate the effect of aging of the composite and the adhesive interface on composite-composite repair bond strength. Methacrylate-based composite resin (Clearfil AP-X, composite A) and silorane-based composite resin (Filtek P90, composite B) and their corresponding adhesive, Clearfil SE Bond (adhesive a) and Filtek P90 System Adhesive (adhesive b), were selected in this study. Twenty-four substrates were prepared from composite A or B separately and divided into three groups, each group had 8 substrates: group one, new composites were adhered to the substrates with the use of adhesive a or b, followed by cutting the blocks into sticks; group two, new composites were adhered to the substrates using adhesive a or b, followed by cutting into sticks and thermal cycling; group three, substrates were thermocycled, then polished and adhered new composites using adhesive a or b, followed by cutting into sticks. Each group had 8 combinations of substrate(A, B)-adhesive(a, b)-repair composite (A, B). Fifteen sticks without flaws in each combination of 3 groups were selected utilizing stereomicroscope. The data were analyzed by independent samples t test. In group two, the microtensile strength(MS) of combinations using adhesive a and composite A or B to repair [A-a-A: (45.0 ± 3.2) MPa, B-a-A: (41.7 ± 3.3) MPa, A-a-B: (28.6 ± 3.9) MPa, B-a-B: (47.7 ± 6.6) MPa], and using adhesive b and composite A to repair [A-b-A: (44.2 ± 4.7) MPa, B-b-A: (38.0 ± 3.2) MPa] decreased significantly compared with corresponding combinations in group 1[A-a-A: (70.7 ± 5.5) MPa, B-a-A: (60.3 ± 5.1) MPa, A-a-B: (44.2 ± 1.6) MPa, B-a-B: (54.1 ± 3.2) MPa, A-b-A: (65.6 ± 7.2) MPa, B-b-A: (59.1 ± 4.1) MPa] (P<0.05). However, there was no significant difference between the MS of combinations using adhesive b and composite B to repair in group one and the MS of combinations in group two (P>0.05). The MS of all combinations in group three decreased significantly (P<0.05). Aging of the composite and the adhesive interface might affect the composite-composite repair bond strength.

No increased risk of carcinogenesis with mesh-based hernia repairs.

PubMed

Chughtai, Bilal; Sedrakyan, Art; Thomas, Dominique; Mao, Jialin; Eilber, Karyn S; Clemens, J Quentin; Anger, Jennifer T

2017-12-06

The use of synthetic mesh has been placed under considerable scrutiny. We sought to evaluate whether there is a link between placement of synthetic polypropylene mesh for hernia repair and a subsequent cancer diagnosis. Adult men undergoing mesh-based hernia repair from January 2008-December 2009 in New York State were identified and followed through December 2014. Control cohorts of men undergoing cholecystectomy and total knee replacement were control cohorts. 1894 patients undergoing hernia repair, 912 patients in the cholecystectomy control cohort, and 1099 in the TKA control cohort with a cancer diagnosis. In the matched analyses of mesh-based hernia repair and cholecystectomy patients 6.5% vs. 7.1% developed cancer. In the matched analysis of hernia patients and TKA patients, 9.3% vs. 9.1% developed cancer. No association between mesh-based hernia surgery and increased risk of cancer was found. Mesh-based hernia repair was not associated with an increased risk of subsequent development of cancer in men. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo verification of radiation dose delivered to healthy tissue during radiotherapy for breast cancer

NASA Astrophysics Data System (ADS)

Lonski, P.; Taylor, M. L.; Hackworth, W.; Phipps, A.; Franich, R. D.; Kron, T.

2014-03-01

Different treatment planning system (TPS) algorithms calculate radiation dose in different ways. This work compares measurements made in vivo to the dose calculated at out-of-field locations using three different commercially available algorithms in the Eclipse treatment planning system. LiF: Mg, Cu, P thermoluminescent dosimeter (TLD) chips were placed with 1 cm build-up at six locations on the contralateral side of 5 patients undergoing radiotherapy for breast cancer. TLD readings were compared to calculations of Pencil Beam Convolution (PBC), Anisotropic Analytical Algorithm (AAA) and Acuros XB (XB). AAA predicted zero dose at points beyond 16 cm from the field edge. In the same region PBC returned an unrealistically constant result independent of distance and XB showed good agreement to measured data although consistently underestimated by ~0.1 % of the prescription dose. At points closer to the field edge XB was the superior algorithm, exhibiting agreement with TLD results to within 15 % of measured dose. Both AAA and PBC showed mixed agreement, with overall discrepancies considerably greater than XB. While XB is certainly the preferable algorithm, it should be noted that TPS algorithms in general are not designed to calculate dose at peripheral locations and calculation results in such regions should be treated with caution.

Exercise induces autophagy in peripheral tissues and in the brain.

PubMed

He, Congcong; Sumpter, Rhea; Levine, Beth

2012-10-01

We recently identified physical exercise as a newly defined inducer of autophagy in vivo. Exercise induced autophagy in multiple organs involved in metabolic regulation, such as muscle, liver, pancreas and adipose tissue. To study the physiological role of exercise-induced autophagy, we generated mice with a knock-in nonphosphorylatable mutation in BCL2 (Thr69Ala, Ser70Ala and Ser84Ala) (BCL2 AAA) that are defective in exercise- and starvation-induced autophagy but not in basal autophagy. We found that BCL2 AAA mice could not run on a treadmill as long as wild-type mice, and did not undergo exercise-mediated increases in skeletal glucose muscle uptake. Unlike wild-type mice, the BCL2 AAA mice failed to reverse high-fat diet-induced glucose intolerance after 8 weeks of exercise training, possibly due to defects in signaling pathways that regulate muscle glucose uptake and metabolism during exercise. Together, these findings suggested a hitherto unknown important role of autophagy in mediating exercise-induced metabolic benefits. In the present addendum, we show that treadmill exercise also induces autophagy in the cerebral cortex of adult mice. This observation raises the intriguing question of whether autophagy may in part mediate the beneficial effects of exercise in neurodegeneration, adult neurogenesis and improved cognitive function.

National Trends of Thoracic Endovascular Aortic Repair (TEVAR) Versus Open Repair in Blunt Thoracic Aortic Injury.

PubMed

Grigorian, Areg; Spencer, Dean; Donayre, Carlos; Nahmias, Jeffry; Schubl, Sebastian; Gabriel, Viktor; Barrios, Cristobal

2018-06-07

Blunt thoracic aortic injury (BTAI) occurs in <1% of all trauma admissions. Considering the advent of multiple thoracic endovascular aortic repair (TEVAR) devices over the past decade, improved outcomes of TEVAR supported in the literature, rapid diagnosis and improved preoperative planning of BTAI using computed tomography imaging, we hypothesized that the national incidence of TEVAR in BTAI has increased while open repair has decreased. In addition, we hypothesized that the mortality risk in BTAI patients undergoing TEVAR would be lower than open repair. This was a retrospective analysis of the National Trauma Data Bank from 2007-2015. The primary end-points of interest included the incidence of TEVAR and open repair, as well as mortality in BTAI patients undergoing intervention. Covariates were included in a multivariable analysis to determine risk for mortality in BTAI patients undergoing open repair versus TEVAR. We identified 3,628 BTAI patients undergoing intervention. Of these, 3,226 underwent TEVAR (87.9%) and 445 (12.1%) underwent open repair. Compared to open repair, TEVAR had a shorter mean length of stay (19.8 vs. 21.3 days, p<0.05) and lower rates of acute kidney injury (5.6% vs. 9.0%, p<0.05) and mortality (8.8% vs. 12.8%, p<0.05). Open repair had greater risk for mortality compared to TEVAR (OR=1.63, CI=1.19-2.23, p<0.05). The rate of open repair decreased from 7.4% in 2007 to 1.9% in 2015, while TEVAR increased from 12.1% to 25.7% during the same time-period. We confirmed previous findings that endovascular repair is associated with decreased mortality, length of stay and major complications including acute kidney injury. Future investigations should focus on identifying the ideal patient candidate for TEVAR and elucidate precise indications for TEVAR in BTAI. Copyright © 2018. Published by Elsevier Inc.

Secondary procedures after infrarenal abdominal aortic aneurysms endovascular repair with second-generation endografts.

PubMed

Bartoli, Michel A; Thevenin, Benjamin; Sarlon, Gabrielle; Giorgi, Roch; Albertini, Jean Noël; Lerussi, Gilles; Branchereau, Alain; Magnan, Pierre-Edouard

2012-02-01

To study the incidence, the types, and the results of secondary procedures performed after endovascular treatment of infrarenal abdominal aortic aneurysm (AAA). To compare the population of patients who underwent secondary procedure (P2) with the population of those who did not require it. Between 1998 and 2008, this study included all the patients electively treated for AAA with stentgrafts that were still available on the market on January 1, 2009. Data were prospectively collected and retrospectively analyzed. The postoperative follow-up included at least a systematic computed tomography scan at 6, 12, 18, and 24 months and then every year. P2 were defined as any additionnal procedures performed to treat aneurysm related complications after initial stentgraft implantation. We studied 162 patients with a mean 40 ± 31 months' follow-up. In 32 patients (19.7%), there were 46 P2, 3 of them were surgical conversion and 1 with endovascular conversion. Thirty-nine P2 were scheduled, and seven were performed in emergency. Nine patients underwent more than one P2. P2 was indicated for type II endoleak in 17 cases, 13 of them with a diameter increase; for type I endoleak in 10 cases; for AAA rupture in 3 cases; for occlusion or stentgraft stenosis in 13 cases; and for 1 type III endoleak, 1 endotension, and 1 femoro-femoral crossover bypass infection. Two ruptures occurred in patients who had undergone P2. The immediate technical success was 89.1%. At 30 days, morbidity was 10.9%, and there was no mortality. Survival rates at 3 and 5 years were respectively 85.2% and 71.9% in patients with secondary procedure and 70.6% and 47.5% in the others (p = 0.046). In patients treated for AAA with second generation stentgrafts, in the long term, secondary procedure rate was 19.7%. Survival rate for patients who underwent a secondary procedure was better, which was probably related to the fact that they were younger at the time of stentgraft implantation. Large AAA diameter was a secondary-procedure risk factor. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Comparison of the endurant bifurcated endograft vs. aortouni-iliac stent-grafting in patients with abdominal aortic aneurysms: experience from the ENGAGE registry.

PubMed

Tang, Tjun; Sadat, Umar; Walsh, Stewart; Hayes, Paul D

2013-04-01

To compare the 1-year outcomes after repair of abdominal aortic aneurysms (AAA) with the bifurcated vs. aortouni-iliac (AUI) configuration of the Endurant stent-graft. The study population comprised 1172 patients (1053 men; mean age 73.1±8.1 years, range 43-93) with unruptured infrarenal AAAs treated as part of the Endurant Stent Graft Natural Selection Global Post-market Registry (ENGAGE; ClinicalTrials.gov identifier NCT00870051). The primary outcome measure was treatment success at 12 months, defined by the composite of successful endograft deployment and the absence of type I/III endoleak, migration, rupture, or conversion to open surgery. Secondary outcome measures included endoleak, graft patency, migration, secondary procedures, and all-cause mortality. Among 1172 patients in ENGAGE, 1089 (92.9%) were treated with a bifurcated device and 83 (7.1%) received an AUI with femorofemoral bypass. Both groups were comparable with regard to demographics and baseline comorbidities, with the exception of a higher rate of cardiopulmonary disease in the AUI group. Successful deployment was achieved in all patients in the both groups. Postoperative complications occurred more frequently in the AUI patients, and the AUI group had an increased length of hospital stay (p=0.01). Endoleaks were more frequent in the AUI group at the conclusion of the procedure, a difference that vanished by 30 days. At 1 year, there were no incidences of graft kinking or stent fracture in either group. The rate of secondary procedures (5.3% in AUI patients and 4.9% for bifurcated cases) and all-cause mortality (10.5% and 8.6%, respectively) were similar in the two groups at 30 days and 1 year. The results of endovascular aneurysm repair with an Endurant AUI device appear similar to that after a bifurcated endovascular repair, with the exception of an increased length of hospital stay in the AUI group. An AUI device should be considered as an option in patients with anatomy unsuitable for a bifurcated repair.

SEM AutoAnalysis: enhancing photomask and NIL defect disposition and review

NASA Astrophysics Data System (ADS)

Schulz, Kristian; Egodage, Kokila; Tabbone, Gilles; Ehrlich, Christian; Garetto, Anthony

2017-06-01

For defect disposition and repair verification regarding printability, AIMS™ is the state of the art measurement tool in industry. With its unique capability of capturing aerial images of photomasks it is the one method that comes closest to emulating the printing behaviour of a scanner. However for nanoimprint lithography (NIL) templates aerial images cannot be applied to evaluate the success of a repair process. Hence, for NIL defect dispositioning scanning, electron microscopy (SEM) imaging is the method of choice. In addition, it has been a standard imaging method for further root cause analysis of defects and defect review on optical photomasks which enables 2D or even 3D mask profiling at high resolutions. In recent years a trend observed in mask shops has been the automation of processes that traditionally were driven by operators. This of course has brought many advantages one of which is freeing cost intensive labour from conducting repetitive and tedious work. Furthermore, it reduces variability in processes due to different operator skill and experience levels which at the end contributes to eliminating the human factor. Taking these factors into consideration, one of the software based solutions available under the FAVOR® brand to support customer needs is the aerial image evaluation software, AIMS™ AutoAnalysis (AAA). It provides fully automated analysis of AIMS™ images and runs in parallel to measurements. This is enabled by its direct connection and communication with the AIMS™tools. As one of many positive outcomes, generating automated result reports is facilitated, standardizing the mask manufacturing workflow. Today, AAA has been successfully introduced into production at multiple customers and is supporting the workflow as described above. These trends indeed have triggered the demand for similar automation with respect to SEM measurements leading to the development of SEM AutoAnalysis (SAA). It aims towards a fully automated SEM image evaluation process utilizing a completely different algorithm due to the different nature of SEM images and aerial images. Both AAA and SAA are the building blocks towards an image evaluation suite in the mask shop industry.

Chronic Kidney Disease Is Positively and Diabetes Mellitus Is Negatively Associated with Abdominal Aortic Aneurysm

PubMed Central

Uchida, Haruhito A.; Kakio, Yuki; Umebayashi, Ryoko; Okuyama, Yuka; Fujii, Yasuhiro; Ozawa, Susumu; Yoshida, Masashi; Oshima, Yu; Sano, Shunji; Wada, Jun

2016-01-01

Background and Aims Chronic kidney disease (CKD) and diabetes mellitus (DM) are considered as risk factors for cardiovascular diseases. The purpose of this study was to clarify the relationship of CKD and DM with the presence of abdominal aortic aneurysm (AAA). Methods We enrolled 261 patients with AAA (AAA+) and age-and-sex matched 261 patients without AAA (AAA-) at two hospitals between 2008 and 2014, and examined the association between the risk factors and the presence of AAA. Furthermore, in order to investigate the prevalence of AAA in each group, we enrolled 1126 patients with CKD and 400 patients with DM. Results The presence of CKD in patients with AAA+ was significantly higher than that in patients with AAA- (AAA+; 65%, AAA-; 52%, P = 0.004). The presence of DM in patients with AAA+ was significantly lower than that in patients with AAA- (AAA+; 17%, AAA-; 35%, P < 0.001). A multivariate logistic regression analysis demonstrated that hypertension, ischemic heart disease and CKD were independent determinants, whereas, DM was a negatively independent determinant, for the presence of AAA. The prevalence of AAA in patients with CKD 65 years old and above was 5.1%, whereas, that in patients with DM 65 years old and above was only 0.6%. Conclusion CKD is a positively associated with the presence of AAA. In contrast, DM is a negatively associated with the presence of AAA in Japanese population. PMID:27764090

A NASTRAN Vibration Model of the AH-1G Helicopter Airframe. Volume 1

DTIC Science & Technology

1974-06-01

Bulkhead .012 ZZ 1863343 Bulkhead .012 AAA 1863345 Bulkhead .012 j EBB 1863546 Bulkhead .012 j ccc 1863746 Bulkhead .012 \\ ODD 1863748...123 12) 123 RULE AAA AAA AAA AAA BBB EBB AAA AAA AAA AAA BBB BBB OMIT D.O.F. 456 456 123 123 123 123 123 123 123 123 RULE...load in the member Increases. The program determines the section properties, unsytnmetrical bending stresses, element loads and shear flows for a

Morphological State as a Predictor for Reintervention and Mortality After EVAR for AAA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohrlander, Tomas; Dencker, Magnus; Acosta, Stefan, E-mail: stefan.acosta@telia.com

2012-10-15

Purpose: This study was designed to assess aorto-iliac morphological characteristics in relation to reintervention and all-cause long-term mortality in patients undergoing standard EVAR for infrarenal AAA. Methods: Patients treated with EVAR (Zenith{sup Registered-Sign} Stentgrafts, Cook) between May 1998 and February 2006 were prospectively enrolled in a computerized database where comorbidities and preoperative aneurysm morphology were entered. Reinterventions and mortality were checked until December 1, 2010. Median follow-up time was 68 months. Results: A total of 304 patients were included, of which 86% were men. Median age was 74 years. The reintervention rate was 23.4% (71/304). A greater diameter of themore » common iliac artery (p = 0.037; hazard ratio (HR) 1.037 [1.002-1.073]) was an independent factor for an increased number of reinterventions. The 30-day mortality rate was 3.0% (9/304). Aneurysm-related deaths due to AAA occurred in 4.9% (15/304). Five patients died due to a concomitant ruptured thoracic aortic aneurysm. The mortality until end of follow-up was 54.3% (165/304). The proportion of deaths caused by vascular diseases was 61.6%. The severity of angulation of the iliac arteries (p = 0.014; HR 1.018 [95% confidence interval (CI) 1.004-1.033]) and anemia (p = 0.044; HR 2.79 [95% CI 1.029-7.556]) remained as independent factors associated with all-cause long-term mortality. The crude reintervention-free survival rate at 1, 3, and 5 years was 84.5%, 64.8%, and 51.6%, respectively. Conclusions: The initial aorto-iliac morphological state in patients scheduled for standard EVAR for AAA seems to be strongly related to the need for reinterventions and long-term mortality.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iwai, P; Lins, L Nadler

Purpose: There is a lack of studies with significant cohort data about patients using pacemaker (PM), implanted cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device undergoing radiotherapy. There is no literature comparing the cumulative doses delivered to those cardiac implanted electronic devices (CIED) calculated by different algorithms neither studies comparing doses with heterogeneity correction or not. The aim of this study was to evaluate the influence of the algorithms Pencil Beam Convolution (PBC), Analytical Anisotropic Algorithm (AAA) and Acuros XB (AXB) as well as heterogeneity correction on risk categorization of patients. Methods: A retrospective analysis of 19 3DCRT ormore » IMRT plans of 17 patients was conducted, calculating the dose delivered to CIED using three different calculation algorithms. Doses were evaluated with and without heterogeneity correction for comparison. Risk categorization of the patients was based on their CIED dependency and cumulative dose in the devices. Results: Total estimated doses at CIED calculated by AAA or AXB were higher than those calculated by PBC in 56% of the cases. In average, the doses at CIED calculated by AAA and AXB were higher than those calculated by PBC (29% and 4% higher, respectively). The maximum difference of doses calculated by each algorithm was about 1 Gy, either using heterogeneity correction or not. Values of maximum dose calculated with heterogeneity correction showed that dose at CIED was at least equal or higher in 84% of the cases with PBC, 77% with AAA and 67% with AXB than dose obtained with no heterogeneity correction. Conclusion: The dose calculation algorithm and heterogeneity correction did not change the risk categorization. Since higher estimated doses delivered to CIED do not compromise treatment precautions to be taken, it’s recommend that the most sophisticated algorithm available should be used to predict dose at the CIED using heterogeneity correction.« less

[The role of estrogen in the formation and development of abdominal aortic aneurysm: experiment with rats].

PubMed

Wu, Xiao-fei; Zhang, Jian; Xin, Shi-jie; Duan, Zhi-quan; Zhang, Gong

2007-02-13

To investigate the role of estrogen in the formation and development of abdominal aortic aneurysm (AAA). Twenty male Wistar rats were randomly divided into 2 equal groups: experiment group, injected with 17-beta estradiol (E2) intraperitoneally 1 week before the establishment of AAA once a day for 3 weeks (until 2 weeks after the establishment of AAA), and underwent infusion of pancreatic elastase into the infrarenal abdominal aorta through a catheter inserted into the left common iliac artery o as to establish the AAA model, and control group, injected with normal saline intraperitoneally for 3 weeks. Two weeks after the establishment of AAA model, the rats underwent laparotomy, blood samples were collected from vena cava inferior to detect the level of E2 by radioimmunoassay and then the aneurysms were harvested to undergo immunohistochemistry and real-time PCR to detect the protein expression and mRNA expression of matrix metalloproteinase (MMP)-2 and MMP-9. The plasma E2 level of the experiment group was (28+/-6) pg/ml, significantly higher than that of the control group [(5.86+/-0.24) pg/ml, P<0.01]. The aorta dilatation rate of the experiment group was (103+/-4)%, significantly lower than that of the control group [(172+/-13)%, P<0.01]. The destruction of arterial wall, degradation of elastic fibers, and infiltration of inflammatory cells were all more severe in the control group than in the experiment group. The relative mRNA expression of MMP-2 of the experiment group was 0.07+/-0.04, significantly lower than that of the control group (0.22+/-0.07, P<0.01); and the relative mRNA expression of MMP-9 of the experiment group was 1.4+/-0.7, significantly lower than that of the control group (7.4+/-2.8, P<0.01). The protein expression of MMP-2 of the experiment group was (22+/-3)%, significantly lower than that of the control group [(50+/-12)%, P<0.01], and the protein expression of MMP-9 of the experiment group was (23+/-2)%, significantly lower than that of the control group too [(45+/-10)%, P<0.01]. Estrogen inhibits the AAA formation and development by reducing the MMP-2 and MMP-9 mRNA and protein expression and the infiltration of inflammatory cells.

Systematic review of recent evidence for the safety and efficacy of elective endovascular repair in the management of infrarenal abdominal aortic aneurysm.

PubMed

Drury, D; Michaels, J A; Jones, L; Ayiku, L

2005-08-01

Conventional management of abdominal aortic aneurysm (AAA) is by open repair and is associated with a mortality rate of 2-6 per cent. Endovascular aneurysm repair (EVAR) is an alternative technique first introduced in 1991. A systematic review was undertaken of the evidence for the safety and efficacy of elective EVAR in the management of asymptomatic infrarenal AAA. Thirteen electronic bibliographical databases were searched, covering biomedical, health-related, science and social science literature. Outcomes were assessed with respect to efficacy (successful deployment, technical success, conversion rates and secondary intervention rates) and safety (30-day mortality rate, procedure morbidity rates and technical issues-endoleaks, graft thrombosis, stenosis and migration). Of 606 reports identified, 61 met the inclusion criteria (three randomized and 15 non-randomized controlled trials, and 43 uncontrolled studies). There were 29 059 participants in total; 19,804 underwent EVAR. Deployment was successful in 97.6 per cent of cases. Technical success (complete aneurysm exclusion) was 81.9 per cent at discharge and 88.8 per cent at 30 days. Secondary intervention to treat endoleak or maintain graft patency was required in 16.2 per cent of patients. Mean stay in the intensive care unit and mean hospital stay were significantly shorter following EVAR. The 30-day mortality rate for EVAR was 1.6 per cent (randomized controlled trials) and 2.0 per cent in nonrandomized trials and case series. Technical complications comprised stent migration (4.0 per cent), graft limb thrombosis (3.9 per cent), endoleak (type I, 6.8 per cent; type II, 10.3 per cent; type III, 4.2 per cent) and access artery injury (4.8 per cent). EVAR is technically effective and safe, with lower short-term morbidity and mortality rates than open surgery. However, there is a need for extended follow-up as the long-term success of EVAR in preventing aneurysm-related deaths is not yet known.

Family Members of Patients with Abdominal Aortic Aneurysms are at Increased Risk for Aneurysms: Analysis of 618 Probands and their Families from the Liège AAA Family Study

PubMed Central

Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T.; Tromp, Gerard; Kuivaniemi, Helena

2014-01-01

Background The objectives were to answer the following questions using a well-characterized population in Liège, Belgium: 1) what percentage of abdominal aortic aneurysm (AAA) patients have a positive family history for AAA, 2) what is the prevalence of AAAs among relatives of AAA patients; and 3) do familial and sporadic AAA cases differ in clinical characteristics. Methods and Results Unrelated AAA patients diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. In the initial interview 62 (10%) of the 618 AAA patients reported a positive family history for AAA. We divided the 618 patients into two study groups: Group I: 296 AAA patients (268; 91% males) were followed up with computerized tomography combined with positron emission tomography, and Group II: 322 AAA patients (295; 92% males) whose families were invited to ultrasonography screening. Ultrasonography screening identified 24 new AAAs among 186 relatives (≥ 50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonography screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P<0.0001). Conclusions The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis and provide rationale for targeted screening of relatives of AAA patients. PMID:24365082

Family members of patients with abdominal aortic aneurysms are at increased risk for aneurysms: analysis of 618 probands and their families from the Liège AAA Family Study.

PubMed

Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T; Tromp, Gerard; Kuivaniemi, Helena

2014-05-01

The objectives were to answer the following questions with the help of a well-characterized population in Liège, Belgium: 1) what percentage of patients with abdominal aortic aneurysm (AAA) have a positive family history for AAA? 2) what is the prevalence of AAAs among relatives of patients with AAA? and 3) do familial and sporadic AAA cases differ in clinical characteristics? Patients with unrelated AAA diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. We divided the 618 patients into 2 study groups: group I, 296 patients with AAA (268; 91% men) were followed up with computerized tomography combined with positron emission tomography; and group II, 322 patients with AAA (295; 92% men) whose families were invited to ultrasonographic screening. In the initial interview, 62 (10%) of the 618 patients with AAA reported a positive family history for AAA. Ultrasonographic screening identified 24 new AAAs among 186 relatives (≥50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonographic screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P < 0.0001). The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis, and provide rationale for targeted screening of relatives of patients with AAA. Copyright © 2014 Elsevier Inc. All rights reserved.

Outcomes in adult pectus excavatum patients undergoing Nuss repair

PubMed Central

Ewais, MennatAllah M; Chaparala, Shivani; Uhl, Rebecca

2018-01-01

Pectus excavatum (PEx) is one of the most common congenital chest wall deformities. Depending on the severity, presentation of PEx may range from minor cosmetic issues to disabling cardiopulmonary symptoms. The effect of PEx on adult patients has not been extensively studied. Symptoms may not occur until the patient ages, and they may worsen over the years. More recent publications have implied that PEx may have significant cardiopulmonary implications and repair is of medical benefit. Adults presenting for PEx repair can undergo a successful repair with a minimally invasive “Nuss” approach. Resolution of symptoms, improved quality of life, and satisfying results are reported. PMID:29430201

Outcomes and Resource Utilization of Endoscopic Mass-Closure Technique for Laryngeal Clefts.

PubMed

Balakrishnan, Karthik; Cheng, Esther; de Alarcon, Alessandro; Sidell, Douglas R; Hart, Catherine K; Rutter, Michael J

2015-07-01

To compare resource utilization and clinical outcomes between endoscopic mass-closure and open techniques for laryngeal cleft repair. Case series with chart review. Tertiary academic children's hospital. Pediatric patients undergoing repair for Benjamin-Inglis type 1-3 laryngeal clefts over a 15-year period. All 20 patients undergoing endoscopic repair were included. Eight control patients undergoing open repair were selected using matching by age and cleft type. Demographic, clinical, and resource utilization data were collected. Twenty-eight patients were included (20 endoscopic, 8 open). Mean age, rates of tracheostomy and vocal fold immobility, and distribution of cleft types were not different between the 2 groups (all P > .2). Mean operative time (P = .004) and duration of hospital stay (P < .001) were significantly shorter in the endoscopic group. All repairs were intact in both groups at final postoperative endoscopy. Rates of persistent laryngeal penetration or aspiration on swallow study were not different between groups (P = 1.000), although results were available for only 11 patients. Endoscopic laryngeal cleft repair using a mass-closure technique provides a durable result while requiring significantly shorter operative times and hospital stays than open repair and avoiding the potential morbidity of laryngofissure. However, open repair may allow the simultaneous performance of other airway reconstructive procedures and may be a useful salvage technique when endoscopic repair fails. Postoperative swallowing results require further study. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Nuclear ARP2/3 drives DNA break clustering for homology-directed repair.

PubMed

Schrank, Benjamin R; Aparicio, Tomas; Li, Yinyin; Chang, Wakam; Chait, Brian T; Gundersen, Gregg G; Gottesman, Max E; Gautier, Jean

2018-06-20

DNA double-strand breaks repaired by non-homologous end joining display limited DNA end-processing and chromosomal mobility. By contrast, double-strand breaks undergoing homology-directed repair exhibit extensive processing and enhanced motion. The molecular basis of this movement is unknown. Here, using Xenopus laevis cell-free extracts and mammalian cells, we establish that nuclear actin, WASP, and the actin-nucleating ARP2/3 complex are recruited to damaged chromatin undergoing homology-directed repair. We demonstrate that nuclear actin polymerization is required for the migration of a subset of double-strand breaks into discrete sub-nuclear clusters. Actin-driven movements specifically affect double-strand breaks repaired by homology-directed repair in G2 cell cycle phase; inhibition of actin nucleation impairs DNA end-processing and homology-directed repair. By contrast, ARP2/3 is not enriched at double-strand breaks repaired by non-homologous end joining and does not regulate non-homologous end joining. Our findings establish that nuclear actin-based mobility shapes chromatin organization by generating repair domains that are essential for homology-directed repair in eukaryotic cells.

Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm.

PubMed

Sawada, Hisashi; Hao, Hiroyuki; Naito, Yoshiro; Oboshi, Makiko; Hirotani, Shinichi; Mitsuno, Masataka; Miyamoto, Yuji; Hirota, Seiichi; Masuyama, Tohru

2015-06-01

Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive. Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression. © 2015 American Heart Association, Inc.

Staff members' perceptions of an animal-assisted activity.

PubMed

Bibbo, Jessica

2013-07-01

To examine the perceptions of staff members toward the implementation of an animal-assisted activity (AAA) in an outpatient regional cancer center. Quasi-experimental, post-test design. An adult outpatient regional cancer center in northern California. 34 facility staff members. Self-report questionnaire following four weeks of AAA visitation. Visits took place three times a week for a total of 12 visits. Perceptions of the AAA. Previous perceptions toward AAA influenced the perceptions of the visitation's efficacy. Direct and indirect interaction with the visiting AAA teams was positively associated with perceptions of the AAA. A disagreement occurred that the AAA had caused extra stress or work for staff. Enjoyment of interacting with the dog handler was not significantly different from interacting with the dog; however, it was more positively correlated to acceptance of the AAA. The study provided evidence that the AAA was generally accepted by staff members. Individual staff members' perceptions of dogs and AAAs can influence their receptivity to AAA interventions. Interaction with AAA teams should be voluntary and available for patients and staff members. AAA may be introduced into facilities without creating the perception of extra stress or work for staff members. Providing staff the opportunity to interact with visiting AAA teams may be beneficial for the success of such programs. The human handler in AAA teams may play a vital role in the staff acceptance of such programs.

Risk of abdominal aortic aneurysm (AAA) among male and female relatives of AAA patients.

PubMed

van de Luijtgaarden, Koen M; Rouwet, Ellen V; Hoeks, Sanne E; Stolker, Robert J; Verhagen, Hence Jm; Majoor-Krakauer, Danielle

2017-04-01

Sex affects the presentation, treatment, and outcomes of abdominal aortic aneurysm (AAA). Although AAAs are less prevalent in women, at least in the general population, women with an AAA have a poorer prognosis in comparison to men. Sex differences in the genetic predisposition for aneurysm disease remain to be established. In this study we investigated the familial risk of AAA for women compared to men. All living AAA patients included in a 2004-2012 prospective database were invited to the multidisciplinary vascular/genetics outpatient clinic between 2009 and 2012 for assessment of family history using detailed questionnaires. AAA risk for male and female relatives was calculated separately and stratified by sex of the AAA patients. Families of 568 AAA patients were investigated and 22.5% of the patients had at least one affected relative. Female relatives had a 2.8-fold and male relatives had a 1.7-fold higher risk than the estimated sex-specific population risk. Relatives of female AAA patients had a higher aneurysm risk than relatives of male patients (9.0 vs 5.9%, p = 0.022), corresponding to 5.5- and 2.0-fold increases in aneurysm risk in the female and male relatives, respectively. The risk for aortic aneurysm in relatives of AAA patients is higher than expected from population risk. The excess risk is highest for the female relatives of AAA patients and for the relatives of female AAA patients. These findings endorse targeted AAA family screening for female and male relatives of all AAA patients.

46 CFR Sec. 17 - Performance of work resulting from damage sustained while undergoing repairs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP Sec. 17 Performance of work resulting... performance of repairs under the NSA Master Contract, negotiations for accomplishment of work necessary to...

46 CFR Sec. 17 - Performance of work resulting from damage sustained while undergoing repairs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP Sec. 17 Performance of work resulting... performance of repairs under the NSA Master Contract, negotiations for accomplishment of work necessary to...

46 CFR Sec. 17 - Performance of work resulting from damage sustained while undergoing repairs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP Sec. 17 Performance of work resulting... performance of repairs under the NSA Master Contract, negotiations for accomplishment of work necessary to...

46 CFR Sec. 17 - Performance of work resulting from damage sustained while undergoing repairs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP Sec. 17 Performance of work resulting... performance of repairs under the NSA Master Contract, negotiations for accomplishment of work necessary to...

46 CFR Sec. 17 - Performance of work resulting from damage sustained while undergoing repairs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP Sec. 17 Performance of work resulting... performance of repairs under the NSA Master Contract, negotiations for accomplishment of work necessary to...

CXCL8 hyper-signaling in the aortic abdominal aneurysm.

PubMed

Kokje, Vivianne B C; Gäbel, Gabor; Dalman, Ron L; Koole, Dave; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

2018-08-01

There are indications for elevated CXCL8 levels in abdominal aortic aneurysm disease (AAA). CXCL8 is concurrently involved in neutrophil-mediated inflammation and angiogenesis, two prominent and distinctive characteristics of AAA. As such we considered an evaluation of a role for CXCL8 in AAA progression relevant. ELISA's, real time PCR and array analysis were used to explore CXCL8 signaling in AAA wall samples. A role for CXCL8 in AAA disease was tested through the oral CXCR1/2 antagonist DF2156A in the elastase model of AAA disease. There is an extreme disparity in aortic wall CXCL8 content between AAA and aortic atherosclerotic disease (median [IQR] aortic wall CXCL8 content: 425 [141-1261] (AAA) vs. 23 [2.8-89] (atherosclerotic aorta) µg/g protein (P < 1 · 10 -14 )), and abundant expression of the CXCR1 and 2 receptors in AAA. Array analysis followed by pathway analysis showed that CXCL8 hyper-expression in AAA is followed increased by IL-8 signaling (Z-score for AAA vs. atherosclerotic control: 2.97, p < 0.0001). Interference with CXCL8 signaling through DF2156A fully abrogated AAA formation and prevented matrix degradation in the murine elastase model of AAA disease (p < 0.001). CXCL8-signaling is a prominent and distinctive feature of AAA, interference with the pathway constitutes a promising target for medical stabilization of AAA. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Progressive shortfall in open aneurysm experience for vascular surgery trainees with the impact of fenestrated and branched endovascular technology.

PubMed

Dua, Anahita; Koprowski, Steven; Upchurch, Gilbert; Lee, Cheong J; Desai, Sapan S

2017-01-01

In 2014, we published a series of articles in the Journal of Vascular Surgery that detailed the decrease in volume of open aneurysm repair (OAR) completed for abdominal aortic aneurysm (AAA) by vascular surgery trainees. At that time, only data points from 2000 through 2011 were available, and reliable predictions could only be made through 2015. Lack of data on endovascular aneurysm repair (EVAR) using fenestrated (FEVAR) and branched (BrEVAR) endografts also affected our findings. Despite these limitations, our predictions for OAR completed by vascular trainees were accurate for 2012 to 2014. This report uses updated data points through 2014 in conjunction with data on FEVAR and BrEVAR obtained from industry to predict trends in OAR and how it will affect vascular surgery training through 2020. An S-curve modified logistic function was used to model the effect of introducing new technologies (EVAR, FEVAR, BrEVAR) on the standard management of AAA with OAR starting in the year 2000, similar to the technique that we have previously described. Weighted samples and data from the United States Census Bureau were used in conjunction with volume estimates derived from the National Inpatient Sample, State Inpatient Databases, and industry sources to determine trends in OAR and EVAR. The number of cases completed at teaching hospitals was calculated using the National Inpatient Sample, and Accreditation Council for Graduate Medical Education case logs were used to forecast the number of cases completed by vascular surgery trainees through 2020. Sensitivity analysis and trend analysis were completed. Approximately 45,000 AAA repairs are completed annually in the United States, but only 15% of these are now completed using OAR compared with >50% just a decade ago. Further, with the accelerating adoption of FEVAR and BrEVAR, and expanding indications for standard EVAR, our model predicts that <3000 OARs will be completed annually by 2020. Because only a subset of these cases are completed at teaching institutions, our model predicts that a vascular surgery trainee in a fellowship program will complete only one to two OARs, whereas trainees in a 0+5 program may complete two to three OARs. Our initial prediction in the 2014 report was that vascular trainees would complete approximately five OARs by 2020. After incorporating new data on BrEVAR, FEVAR, and the accelerating pace of EVAR use between 2012 and 2014, it now appears that vascular trainees will complete one to three OARs during their training. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Collagen Augmentation Improves the Quality of Cartilage Repair After Microfracture in Patients Undergoing High Tibial Osteotomy: A Randomized Controlled Trial.

PubMed

Kim, Man Soo; Koh, In Jun; Choi, Young Jun; Pak, Kyu Hyung; In, Yong

2017-07-01

The quality of cartilage repair after marrow stimulation is unpredictable. To overcome the shortcomings of the microfracture technique, various augmentation techniques have been developed. However, their efficacies remain unclear. The quality of cartilage repair and clinical outcomes would be superior in patients undergoing high tibial osteotomy (HTO) with microfracture and collagen augmentation compared to those undergoing HTO with microfracture alone without collagen augmentation for the treatment of medial compartment osteoarthritis (OA) of the knee. Randomized controlled trial; Level of evidence, 2. Twenty-eight patients undergoing HTO were randomized into 2 groups: microfracture alone (group 1, n = 14) or microfracture with collagen augmentation (group 2, n = 14). At 1 year postoperatively, second-look arthroscopic surgery and biopsy of repaired cartilage were performed at the time of HTO plate removal. Biopsy specimens were graded using the International Cartilage Repair Society Visual Assessment Scale II (ICRS II). In addition, imaging outcomes in terms of the magnetic resonance observation of cartilage repair tissue (MOCART) score were assessed based on magnetic resonance imaging (MRI). Finally, clinical outcomes in terms of the visual analog scale (VAS) for pain score, Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, and Tegner activity scale score were evaluated. The mean ICRS II score in group 2 was significantly higher than that in group 1 (1053.2 vs 885.4, respectively; P = .002). Group 2 showed greater improvement in tissue morphology, cell morphology, surface architecture, middle/deep zone assessment, and overall assessment compared with group 1 ( P < .050 for all comparisons). Imaging outcomes based on the MOCART score were superior in group 2 compared to those in group 1 on MRI at 1 year postoperatively (64.6 vs 45.4, respectively; P = .001). The degree of defect repair was better in group 2 than in group 1 ( P = .040). Clinical outcomes in terms of the VAS for pain score, KOOS, IKDC score, and Tegner activity scale score were improved in both groups without between-group differences ( P > .100 for all comparisons). The quality of cartilage repair after microfracture with collagen augmentation was superior to that after microfracture alone in patients undergoing HTO. Clinical results after 1 year did not reflect this difference in tissue repair. Therefore, a longer follow-up of the cohort is needed to answer this question.

Minimal cosmetic revision required after minimally invasive pectus repair.

PubMed

Murphy, Brittany L; Naik, Nimesh D; Roskos, Penny L; Glasgow, Amy E; Moir, Christopher R; Habermann, Elizabeth B; Klinkner, Denise B

2018-05-09

Despite surgical correction procedures for pectus deformities, remaining cosmetic asymmetry may have significant psychological effects. We sought to evaluate factors associated with plastic surgery (PS) consultation and procedures for these deformities at an academic institution. We reviewed patients aged 0-21 diagnosed with a pectus excavatum or carinatum deformity at our institution between January 2001 and October 2016. Pectus diagnoses were identified by ICD-9/ICD-10 codes and surgical repair by CPT codes; patients receiving PS consultation were identified by clinical note service codes. Student's t tests, Fisher's exact tests, and Chi-squared tests were utilized. 2158 patients were diagnosed with a pectus deformity; 442 (20.4%) underwent surgical correction. 19/442 (4.3%) sought PS consultation, either for pectus excavatum [14/19 (73.7%)], carinatum [4/19 (21.0%)], and both [1/19 (5.3%)], (p = 0.02). Patients seeking PS consultation were more likely to be female (p < 0.01), have scoliosis (p = 0.02), or undergo an open repair (p < 0.01). The need for PS consultation did not correlate with Haller index, p = 0.78. PS consultation associated with pectus deformity repair was rare, occurring in < 5% of patients undergoing repair. Patients who consulted PS more commonly included females, patients with scoliosis, and those undergoing open repair. These patients would likely benefit most from multidisciplinary pre-operative discussions regarding repair of the global deformity.

Perioperative outcomes and complications of open vs laparoscopic extraperitoneal inguinal hernia repair in a mature surgical practice.

PubMed

Winslow, E R; Quasebarth, M; Brunt, L M

2004-02-01

Although the laparoscopic totally extraperitoneal (TEP) approach to hernia repair has been associated with less pain and a faster postoperative recovery than traditional open repair, many practicing surgeons have been reluctant to adopt this technique because of the lengthy operative times and the learning curve for this procedure. Data from all patients undergoing TEP repair since 1997 and open mesh repair (OPEN) since 1999 were collected prospectively. Selection of surgical approach was based on local hernia factors, anesthetic risk, previous abdominal surgery, and patient preference. Statistical analyses were performed using unpaired t-tests and chi-squared tests. Data are mean +/- SD. TEP repairs were performed in 147 patients and open repairs in 198 patients. Patients in the OPEN group were significantly older (59 +/- 19 years OPEN vs 51 +/- 13 years TEP) and had a higher ASA (1.9 +/- 0.7 OPEN vs 1.5 +/- 0.6 TEP; p < 0.01). TEP repairs were more likely to be carried out for bilateral (33% TEP, 5% OPEN) or recurrent hernias (31% TEP, 11% OPEN) than were open repairs ( p < 0.01). Concurrent procedures accompanied 31% of TEP and 12% of OPEN repairs ( p < 0.01). Operative times (min) were significantly shorter in the TEP group for both unilateral (63 +/- 22 TEP, 70 +/- 20 OPEN; p = 0.02) and bilateral (78 +/- 27 TEP, 102 +/- 27 OPEN; p = 0.01) repairs. Mean operative times decreased over time in the TEP group for both unilateral and bilateral repairs ( p < 0.01). Patients undergoing TEP were more likely ( p < 0.01) to develop urinary retention (7.9% TEP, 1.1% OPEN), but were less likely ( p < 0.01) to have skin numbness (2.8% TEP, 35.8% OPEN) or prolonged groin discomfort (1.4% TEP, 5.3% OPEN). Despite a higher proportion of patients undergoing bilateral repairs, recurrent hernia repair, and concurrent procedures, operative times are shorter for laparoscopic TEP repair than for open mesh repair. TEP repairs can be performed efficiently and without major complications, even when the learning curve is included.

Beneficial effect of statins on total mortality in abdominal aortic aneurysm (AAA) repair.

PubMed

Mathisen, Sven Ross; Abdelnoor, Michael

2017-10-01

In this single center, retrospective cohort study we wished to compare early and total mortality for all patients treated for abdominal aortic aneurysms (AAA) with open surgery who were taking statins compared to those who were not. A cohort of 640 patients with AAA was treated with open surgery between 1999 and 2012. Patients were consecutively recruited from a source population of 390,000; 21.3% were female, and the median age was 73 years. The median follow-up was 3.93 years, with an interquartile range of 1.79-6.58 years. The total follow-up was 2855 patient-years. An explanatory strategy was used. The propensity score (PS) was implemented to control for selection bias and confounders. The crude effect of statin use showed a 78% reduction of the 30-day mortality. A stratified analysis using the Mantel-Haenszel method on quintiles of the PS gave an adjusted effect of the odds ratio equal to 0.43 (95% CI: 0.18-0.96), indicating a 57% reduction of the 30-day mortality for statin users. The adjusted rate ratio was 0.62 (95% CI: 0.45-0.83), indicating a reduction of long-term mortality of 38% for statin users compared to non-users for a median follow-up of 3.93 years. This retrospective cohort study showed a significant beneficial effect of statin use on early and long-term survival for patients treated with open surgery. To be conclusive, our results need to be replicated by a randomized clinical trial.

Effect of a High-sucrose Diet on Abdominal Aortic Aneurysm Development in a Hypoperfusion-induced Animal Model.

PubMed

Miyamoto, Chie; Kugo, Hirona; Hashimoto, Keisuke; Sawaragi, Ayaka; Zaima, Nobuhiro; Moriyama, Tatsuya

2018-05-01

Abdominal aortic aneurysm (AAA) is a vascular disease that results in rupture of the abdominal aorta. The risk factors for the development of AAA include smoking, male sex, hypertension, and age. AAA has a high mortality rate, but therapy for AAA is restricted to surgery in cases of large aneurysms. Clarifying the effect of dietary food on the development of AAA would be helpful for patients with AAAs. However, the relationship between dietary habits and the development of AAA is largely unknown. In our previous study, we demonstrated that adipocytes in vascular wall can induce the rupture of AAA. Therefore, we focused on the diet-induced abnormal triglyceride metabolism, which has the potential to drive AAA development. In this study, we have evaluated the effects of a high-sucrose diet on the development of AAA in a vascular hypoperfusion-induced animal model. A high sucrose diet induced high serum TG level and fatty liver. However, the AAA rupture risk and the AAA diameter were not significantly different between the control and high-sucrose groups. The intergroup differences in the elastin degradation score and collagen-positive area were insignificant. Moreover, matrix metalloproteinases, macrophages, and monocyte chemoattractant protein-1-positive areas did not differ significantly between groups. These results suggest that a high-sucrose diet does not affect the appearance of vascular adipocyte and AAA development under the vascular hypoperfusion condition.

Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration.

PubMed

Qi, Y; Liu, H; Daniels, M P; Zhang, G; Xu, H

2016-02-01

Mitochondrial AAA (ATPases Associated with diverse cellular Activities) proteases i-AAA (intermembrane space-AAA) and m-AAA (matrix-AAA) are closely related and have major roles in inner membrane protein homeostasis. Mutations of m-AAA proteases are associated with neuromuscular disorders in humans. However, the role of i-AAA in metazoans is poorly understood. We generated a deletion affecting Drosophila i-AAA, dYME1L (dYME1L(del)). Mutant flies exhibited premature aging, progressive locomotor deficiency and neurodegeneration that resemble some key features of m-AAA diseases. dYME1L(del) flies displayed elevated mitochondrial unfolded protein stress and irregular cristae. Aged dYME1L(del) flies had reduced complex I (NADH/ubiquinone oxidoreductase) activity, increased level of reactive oxygen species (ROS), severely disorganized mitochondrial membranes and increased apoptosis. Furthermore, inhibiting apoptosis by targeting dOmi (Drosophila Htra2/Omi) or DIAP1, or reducing ROS accumulation suppressed retinal degeneration. Our results suggest that i-AAA is essential for removing unfolded proteins and maintaining mitochondrial membrane architecture. Loss of i-AAA leads to the accumulation of oxidative damage and progressive deterioration of membrane integrity, which might contribute to apoptosis upon the release of proapoptotic molecules such as dOmi. Containing ROS level could be a potential strategy to manage mitochondrial AAA protease deficiency.

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

PubMed Central

Wu, Xiaoyu; Cakmak, Sinan; Wortmann, Markus; Hakimi, Maani; Zhang, Jian; Böckler, Dittmar; Dihlmann, Susanne

2016-01-01

Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of AAA patients and age/sex-matched non-AAA patients. Male PBMC were found to express significantly higher mRNA levels of AIM2, NLRP3, ASC (PYCARD), CASP1, CASP5, and IL1B (all P < 0.0001) than female PBMC. Within the male patients, PBMC of AAA patients displayed increased mRNA levels of NLRP3 (P = 0.044), CASP1 (P = 0.032) and IL1B (P = 0.0004) compared with matched non-AAA PBMC, whereas there was no difference between female AAA and non-AAA patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all AAA patients than in matched controls (P = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased (P = 0.014 and P = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 versus 0.01 pg/mL) and IL-1β plasma levels (mean = 12.07 versus 0.04 pg/mL) in AAA patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to AAA-pathogenesis. The AAA-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of AAA patients. PMID:27474483

A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein

PubMed Central

Gleave, Emma S.; Schmidt, Helgo; Carter, Andrew P.

2014-01-01

Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. PMID:24680784

Association of left subclavian artery coverage without revascularization and spinal cord ischemia in patients undergoing thoracic endovascular aortic repair: A Vascular Quality Initiative® analysis.

PubMed

Teixeira, Pedro Gr; Woo, Karen; Beck, Adam W; Scali, Salvatore T; Weaver, Fred A

2017-12-01

Objectives Investigate the impact of left subclavian artery coverage without revascularization on spinal cord ischemia development in patients undergoing thoracic endovascular aortic repair. Methods The Vascular Quality Initiative thoracic endovascular aortic repair module (April 2011-July 2014) was analyzed. Patients undergoing left subclavian artery coverage were divided into two groups according to revascularization status. The association between left subclavian artery revascularization with the primary outcome of spinal cord ischemia and the secondary outcome of stroke was assessed with multivariable analysis adjusting for between-group baseline differences. Results The left subclavian artery was covered in 508 (24.6%) of the 2063 thoracic endovascular aortic repairs performed. Among patients with left subclavian artery coverage, 58.9% underwent revascularization. Spinal cord ischemia incidence was 12.1% in the group without revascularization compared to 8.5% in the group undergoing left subclavian artery revascularization (odds ratio (95%CI): 1.48(0.82-2.68), P = 0.189). Multivariable analysis adjustment identified an independent association between left subclavian artery coverage without revascularization and the incidence of spinal cord ischemia (adjusted odds ratio (95%CI): 2.29(1.03-5.14), P = 0.043). Although the incidence of stroke was also higher for the group with a covered and nonrevascularized left subclavian artery (12.1% versus 8.5%), this difference was not statistically significant after multivariable analysis (adjusted odds ratio (95%CI): 1.55(0.74-3.26), P = 0.244). Conclusion For patients undergoing left subclavian artery coverage during thoracic endovascular aortic repair, the addition of a revascularization procedure was associated with a significantly lower incidence of spinal cord ischemia.

Randomized clinical trial of remote ischaemic preconditioning versus no preconditioning in the prevention of perioperative myocardial infarction during open surgery for ruptured abdominal aortic aneurysm.

PubMed

Pedersen, T F; Budtz-Lilly, J; Petersen, C N; Hyldgaard, J; Schmidt, J-O; Kroijer, R; Grønholdt, M-L; Eldrup, N

2018-06-01

Remote ischaemic preconditioning (RIPC) has been suggested as a means of protecting vital organs from reperfusion injury during major vascular surgery. This study was designed to determine whether RIPC could reduce the incidence of perioperative myocardial infarction (MI) during open surgery for ruptured abdominal aortic aneurysm (AAA). Secondary aims were to see if RIPC could reduce 30-day mortality, multiple organ failure, acute intestinal ischaemia, acute kidney injury and ischaemic stroke. This randomized, non-blinded clinical trial was undertaken at three vascular surgery centres in Denmark. Patients who had open surgery for ruptured AAA were randomized to intervention with RIPC or control in a 1 : 1 ratio. Postoperative complications and deaths were registered, and ECG and blood samples were obtained daily during the hospital stay. Of 200 patients randomized, 142 (72 RIPC, 70 controls) were included. There was no difference in rates of perioperative MI between the RIPC and control groups (36 versus 43 per cent respectively), or in rates of organ failure. However, in the per-protocol analysis 30-day mortality was significantly reduced in the RIPC group (odds ratio 0·46, 95 per cent c.i. 0·22 to 0·99; P = 0·048). RIPC did not reduce the incidence of perioperative MI in patients undergoing open surgery for ruptured AAA. Registration number: NCT00883363 ( http://www.clinicaltrials.gov).

Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm

PubMed Central

Sasaki, Takeshi; Sano, Masaki; Yamamoto, Naoto; Saito, Takaaki; Inuzuka, Kazunori; Hayasaka, Takahiro; Goto-Inoue, Naoko; Sugiura, Yuki; Sato, Kohji; Kugo, Hirona; Moriyama, Tatsuya; Konno, Hiroyuki; Setou, Mitsutoshi; Unno, Naoki

2015-01-01

The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30–49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA. PMID:26308526

Non-Elective Paraesophageal Hernia Repair Portends Worse Outcomes in Comparable Patients: a Propensity-Adjusted Analysis.

PubMed

Tam, Vernissia; Luketich, James D; Winger, Daniel G; Sarkaria, Inderpal S; Levy, Ryan M; Christie, Neil A; Awais, Omar; Shende, Manisha R; Nason, Katie S

2017-01-01

Patients undergoing non-elective paraesophageal hernia repair (PEHR) have worse perioperative outcomes. Because they are usually older and sicker, however, these patients may be more prone to adverse events, independent of surgical urgency. Our study aimed to determine whether non-elective PEHR is associated with differential postoperative outcome compared to elective repair, using propensity-score weighting. We abstracted data for patients undergoing PEHR (n = 924; non-elective n = 171 (19 %); 1997-2010). Using boosted regression, we generated a propensity-weighted dataset. Odds of 30-day/in-hospital mortality and major complications after non-elective surgery were determined. Patients undergoing non-elective repair were significantly older, had more adverse prognostic factors, and significantly more major complications (38 versus 18 %; p < 0.001) and death (8 versus 1 %; p < 0.001). After propensity weighting, median absolute percentage bias across 28 propensity-score variables improved from 19 % (significant imbalance) to 5.6 % (well-balanced). After adjusting propensity-weighted data for age and comorbidity score, odds of major complications were still nearly two times greater (OR 1.67, CI 1.07-2.61) and mortality nearly three times greater (OR 2.74, CI 0.93-8.1) than for elective repair. Even after balancing significant differences in baseline characteristics, non-elective PEHR was associated with worse outcomes than elective repair. Symptomatic patients should be referred for elective repair by experienced surgeons.

Surgical RF ablation of atrial fibrillation in patients undergoing mitral valve repair for Barlow disease.

PubMed

Rostagno, Carlo; Droandi, G; Gelsomino, S; Carone, E; Gensini, G F; Stefàno, P L

2013-01-01

At present, limited experience exists on the treatment of atrial fibrillation (AF) in patients undergoing mitral valve repair (MVR) for Barlow disease. The aim of this investigation was to prospectively evaluate the radiofrequency ablation of AF in patients undergoing MVR for severe regurgitation due to Barlow disease. From January 1, 2007 to December 31, 2010, out of 85 consecutive patients with Barlow disease, 27 with AF underwent RF ablation associated with MVR. They were examined every 4 months in the first year after surgery and thereafter twice yearly. At follow-up, AF was observed in 4/25 (16.0%). NYHA (New York Heart Association) functional class improved significantly, with no patients in class III or IV (before surgery, 81.5% had been). Otherwise, among 58 patients in sinus rhythm, 6 (11%) developed AF during follow-up. No clinical or echocardiographic predictive factor was found in this subgroup. Results from our investigation suggest that radiofrequency ablation of AF in patients with Barlow disease undergoing MVR for severe regurgitation is effective and should be considered in every patient with Barlow disease and AF undergoing valve surgical repair. Copyright © 2013 S. Karger AG, Basel.

Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine.

PubMed

Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

2015-09-01

Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA-spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA-spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients.

Lifetime Risk and Risk Factors for Abdominal Aortic Aneurysm in a 24-Year Prospective Study: The ARIC Study (Atherosclerosis Risk in Communities).

PubMed

Tang, Weihong; Yao, Lu; Roetker, Nicholas S; Alonso, Alvaro; Lutsey, Pamela L; Steenson, Carol C; Lederle, Frank A; Hunter, David W; Bengtson, Lindsay G S; Guan, Weihua; Missov, Emil; Folsom, Aaron R

2016-12-01

Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs. In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987-1989) to visit 4 (1996-1998). We followed up participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through 85 years of age. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval, 4.8-6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower AAA lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2-1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA. At least 1 in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA. © 2016 American Heart Association, Inc.

From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.

PubMed

Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J

2014-07-03

Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

[Identifying barriers to screening for abdominal aortic aneurysm in general practice: Qualitative study of 14 general practitioners in Paris].

PubMed

Niclot, J; Stansal, A; Saint-Lary, O; Lazareth, I; Priollet, P

2018-05-01

Abdominal aortic aneurysm (AAA) is a silent pathology with often fatal consequences in case of rupture. AAA screening, recommended in France and many other countries, has shown its effectiveness in reducing specific mortality. However, AAA screening rate remains insufficient. To identify barriers to AAA screening in general practice. Qualitative study carried out during 2016 among general practitioners based in Paris. Fourteen physicians were included. Most of the barriers were related to the physician: unawareness about AAA and screening recommendations, considering AAA as a secondary question not discussed with the patient, abdominal aorta not included in cardiovascular assessment, no search for a familial history of AAA, AAA considered a question for the specialist, lack of time, lack of training, numerous screenings to propose, oversight. Some barriers are related to the patient: unawareness of the pathology and family history of AAA, refusal, questioning the pertinence of the doctor's comments, failure to respect the care pathway. Others are related to AAA: source of anxiety, low prevalence, rarity of complications. The remaining barriers are related to screening: cost-benefit and risk-benefit ratios, sonographer unavailability, constraint for the patient, overmedicalization. Information and training of general practitioners about AAA must be strengthened in order to optimize AAA screening and reduce specific mortality. Copyright © 2018. Published by Elsevier Masson SAS.

Matricellular protein CCN3 mitigates abdominal aortic aneurysm

PubMed Central

Zhang, Chao; van der Voort, Dustin; Shi, Hong; Qing, Yulan; Hiraoka, Shuichi; Takemoto, Minoru; Yokote, Koutaro; Moxon, Joseph V.; Norman, Paul; Rittié, Laure; Atkins, G. Brandon; Gerson, Stanton L.; Shi, Guo-Ping; Golledge, Jonathan; Dong, Nianguo; Perbal, Bernard; Prosdocimo, Domenick A.

2016-01-01

Abdominal aortic aneurysm (AAA) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation and progression are incompletely understood. Extracellular matrix proteins play an integral role in modulating vascular homeostasis in health and disease. Here, we determined that the expression of the matricellular protein CCN3 is strongly reduced in rodent AAA models, including angiotensin II–induced AAA and elastase perfusion–stimulated AAA. CCN3 levels were also reduced in human AAA biopsies compared with those in controls. In murine models of induced AAA, germline deletion of Ccn3 resulted in severe phenotypes characterized by elastin fragmentation, vessel dilation, vascular inflammation, dissection, heightened ROS generation, and smooth muscle cell loss. Conversely, overexpression of CCN3 mitigated both elastase- and angiotensin II–induced AAA formation in mice. BM transplantation experiments suggested that the AAA phenotype of CCN3-deficient mice is intrinsic to the vasculature, as AAA was not exacerbated in WT animals that received CCN3-deficient BM and WT BM did not reduce AAA severity in CCN3-deficient mice. Genetic and pharmacological approaches implicated the ERK1/2 pathway as a critical regulator of CCN3-dependent AAA development. Together, these results demonstrate that CCN3 is a nodal regulator in AAA biology and identify CCN3 as a potential therapeutic target for vascular disease. PMID:26974158

A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

PubMed

Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

2014-06-01

Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals.

PubMed

Parthasarathy, Anutthaman; Cross, Penelope J; Dobson, Renwick C J; Adams, Lily E; Savka, Michael A; Hudson, André O

2018-01-01

Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (AAA) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the AAA pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The AAA and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the AAA by microbes and plants, and the branching out of AAA metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of AAA must obtain these primary metabolites from their diet. Therefore, the metabolism of AAA by the host animal and the resident microflora are important for the health of all animals. In addition, the AAA metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful AAA-derived compounds produced by gut bacteria are discussed. Apart from the AAA biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with AAA catabolism in plants, AAA degradation via the monoamine and kynurenine pathways in animals, and AAA catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key AAA-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type III CoA-transferase. The past development and current potential for interventions including the development of herbicides and antibiotics that target key enzymes in AAA-related pathways, as well as AAA-linked secondary metabolism leading to antimicrobials are also discussed.

A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals

PubMed Central

Parthasarathy, Anutthaman; Cross, Penelope J.; Dobson, Renwick C. J.; Adams, Lily E.; Savka, Michael A.; Hudson, André O.

2018-01-01

Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (AAA) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the AAA pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The AAA and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the AAA by microbes and plants, and the branching out of AAA metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of AAA must obtain these primary metabolites from their diet. Therefore, the metabolism of AAA by the host animal and the resident microflora are important for the health of all animals. In addition, the AAA metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful AAA-derived compounds produced by gut bacteria are discussed. Apart from the AAA biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with AAA catabolism in plants, AAA degradation via the monoamine and kynurenine pathways in animals, and AAA catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key AAA-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type III CoA-transferase. The past development and current potential for interventions including the development of herbicides and antibiotics that target key enzymes in AAA-related pathways, as well as AAA-linked secondary metabolism leading to antimicrobials are also discussed. PMID:29682508

Peak AAA fatty acid homolog contaminants present in the dietary supplement l-Tryptophan associated with the onset of eosinophilia-myalgia syndrome.

PubMed

Klarskov, Klaus; Gagnon, Hugo; Racine, Mathieu; Boudreault, Pierre-Luc; Normandin, Chad; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

2018-05-22

The eosinophilia-myalgia syndrome (EMS) outbreak that occurred in the USA and elsewhere in 1989 was caused by the ingestion of Showa Denko K.K. (SD) L-tryptophan (L-Trp). "Six compounds" detected in the L-Trp were reported as case-associated contaminants. Recently the final and most statistically significant contaminant, "Peak AAA" was structurally characterized. The "compound" was actually shown to be two structural isomers resulting from condensation reactions of L-Trp with fatty acids derived from the bacterial cell membrane. They were identified as the indole C-2 anteiso (AAA 1 -343) and linear (AAA 2 -343) aliphatic chain isomers. Based on those findings, we utilized a combination of on-line HPLC-electrospray ionization mass spectrometry (LC-MS), as well as both precursor and product ion tandem mass spectrometry (MS/MS) to facilitate identification of a homologous family of condensation products related to AAA 1 -343 and AAA 2 -343. We structurally characterized eight new AAA 1 -XXX/AAA 2 -XXX contaminants, where XXX represents the integer molecular ions of all the related homologs, differing by aliphatic chain length and isomer configuration. The contaminants were derived from the following fatty acids of the bacterial cell membrane, 5-methylheptanoic acid (anteiso-C8:0) for AAA 1 -315; n-octanoic acid (n-C8:0) for AAA 2 -315; 6-methyloctanoic acid (anteiso-C9:0) for AAA 1 -329; n-nonanoic acid (n-C9:0) for AAA 2 -329; 10-methyldodecanoic acid (anteiso-C13:0) for AAA 1 -385; n-tridecanoic acid (n-C13:0) for AAA 2 -385; 11-methyltridecanoic acid (anteiso-C14:0) for AAA 1 -399; and n-tetradecanoic acid (n-C14:0) for AAA 2 -399. The concentration levels for these contaminants were estimated to be 0.1-7.9 μg / 500 mg of an individual SD L-Trp tablet or capsule The structural similarity of these homologs to case-related contaminants of Spanish Toxic Oil Syndrome (TOS) is discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

AAA Foundation for Traffic Safety

MedlinePlus

... of Top Deadly Mistakes Made by Teen Drivers -- AAA AAA: Road debris causes avoidable crashes, deaths Save the ... and 500 deaths! Foundation News Stay Tuned New AAA Foundation for Traffic Safety website coming Fall 2017 ...

Aryl acylamidase activity exhibited by butyrylcholinesterase is higher in chick than in horse, but much lower than in fetal calf serum.

PubMed

Weitnauer, E; Robitzki, A; Layer, P G

1998-10-02

Several side activities have been attributed to butyrylcholinesterase (BChE), including aryl acylamidase (AAA) activity, which is an amidase-like activity with unknown physiological function splitting the artificial substrate o-nitroacetanilide. For avians, extensive developmental data have pointed to neurogenetic functions of BChE, however, a possible AAA activity of BChE has not been studied. In this study, we first compare the relative levels of AAA exhibited by BChE in whole sera from chick, fetal calves (FCS) and horse. Remarkably, FCS exhibits a 400-fold higher ratio of AAA/BChE than horse and 80-fold higher than chick serum. We then show that an immunoisolated preparation of BChE from chicken serum presents significant activity for AAA. Both in sera and with the purified enzyme, the AAA activity is fully inhibited by anticholinesterase drugs, showing that AAA activity is exclusively conveyed by the BChE molecule. Noticeably, AAA inhibition even occurs at lower drug concentrations than that of BChE activity itself. Moreover, AAA is sensitive to serotonin. These data indicate that (1) AAA is a general feature of serum BChE of vertebrates including avians, (2) AAA is effectively inhibited by cholinergic and serotonergic agents, and (3) AAA may have a developmental role, since it is much pronounced in a serum from fetal animals. Functionally, deamination of neuropeptides, a link between cholinergic and serotonergic neurotransmitter systems, and roles in lipoprotein metabolism could be relevant.

Advanced endografting techniques: snorkels, chimneys, periscopes, fenestrations, and branched endografts.

PubMed

Kansagra, Kartik; Kang, Joseph; Taon, Matthew-Czar; Ganguli, Suvranu; Gandhi, Ripal; Vatakencherry, George; Lam, Cuong

2018-04-01

The anatomy of aortic aneurysms from the proximal neck to the access vessels may create technical challenges for endovascular repair. Upwards of 30% of patients with abdominal aortic aneurysms (AAA) have unsuitable proximal neck morphology for endovascular repair. Anatomies considered unsuitable for conventional infrarenal stent grafting include short or absent necks, angulated necks, conical necks, or large necks exceeding size availability for current stent grafts. A number of advanced endovascular techniques and devices have been developed to circumvent these challenges, each with unique advantages and disadvantages. These include snorkeling procedures such as chimneys, periscopes, and sandwich techniques; "homemade" or "back-table" fenestrated endografts as well as manufactured, customized fenestrated endografts; and more recently, physician modified branched devices. Furthermore, new devices in the pipeline under investigation, such as "off-the-shelf" fenestrated stent grafts, branched stent grafts, lower profile devices, and novel sealing designs, have the potential of solving many of the aforementioned problems. The treatment of aortic aneurysms continues to evolve, further expanding the population of patients that can be treated with an endovascular approach. As the technology grows so do the number of challenging aortic anatomies that endovascular specialists take on, further pushing the envelope in the arena of aortic repair.

Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

PubMed

An, Young Jun; Na, Jung-Hyun; Kim, Myung-Il; Cha, Sun-Shin

2015-10-01

Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.

Gender disparities in the utilization of laparoscopic groin hernia repair.

PubMed

Thiels, Cornelius A; Holst, Kimberly A; Ubl, Daniel S; McKenzie, Travis J; Zielinski, Martin D; Farley, David R; Habermann, Elizabeth B; Bingener, Juliane

2017-04-01

Clinical treatment guidelines have suggested that laparoscopic hernia repair should be the preferred approach in both men and women with bilateral or recurrent elective groin hernias. Anecdotal evidence suggests, however, that women are less likely to undergo a laparoscopic repair than men, and therefore, we aimed to delineate if these disparities persisted after controlling for patient factors and comorbidities. The American College of Surgeons National Surgical Quality Improvement Project data were abstracted for all elective groin hernia repairs between 2005 and 2014. Univariate analysis was used to compare rates of laparoscopic surgery between men and women. Multivariable analysis was performed, controlling for patient demographics, preoperative comorbidities, and year of surgery. Over the 10-y period, 141,490 patients underwent elective groin hernia repair, of which 13,325 were women (9.4%). The rate of general anesthesia utilization was high in both men (81.3%) and women (77.2%) with 75.1% of open repairs being performed under general anesthesia. Overall, 20.2% of women underwent laparoscopic repair compared with 28.0% of men (P < 0.01). Women tended to be older, had a lesser body mass index, and slightly greater American Anesthesia Association (all P < 0.05). On multivariable regression, women had decreased odds of undergoing a laparoscopic approach compared with men (odds ratio: 0.70; 95% confidence interval, 0.67-0.73, P < 0.01). In the elective setting, women were less likely to undergo laparoscopic repair of groin hernias than men. Although we are unable to ascertain underlying causes for these gender disparities, these data suggest that there remains a disparity in the management of groin hernias in women. Copyright © 2016 Elsevier Inc. All rights reserved.

Early Primary Care Provider Follow-up and Readmission After High-Risk Surgery

PubMed Central

Brooke, Benjamin S.; Stone, David H.; Cronenwett, Jack L.; Nolan, Brian; DeMartino, Randall R.; MacKenzie, Todd A.; Goodman, David C.; Goodney, Philip P.

2014-01-01

IMPORTANCE Follow-up with a primary care provider (PCP) in addition to the surgical team is routinely recommended to patients discharged after major surgery despite no clear evidence that it improves outcomes. OBJECTIVE To test whether PCP follow-up is associated with lower 30-day readmission rates after open thoracic aortic aneurysm (TAA) repair and ventral hernia repair (VHR), surgical procedures known to have a high and low risk of readmission, respectively. DESIGN, SETTING, AND PARTICIPANTS In a cohort of Medicare beneficiaries discharged to home after open TAA repair (n = 12 679) and VHR (n = 52 807) between 2003 to 2010, we compared 30-day readmission rates between patients seen and not seen by a PCP within 30 days of discharge and across tertiles of regional primary care use. We stratified our analysis by the presence of complications during the surgical (index) admission. MAIN OUTCOMES AND MEASURES Thirty-day readmission rate. RESULTS Overall, 2619 patients (20.6%) undergoing open TAA repair and 4927 patients (9.3%) undergoing VHR were readmitted within 30 days after surgery. Complications occurred in 4649 patients (36.6%) undergoing open TAA repair and 4528 patients (8.6%) undergoing VHR during their surgical admission. Early follow-up with a PCP significantly reduced the risk of readmission among open TAA patients who experienced perioperative complications, from 35.0% (without follow-up) to 20.4% (with follow-up) (P < .001). However, PCP follow-up made no significant difference in patients whose hospital course was uncomplicated (19.4% with follow-up vs 21.9% without follow-up; P = .31). In comparison, early follow-up with a PCP after VHR did not reduce the risk of readmission, regardless of complications. In adjusted regional analyses, undergoing open TAA repair in regions with high compared with low primary care use was associated with an 18% lower likelihood of 30-day readmission (odds ratio, 0.82; 95% CI, 0.71–0.96; P = .02), whereas no significant difference was found among patients after VHR. CONCLUSIONS AND RELEVANCE Follow-up with a PCP after high-risk surgery (eg, open TAA repair), especially among patients with complications, is associated with a lower risk of hospital readmission. Patients undergoing lower-risk surgery (eg, VHR) do not receive the same benefit from early PCP follow-up. Identifying high-risk surgical patients who will benefit from PCP integration during care transitions may offer a low-cost solution toward limiting readmissions. PMID:25074237

Early and mid-term clinical outcome in younger and elderly patients undergoing mitral valve repair with or without tricuspid valve repair.

PubMed

Renner, André; Zittermann, Armin; Aboud, Anas; Hakim-Meibodi, Kavous; Börgermann, Jochen; Gummert, Jan F

2015-01-01

Data regarding durability and midterm benefits of mitral valve (MV) repair in elderly patients are scarce. To evaluate the feasibility and safety of MV repair in elderly patients, we performed a retrospective data analysis. We compared clinical outcomes in younger patients (<75 years: n = 462) and older patients (≥75 years: n = 100) undergoing MV repair with or without tricuspid valve (TV) repair. The primary end-point was 30-day mortality. The preoperative risk profile (EuroSCORE, NYHA class, percentage pulmonary hypertension, percentage diabetes) was higher in older patients compared with younger patients. Nevertheless, operative complications such as low cardiac output syndrome, stroke, infections, the need of haemofiltration and IABP use did not differ significantly between the two groups. The thirty-day mortality rate was 0% in older patients and 1% in younger patients (P = 0.30). In the subgroup of patients with double valve repair, the 30-day mortality rate in older patients (n = 28) and younger patients (n = 46) was 0 and 4%, respectively (P = 0.27). In older and younger patients, the 6-month mortality rate was 4 and 2%, respectively (P = 0.16), and the 1-year mortality rate was 10 and 3%, respectively (P = 0.001). The propensity score-adjusted odds ratio of 1-year mortality with the group of younger patients as a reference was 2.04 (95% confidence interval: 0.77-5.40; P = 0.15) for older patients. Freedom from 1-year reoperation did not differ significantly between age groups. Data demonstrate excellent postoperative mortality rates in older patients undergoing MV repair with or without TV repair. Consequently, even in older patients with numerous comorbidities, MV repair should be considered a suitable surgical method. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

PubMed

Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

2011-07-01

ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms.

PubMed

Khosla, S; Morris, D R; Moxon, J V; Walker, P J; Gasser, T C; Golledge, J

2014-10-01

Abdominal aortic aneurysm (AAA) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA. The MEDLINE database was searched on 25 May 2013. Case-control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. Nine studies assessing 348 individuals were identified and used in the meta-analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured AAAs showed that PWS was significantly greater in the symptomatic/ ruptured AAAs compared with the asymptomatic intact AAAs (SMD 0·95, 95 per cent confidence interval 0·71 to 1·18; P < 0·001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0·68, 0·39 to 0·96; P < 0·001). Minimal heterogeneity between studies was noted (I(2)  = 0 per cent). This study suggests that PWS is greater in symptomatic or ruptured AAA than in asymptomatic intact AAA. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

PubMed

Htun, Nay Min; Peter, Karlheinz

2014-10-01

Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer

PubMed Central

Banerjee, Rajat; Russo, Nickole; Liu, Min; Basrur, Venkatesha; Bellile, Emily; Palanisamy, Nallasivam; Scanlon, Christina S.; van Tubergen, Elizabeth; Inglehart, Ronald C.; Metwally, Tarek; Mani, Ram-Shankar; Yocum, Anastasia; Nyati, Mukesh K.; Castilho, Rogerio M.; Varambally, Sooryanarayana; Chinnaiyan, Arul M.

2014-01-01

Head and neck cancer (SCCHN) is a common, aggressive, treatment-resistant cancer with a high recurrence rate and mortality, but the mechanism of treatment-resistance remains unclear. Here we describe a mechanism where the AAA-ATPase TRIP13 promotes treatment-resistance. Overexpression of TRIP13 in non-malignant cells results in malignant transformation. High expression of TRIP13 in SCCHN leads to aggressive, treatment-resistant tumors and enhanced repair of DNA damage. Using mass spectrometry, we identify DNA-PKcs complex proteins that mediate non homologous end joining (NHEJ), as TRIP13 binding partners. Using repair-deficient reporter systems, we show that TRIP13 promotes NHEJ, even when homologous recombination is intact. Importantly, overexpression of TRIP13 sensitizes SCCHN to an inhibitor of DNA-PKcs. Thus, this study defines a new mechanism of treatment resistance in SCCHN and underscores the importance of targeting NHEJ to overcome treatment failure in SCCHN and potentially in other cancers that overexpress TRIP13. PMID:25078033

Comparison of implant cost and surgical time in arthroscopic transosseous and transosseous equivalent rotator cuff repair.

PubMed

Black, Eric M; Austin, Luke S; Narzikul, Alexa; Seidl, Adam J; Martens, Kelly; Lazarus, Mark D

2016-09-01

We investigated the cost savings associated with arthroscopic transosseous (anchorless) double-row rotator cuff repair compared with double-row anchored (transosseous-equivalent [TOE]) repair. All patients undergoing double-row arthroscopic rotator cuff repair from 2009 to 2012 by a single surgeon were eligible for inclusion. The study included 2 consecutive series of patients undergoing anchorless or TOE repair. Excluded from the study were revision repairs, subscapularis repairs, patients with poor tendon quality or excursion requiring medialized repair, and partial repairs. Rotator cuff implant costs (paid by the institution) and surgical times were compared between the 2 groups, controlling for rotator cuff tear size and additional procedures performed. The study included 344 patients, 178 with TOE repairs and 166 with anchorless repairs. Average implant cost for TOE repairs was $1014.10 ($813.00 for small, $946.67 for medium, $1104.56 for large, and $1507.29 for massive tears). This was significantly more expensive compared with anchorless repairs, which averaged $678.05 ($659.75 for small, $671.39 for medium, $695.55 for large, and $716.00 for massive tears). Average total operative time in TOE and anchorless groups was not significantly different (99 vs. 98 minutes). There was larger (although not statistically significant) case time variation in the TOE group. Compared with TOE repair, anchorless rotator cuff repair provides substantial implant-related cost savings, with no significant differences in surgical time for medium and large rotator cuff tears. Case time for TOE repair varied more with extremes in tear size. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease

PubMed Central

Moran, Corey S.; Schreurs, Charlotte; Lindeman, Jan H. N.; Walker, Philip J.; Nataatmadja, Maria; West, Malcolm; Holdt, Lesca M.; Hinterseher, Irene; Pilarsky, Christian; Golledge, Jonathan

2015-01-01

Abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) represent common causes of morbidity and mortality in elderly populations which were previously believed to have common aetiologies. The aim of this study was to assess the gene expression in human AAA and AOD. We performed microarrays using aortic specimen obtained from 20 patients with small AAAs (≤ 55mm), 29 patients with large AAAs (> 55mm), 9 AOD patients, and 10 control aortic specimens obtained from organ donors. Some differentially expressed genes were validated by quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014 differentially expressed genes in small and large AAAs, respectively. Immune-related pathways including cytokine-cytokine receptor interaction and T-cell-receptor signalling were upregulated in both small and large AAAs. Examples of validated genes included CTLA4 (2.01-fold upregulated in small AAA, P = 0.002), NKTR (2.37-and 2.66-fold upregulated in small and large AAA with P = 0.041 and P = 0.015, respectively), and CD8A (2.57-fold upregulated in large AAA, P = 0.004). 1,765 differentially expressed genes were identified in AOD. Pathways upregulated in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In conclusion, the AAA and AOD transcriptomes were very different suggesting that AAA and AOD have distinct pathogenic mechanisms. PMID:25944698

Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein*

PubMed Central

Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

2013-01-01

The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function. PMID:23979136

Structural insights into the unusually strong ATPase activity of the AAA domain of the Caenorhabditis elegans fidgetin-like 1 (FIGL-1) protein.

PubMed

Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

2013-10-11

The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function.

Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine

PubMed Central

Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

2015-01-01

Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA–spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA–spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients. PMID:26158885

Mitochondrial AAA proteases--towards a molecular understanding of membrane-bound proteolytic machines.

PubMed

Gerdes, Florian; Tatsuta, Takashi; Langer, Thomas

2012-01-01

Mitochondrial AAA proteases play an important role in the maintenance of mitochondrial proteostasis. They regulate and promote biogenesis of mitochondrial proteins by acting as processing enzymes and ensuring the selective turnover of misfolded proteins. Impairment of AAA proteases causes pleiotropic defects in various organisms including neurodegeneration in humans. AAA proteases comprise ring-like hexameric complexes in the mitochondrial inner membrane and are functionally conserved from yeast to man, but variations are evident in the subunit composition of orthologous enzymes. Recent structural and biochemical studies revealed how AAA proteases degrade their substrates in an ATP dependent manner. Intersubunit coordination of the ATP hydrolysis leads to an ordered ATP hydrolysis within the AAA ring, which ensures efficient substrate dislocation from the membrane and translocation to the proteolytic chamber. In this review, we summarize recent findings on the molecular mechanisms underlying the versatile functions of mitochondrial AAA proteases and their relevance to those of the other AAA+ machines. Copyright © 2011 Elsevier B.V. All rights reserved.

Science, Society, and Social Networking

NASA Astrophysics Data System (ADS)

White, K. S.; Lohwater, T.

2009-12-01

The increased use of social networking is changing the way that scientific societies interact with their members and others. The American Association for the Advancement of Science (AAAS) uses a variety of online networks to engage its members and the broader scientific community. AAAS members and non-members can interact with AAAS staff and each other on AAAS sites on Facebook, YouTube, and Twitter, as well as blogs and forums on the AAAS website (www.aaas.org). These tools allow scientists to more readily become engaged in policy by providing information on current science policy topics as well as methods of involvement. For example, members and the public can comment on policy-relevant stories from Science magazine’s ScienceInsider blog, download a weekly policy podcast, receive a weekly email update of policy issues affecting the scientific community, or watch a congressional hearing from their computer. AAAS resource websites and outreach programs, including Communicating Science (www.aaas.org/communicatingscience), Working with Congress (www.aaas.org/spp/cstc/) and Science Careers (http://sciencecareers.sciencemag.org) also provide tools for scientists to become more personally engaged in communicating their findings and involved in the policy process.

APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

PubMed

Zarrouk, Moncef; Keshavarz, Kave; Lindblad, Bengt; Gottsäter, Anders

2013-11-01

To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] μg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 μg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

AAA-ATPases in Protein Degradation

PubMed Central

Yedidi, Ravikiran S.; Wendler, Petra; Enenkel, Cordula

2017-01-01

Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea. PMID:28676851

AAA-ATPases in Protein Degradation.

PubMed

Yedidi, Ravikiran S; Wendler, Petra; Enenkel, Cordula

2017-01-01

Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea.

Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate

PubMed Central

Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E

2012-01-01

Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA. PMID:23173106

Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate.

PubMed

Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E

2012-01-01

Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA.

Two C-C Family Chemokines, Eotaxin and RANTES, Are Novel Independent Plasma Biomarkers for Abdominal Aortic Aneurysm.

PubMed

Jones, Gregory T; Phillips, L Victoria; Williams, Michael J A; van Rij, Andre M; Kabir, Tasnuva D

2016-04-28

Inflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm (AAA). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of AAA. Tissue profiles of 27 inflammatory cytokine were examined in AAA (n=14) and nonaneurysmal (n=14) aortic tissues. Three cytokines, regulated upon activation normally T-cell expressed and secreted (RANTES), eotaxin, and macrophage inflammatory protein 1 beta (MIP-1b), had increased expression in AAA, particularly within the adventitial layer of the aortic wall. Basic fibroblast growth factor (bFGF) had reduced expression in all layers of the AAA wall. Examination of the circulating plasma profiles of AAA (n=442) and AAA-free controls (n=970) suggested a (risk factor adjusted) AAA-association with eotaxin, RANTES, and high sensitivity C-reactive protein (hsCRP). A plasma inflammatory cytokine score, calculated using these three markers, suggested a strong risk association with AAA (odds ratio, 4.8; 95% CI, 3.5-6.7; P<0.0001), independent of age, sex, history of ischemic heart disease, and smoking. Contrary to reports suggesting a distinct T helper 2-associated inflammatory profile in AAA, this current study suggests a more-generalized pattern of inflammation, albeit with some potentially distinct features, including elevated plasma eotaxin and decreased plasma RANTES. In combination with hsCRP, these markers may have potential utility as AAA biomarkers. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Time trends in hospital admissions and mortality due to abdominal aortic aneurysms in France, 2002-2013.

PubMed

Robert, M; Juillière, Y; Gabet, A; Kownator, S; Olié, V

2017-05-01

Abdominal aortic aneurysms (AAA) are serious disease with a high fatality rate but recent epidemiologic data showed a decrease of AAA mortality. Our objective was to estimate, in France, the hospitalization, inhospital mortality and mortality rates due to AAA and to analyze their trends over time. Hospitalization data were extracted from the hospital discharge summaries in the national database between 2002 and 2013. The analysis covered all patients hospitalized for AAA as a principal diagnosis. During the same period, all death certificates mentioning AAA as an initial cause of death were included in the study. Crude and standardized rates were calculated according to age and sex. Poisson regression was used to analyze the average annual percent change. In 2013, there were 8853 patients hospitalized for AAA in France (7986 unruptured and 867 ruptured). Between 2002 and 2013, the rate of patients hospitalized for unruptured AAA decreased slightly in men (-5.0%) but increased in women (+5.2%). By contrast, the rate of patients hospitalized for ruptured AAA has decreased by >20% in men and women. The proportion of endovascular treatment of unruptured AAA rose from <10% in 2005 to 35% in women and 40% in men in 2013. In 2013, 939 deaths from AAA were recorded. Mortality for this disease declined significantly from 2002 to 2013 in men and women. The unfavorable epidemiological trends in women and important evolution of the management of AAA call for an epidemiological surveillance of this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Umbilical hernia repair in pregnant patients: review of the American College of Surgeons National Surgical Quality Improvement Program.

PubMed

Haskins, I N; Rosen, M J; Prabhu, A S; Amdur, R L; Rosenblatt, S; Brody, F; Krpata, D M

2017-10-01

Umbilical hernias present commonly during pregnancy secondary to increased intra-abdominal pressure. As a result, umbilical hernia incarceration or strangulation may affect pregnant females. The purpose of this study is to detail the operative management and 30-day outcomes of umbilical hernias in pregnant patients using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). All female patients undergoing umbilical hernia repair during pregnancy were identified within the ACS-NSQIP. Preoperative patient variables, intraoperative variables, and 30-day patient morbidity and mortality outcomes were investigated using a variety of statistical tests. A total of 126 pregnant patients underwent umbilical hernia repair from 2005 to 2014; 73 (58%) had incarceration or strangulation at the time of surgical intervention. The majority of patients (95%) underwent open umbilical hernia repair. Superficial surgical site infection was the most common morbidity in patients undergoing open umbilical hernia repair. Based on review of the ACS-NSQIP database, the incidence of umbilical hernia repair during pregnancy is very low; however, the majority of patients required repair for incarceration of strangulation. When symptoms develop, these hernias can be repaired with minimal 30-day morbidity to the mother. Additional studies are needed to determine the long-term recurrence rate of umbilical hernia repairs performed in pregnant patients and the effects of surgical intervention and approach on the fetus.

Immediate costs of mini-open versus arthroscopic rotator cuff repair in an Asian population.

PubMed

Hui, Yik Jing; Teo, Alex Quok An; Sharma, Siddharth; Tan, Bryan Hsi Ming; Kumar, V Prem

2017-01-01

While there has been increasing interest in minimally invasive surgery, the expenses incurred by patients undergoing this form of surgery have not been comprehensively studied. The authors compared the costs borne by patients undergoing arthroscopic rotator cuff repair with the standard mini-open repair at a tertiary hospital in an Asian population. This was a retrospective cohort study. The authors studied the inpatient hospital bills of patients following rotator cuff tear repair between January 2010 and October 2014 via the hospital electronic medical records system. 148 patients had arthroscopic repair and 78 had mini-open repair. The cost of implants, consumables, and the total cost of hospitalization were analyzed. Operative times and length of stay for both procedures were also studied. Constant scores and American Shoulder Elbow Scores (ASES) were recorded preoperatively and at 1 year postoperatively. Three fellowship-trained surgeons performed arthroscopic repairs and one performed the mini-open repair. The cost of implants and consumables was significantly higher with arthroscopic repair. The duration of surgery was also significantly longer with that technique. There was no difference in length of stay between the two techniques. There was also no difference in Constant scores or ASES scores, both preoperatively and at 1 year postoperatively. The immediate costs of mini-open repair of rotator cuff tears are significantly less than that of arthroscopic repair. Most of the difference arises from the cost of implants and consumables. Equivalent functional outcomes from both techniques suggest that mini-open repair may be more cost-effective.

Sports Hernia Treatment

PubMed Central

Economopoulos, Kostas J.; Milewski, Matthew D.; Hanks, John B.; Hart, Joseph M.; Diduch, David R.

2013-01-01

Background: The minimal repair technique for sports hernias repairs only the weak area of the posterior abdominal wall along with decompressing the genitofemoral nerve. This technique has been shown to return athletes to competition rapidly. This study compares the clinical outcomes of the minimal repair technique with the traditional modified Bassini repair. Hypothesis: Athletes undergoing the minimal repair technique for a sports hernia would return to play more rapidly compared with athletes undergoing the traditional modified Bassini repair. Methods: A retrospective study of 28 patients who underwent sports hernia repair at the authors’ institution was performed. Fourteen patients underwent the modified Bassini repair, and a second group of 14 patients underwent the minimal repair technique. The 2 groups were compared with respect to time to return to sport, return to original level of competition, and clinical outcomes. Results: Patients in the minimal repair group returned to sports at a median of 5.6 weeks (range, 4-8 weeks), which was significantly faster compared with the modified Bassini repair group, with a median return of 25.8 weeks (range, 4-112 weeks; P = 0.002). Thirteen of 14 patients in the minimal repair group returned to sports at their previous level, while 9 of 14 patients in the Bassini group were able to return to their previous level of sport (P = 0.01). Two patients in each group had recurrent groin pain. One patient in the minimal repair group underwent revision hernia surgery for recurrent pain, while 1 patient in the Bassini group underwent hip arthroscopy for symptomatic hip pain. Conclusion: The minimal repair technique allows athletes with sports hernias to return to play faster than patients treated with the modified Bassini. PMID:24427419

Molecularly Defined Nanostructures Based on a Novel AAA-DDD Triple Hydrogen-Bonding Motif.

PubMed

Papmeyer, Marcus; Vuilleumier, Clément A; Pavan, Giovanni M; Zhurov, Konstantin O; Severin, Kay

2016-01-26

A facile and flexible method for the synthesis of a new AAA-DDD triple hydrogen-bonding motif is described. Polytopic supramolecular building blocks with precisely oriented AAA and DDD groups are thus accessible in few steps. These building blocks were used for the assembly of large macrocycles featuring four AAA-DDD interactions and a macrobicyclic complex with a total of six AAA-DDD interactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.

PubMed

Smallwood, L; Warrington, N; Allcock, R; van Bockxmeer, F; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

2009-08-01

To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (AAA). Cases and controls were recruited from a trial of screening for AAAs. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with AAA (n=678) and in controls (n=659) was examined using multivariate analyses. The association with AAA expansion (n=638) was also assessed. In multivariate analyses with adjustments for multiple testing, no association between either SNP and AAA presence or expansion was detected. MMP2 -1360C>T and +649C>T variants are not risk factors for AAA.

Molecular Mechanisms of Soft Tissue Regeneration and Bone Formation in Mice: Implication in Fracture Repair and Wound Healing in Humans

DTIC Science & Technology

2008-04-01

designed in this study: Mg4718-F: 5’-GCA TTT TGA TCC CTT ATA ATA CA-3’ Mg4718-R: 5’- GTG GAA GAC CCT TGA ATG G-3’ Mg4723-F: 5’-GCA TAG CCA ACA AAA...GAA ATC TAA TG-3’ Mg4723-R: 5’-GCA GTG TAG CTC AGT GGT AGA TCA C-3’ After each cross, the progenies were genotyped as described above. We have also...mutant F2 mice. PPD is a likelihood statistic that gives rise to the 95% confidence intervals, which is indicated by gray horizontal bars. cM

The accuracy of combined physical examination and ultrasonography for the detection of abdominal aorta aneurysm.

PubMed

Cârstea, Doina; Streba, Letiţia Adela Maria; Glodeanu, Adina; Cârstea, A P; Vancu, Mihaela; Ninulescu, Ana-Maria

2008-01-01

Atherosclerosis is the most frequent cause in the appearance of an abdominal aorta aneurysm (AAA) and plays an important role in his development. Most AAA does not cause any symptoms, especially when talking about elderly patients, however, many of those aneurysms can be detected during physical examination. Their detection is very important because the natural evolution and the major reason in treating AAA is their tendency to rupture. We present the case of an adult man with a complex clinical pathology, but not related to the AAA. The diagnosis of the AAA has been suspicion through palpation, and the abdominal ultrasound exam confirmed it. This case is particular interesting, as the AAA requires surgical intervention, while patient's health status was poor. An essential issue is establishing the importance of the AAA screening, when there are no symptoms present. For now, there are not satisfactory studies to be used as a guide.

Computed tomography angiography-fluoroscopy image fusion allows visceral vessel cannulation without angiography during fenestrated endovascular aneurysm repair.

PubMed

Schwein, Adeline; Chinnadurai, Ponraj; Behler, Greg; Lumsden, Alan B; Bismuth, Jean; Bechara, Carlos F

2018-07-01

Fenestrated endovascular aneurysm repair (FEVAR) is an evolving technique to treat juxtarenal abdominal aortic aneurysms (AAAs). Catheterization of visceral and renal vessels after the deployment of the fenestrated main body device is often challenging, usually requiring additional fluoroscopy and multiple digital subtraction angiograms. The aim of this study was to assess the clinical utility and accuracy of a computed tomography angiography (CTA)-fluoroscopy image fusion technique in guiding visceral vessel cannulation during FEVAR. Between August 2014 and September 2016, all consecutive patients who underwent FEVAR at our institution using image fusion guidance were included. Preoperative CTA images were fused with intraoperative fluoroscopy after coregistering with non-contrast-enhanced cone beam computed tomography (syngo 3D3D image fusion; Siemens Healthcare, Forchheim, Germany). The ostia of the visceral vessels were electronically marked on CTA images (syngo iGuide Toolbox) and overlaid on live fluoroscopy to guide vessel cannulation after fenestrated device deployment. Clinical utility of image fusion was evaluated by assessing the number of dedicated angiograms required for each visceral or renal vessel cannulation and the use of optimized C-arm angulation. Accuracy of image fusion was evaluated from video recordings by three raters using a binary qualitative assessment scale. A total of 26 patients (17 men; mean age, 73.8 years) underwent FEVAR during the study period for juxtarenal AAA (17), pararenal AAA (6), and thoracoabdominal aortic aneurysm (3). Video recordings of fluoroscopy from 19 cases were available for review and assessment. A total of 46 vessels were cannulated; 38 of 46 (83%) of these vessels were cannulated without angiography but based only on image fusion guidance: 9 of 11 superior mesenteric artery cannulations and 29 of 35 renal artery cannulations. Binary qualitative assessment showed that 90% (36/40) of the virtual ostia overlaid on live fluoroscopy were accurate. Optimized C-arm angulations were achieved in 35% of vessel cannulations (0/9 for superior mesenteric artery cannulation, 12/25 for renal arteries). Preoperative CTA-fluoroscopy image fusion guidance during FEVAR is a valuable and accurate tool that allows visceral and renal vessel cannulation without the need of dedicated angiograms, thus avoiding additional injection of contrast material and radiation exposure. Further refinements, such as accounting for device-induced aortic deformation and automating the image fusion workflow, will bolster this technology toward optimal routine clinical use. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Aortic valve insufficiency in the teenager and young adult: the role of prosthetic valve replacement.

PubMed

Bradley, Scott M

2013-10-01

The contents of this article were presented in the session "Aortic insufficiency in the teenager" at the congenital parallel symposium of the 2013 Society of Thoracic Surgeons (STS) annual meeting. The accompanying articles detail the approaches of aortic valve repair and the Ross procedure.(1,2) The current article focuses on prosthetic valve replacement. For many young patients requiring aortic valve surgery, either aortic valve repair or a Ross procedure provides a good option. The advantages include avoidance of anticoagulation and potential for growth. In other patients, a prosthetic valve is an appropriate alternative. This article discusses the current state of knowledge regarding mechanical and bioprosthetic valve prostheses and their specific advantages relative to valve repair or a Ross procedure. In current practice, young patients requiring aortic valve surgery frequently undergo valve replacement with a prosthetic valve. In STS adult cardiac database, among patients ≤30 years of age undergoing aortic valve surgery, 34% had placement of a mechanical valve, 51% had placement of a bioprosthetic valve, 9% had aortic valve repair, and 2% had a Ross procedure. In the STS congenital database, among patients 12 to 30 years of age undergoing aortic valve surgery, 21% had placement of a mechanical valve, 18% had placement of a bioprosthetic valve, 30% had aortic valve repair, and 24% had a Ross procedure. In the future, the balance among these options may be altered by design improvements in prosthetic valves, alternatives to warfarin, the development of new patch materials for valve repair, and techniques to avoid Ross autograft failure.

Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

PubMed Central

Burillo, Elena; Jorge, Inmaculada; Martínez-López, Diego; Camafeita, Emilio; Blanco-Colio, Luis Miguel; Trevisan-Herraz, Marco; Ezkurdia, Iakes; Egido, Jesús; Michel, Jean-Baptiste; Meilhac, Olivier; Vázquez, Jesús; Martin-Ventura, Jose Luis

2016-01-01

High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA. PMID:27934969

High aryl acylamidase activity associated with cobra venom acetylcholinesterase: biological significance.

PubMed

Rajesh, Ramanna V; Layer, Paul G; Boopathy, Rathanam

2009-01-01

Investigation of the non-classical functions of cholinesterases (ChEs) has been the subject of interest in the past three decades. One of which is aryl acylamidase (AAA) activity associated with ChEs, but characterized in in vitro, as an enzyme, splitting the artificial substrate o-nitroacetanilide with unknown physiological function. In the present study, we have compared levels of AAA activity of AChE from different sources like goat brain, electric eel organ and from venoms of different snakes. Remarkably cobra venom showed the highest AAA activity and also high AAA/AChE ratio. Both serotonergenic and cholinergic inhibitors inhibited the cobra venom AAA activity in a concentration dependent manner, which also underlines the association of AAA with AChE of cobra venom. The study becomes interesting because of i) the cobra venom AChE exists in monomeric globular forms; ii) in Alzheimer's disease too the most abundant forms of cholinesterases are monomeric globular forms, thought to be involved in the pathogenesis of Alzheimer's disease; iii) the effect of Alzheimer's disease drugs on the AAA activity of cobra venom, indicated that AAA activity of cobra venom was more sensitive than AChE and iv) Huperzine and Tacrine showed more pronounced effect on AAA. Thus, this study elucidates the high AAA associated with cobra venom AChE may serve as one of the prominent activity to test the pharmacological effect of AD drugs, as other sources were found to have lower activity.

TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.

PubMed

Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad

2017-11-01

Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.

Genetic analysis on HLA loci in Japanese patients with abdominal aortic aneurysm.

PubMed

Sugimoto, T; Sada, M; Miyamoto, T; Yao, H

2003-08-01

autoimmunity has been proposed as one of the pathogenesis of abdominal aortic aneurysm (AAA). There is also a likelihood that when aorto-iliac occlusive disease (AIOD) coexists with AAA, some other occlusive atherosclerotic diseases, such as ischemic heart disease and cerebrovascular disease, may develop, leading to a very poor long-term prognosis. Previous studies using serological HLA typing showed that HLA-DR15 was a risk factor for AAA. In this study, we performed HLA-DNA typing by PCR to clarify the relationship between AAA and HLA genotypes in Japanese patients with AAA. In addition, we analyzed whether HLA genotypes are involved in the pathogenesis of AIOD. we examined 78 HLA genotypes of class I (HLA-A and -B) and class II (HLA-DR) and found that 60.4 and 30.4% of 49 AAA patients had HLA-A2 and HLA-B61, respectively. These frequencies were significantly higher than those in control individuals (HLA-A2, p < 0.05; HLA-B61, p < 0.005). We also found that 55.6% of nine AAA patients with AIOD had both HLA-B52 and HLA-DR B1*1502. In contrast, only 10.0% each of 40 AAA patients without AIOD showed HLA-B53 or HLA-DR B1*1502. this study showed that HLA A-2 and HLA B-61, but not HLA DR-15, were important genetic risk factors for the development of AAA among the Japanese population. We also found high frequencies of HLA-B52 and HLA-DR B1*1502 in the AAA patients with AIOD than in those without, although this must be confirmed using a larger number of AAA patients with AIOD.

Inhibition of plasmin-mediated TAFI activation may affect development but not progression of abdominal aortic aneurysms

PubMed Central

Bridge, Katherine; Revill, Charlotte; Macrae, Fraser; Bailey, Marc; Yuldasheva, Nadira; Wheatcroft, Stephen; Butlin, Roger; Foster, Richard; Scott, D. Julian; Gils, Ann; Ariёns, Robert

2017-01-01

Objective Thrombin-activatable fibrinolysis inhibitor (TAFI) reduces the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Studies in TAFI-deficient mice have implicated a potential role for TAFI in Abdominal Aortic Aneurysm (AAA) disease. The role of TAFI inhibition on AAA formation in adult ApoE-/- mice is unknown. The aim of this paper was to investigate the effects of TAFI inhibition on AAA development and progression. Methods Using the Angiotensin II model of AAA, male ApoE-/- mice were infused with Angiotensin II 750ng/kg/min with or without a monoclonal antibody inhibitor of plasmin-mediated activation of TAFI, MA-TCK26D6, or a competitive small molecule inhibitor of TAFI, UK-396082. Results Inhibition of TAFI in the Angiotensin II model resulted in a decrease in the mortality associated with AAA rupture (from 40.0% to 16.6% with MA-TCK26D6 (log-rank Mantel Cox test p = 0.16), and 8.3% with UK-396082 (log-rank Mantel Cox test p = 0.05)). Inhibition of plasmin-mediated TAFI activation reduced the incidence of AAA from 52.4% to 30.0%. However, late treatment with MA-TCK26D6 once AAA were already established had no effect on the progression of AAA in this model. Conclusions The formation of intra-mural thrombus is responsible for the dissection and early rupture in the angiotensin II model of AAA, and this process can be prevented through inhibition of TAFI. Late treatment with a TAFI inhibitor does not prevent AAA progression. These data may indicate a role for inhibition of plasmin-mediated TAFI activation in the early stages of AAA development, but not in its progression. PMID:28472123

Combination of endovascular graft exclusion and drug therapy in AAA with hypertension or hyperglycemia.

PubMed

Wang, Dile; Qu, Bihui; He, Tao

2017-08-01

The objective of the present study was to evaluate the efficacy of combination of endovascular graft exclusion and drugs for hypertension/hyperglycemia for the treatment of abdominal aortic aneurysm (AAA). We analyzed 156 patients with AAA. Eighty-four patients were hypertensive and 72 were hyperglycemic. After endovascular graft exclusion, hypertensive patients were divided into four groups and treated with cyclopenthiazide, reserpine, propranolol, and placebo respectively. Hyperglycemic patients were divided into three groups and treated with metformin, insulin, and placebo respectively. Body temperature and peripheral blood leukocytes were measured at day 1, 2, 7, and 14 after endovascular graft exclusion. Size of AAAs, blood pressure, and blood sugar were measured again after 1 year. In hypertensive patients, the size of AAAs reduced after endovascular graft exclusion, while the combined treatments with cyclopenthiazide, reserpine, or propranolol helped to reduce blood pressure (blood pressure decrease <10 mmHg (18/21), <10 mmHg (12/21), <10 mmHg (8/21), and <10 mmHg (10/21) in the control group, cyclopenthiazide group, reserpine group, and propranolol group, respectively. AAA size decreased in the control group (P<0.001) and in the other three groups (P<0.0001). Similar results were obtained in hyperglycemic patients. The size of AAAs reduced after endovascular graft exclusion. Combined treatment with Metformin and Insulin reduced blood sugar (control, blood sugar >7.8 mmol/L (22/24), AAA size (P<0.001); metformin, blood sugar >7.8 mmol/L (14/24), AAA size (P<0.0001); insulin, blood sugar >7.8 mmol/L (11/24), AAA size (P<0.0001). Combination of endovascular graft exclusion with medicine is more effective than the former treatment alone for AAA therapy.

NASA Airborne Astronomy Ambassadors (AAA) Professional Development and NASA Connections

NASA Astrophysics Data System (ADS)

Backman, D. E.; Clark, C.; Harman, P. K.

2017-12-01

NASA's Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content learning, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong's B703 science research aircraft facility in Palmdale, California, and (3) ongoing opportunities for connection with NASA astrophysics and planetary science Subject Matter Experts (SMEs). AAA implementation in 2016-18 involves partnerships between the SETI Institute and seven school districts in northern and southern California. AAAs in the current cohort were selected by the school districts based on criteria developed by AAA program staff working with WestEd evaluation consultants. The selected teachers were then randomly assigned by WestEd to a Group A or B to support controlled testing of student learning. Group A completed their PD during January - August 2017, then participated in NASA SOFIA science flights during fall 2017. Group B will act as a control during the 2017-18 school year, then will complete their professional development and SOFIA flights during 2018. A two-week AAA electromagnetic spectrum and multi-wavelength astronomy curriculum aligned with the Science Framework for California Public Schools and Next Generation Science Standards was developed by program staff for classroom delivery. The curriculum (as well as the AAA's pre-flight PD) capitalizes on NASA content by using "science snapshot" case studies regarding astronomy research conducted by SOFIA. AAAs also interact with NASA SMEs during flight weeks and will translate that interaction into classroom content. The AAA program will make controlled measurements of student gains in standards-based learning plus changes in student attitudes towards STEM, and observe & record the AAAs' implementation of curricular changes. Funded by NASA: NNX16AC51

Characterization of the Modular Design of the Autolysin/Adhesin Aaa from Staphylococcus Aureus

PubMed Central

Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

2012-01-01

Background Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Methodology/Principal Findings Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. Conclusions/Significance We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for Aaa in the pathogenesis of S. aureus infections. PMID:22768285

Characterization of the modular design of the autolysin/adhesin Aaa from Staphylococcus aureus.

PubMed

Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

2012-01-01

Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for Aaa in the pathogenesis of S. aureus infections.

The interleukin-10-1082 'A' allele and abdominal aortic aneurysms.

PubMed

Bown, Matthew J; Lloyd, Geraint M; Sandford, Rebecca M; Thompson, John R; London, Nicholas J M; Samani, Nilesh J; Sayers, Robert D

2007-10-01

Abdominal aortic aneurysms (AAA) are caused by inflammatory processes in the wall of the aorta resulting in degradation of structural proteins. This inflammatory process is mediated, in part, by cytokines, and interleukin-10 (IL-10) is a predominantly anti-inflammatory cytokine. A single nucleotide polymorphism in the promoter region of the IL-10 gene that affects transcription has been associated with AAA in a small study. The aim of this study was to determine whether this polymorphism is associated with AAA and also examine its effect on the growth of small AAA. A case control study was performed. A total of 389 patients with AAA and 404 healthy controls were recruited. IL-10-1082 polymorphisms were determined by polymerase chain reaction-based methods. In the case of patients with small AAA (<5.5 cm), serial size measurements were recorded to determine mean growth rate. There was a statistically significant difference both in allele and genotype frequencies between the case and control groups with the IL-10-1082 'A' allele being more common in the AAA group (P = .006). In the AAA group, genotype frequencies were as follows: GG 84, GA 201, and AA 104. In the control group, the genotype frequencies were GG 118, GA 205, and AA 81. The odds ratio for the 'A' allele as a risk factor for AAA was 1.50 (95% confidence interval 1.09 to 2.07). Regression modeling revealed that the IL-10-1082 genotype was, however, not independently associated with AAA if age, tobacco use, hypertension, and history of coronary or peripheral artery disease was taken into account. There was a trend towards lower plasma IL-10 level in IL-10 AA carriers, but the IL-10 'A' allele did not have any discernible effect on the growth of small AAA. This study demonstrates that the IL-10-1082 'A' allele is associated with AAA, although this association is likely to be secondary to an association between IL-10-1082 genotype and other markers of cardiovascular disease rather than AAA per se.

Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm.

PubMed

Miyagawa, Kotaro; Ogata, Takehiro; Ueyama, Tomomi; Kasahara, Takeru; Nakanishi, Naohiko; Naito, Daisuke; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Nishi, Masahiro; Kimura, Taizo; Yamada, Hiroyuki; Aoki, Hiroki; Matoba, Satoaki

2017-06-03

Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC -/- ) mice subjected to periaortic application of CaCl 2 developed AAAs. Six weeks after CaCl 2 treatment, internal and external aortic diameters were significantly increased in MURC -/- AAAs compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica media of MURC -/- AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC -/- AAAs compared with WT AAAs at 5 days after CaCl 2 treatment. At 6 weeks after CaCl 2 treatment, MURC -/- AAAs exhibited attenuated JNK activity compared with WT AAAs. There was no difference in the activity of MMP-2 or -9 between saline and CaCl 2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFα-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC -/- , apolipoprotein E -/- (ApoE -/- ), and MURC/Cavin-4 and ApoE double-knockout (MURC -/- ApoE -/- ) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE -/- and MURC -/- ApoE -/- mice infused for 4 weeks with Ang II, AAAs were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC -/- ApoE -/- mice compared with Ang II-infused ApoE -/- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates AAA progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA progression. Copyright © 2017 Elsevier Inc. All rights reserved.

The Antiaircraft Journal. Volume 94, Number 6, November-December 1951

DTIC Science & Technology

1951-12-01

authorized by the Visiting Forces Act. Getting their heads together, the Yanks and Tommies have discovered each other to be pretty regular fellows...Francis A., to 3Sth AAA Brig, Ft Meade, Md. McDaniel, Otto L., to Hq Fourth Army, Ft Sam Houston, Tex. Pape, Robin B., to SOth AAA Gp, Ft Totten , NY...to 71 Sth AAA Gun Bn, Ft Totten , NJ. Kee, Pat M., to 209th AAA Gp, Indiantown Gap, Pa. Kennaman, Jack R., to SOlst AAA Gun Bn, North Richland, Wash

Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis

DTIC Science & Technology

2016-07-01

5’-aat tat ttt ata tgg aat gag caa gta tgt ttt atc ata att gac cag ttc att tca agg acc ttc aaa aat ata cct acg aat tcg agc tcg ttt aaa c-3’), or...oTsc13 (5’-tta aga gtt cag att tgc ttt atg tgg tta ttc tgc tga agg tcc taa ttt att gac gtt gaa aaa taa agg cca cat agc gga tcc ccg ggt taa tta a-3...and oTsc14 (5’-ata aaa aaa att aat taa tga tgg caa ggc aca atc gta atc aat ctt tta att tag gac ttt tta tat gcc ctt atg gcg aat tcg agc tcg ttt aaa c

Cryo-EM structure of a helicase loading intermediate containing ORC–Cdc6–Cdt1–MCM2-7 bound to DNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Jingchuan; Evrin, Cecile; Samel, Stefan A.

2013-07-14

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC–Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC–Cdc6 and Cdt1–MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC–Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC–Cdc6 undergoes a concertedmore » change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC–Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action.« less

Gorham disease of the lumbar spine with an abdominal aortic aneurysm: a case report.

PubMed

Kakuta, Yohei; Iizuka, Haku; Kobayashi, Ryoichi; Iizuka, Yoichi; Takahashi, Toru; Mohara, Jun; Takagishi, Kenji

2014-01-01

Reports of Gorham disease of the lumbar spine complicated by abdominal aortic aneurysms are rare. We herein report the case of a patient with Gorham disease of the lumber spine involving an abdominal aortic aneurysm (AAA). Case report. A 49-year-old man had a 1-month history of right leg pain and severe low back pain. Plain lumbar radiography revealed an osteolytic lesion in the L4 vertebral body. Computed tomography images demonstrated the presence of an extensive osteolytic lesion in the L4 vertebral body and an AAA in front of the L4 vertebral body. The patient underwent mass resection, spinal reconstruction, and blood vessel prosthesis implantation. During surgery, it was found that the wall of the aorta had completely disappeared and was shielded by the tumor mass; therefore, we speculated that the mass in the lumbar spine had directly invaded the aorta. The patient was able to walk without right leg or low back pain 1 year after undergoing surgery. No recurrence was demonstrated in the magnetic resonance images taken 1 year and 10 months after surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus.

PubMed

Walford, Geoffrey A; Davis, Jaclyn; Warner, A Sofia; Ackerman, Rachel J; Billings, Liana K; Chamarthi, Bindu; Fanelli, Rebecca R; Hernandez, Alicia M; Huang, Chunmei; Khan, Sabina Q; Littleton, Katherine R; Lo, Janet; McCarthy, Rita M; Rhee, Eugene P; Deik, Amy; Stolerman, Elliot; Taylor, Andrew; Hudson, Margo S; Wang, Thomas J; Altshuler, David; Grant, Richard W; Clish, Clary B; Gerszten, Robert E; Florez, Jose C

2013-12-01

Elevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D. A liquid chromatography-mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: (1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; (2) two days of twice daily metformin 500 mg orally; and (3) a 75-g OGTT. Percent change in BCAA/AAAs was determined after each intervention. Following glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P<0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P=0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P<0.05). BCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D. © 2013.

Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus

PubMed Central

Walford, Geoffrey A.; Davis, Jaclyn; Warner, A. Sofia; Ackerman, Rachel J.; Billings, Liana K.; Chamarthi, Bindu; Fanelli, Rebecca R.; Hernandez, Alicia M.; Huang, Chunmei; Khan, Sabina Q.; Littleton, Katherine R.; Lo, Janet; McCarthy, Rita M.; Rhee, Eugene P.; Deik, Amy; Stolerman, Elliot; Taylor, Andrew; Hudson, Margo S.; Wang, Thomas J.; Altshuler, David; Grant, Richard W.; Clish, Clary B.; Gerszten, Robert E.; Florez, Jose C.

2013-01-01

Objective Elevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D. Materials and Methods A liquid chromatography-mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: 1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; 2) two days of twice daily metformin 500 mg orally; and 3) a 75-gram OGTT. Percent change in BCAA/AAAs was determined after each intervention. Results Following glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P<0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P=0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P<0.05). Conclusions BCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D. PMID:23953891

Enhancing human-animal relationships through veterinary medical instruction in animal-assisted therapy and animal-assisted activities.

PubMed

Schaffer, Caroline Brunsman

2008-01-01

Instruction in animal-assisted therapy (AAT) and animal-assisted activities (AAAs) teaches veterinary medical students to confidently and assertively maximize the benefits and minimize the risks of this union of animals and people. Instruction in AAT/AAA also addresses requirements by the American Veterinary Medical Association Council on Education that accredited schools/colleges of veterinary medicine include in their standard curriculum the topics of the human-animal bond, behavior, and the contributions of the veterinarian to the overall public and professional health care teams. Entry-level veterinarians should be prepared to: (1) assure that animals who provide AAT/AAA are healthy enough to visit nursing homes, hospitals, or other institutions; (2) promote behavior testing that selects animals who will feel safe, comfortable, and connected; (3) advise facilities regarding infection control and ways to provide a safe environment where the animals, their handlers, and the people being visited will not be injured or become ill; and (4) advocate for their patients and show compassion for their clients when animals are determined to be inappropriate participants in AAT/AAA programs. This article presents AAT/AAA terminology, ways in which veterinarians can advocate for AAT/AAA, the advantages of being involved in AAT/AAA, a model AAT/AAA practicum from Tuskegee University's School of Veterinary Medicine (TUSVM), and examples of co-curricular activities in AAT/AAA by TUSVM's student volunteers.

Lipoprotein(a) Levels in Patients With Abdominal Aortic Aneurysm.

PubMed

Kotani, Kazuhiko; Sahebkar, Amirhossein; Serban, Maria-Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P; Mariscalco, Giovanni; Jones, Steven R; Martin, Seth; Blaha, Michael J; Toth, Peter P; Rizzo, Manfredi; Kostner, Karam; Rysz, Jacek; Banach, Maciej

2017-02-01

Circulating markers relevant to the development of abdominal aortic aneurysm (AAA) are currently required. Lipoprotein(a), Lp(a), is considered a candidate marker associated with the presence of AAA. The present meta-analysis aimed to evaluate the association between circulating Lp(a) levels and the presence of AAA. The PubMed-based search was conducted up to April 30, 2015, to identify the studies focusing on Lp(a) levels in patients with AAA and controls. Quantitative data synthesis was performed using a random effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Overall, 9 studies were identified. After a combined analysis, patients with AAA were found to have a significantly higher level of Lp(a) compared to the controls (SMD: 0.87, 95% CI: 0.41-1.33, P < .001). This result remained robust in the sensitivity analysis, and its significance was not influenced after omitting each of the included studies from the meta-analysis. The present meta-analysis confirmed a higher level of circulating Lp(a) in patients with AAA compared to controls. High Lp(a) levels can be associated with the presence of AAA, and Lp(a) may be a marker in screening for AAA. Further studies are needed to establish the clinical utility of measuring Lp(a) in the prevention and management of AAA.

Understanding the molecular mechanism of aryl acylamidase activity of acetylcholinesterase - An in silico study.

PubMed

Chinnadurai, Raj Kumar; Saravanaraman, Ponne; Boopathy, Rathanam

2015-08-15

Acetylcholinesterase (AChE) exhibits two different activities, namely esterase and aryl acylamidase (AAA). Unlike esterase, AAA activity of AChE is inhibited by the active site inhibitors while remaining unaffected by the peripheral anionic site inhibitors. This differential inhibitory pattern of active and peripheral anionic site inhibitors on the AAA activity remains unanswered. To answer this, we investigated the mechanism of binding and trafficking of AAA substrates using in silico tools. Molecular docking of serotonin and AAA substrates (o-nitroacetanilide, and o-nitrotrifluoroacetanilide,) onto AChE shows that these compounds bind at the side door of AChE. Thus, we conceived that the AAA substrates prefer the side door to reach the active site for their catalysis. Further, steered molecular dynamics simulations show that the force required for binding and trafficking of the AAA substrate through the side door is comparatively lesser than their dissociation (900kJ/mol/nm). Among the two substrates, o-nitrotrifluoroacetanilide required lesser force (380kJ/mol/nm) than o-nitroacetanilide the (550kJ/mol/nm) for its binding, thus validating o-nitrotrifluoroacetanilide as a better substrate. With these observations, we resolve that the AAA activity of AChE is mediated through its side door. Therefore, binding of PAS inhibitors at the main door of AChE remain ineffective against AAA activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Introducing AAA-MS, a rapid and sensitive method for amino acid analysis using isotope dilution and high-resolution mass spectrometry.

PubMed

Louwagie, Mathilde; Kieffer-Jaquinod, Sylvie; Dupierris, Véronique; Couté, Yohann; Bruley, Christophe; Garin, Jérôme; Dupuis, Alain; Jaquinod, Michel; Brun, Virginie

2012-07-06

Accurate quantification of pure peptides and proteins is essential for biotechnology, clinical chemistry, proteomics, and systems biology. The reference method to quantify peptides and proteins is amino acid analysis (AAA). This consists of an acidic hydrolysis followed by chromatographic separation and spectrophotometric detection of amino acids. Although widely used, this method displays some limitations, in particular the need for large amounts of starting material. Driven by the need to quantify isotope-dilution standards used for absolute quantitative proteomics, particularly stable isotope-labeled (SIL) peptides and PSAQ proteins, we developed a new AAA assay (AAA-MS). This method requires neither derivatization nor chromatographic separation of amino acids. It is based on rapid microwave-assisted acidic hydrolysis followed by high-resolution mass spectrometry analysis of amino acids. Quantification is performed by comparing MS signals from labeled amino acids (SIL peptide- and PSAQ-derived) with those of unlabeled amino acids originating from co-hydrolyzed NIST standard reference materials. For both SIL peptides and PSAQ standards, AAA-MS quantification results were consistent with classical AAA measurements. Compared to AAA assay, AAA-MS was much faster and was 100-fold more sensitive for peptide and protein quantification. Finally, thanks to the development of a labeled protein standard, we also extended AAA-MS analysis to the quantification of unlabeled proteins.

The Antiaircraft Journal. Volume 95, Number 2, March-April 1952

DTIC Science & Technology

1952-04-01

Command, Yoko- hama. Breuning, E. G., Far East Command, Yoko- hama Cacchiotti, Ralph R., 31st AAA Brig., Ft Lewis, Wash. Colbert , Edward F., 197th AAA Gp...Wilbur B., 47th AAA Brig., Cp Stew- art, Ga. Frick, Edwin J., 336th AAA Gun Bn, Cp Ed- wards. Mass. Gildon, Milo E., USA Alaska, Fort Richard- son

Muscle atrophy and fatty infiltration after an acute rotator cuff repair in a sheep model

PubMed Central

Luan, Tammy; Liu, Xuhui; Easley, Jeremiah T.; Ravishankar, Bharat; Puttlitz, Christian; Feeley, Brian T.

2015-01-01

Summary Introduction rotator cuff tears (RCTs) are the most common tendon injury seen in orthopedic patients. Muscle atrophy and fatty infiltration of the muscle are crucial factors that dictate the outcome following rotator cuff surgery. Though less studied in humans, rotator cuff muscle fibrosis has been seen in animal models as well and may influence outcomes as well. The purpose of this study was to determine if the rotator cuff would develop muscle changes even in the setting of an acute repair in a sheep model. We hypothesized that fatty infiltration and fibrosis would be present even after an acute repair six months after initial surgery. Methods twelve female adult sheep underwent an acute rotator cuff tear and immediate repair on the right shoulder. The left shoulder served as a control and did not undergo a tear or a repair. Six months following acute rotator cuff repairs, sheep muscles were harvested to study atrophy, fatty infiltration, and fibrosis by histological analysis, western blotting, and reverse transcription polymerase chain reaction (RT-PCR). Results the repair group demonstrated an increase expression of muscle atrophy, fatty infiltration, and fibrosis related genes. Significantly increased adipocytes, muscle fatty infiltration, and collagen deposition was observed in rotator cuff muscles in the tendon repair group compared to the control group. Conclusions rotator cuff muscle undergoes degradation changes including fatty infiltration and fibrosis even after the tendons are repair immediately after rupture. Level of Evidence Basic Science Study. PMID:26261789

A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.

PubMed

Prattes, Michael; Loibl, Mathias; Zisser, Gertrude; Luschnig, Daniel; Kappel, Lisa; Rössler, Ingrid; Grassegger, Manuela; Hromic, Altijana; Krieger, Elmar; Gruber, Karl; Pertschy, Brigitte; Bergler, Helmut

2017-03-17

AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP hydrolysis in the AAA-domains is mediated by a non-catalytic N-terminal domain. The exact mechanisms that transmit the signal from the N-domain and coordinate the individual AAA-domains in the hexameric complex are still the topic of intensive research. Here, we present the characterization of a novel mutant variant of the eukaryotic AAA-ATPase Drg1 that shows dysregulation of ATPase activity and altered interaction with Rlp24, its substrate in ribosome biogenesis. This defective regulation is the consequence of amino acid exchanges at the interface between the regulatory N-domain and the adjacent D1 AAA-domain. The effects caused by these mutations strongly resemble those of pathological mutations of the AAA-ATPase p97 which cause the hereditary proteinopathy IBMPFD (inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia). Our results therefore suggest well conserved mechanisms of regulation between structurally, but not functionally related members of the AAA-family.

Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis

PubMed Central

Cao, Hui; Hu, Xinhua; Zhang, Qiang; Li, Jun; Wang, Junpeng; Shao, Yang; Liu, Bing; Xin, Shijie

2014-01-01

Objectives Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (AAA). We investigated this association between Hcy levels in patients with AAA and unaffected controls by conducting a meta-analysis and systematic review. Methods We conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with AAA compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of AAA as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing AAA patients to the control subjects. Results 7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of AAA (3.29; 95% CI 1.66–6.51). The pooled adjusted OR from a random effect model of only men participants in the AAA compared with the control group was 2.36 (95% CI 0.63–8.82). Conclusion This meta-analysis and systematic review suggested that Hcy significantly increased the risk of AAA. PMID:24465733

Analysis of reactive oxygen metabolites (ROMs) after cardiovascular surgery as a marker of oxidative stress.

PubMed

Kanaoka, Yuji; Inagaki, Ei-ichirou; Hamanaka, Souhei; Masaki, Hisao; Tanemoto, Kazuo

2010-10-01

The transient systemic low perfusion that occurs during cardiovascular surgery leads to oxidative stress and the production of free radicals. A systemic increase of various markers of oxidative stress has been shown to occur during cardiopulmonary bypass (CPB). However, these markers have not been adequately evaluated because they seem to be reactive and short-lived. Here, oxidative stress was measured using the free radical analytical system (FRAS 4) assessing the derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). Blood samples were taken from 21 patients undergoing elective cardiovascular surgery. CPB was used in 15 patients, and abdominal aortic aneurysm (AAA) surgery without CPB was performed in 6. Measurements of d-ROMs and BAP were taken before surgery, 1 day, 1 week, and 2 weeks after surgery, and oxidative stress was evaluated. The d-ROM level increased gradually after cardiovascular surgery up to 2 weeks. Over time, the d-ROM level after surgery involving CPB became higher than that after AAA surgery. This difference reached statistical significance at 1 week and lasted to 2 weeks. The prolongation of CPB was prone to elevate the d-ROM level whereas the duration of the aortic clamp in AAA surgery had no relation to the d-ROM level. The BAP was also elevated after surgery, and was positively correlated with the level of d-ROMs. In this study, patients who underwent cardiovascular surgery involving CPB had significant oxidative damage. The production of ROMs was shown to depend on the duration of CPB. Damage can be reduced if CPB is avoided. When CPB must be used, shortening the CPB time may be effective in reducing oxidative stress.

The dexmedetomidine concentration required after remifentanil anesthesia is three-fold higher than that after fentanyl anesthesia or that for general sedation in the ICU

PubMed Central

Kunisawa, Takayuki; Fujimoto, Kazuhiro; Kurosawa, Atsushi; Nagashima, Michio; Matsui, Koji; Hayashi, Dai; Yamamoto, Kunihiko; Goto, Yuya; Akutsu, Hiroaki; Iwasaki, Hiroshi

2014-01-01

Purpose The general dexmedetomidine (DEX) concentration required for sedation of intensive care unit patients is considered to be approximately 0.7 ng/mL. However, higher DEX concentrations are considered to be required for sedation and/or pain management after major surgery using remifentanil. We determined the DEX concentration required after major surgery by using a target-controlled infusion (TCI) system for DEX. Methods Fourteen patients undergoing surgery for abdominal aortic aneurysms (AAA) were randomly, double-blindly assigned to two groups and underwent fentanyl- or remifentanil-based anesthetic management. DEX TCI was started at the time of closing the peritoneum and continued for 12 hours after stopping propofol administration (M0); DEX TCI was adjusted according to the sedation score and complaints of pain. The doses and concentrations of all anesthetics and postoperative conditions were investigated. Results Throughout the observation period, the predicted plasma concentration of DEX in the fentanyl group was stable at approximately 0.7 ng/mL. In contrast, the predicted plasma concentration of DEX in the remifentanil group rapidly increased and stabilized at approximately 2 ng/mL. The actual DEX concentration at 540 minutes after M0 showed a similar trend (0.54±0.14 [fentanyl] versus 1.57±0.39 ng/mL [remifentanil]). In the remifentanil group, the dopamine dose required and the duration of intubation decreased, and urine output increased; however, no other outcomes improved. Conclusion The DEX concentration required after AAA surgery with remifentanil was three-fold higher than that required after AAA surgery with fentanyl or the conventional DEX concentration for sedation. High DEX concentration after remifentanil affords some benefits in anesthetic management. PMID:25328395

Management of mitral regurgitation in Marfan syndrome: Outcomes of valve repair versus replacement and comparison with myxomatous mitral valve disease.

PubMed

Helder, Meghana R K; Schaff, Hartzell V; Dearani, Joseph A; Li, Zhuo; Stulak, John M; Suri, Rakesh M; Connolly, Heidi M

2014-09-01

The study objective was to evaluate patients with Marfan syndrome and mitral valve regurgitation undergoing valve repair or replacement and to compare them with patients undergoing repair for myxomatous mitral valve disease. We reviewed the medical records of consecutive patients with Marfan syndrome treated surgically between March 17, 1960, and September 12, 2011, for mitral regurgitation and performed a subanalysis of those with repairs compared with case-matched patients with myxomatous mitral valve disease who had repairs (March 14, 1995, to July 5, 2013). Of 61 consecutive patients, 40 underwent mitral repair and 21 underwent mitral replacement (mean [standard deviation] age, 40 [18] vs 31 [19] years; P = .09). Concomitant aortic surgery was performed to a similar extent (repair, 45% [18/40] vs replacement, 43% [9/21]; P = .87). Ten-year survival was significantly better in patients with Marfan syndrome with mitral repair than in those with replacement (80% vs 41%; P = .01). Mitral reintervention did not differ between mitral repair and replacement (cumulative risk of reoperation, 27% vs 15%; P = .64). In the matched cohort, 10-year survival after repair was similar for patients with Marfan syndrome and myxomatous mitral disease (84% vs 78%; P = .63), as was cumulative risk of reoperation (17% vs 12%; P = .61). Patients with Marfan syndrome and mitral regurgitation have better survival with repair than with replacement. Survival and risk of reoperation for patients with Marfan syndrome were similar to those for patients with myxomatous mitral disease. These results support the use of mitral valve repair in patients with Marfan syndrome and moderate or more mitral regurgitation, including those having composite replacement of the aortic root. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Therapeutic strategy for functional tricuspid regurgitation in patients undergoing mitral valve repair for severe mitral regurgitation.

PubMed

Kitai, Takeshi; Furukawa, Yutaka; Murotani, Kenta; Krittanawong, Chayakrit; Kaji, Shuichiro; Koyama, Tadaaki; Okada, Yukikatsu

2017-01-15

The aim of this study was to determine optimal patient selection and selection of a prosthetic ring size for tricuspid valve (TV) repair at the time of mitral valve (MV) repair. We prospectively enrolled 167 consecutive patients undergoing MV repair. TV repair was indicated if patients had at least one of the following conditions representing tricuspid annular dilatation: (1) tricuspid regurgitation (TR)≥moderate, (2) history of right heart failure, (3) atrial fibrillation, and (4) pulmonary hypertension. The size of the ring was targeted to a normal-sized systolic tricuspid annuls in relation to the patient's body surface area (BSA). Serial echocardiographic studies were performed preoperatively, at discharge, and at 1, 3, and 5years postoperatively. Overall, 100 (60%) patients required TV repair, while it was not indicated for 67 (40%) patients. During follow-up, 26 patients showed progression or recurrent TR≥moderate. The TR grade at 5years after MV surgery was 0.8±0.9 in patients with TV repair and 0.9±0.7 in those without TV repair (P=0.69). There were no significant differences between patients with and without TV repair in a composite endpoint of death from any cause, re-do MV or TV surgery, and recurrence or progression of TR≥moderate (P=0.46). Patient selection for TV repair considering not only the grade of TR but clinical signs representing tricuspid annular dilatation is feasible at the time of MV repair. TV repair targeting a normal systolic size in relation to the BSA is a simple and reproducible procedure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Unexpected and just missed: the separate influence of the appraisals of expectancy and proximity on negative emotions.

PubMed

Bossuyt, Evelien; Moors, Agnes; De Houwer, Jan

2014-04-01

Previous research has suggested that a goal-incongruent outcome leads to more intense negative emotions when it is unexpected and close to a goal-congruent outcome. Until now, however, no studies have disentangled the influence of the appraisals of expectancy and proximity on emotions. We experimentally manipulated each of these variables in 3 slot machine experiments and measured emotions via differences in motivation (i.e., the tendency to repair the goal incongruence) and feelings (i.e., disappointment, frustration, and anger). The experiments consisted of a series of trials that each started with the sequential presentation of 3 symbols. In case of a win trial, all symbols were equal (e.g., AAA) and the participant gained 10 cents; in case of a loss trial, one or more of the symbols differed and the participant gained 0 cents. Three different loss trials were compared: unexpected proximal ones (e.g., AAB), expected proximal ones (e.g., ABA), and expected distal ones (e.g., ABC). The tendency to repair was measured online via behavior as well as retrospectively via self-reports; feelings were measured retrospectively (Experiments 1 and 2) or online (Experiment 3). Unexpected losses seemed to increase the tendency to repair as well as feelings of disappointment (in all experiments) and feelings of frustration and anger (in Experiments 1 and 3). Proximal losses increased only the tendency to repair (in all experiments). This suggests that the appraisals of expectancy and proximity have a distinct influence on emotions.

An AAA-DDD triply hydrogen-bonded complex easily accessible for supramolecular polymers.

PubMed

Han, Yi-Fei; Chen, Wen-Qiang; Wang, Hong-Bo; Yuan, Ying-Xue; Wu, Na-Na; Song, Xiang-Zhi; Yang, Lan

2014-12-15

For a complementary hydrogen-bonded complex, when every hydrogen-bond acceptor is on one side and every hydrogen-bond donor is on the other, all secondary interactions are attractive and the complex is highly stable. AAA-DDD (A=acceptor, D=donor) is considered to be the most stable among triply hydrogen-bonded sequences. The easily synthesized and further derivatized AAA-DDD system is very desirable for hydrogen-bonded functional materials. In this case, AAA and DDD, starting from 4-methoxybenzaldehyde, were synthesized with the Hantzsch pyridine synthesis and Friedländer annulation reaction. The association constant determined by fluorescence titration in chloroform at room temperature is 2.09×10(7)  M(-1) . The AAA and DDD components are not coplanar, but form a V shape in the solid state. Supramolecular polymers based on AAA-DDD triply hydrogen bonded have also been developed. This work may make AAA-DDD triply hydrogen-bonded sequences easily accessible for stimuli-responsive materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ticagrelor for Neuroendovascular Procedures: A Case Series.

PubMed

Davis, Kyle; Morrison, Christopher

2018-02-01

The development of thromboembolism is one of the most common complications of neuroendovascular procedures. Although several small studies have deemed clopidogrel safe and effective in the prevention of intracranial stent thrombosis, ticagrelor has yet to be assessed in this setting. The objective of this study was to retrospectively evaluate the safety and efficacy of ticagrelor in patients undergoing neuroendovascular procedures. A retrospective review of patients receiving ticagrelor following neuroendovascular aneurysm repair. A total of 5 patients undergoing neuroendovascular aneurysm repair received ticagrelor for a median of 5 days while hospitalized. Three patients were treated with stent-assisted coiling, while 2 received pipeline embolization devices. All patients received additional low-dose aspirin therapy. One patient received ticagrelor after experiencing a thrombotic event on clopidogrel, while a second patient was treated with ticagrelor after developing a dermatologic reaction to clopidogrel. Three (60%) patients were successfully treated and discharged on ticagrelor therapy. Two patients experienced cerebrovascular accidents following aneurysm repair while receiving ticagrelor, one of which was potentially due to medication omission. One (20%) patient receiving ticagrelor experienced a small retroperitoneal hematoma; however, ticagrelor therapy was continued without further complication. Therapy with ticagrelor may be a safe and effective treatment option for patients undergoing neuroendovascular aneurysm repair. However, future studies are warranted to substantiate these findings.

Treatment strategy for ruptured abdominal aortic aneurysms.

PubMed

Davidovic, L

2014-07-01

Rupture is the most serious and lethal complication of the abdominal aortic aneurysm. Despite all improvements during the past 50 years, ruptured abdominal aortic aneurysms are still associated with very high mortality. Namely, including patients who die before reaching the hospital, the mortality rate due to abdominal aortic aneurysm rupture is 90%. On the other hand, during the last twenty years, the number of abdominal aortic aneurysms significantly increased. One of the reasons is the fact that in majority of countries the general population is older nowadays. Due to this, the number of degenerative AAA is increasing. This is also the case for patients with abdominal aortic aneurysm rupture. Age must not be the reason of a treatment refusal. Optimal therapeutic option ought to be found. The following article is based on literature analysis including current guidelines but also on my Clinics significant experience. Furthermore, this article show cases options for vascular medicine in undeveloped countries that can not apply endovascular procedures at a sufficient level and to a sufficient extent. At this moment the following is evident. Thirty-day-mortality after repair of ruptured abdominal aortic aneurysms is significantly lower in high-volume hospitals. Due to different reasons all ruptured abdominal aortic aneurysms are not suitable for EVAR. Open repair of ruptured abdominal aortic aneurysm should be performed by experienced open vascular surgeons. This could also be said for the treatment of endovascular complications that require open surgical conversion. There is no ideal procedure for the treatment of AAA. Each has its own advantages and disadvantages, its own limits and complications, as well as indications and contraindications. Future reductions in mortality of ruptured abdominal aortic aneurysms will depend on implementation of population-based screening; on strategies to prevent postoperative organ injury and also on new medical technology improvements. Taking this into consideration, education of young vascular surgeons in endovascular but also in open aortic surgery, is of vast importance.

Levels of H-ras codon 61 CAA to AAA mutation: response to 4-ABP-treatment and Pms2-deficiency.

PubMed

Parsons, Barbara L; Delongchamp, Robert R; Beland, Frederick A; Heflich, Robert H

2006-01-01

DNA mismatch repair (MMR) deficiencies result in increased frequencies of spontaneous mutation and tumor formation. In the present study, we tested the hypothesis that a chemically-induced mutational response would be greater in a mouse with an MMR-deficiency than in the MMR-proficient mouse models commonly used to assay for chemical carcinogenicity. To accomplish this, the induction of H-ras codon 61 CAA-->AAA mutation was examined in Pms2 knockout mice (Pms2-/-, C57BL/6 background) and sibling wild-type mice (Pms2+/+). Groups of five or six neonatal male mice were treated with 0.3 micromol 4-aminobiphenyl (4-ABP) or the vehicle control, dimethylsulfoxide. Eight months after treatment, liver DNAs were isolated and analysed for levels of H-ras codon 61 CAA-->AAA mutation using allele-specific competitive blocker-PCR. In Pms2-proficient and Pms2-deficient mice, 4-ABP treatment caused an increase in mutant fraction (MF) from 1.65x10(-5) to 2.91x10(-5) and from 3.40x10(-5) to 4.70x10(-5), respectively. Pooling data from 4-ABP-treated and control mice, the approximately 2-fold increase in MF observed in Pms2-deficient as compared with Pms2-proficient mice was statistically significant (P=0.0207) and consistent with what has been reported previously in terms of induction of G:C-->T:A mutation in a Pms2-deficient background. Pooling data from both genotypes, the increase in H-ras MF in 4-ABP-treated mice, as compared with control mice, did not reach the 95% confidence level of statistical significance (P=0.0606). The 4-ABP treatment caused a 1.76-fold and 1.38-fold increase in average H-ras MF in Pms2-proficient and Pms2-deficient mice, respectively. Furthermore, the levels of induced mutation in Pms2-proficient and Pms2-deficient mice were nearly identical (1.26x10(-5) and 1.30x10(-5), respectively). We conclude that Pms2-deficiency does not result in an amplification of the H-ras codon 61 CAA-->AAA mutational response induced by 4-ABP.

Femoral incision morbidity following endovascular aortic aneurysm repair.

PubMed

Slappy, A L Jackson; Hakaim, Albert G; Oldenburg, W Andrew; Paz-Fumagalli, Ricardo; McKinney, J Mark

2003-01-01

Currently available aortic stent-grafts require bilateral femoral incisions for device deployment. The incidence of morbidity (infection, lymphatic complications, breakdown) of vertical, infrainguinal incisions used in endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs) was assessed, and the natural history of asymptomatic groin fluid collections following such procedures was determined. Between June 1999 and February 2001, 77 consecutive patients underwent EVAR for AAAs utilizing bilateral vertical femoral incisions. Fifty-nine (77%) bifurcated stent-grafts (BSGs), and 18 (23%) aortouniiliac (AUI) devices, with femorofemoral bypass were performed. Patients returned at 2 weeks, 1 month, and 6 months for physical examination, and 1 month and 6 months for abdominal and pelvic computed tomography (CT) scans. The presence of fluid collections was determined from the dictation report of the attending radiologist. Data are reported as (n) mean +/-SE. Patient characteristics were compared using Fisher's exact test; p<0.05 considered significant. There were 72 males and 5 females, age 75 +/-6.4 years and aneurysm size (77) 5.6 +/-0.8 cm. There were no cases of wound breakdown or lymph fistula. Wound infections occurred in 3/150 incisions (2%), 2/34 AUI incisions (6%), and 1/116 BSG incisions (0.86%). There was no statistical difference (p=0.13) between graft types (BSG vs AUI). All infections were diagnosed clinically before the 1-month CT scan, treated without operative intervention or hospitalization, and resolved. There was a significant decrease in the BSG group and overall in asymptomatic wound fluid collections from 1 to 6 months postoperatively. At 1 and 6 months, respectively, the BSG group had 17 (14.6%) and 3 (2.6%) fluid collections out of 116 incisions (p=0.003); the AUI group had 6 (17.6%) and 1 (2.9%) fluid collection(s) out of 34 incisions (p=0.13); and overall 23 (15.3%) and 4 (2.6%) out of 150 incisions (p=0.004). The present study demonstrates that bilateral vertical femoral incisions used in EVAR have a wound infection rate of 2.0%. Infections are usually detected and treated clinically and empirically without the need for hospitalization or surgery. Asymptomatic groin wound fluid collections resolve significantly within 6 months without intervention. Therefore, surgical femoral artery exposure adds little morbidity to the endovascular repair of abdominal aortic aneurysms.

Distal small bowel motility and lipid absorption in patients following abdominal aortic aneurysm repair surgery

PubMed Central

Fraser, Robert J; Ritz, Marc; Matteo, Addolorata C Di; Vozzo, Rosalie; Kwiatek, Monika; Foreman, Robert; Stanley, Brendan; Walsh, Jack; Burnett, Jim; Jury, Paul; Dent, John

2006-01-01

AIM: To investigate distal small bowel motility and lipid absorption in patients following elective abdominal aortic aneurysm (AAA) repair surgery. METHODS: Nine patients (aged 35-78 years; body mass index (BMI) range: 23-36 kg/m2) post-surgery for AAA repair, and seven healthy control subjects (20-50 years; BMI range: 21-29 kg/m2) were studied. Continuous distal small bowel manometry was performed for up to 72 h, during periods of fasting and enteral feeding (Nutrison®). Recordings were analyzed for the frequency, origin, length of migration, and direction of small intestinal burst activity. Lipid absorption was assessed on the first day and the third day post surgery in a subset of patients using the 13C-triolein-breath test, and compared with healthy controls. Subjects received a 20-min intraduodenal infusion of 50 mL liquid feed mixed with 200 μL 13C-triolein. End-expiratory breath samples were collected for 6 h and analyzed for 13CO2 concentration. RESULTS: The frequency of burst activity in the proximal and distal small intestine was higher in patients than in healthy subjects, under both fasting and fed conditions (P < 0.005). In patients there was a higher proportion of abnormally propagated bursts (71% abnormal), which began to normalize by d 3 (25% abnormal) post-surgery. Lipid absorption data was available for seven patients on d 1 and four patients on d 3 post surgery. In patients, absorption on d 1 post-surgery was half that of healthy control subjects (AUC 13CO2 1 323 ± 244 vs 2 646 ±365; P < 0.05, respectively), and was reduced to the one-fifth that of healthy controls by d 3 (AUC 13CO2 470 ± 832 vs 2 646 ± 365; P < 0.05, respectively). CONCLUSION: Both proximal and distal small intestinal motor activity are transiently disrupted in critically ill patients immediately after major surgery, with abnormal motility patterns extending as far as the ileum. These motor disturbances may contribute to impaired absorption of enteral nutrition, especially when intraluminal processing is necessary for efficient digestion. PMID:16489672

LMIP/AAA: Local Authentication, Authorization and Accounting (AAA) Protocol for Mobile IP

NASA Astrophysics Data System (ADS)

Chenait, Manel

Mobile IP represents a simple and scalable global mobility solution. However, it inhibits various vulnerabilities to malicious attacks and, therefore, requires the integration of appropriate security services. In this paper, we discuss two authentication schemes suggested for Mobile IP: standard authentication and Mobile IP/AAA authentication. In order to provide Mobile IP roaming services including identity verication, we propose an improvement to Mobile/AAA authentication scheme by applying a local politic key management in each domain, hence we reduce hando latency by avoiding the involvement of AAA infrastructure during mobile node roaming.

Sex differences in abdominal aortic aneurysms.

PubMed

Boese, Austin C; Chang, Lin; Yin, Ke-Jie; Chen, Y Eugene; Lee, Jean-Pyo; Hamblin, Milton H

2018-06-01

Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.

SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells.

PubMed

Toghill, Bradley J; Saratzis, Athanasios; Freeman, Peter J; Sylvius, Nicolas; Bown, Matthew J

2018-01-01

Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter ( P  < 0.0001, R 2  = 0.3175).We then determined CpG methylation status of regulatory regions in genes located at AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). In IL6R , 2 CpGs were hyper-methylated ( P  = 0.0145); in ERG , 13 CpGs were hyper-methylated ( P  = 0.0005); in SERPINB9 , 6 CpGs were hypo-methylated ( P  = 0.0037) and 1 CpG was hyper-methylated ( P  = 0.0098); and in SMYD2 , 4 CpGs were hypo-methylated ( P  = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation of SMYD2 and SERPINB9 in AAA, and a direct linear relationship between SMYD2 promoter methylation and SMYD2 expression ( P  = 0.038). Furthermore, downregulation of SMYD2 at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. This study is the first to assess DNA methylation in VSMCs from individuals with AAA using NGS, and provides further evidence there is an epigenetic basis to AAA. Our study shows that methylation status of the SMYD2 promoter may be linked with decreased SMYD2 expression in disease pathobiology. In support of our work, downregulated SMYD2 has previously been associated with adverse cardiovascular physiology and inflammation, which are both hallmarks of AAA. The identification of such adverse epigenetic modifications could potentially contribute towards the development of epigenetic treatment strategies in the future.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badkul, R; Nicolai, W; Pokhrel, D

Purpose: To compare the impact of Pencil Beam(PB) and Anisotropic Analytic Algorithm(AAA) dose calculation algorithms on OARs and planning target volume (PTV) in thoracic spine stereotactic body radiation therapy (SBRT). Methods: Ten Spine SBRT patients were planned on Brainlab iPlan system using hybrid plan consisting of 1–2 non-coplanar conformal-dynamic arcs and few IMRT beams treated on NovalisTx with 6MV photon. Dose prescription varied from 20Gy to 30Gy in 5 fractions depending on the situation of the patient. PB plans were retrospectively recalculated using the Varian Eclipse with AAA algorithm using same MUs, MLC pattern and grid size(3mm).Differences in dose volumemore » parameters for PTV, spinal cord, lung, and esophagus were analyzed and compared for PB and AAA algorithms. OAR constrains were followed per RTOG-0631. Results: Since patients were treated using PB calculation, we compared all the AAA DVH values with respect to PB plan values as standard, although AAA predicts the dose more accurately than PB. PTV(min), PTV(Max), PTV(mean), PTV(D99%), PTV(D90%) were overestimated with AAA calculation on average by 3.5%, 1.84%, 0.95%, 3.98% and 1.55% respectively as compared to PB. All lung DVH parameters were underestimated with AAA algorithm mean deviation of lung V20, V10, V5, and 1000cc were 42.81%,19.83%, 18.79%, and 18.35% respectively. AAA overestimated Cord(0.35cc) by mean of 17.3%; cord (0.03cc) by 12.19% and cord(max) by 10.5% as compared to PB. Esophagus max dose were overestimated by 4.4% and 5cc by 3.26% for AAA algorithm as compared to PB. Conclusion: AAA overestimated the PTV dose values by up to 4%.The lung DVH had the greatest underestimation of dose by AAA versus PB. Spinal cord dose was overestimated by AAA versus PB. Given the critical importance of accuracy of OAR and PTV dose calculation for SBRT spine, more accurate algorithms and validation of calculated doses in phantom models are indicated.« less

Flow stagnation volume and abdominal aortic aneurysm growth: Insights from patient-specific computational flow dynamics of Lagrangian-coherent structures.

PubMed

Joly, Florian; Soulez, Gilles; Garcia, Damien; Lessard, Simon; Kauffmann, Claude

2018-01-01

Abdominal aortic aneurysms (AAA) are localized, commonly-occurring dilations of the aorta. When equilibrium between blood pressure (loading) and wall mechanical resistance is lost, rupture ensues, and patient death follows, if not treated immediately. Experimental and numerical analyses of flow patterns in arteries show direct correlations between wall shear stress and wall mechano-adaptation with the development of zones prone to thrombus formation. For further insights into AAA flow topology/growth interaction, a workout of patient-specific computational flow dynamics (CFD) is proposed to compute finite-time Lyapunov exponents and extract Lagrangian-coherent structures (LCS). This computational model was first compared with 4-D phase-contrast magnetic resonance imaging (MRI) in 5 patients. To better understand the impact of flow topology and transport on AAA growth, hyperbolic, repelling LCS were computed in 1 patient during 8-year follow-up, including 9 volumetric morphologic AAA measures by computed tomography-angiography (CTA). LCS defined barriers to Lagrangian jet cores entering AAA. Domains enclosed between LCS and the aortic wall were considered to be stagnation zones. Their evolution was studied during AAA growth. Good correlation - 2-D cross-correlation coefficients of 0.65, 0.86 and 0.082 (min, max, SD) - was obtained between numerical simulations and 4-D MRI acquisitions in 6 specific cross-sections from 4 patients. In follow-up study, LCS divided AAA lumens into 3 dynamically-isolated zones: 2 stagnation volumes lying in dilated portions of the AAA, and circulating volume connecting the inlet to the outlet. The volume of each zone was tracked over time. Although circulating volume remained unchanged during 8-year follow-up, the AAA lumen and main stagnation zones grew significantly (8 cm 3 /year and 6 cm 3 /year, respectively). This study reveals that transient transport topology can be quantified in patient-specific AAA during disease progression by CTA, in parallel with lumen morphology. It is anticipated that analysis of the main AAA stagnation zones by patient-specific CFD on a yearly basis could help to predict AAA growth and rupture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mutant Analysis Reveals Allosteric Regulation of ClpB Disaggregase

PubMed Central

Franke, Kamila B.; Bukau, Bernd; Mogk, Axel

2017-01-01

The members of the hexameric AAA+ disaggregase of E. coli and S. cerevisiae, ClpB, and Hsp104, cooperate with the Hsp70 chaperone system in the solubilization of aggregated proteins. Aggregate solubilization relies on a substrate threading activity of ClpB/Hsp104 fueled by ATP hydrolysis in both ATPase rings (AAA-1, AAA-2). ClpB/Hsp104 ATPase activity is controlled by the M-domains, which associate to the AAA-1 ring to downregulate ATP hydrolysis. Keeping M-domains displaced from the AAA-1 ring by association with Hsp70 increases ATPase activity due to enhanced communication between protomers. This communication involves conserved arginine fingers. The control of ClpB/Hsp104 activity is crucial, as hyperactive mutants with permanently dissociated M-domains exhibit cellular toxicity. Here, we analyzed AAA-1 inter-ring communication in relation to the M-domain mediated ATPase regulation, by subjecting a conserved residue of the AAA-1 domain subunit interface of ClpB (A328) to mutational analysis. While all A328X mutants have reduced disaggregation activities, their ATPase activities strongly differed. ClpB-A328I/L mutants have reduced ATPase activity and when combined with the hyperactive ClpB-K476C M-domain mutation, suppress cellular toxicity. This underlines that ClpB ATPase activation by M-domain dissociation relies on increased subunit communication. The ClpB-A328V mutant in contrast has very high ATPase activity and exhibits cellular toxicity on its own, qualifying it as novel hyperactive ClpB mutant. ClpB-A328V hyperactivity is however, different from that of M-domain mutants as M-domains stay associated with the AAA-1 ring. The high ATPase activity of ClpB-A328V primarily relies on the AAA-2 ring and correlates with distinct conformational changes in the AAA-2 catalytic site. These findings characterize the subunit interface residue A328 as crucial regulatory element to control ATP hydrolysis in both AAA rings. PMID:28275610

Prevalence of previously undiagnosed abdominal aortic aneurysms in the area of Como: the ComoCuore "looking for AAA" ultrasonography screening.

PubMed

Corrado, Giovanni; Durante, Alessandro; Genchi, Vincenzo; Trabattoni, Loris; Beretta, Sandro; Rovelli, Enza; Foglia-Manzillo, Giovanni; Ferrari, Giovanni

2016-08-01

The prognosis for abdominal aortic aneurysm (AAA) rupture is poor. Long-term follow-up of population-based randomized trials has demonstrated that ultrasound (US) screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates and is cost-effective. We though to prospectively perform during a 26-month period a limited US examination of the infrarenal aorta in volunteers of both gender aged 60-85 years without history of AAA living in the area of Como, Italy. From September 2010 to November 2013 ComoCuore, a no-profit nongovernmental association, enrolled 1555 people (aged 68.8 ± 6.8 years; 48.6 % males). Clinical data and a US imaging of the aorta were collected for each participant. AAA was found in 22 volunteers (1.4 %) mainly males (2.5 % in males vs. 0.4 % in females p = 0.005). Overall, the prevalence of cardiovascular risk factors was higher in patients with vs. without AAA (mean 2.9 ± 3.0 vs. 1.4 ± 1.0 respectively, p < 0.0001). Independent predictors of AAA on multivariate analysis were age (OR 1.14, 1.06-1.22; p < 0.0001), male gender (OR 8.23, 1.79-37.91; p = 0.007), and both current (OR 4.98, 1.57-15.79; p = 0.007) and previous smoking (OR 2.76, 1.12-8.94; p = 0.03). Our study confirms the feasibility of one time US screening for AAA in a large cohort of asymptomatic people. Independent predictors of AAA were male sex, older age and a history of smoking. Accordingly to recent data the prevalence of AAA seems to be declining, maybe due to a reduction of smoking in Italy.

Sleep disturbance associated with rotator cuff tear: correction with arthroscopic rotator cuff repair.

PubMed

Austin, Luke; Pepe, Matthew; Tucker, Bradford; Ong, Alvin; Nugent, Robert; Eck, Brandon; Tjoumakaris, Fotios

2015-06-01

Sleep disturbance is a common complaint of patients with a rotator cuff tear. Inadequate and restless sleep, along with pain, is often a driving symptom for patients to proceed with rotator cuff repair. To date, no studies have examined sleep disturbance in patients undergoing rotator cuff repair, and there is no evidence that surgery improves sleep disturbance. Sleep disturbance is prevalent in patients with a symptomatic rotator cuff tear, and sleep disturbance improves after arthroscopic rotator cuff repair. Case series; Level of evidence, 4. A total of 56 patients undergoing arthroscopic rotator cuff repair for full-thickness tears were enrolled in a prospective study. Patients were surveyed preoperatively and postoperatively at intervals of 2, 6, 12, 18, and 24 weeks. Patient outcomes were scored using the Pittsburgh Sleep Quality Index (PSQI), Simple Shoulder Test (SST), visual analog scale for pain (VAS), and single assessment numeric evaluation (SANE). Demographic and surgical factors were also collected for analysis. Preoperative PSQI scores indicative of sleep disturbance were reported in 89% of patients. After surgery, a statistically significant improvement in PSQI was achieved at 3 months (P = .0012; 91% follow-up) and continued through 6 months (P = .0179; 93% follow-up). Six months after surgery, only 38% of patients continued to have sleep disturbance. Multivariable linear regression of all surgical and demographic factors versus PSQI was performed and demonstrated that preoperative and prolonged postoperative narcotic use negatively affected sleep. Sleep disturbance is common in patients undergoing rotator cuff repair. After surgery, sleep disturbance improves to levels comparable with those of the general public. Preoperative and prolonged postoperative use of narcotic pain medication negatively affects sleep. © 2015 The Author(s).

Attenuation of aortic aneurysms with stem cells from different genders.

PubMed

Davis, John P; Salmon, Morgan; Pope, Nicolas H; Lu, Guanyi; Su, Gang; Sharma, Ashish K; Ailawadi, Gorav; Upchurch, Gilbert R

2015-11-01

No medical therapies are yet available to slow abdominal aortic aneurysm (AAA) growth. This study sought to investigate the effect of different genders of bone marrow-derived mesenchymal stem cells (MSC) on AAA growth in a murine AAA model. Given the decreased rate of AAA in women, it is hypothesized that female MSC would attenuate AAA growth more so than male MSC. Aortas of 8-10-wk-old male C57Bl/6 mice were perfused with purified porcine pancreatic elastase to induce AAA formation. Bone marrow-derived MSC from male and female mice were dosed via tail vein injection (3 million cells per dose, 500 μL of volume per injection) on postaortic perfusion days 1, 3, and 5. Aortas were harvested after 14 d. Mean aortic dilation in the elastase group was 121 ± 5.2% (mean ± standard error of the mean), while male MSC inhibited AAA growth (87.8 ± 6.9%, P = 0.008) compared with that of elastase. Female MSC showed the most marked attenuation of AAA growth (75.2 ± 8.3% P = 0.0004). Proinflammatory cytokines tumor necrosis factor α, interleukin 1β, and monocyte chemotactic protein-1 (MCP-1) were only decreased in tissues treated with female MSC (P = 0.017, P = 0.001, and P < 0.0001, respectively, when compared with elastase). These data exhibit that female MSC more strongly attenuate AAA growth in the murine model. Furthermore, female MSC and male MSC inhibit proinflammatory cytokines at varying levels. The effects of MSC on aortic tissue offer a promising insight into biologic therapies for future medical treatment of AAAs in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

The prevalence of abdominal aortic aneurysms in the rural/urban population in central Poland - Gniewkowo Aortic Study.

PubMed

Dereziński, Tadeusz L; Fórmankiewicz, Bartosz; Migdalski, Arkadiusz; Brazis, Paweł; Jakubowski, Grzegorz; Woda, Łukasz; Jawień, Arkadiusz

2017-01-01

Abdominal aortic aneurysm (AAA) is a widening of the aorta below the renal arteries with a diameter equal to or greater than 3 cm. The prevalence of AAA is estimated at 4-8% in men aged 65 years or older and 1-2% among women over 65 years old. Participation in screening programmes has decreased the number of aortic ruptures. All men aged 60 years and older, and women aged 65 years and older living in the rural/urban commune in central Poland were invited to participate in the study. In total 922 persons (61% of the invited population) entered the study. The men were divided into two groups: 60-64 years old, and 65 years and older. Screening abdomen ultrasound was performed and demographic data was collected. Among the 922 examined persons two (1.01%) AAAs were diagnosed in the group of men 60-64 years of age, three (0.82%) AAAs amongst women ≥ 65 years old, and 33 (9.29%) AAAs were found in the group of men aged 65 years and older. A positive relationship between the presence of AAA and smoking (p = 0.0048), age of men (p = 0.0009), and history of myocardial infarction/acute coronary syndrome (MI/ACS) (p = 0.0079) was found. There was no correlation between the frequency of AAA and diabetes mellitus (p = 0.46), hypertension (p = 0.38), and family history of AAA (p = 0.44). The prevalence of AAA in men aged 65 years and older is seemingly larger than in previously conducted studies, while among men 60-64 years of age and women aged ≥ 65 it is similar. Older age, smoking, and a history of MI/ACS were the most important risk factors of AAA occurrence.

Clinical Efficacy of Transthoracic Echocardiography for Screening Abdominal Aortic Aneurysm in Turkish Patients.

PubMed

Kilic, Salih; Saracoglu, Erhan; Cekici, Yusuf

2018-03-01

The objective of this study was to investigate the prevalence of abdominal aortic aneurysm (AAA) in Turkish patients aged ≥ 65 years, and to demonstrate the applicability of echocardiography to AAA screening. Transthoracic echocardiography (TTE) was performed in all consecutive patients aged ≥ 65 years who were referred to cardiology clinics or were referred from other outpatient clinics. The abdominal aorta (AA) of each patient was scanned using the same probe, and the time spent was recorded. Demographic and clinic characteristics of the patients were recorded at the end of the echocardiography. Among 1948 patients (mean age 70.9 ± 6 years; 49.8% male), the AA was visualized in 96.3%. AAA was identified in 3.7% (69/1878) of the patients, of whom AAA was previously known in 20.3% (n = 14). The prevalence of unknown AAA was 2.93%. The average time needed to scan and measure the AA was 1 minute and 3 seconds (±23 seconds). Aortic root diameters were significantly higher in the patients with AAA than in those without AAA (34.7 ± 4.2 vs. 29.8 ± 4.7; p < 0.001). Age (per 1 year increase) [odds ratio (OR), 1.245; p < 0.001], male gender (OR, 5.382; p < 0.001), smoking (OR, 2.118; p = 0.037), and aortic root diameter (per 1 mm increase) (OR, 1.299; p < 0.001) were independent predictors of AAA. This study is important in that it showed a high prevalence of AAA in Turkish patients aged ≥ 65 years, and demonstrated that AAA can be visualized in the majority of patients in as little as 1 minute during TTE.

Identification of a genetic variant associated with abdominal aortic aneurysms on chromosome 3p12.3 by genome wide association.

PubMed

Elmore, James R; Obmann, Melissa A; Kuivaniemi, Helena; Tromp, Gerard; Gerhard, Glenn S; Franklin, David P; Boddy, Amy M; Carey, David J

2009-06-01

The goal of this project was to identify genetic variants associated with abdominal aortic aneurysms (AAAs). A genome wide association study was carried out using pooled DNA samples from 123 AAA cases and 112 controls matched for age, gender, and smoking history using Affymetrix 500K single nucleotide polymorphism (SNP) arrays (Affymetrix, Inc, Santa Clara, Calif). The difference in mean allele frequency between cases and controls was calculated for each SNP and used to identify candidate genomic regions. Association of candidate SNPs with AAA was confirmed by individual TaqMan genotype assays in a total of 2096 cases and controls that included an independent replication sample set. A genome wide association study of AAA cases and controls identified a candidate AAA-associated haplotype on chromosome 3p12.3. By individual genotype analysis, four SNPs in this region were significantly associated with AAA in cases and controls from the original study population. One SNP in this region (rs7635818) was genotyped in a total of 502 cases and 736 controls from the original study population (P = .017) and 448 cases and 410 controls from an independent replication sample (P = .013; combined P value = .0028; combined odds ratio [OR] = 1.33). An even stronger association with AAA was observed in a subset of smokers (391 cases, 241 controls, P = .00041, OR = 1.80), which represent the highest risk group for AAA. The AAA-associated haplotype is located approximately 200 kbp upstream of the CNTN3 gene transcription start site. This study identifies a region on chromosome 3 that is significantly associated with AAA in 2 distinct study populations.

Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice.

PubMed

Ni, Xian-Qiang; Lu, Wei-Wei; Zhang, Jin-Sheng; Zhu, Qing; Ren, Jin-Ling; Yu, Yan-Rong; Liu, Xiu-Ying; Wang, Xiu-Jie; Han, Mei; Jing, Qing; Du, Jie; Tang, Chao-Shu; Qi, Yong-Fen

2018-06-26

Endoplasmic reticulum stress (ERS) is involved in the development of abdominal aortic aneurysm (AAA). Since bioactive peptide intermedin (IMD)1-53 protects against AAA formation, here we investigated whether IMD1-53 attenuates AAA by inhibiting ERS. AAA model was induced by angiotensin II (AngII) in ApoE KO mouse background. AngII-treated mouse aortas showed increased ERS gene transcription of caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating transcription factor 4(ATF4).The protein level of ERS marker glucose regulated protein 94(GRP94), ATF4 and C/EBP homologous protein 10(CHOP) was also up-regulated by AngII. Increased ERS levels were accompanied by severe VSMC apoptosis in human AAA aorta. In vivo administration of IMD1-53 greatly reduced AngII-induced AAA and abrogated the activation of ERS. To determine whether IMD inhibited AAA by ameliorating ERS, we used 2 non-selective ERS inhibitors phenyl butyrate (4-PBA) and taurine (TAU). Similar to IMD, PBA, and TAU significantly reduced the incidence of AAA and AAA-related pathological disorders. In vitro, AngII infusion up-regulated CHOP, caspase12 expression and led to VSMC apoptosis. IMD siRNA aggravated the CHOP, caspase12-mediated VSMC apoptosis, which was abolished by ATF4 silencing. IMD infusion promoted the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in aortas in ApoE KO mice, and the AMPK inhibitor compound C abolished the protective effect of IMD on VSMC ERS and apoptosis induced by AngII. In conclusion, IMD may protect against AAA formation by inhibiting ERS via activating AMPK phosphorylation.

Plasma D-dimer as a predictor of the progression of abdominal aortic aneurysm.

PubMed

Vele, E; Kurtcehajic, A; Zerem, E; Maskovic, J; Alibegovic, E; Hujdurovic, A

2016-11-01

Essentials D-dimer could provide important information about abdominal aortic aneurysm (AAA) progression. The greatest diameter of the infrarenal aorta and the value of plasma D-dimer were determined. AAA progression is correlated with increasing plasma D-dimer levels. The increasing value of plasma D-dimer could be a predictor of aneurysm progression. Background The natural course of abdominal aortic aneurysm (AAA) is mostly asymptomatic and unpredictable. D-dimer could provide potentially important information about subsequent AAA progression. Objectives The aims of this study were to establish the relationship between the progression of an abdominal aortic aneurysm (AAA) and plasma D-dimer concentration over a 12-month period and determine the value of plasma D-dimer in patients with sub-aneurysmal aortic dilatation. Patients/Methods This was a prospective observational study that involved 33 patients with an AAA, 30 patients with sub-aneurysmal aortic dilatation and 30 control subjects. The greatest diameter of the infrarenal aorta, which was assessed by ultrasound, and the value of plasma D-dimer were determined for all subjects at baseline assessment, as well as after 12 months for those with an AAA. Results A positive correlation was found between the diameter of an AAA and plasma D-dimer concentration at the baseline and the control measurement stages. There was a strong positive correlation between AAA progression and increasing plasma D-dimer concentration over a 12-month period. Among patients with sub-aneurysmal aortic dilatation (n = 30), the value of plasma D-dimer was higher compared with matched controls (n = 30). Conclusions There is a strongly positive correlation between AAA progression and increasing plasma D-dimer concentration. The value of plasma D-dimer is higher in patients with sub-aneurysmal aortic dilatation than in control subjects. © 2016 International Society on Thrombosis and Haemostasis.

Ultrasound-guided transversus abdominis plane block in patients undergoing open inguinal hernia repair: 0.125% bupivacaine provides similar analgesic effect compared to 0.25% bupivacaine.

PubMed

Erdoğan Arı, Dilek; Yıldırım Ar, Arzu; Karadoğan, Firdevs; Özcabı, Yetkin; Koçoğlu, Ayşegül; Kılıç, Fatih; Akgün, Fatma Nur

2016-02-01

To evaluate the effectiveness of 0.125% bupivacaine compared to 0.25% bupivacaine for ultrasound-guided transversus abdominis plane (TAP) block in patients undergoing open inguinal hernia repair. Randomized, double-blind study. Educational and research hospital. Forty adult patients of American Society of Anesthesiologists physical status I-III undergoing elective primary unilateral open inguinal hernia repair under spinal anesthesia. Patients in group I received 20 mL of 0.25% bupivacaine, whereas patients in group II received 20 mL of 0.125% bupivacaine for TAP block at the end of the surgery. Pain intensity was assessed at rest and during coughing using 10-cm visual analog scale score at 5, 15, 30, and 45 minutes and 1, 2, 4, 6, 12, and 24 hours after TAP block. Morphine consumption and time to first morphine requirement were recorded. Visual analog scale scores at rest and during coughing were not significantly different between groups at all time points measured. Twenty-four hours of morphine consumption (7.72±7.33 mg in group I and 6.06±5.20 mg in group II; P=.437) and time to first morphine requirement (182.35±125.16 minutes in group I and 143.21±87.28 minutes in group II; P=.332) were not different between groups. 0.125% Bupivacaine provides similar analgesic effect compared to 0.25% bupivacaine for ultrasound-guided TAP block in patients undergoing open inguinal hernia repair. Copyright © 2016 Elsevier Inc. All rights reserved.

Statins: the holy grail of Abdominal Aortic Aneurysm (AAA) growth attenuation? A systematic review of the literature.

PubMed

Dunne, Jonathan A; Bailey, Marc A; Griffin, Kathryn J; Sohrabi, Soroush; Coughlin, Patrick A; Scott, D Julian A

2014-01-01

In the era of Abdominal Aortic Aneurysm (AAA) screening, pharmacotherapies to attenuate AAA growth are sought. HMG Co-A reductase inhibitors (statins) have pleiotropic actions independent of their lipid lowering effects and have been suggested as potential treatment for small AAAs. We systematically review the clinical evidence for this effect. Medline, EMBASE and the Cochrane Central Register of Controlled Trials (1950-2011) were searched for studies reporting data on the role of statin therapy on AAA growth rate. No language restrictions were placed on the search. References of retrieved articles and pertinent journals were hand searched. Included studies were reviewed by 2 independent observers. The search retrieved 164 papers, 100 were irrelevant based on their title, 47 were reviews and 1 was a letter. 8 studies were excluded based on review of their abstract leaving 8 for inclusion in the study. Eight observational clinical studies with a total of 4,466 patients were reviewed. Four studies demonstrated reduced AAA expansion in statin users while 4 studies failed to demonstrate this effect. The method of determining AAA growth rates varied significantly between the studies and the ability of many studies to control for misclassification bias was poor. The claim that statins attenuate AAA growth remains questionable. Further prospective studies with stringent identification and verification of statin usage and a standardised method of estimating AAA growth rates are required. Statin type and dose also merit consideration.

Association between osteopontin and human abdominal aortic aneurysm.

PubMed

Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

2007-03-01

In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

Short-term complications associated with the use of transvaginal mesh in pelvic floor reconstructive surgery: Results from a multi-institutional prospectively maintained dataset.

PubMed

Caveney, Maxx; Haddad, Devin; Matthews, Catherine; Badlani, Gopal; Mirzazadeh, Majid

2017-11-01

Vaginal reconstructive surgery can be performed with or without mesh. We sought to determine comparative rates of perioperative complications of native tissue versus vaginal mesh repairs for pelvic organ prolapse. Using the National Surgical Quality Improvement Program (NSQIP) database, we concatenated surgical data from vaginal procedures for prolapse repair, including anterior and posterior colporrhaphy, paravaginal defect repair, enterocele repair, and vaginal colpopexy using Current Procedural Terminology (CPT) coding. We stratified this data by the modifier associated with mesh usage at the time of the procedure. We then compared 30-day perioperative outcomes, postoperative complications (bleeding, infection, etc), and readmission rates between women with and without mesh-based repairs. We identified 10 657 vaginal reconstructive procedures without mesh and 959 mesh-based repairs from 2009 through 2013. Patients undergoing mesh repair were more likely to experience at least one complication than native tissue repair (9.28% vs 6.15%, P < 0.001), with the overall complication rate also being higher in the mesh group (11.37% vs 9.39%, P = 0.03). Procedures with mesh had a higher rate of perioperative bleeding requiring transfusion than native tissue repair (2.3% vs 0.49%, P < 0.001), and organ surgical site infection (SSI) (0.52% vs 0.17%, P = 0.02). There were no significant differences in rates of readmission, superficial, or deep SSIs, pneumonia, urinary tract infection, sepsis, or renal failure. The use of vaginal mesh for pelvic organ prolapse repair appears to result in a higher rate of perioperative complications than native tissue repair. Patients undergoing these procedures should be counselled preoperatively concerning these risks. © 2017 Wiley Periodicals, Inc.

Protein quality control in organelles - AAA/FtsH story.

PubMed

Janska, Hanna; Kwasniak, Malgorzata; Szczepanowska, Joanna

2013-02-01

This review focuses on organellar AAA/FtsH proteases, whose proteolytic and chaperone-like activity is a crucial component of the protein quality control systems of mitochondrial and chloroplast membranes. We compare the AAA/FtsH proteases from yeast, mammals and plants. The nature of the complexes formed by AAA/FtsH proteases and the current view on their involvement in degradation of non-native organellar proteins or assembly of membrane complexes are discussed. Additional functions of AAA proteases not directly connected with protein quality control found in yeast and mammals but not yet in plants are also described shortly. Following an overview of the molecular functions of the AAA/FtsH proteases we discuss physiological consequences of their inactivation in yeast, mammals and plants. The molecular basis of phenotypes associated with inactivation of the AAA/FtsH proteases is not fully understood yet, with the notable exception of those observed in m-AAA protease-deficient yeast cells, which are caused by impaired maturation of mitochondrial ribosomal protein. Finally, examples of cytosolic events affecting protein quality control in mitochondria and chloroplasts are given. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

Paraesophageal Hernia Repair: Techniques for Success.

PubMed

Cohn, Tyler D; Soper, Nathaniel J

2017-01-01

With the introduction of laparoscopy, the outcomes of patients undergoing paraesophageal hernia repair have improved dramatically. When the fundamentals of a proper repair are followed, patients can expect to have improvement in gastroesophageal reflux symptoms, including heartburn, regurgitation, chest pain, dysphagia, and dyspnea. Adhering to these principles will alleviate patients' symptoms and avoid reoperation. This article describes the approach to paraesophageal hernia repair, including patient evaluation, operative technique, and postoperative management. Esophageal lengthening and crural reinforcement with mesh are addressed as well. Adhering to the basic techniques outlined in this article should lead to successful and durable patient outcomes following a paraesophageal hernia repair.

Strategy of endovascular versus open repair for patients with clinical diagnosis of ruptured abdominal aortic aneurysm: the IMPROVE RCT.

PubMed

Ulug, Pinar; Hinchliffe, Robert J; Sweeting, Michael J; Gomes, Manuel; Thompson, Matthew T; Thompson, Simon G; Grieve, Richard J; Ashleigh, Raymond; Greenhalgh, Roger M; Powell, Janet T

2018-05-01

Ruptured abdominal aortic aneurysm (AAA) is a common vascular emergency. The mortality from emergency endovascular repair may be much lower than the 40-50% reported for open surgery. To assess whether or not a strategy of endovascular repair compared with open repair reduces 30-day and mid-term mortality (including costs and cost-effectiveness) among patients with a suspected ruptured AAA. Randomised controlled trial, with computer-generated telephone randomisation of participants in a 1 : 1 ratio, using variable block size, stratified by centre and without blinding. Vascular centres in the UK ( n  = 29) and Canada ( n  = 1) between 2009 and 2013. A total of 613 eligible participants (480 men) with a ruptured aneurysm, clinically diagnosed at the trial centre. A total of 316 participants were randomised to the endovascular strategy group (immediate computerised tomography followed by endovascular repair if anatomically suitable or, if not suitable, open repair) and 297 were randomised to the open repair group (computerised tomography optional). The primary outcome measure was 30-day mortality, with 30-day reinterventions, costs and disposal as early secondary outcome measures. Later outcome measures included 1- and 3-year mortality, reinterventions, quality of life (QoL) and cost-effectiveness. The 30-day mortality was 35.4% in the endovascular strategy group and 37.4% in the open repair group [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.66 to 1.28; p  = 0.62, and, after adjustment for age, sex and Hardman index, OR 0.94, 95% CI 0.67 to 1.33]. The endovascular strategy appeared to be more effective in women than in men (interaction test p  = 0.02). More discharges in the endovascular strategy group (94%) than in the open repair group (77%) were directly to home ( p  < 0.001). Average 30-day costs were similar between groups, with the mean difference in costs being -£1186 (95% CI -£2997 to £625), favouring the endovascular strategy group. After 1 year, survival and reintervention rates were similar in the two groups, QoL (at both 3 and 12 months) was higher in the endovascular strategy group and the mean cost difference was -£2329 (95% CI -£5489 to £922). At 3 years, mortality was 48% and 56% in the endovascular strategy group and open repair group, respectively (OR 0.73, 95% CI 0.53 to 1.00; p  = 0.053), with a stronger benefit for the endovascular strategy in the subgroup of 502 participants in whom repair was started for a proven rupture (OR 0.62, 95% CI 0.43 to 0.89; p  = 0.009), whereas aneurysm-related reintervention rates were non-significantly higher in this group. At 3 years, considering all participants, there was a mean difference of 0.174 quality-adjusted life-years (QALYs) (95% CI 0.002 to 0.353 QALYs) and, among the endovascular strategy group, a cost difference of -£2605 (95% CI -£5966 to £702), leading to 88% of estimates in the cost-effectiveness plane being in the quadrant showing the endovascular strategy to be 'dominant'. Because of the pragmatic design of this trial, 33 participants in the endovascular strategy group and 26 in the open repair group breached randomisation allocation. The endovascular strategy was not associated with a significant reduction in either 30-day mortality or cost but was associated with faster participant recovery. By 3 years, the endovascular strategy showed a survival and QALY gain and was highly likely to be cost-effective. Future research could include improving resuscitation for older persons with circulatory collapse, the impact of local anaesthesia and emergency consent procedures. Current Controlled Trials ISRCTN48334791 and NCT00746122. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 31. See the NIHR Journals Library website for further project information.

Abdominal aortic aneurysm: novel mechanisms and therapies.

PubMed

Davis, Frank M; Rateri, Debra L; Daugherty, Alan

2015-11-01

Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, matrix metalloproteinase (MMP)-3, TGFBR2, and SORT1 loci, are associated with AAA development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β, and angiotensin II, are involved in the pathogenesis of AAAs. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Preclinical investigations into pharmacological therapies for AAAs have provided intriguing insight into the roles of microRNAs in regulating many pathological pathways in AAA development. Several large clinical trials are ongoing, seeking to translate preclinical findings into therapeutic options. Recent studies have identified many potential mechanisms involved in AAA pathogenesis that provide insight into the development of a medical treatment for this disease.

The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria.

PubMed

König, Tim; Tröder, Simon E; Bakka, Kavya; Korwitz, Anne; Richter-Dennerlein, Ricarda; Lampe, Philipp A; Patron, Maria; Mühlmeister, Mareike; Guerrero-Castillo, Sergio; Brandt, Ulrich; Decker, Thorsten; Lauria, Ines; Paggio, Angela; Rizzuto, Rosario; Rugarli, Elena I; De Stefani, Diego; Langer, Thomas

2016-10-06

Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca 2+ uniporter MCU. While MAIP1 assists biogenesis of the MCU subunit EMRE, the m-AAA protease degrades non-assembled EMRE and ensures efficient assembly of gatekeeper subunits with MCU. Loss of the m-AAA protease results in accumulation of constitutively active MCU-EMRE channels lacking gatekeeper subunits in neuronal mitochondria and facilitates mitochondrial Ca 2+ overload, mitochondrial permeability transition pore opening, and neuronal death. Together, our results explain neuronal loss in m-AAA protease deficiency by deregulated mitochondrial Ca 2+ homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Structural Elements Regulating AAA+ Protein Quality Control Machines.

PubMed

Chang, Chiung-Wen; Lee, Sukyeong; Tsai, Francis T F

2017-01-01

Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins. In this mini-review, we will discuss structural elements present in AAA+ proteins involved in protein quality control, drawing similarities to their known role in substrate interaction by AAA+ proteins involved in DNA translocation. Elements to be discussed include the pore loop-1, the Inter-Subunit Signaling (ISS) motif, and the Pre-Sensor I insert (PS-I) motif. Lastly, we will summarize our current understanding on the inter-relationship of those structural elements and propose a model how ATP binding and hydrolysis might be coupled to polypeptide translocation in protein quality control machines.

Comparison of Revision Rates of Anterior- and Posterior-Approach Ptosis Surgery: A Retrospective Review of 1519 Cases.

PubMed

Chou, Eva; Liu, Jun; Seaworth, Cathleen; Furst, Meredith; Amato, Malena M; Blaydon, Sean M; Durairaj, Vikram D; Nakra, Tanuj; Shore, John W

To compare revision rates for ptosis surgery between posterior-approach and anterior-approach ptosis repair techniques. This is the retrospective, consecutive cohort study. All patients undergoing ptosis surgery at a high-volume oculofacial plastic surgery practice over a 4-year period. A retrospective chart review was conducted of all patients undergoing posterior-approach and anterior-approach ptosis surgery for all etiologies of ptosis between 2011 and 2014. Etiology of ptosis, concurrent oculofacial surgeries, revision, and complications were analyzed. The main outcome measure is the ptosis revision rate. A total of 1519 patients were included in this study. The mean age was 63 ± 15.4 years. A total of 1056 (70%) of patients were female, 1451 (95%) had involutional ptosis, and 1129 (74.3%) had concurrent upper blepharoplasty. Five hundred thirteen (33.8%) underwent posterior-approach ptosis repair, and 1006 (66.2%) underwent anterior-approach ptosis repair. The degree of ptosis was greater in the anterior-approach ptosis repair group. The overall revision rate for all patients was 8.7%. Of the posterior group, 6.8% required ptosis revision; of the anterior group, 9.5% required revision surgery. The main reason for ptosis revision surgery was undercorrection of one or both eyelids. Concurrent brow lifting was associated with a decreased, but not statistically significant, rate of revision surgery. Patients who underwent unilateral ptosis surgery had a 5.1% rate of Hering's phenomenon requiring ptosis repair in the contralateral eyelid. Multivariable logistic regression for predictive factors show that, when adjusted for gender and concurrent blepharoplasty, the revision rate in anterior-approach ptosis surgery is higher than posterior-approach ptosis surgery (odds ratio = 2.08; p = 0.002). The overall revision rate in patients undergoing ptosis repair via posterior-approach or anterior-approach techniques is 8.7%. There is a statistically higher rate of revision with anterior-approach ptosis repair.

Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy?

PubMed

Dean, Benjamin John Floyd; Franklin, Sarah Louise; Murphy, Richard J; Javaid, Muhammad K; Carr, Andrew Jonathan

2014-12-01

Glucocorticoid injection (GCI) and surgical rotator cuff repair are two widely used treatments for rotator cuff tendinopathy. Little is known about the way in which medical and surgical treatments affect the human rotator cuff tendon in vivo. We assessed the histological and immunohistochemical effects of these common treatments on the rotator cuff tendon. Controlled laboratory study. Supraspinatus tendon biopsies were taken before and after treatment from 12 patients undergoing GCI and 8 patients undergoing surgical rotator cuff repair. All patients were symptomatic and none of the patients undergoing local GCI had full thickness tears of the rotator cuff. The tendon tissue was then analysed using histological techniques and immunohistochemistry. There was a significant increase in nuclei count and vascularity after rotator cuff repair and not after GCI (both p=0.008). Hypoxia inducible factor 1α (HIF-1α) and cell proliferation were only increased after rotator cuff repair (both p=0.03) and not GCI. The ionotropic N-methyl-d-aspartate receptor 1 (NMDAR1) glutamate receptor was only increased after GCI and not rotator cuff repair (p=0.016). An increase in glutamate was seen in both groups following treatment (both p=0.04), while an increase in the receptor metabotropic glutamate receptor 7 (mGluR7) was only seen after rotator cuff repair (p=0.016). The increases in cell proliferation, vascularity and HIF-1α after surgical rotator cuff repair appear consistent with a proliferative healing response, and these features are not seen after GCI. The increase in the glutamate receptor NMDAR1 after GCI raises concerns about the potential excitotoxic tendon damage that may result from this common treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

On the optimization of low-cost FDM 3D printers for accurate replication of patient-specific abdominal aortic aneurysm geometry.

PubMed

Chung, Michael; Radacsi, Norbert; Robert, Colin; McCarthy, Edward D; Callanan, Anthony; Conlisk, Noel; Hoskins, Peter R; Koutsos, Vasileios

2018-01-01

There is a potential for direct model manufacturing of abdominal aortic aneurysm (AAA) using 3D printing technique for generating flexible semi-transparent prototypes. A patient-specific AAA model was manufactured using fused deposition modelling (FDM) 3D printing technology. A flexible, semi-transparent thermoplastic polyurethane (TPU), called Cheetah Water (produced by Ninjatek, USA), was used as the flexible, transparent material for model manufacture with a hydrophilic support structure 3D printed with polyvinyl alcohol (PVA). Printing parameters were investigated to evaluate their effect on 3D-printing precision and transparency of the final model. ISO standard tear resistance tests were carried out on Ninjatek Cheetah specimens for a comparison of tear strength with silicone rubbers. It was found that an increase in printing speed decreased printing accuracy, whilst using an infill percentage of 100% and printing nozzle temperature of 255 °C produced the most transparent results. The model had fair transparency, allowing external inspection of model inserts such as stent grafts, and good flexibility with an overall discrepancy between CAD and physical model average wall thicknesses of 0.05 mm (2.5% thicker than the CAD model). The tear resistance test found Ninjatek Cheetah TPU to have an average tear resistance of 83 kN/m, higher than any of the silicone rubbers used in previous AAA model manufacture. The model had lower cost (4.50 GBP per model), shorter manufacturing time (25 h 3 min) and an acceptable level of accuracy (2.61% error) compared to other methods. It was concluded that the model would be of use in endovascular aneurysm repair planning and education, particularly for practicing placement of hooked or barbed stents, due to the model's balance of flexibility, transparency, robustness and cost-effectiveness.

Benefits and harms of screening men for abdominal aortic aneurysm in Sweden: a registry-based cohort study.

PubMed

Johansson, Minna; Zahl, Per Henrik; Siersma, Volkert; Jørgensen, Karsten Juhl; Marklund, Bertil; Brodersen, John

2018-06-16

Large reductions in the incidence of abdominal aortic aneurysm (AAA) and AAA-related mortality mean that results from randomised trials of screening for the disorder might be out-dated. The aim of this study was to estimate the effect of AAA screening in Sweden on disease-specific mortality, incidence, and surgery. Individual data on the incidence of AAA, AAA mortality, and surgery for AAA in a cohort of men aged 65 years who were invited to screening between 2006 and 2009, were compared with data from an age-matched contemporaneous cohort of men who were not invited for AAA screening. We also analysed national data for all men aged 40-99 years between Jan 1, 1987, and Dec 31, 2015, to explore background trends. Adjustment for confounding was done by weighting the analyses with a propensity score obtained from a logistic regression model on cohort year, marital status, educational level, income, and whether the patient already had an AAA diagnosis at baseline. Adjustment for differential attrition was also done by weighting the analyses with the inverse probability of still being in the cohort 6 years after screening. Generalised estimating equations were used to adjust the variance for repeated measurement and in response to the weighting. AAA mortality in Swedish men has decreased from 36 to ten deaths per 100 000 men aged 65-74 years between the early 2000s and 2015. Mortality decreased at similar rates in all Swedish counties, irrespective of whether AAA screening was offered. After 6 years with screening, we found a non-significant reduction in AAA mortality associated with screening (adjusted odds ratio [aOR] 0·76, 95% CI 0·38-1·51), which means that two men (95% CI -3 to 7) avoid death from AAA for every 10 000 men offered screening. Screening was associated with increased odds of AAA diagnosis (aOR 1·52, 95% CI 1·16-1·99; p=0·002) and an increased risk of elective surgery (aOR 1·59, 95% CI 1·20-2·10; p=0·001), such that for every 10 000 men offered screening, 49 men (95% CI 25-73) were likely to be overdiagnosed, 19 of whom (95% CI 1-37) had avoidable surgery that increased their risk of mortality and morbidity. AAA screening in Sweden did not contribute substantially to the large observed reductions in AAA mortality. The reductions were mostly caused by other factors, probably reduced smoking. The small benefit and substantially less favourable benefit-to-harm balance call the continued justification of the intervention into question. Research Unit and Section for General Practice, FoUU-centrum Fyrbodal, Sweden, and the region of Västra Götaland, Sweden. Copyright © 2018 Elsevier Ltd. All rights reserved.

Low prevalence of abdominal aortic aneurysm in the Seychelles population aged 50 to 65 years.

PubMed

Yerly, Patrick; Madeleine, George; Riesen, Walter; Bovet, Pascal

2013-03-01

The prevalence of abdominal aortic aneurysm (AAA) and its risk factors are well known in Western countries but few data are available from low- and middle- income countries. We are not aware of systematically collected population- based data on AAA in the African region. We evaluated the prevalence of AAA in a population- based cardiovascular survey conducted in the Republic of Seychelles in 2004 (Indian Ocean, African region). Among the 353 participants aged 50 to 64 years and screened with ultrasound, the prevalence of AAA was 0.3% (95% CI: 0- 0.9) and the prevalence of ectatic dilatations of the abdominal aorta was 1.5% (95% CI: 0.2- 2.8). The prevalence of AAA in the general population seemed lower in Seychelles than in Western countries, despite a high prevalence in Seychelles of risk factors of AAA, such as smoking (in men), high blood pressure and hypercholesterolaemia.

Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation

PubMed Central

Annambhotla, Suman; Bourgeois, Sebastian; Wang, Xinwen; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

2010-01-01

Abdominal Aortic Aneurysm (AAA) is an increasingly common clinical condition with fatal implications. It is associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Although significant evidence has emerged in the last decade, the molecular mechanisms of AAA formation remains poorly understood. Currently, the treatment for AAA remains primarily surgical with the lone innovation of endovascular therapy. With advance in the human genome, understanding precisely which molecules and genes mediate AAA development and blocking their activity at the molecular level could lead to important new discoveries and therapies. This review summarizes recent updates in molecular mechanisms of AAA formation including animal models, autoimmune components, infection, key molecules and cytokines, mechanical forces, genetics and pharmacotherapy. This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in AAA. PMID:18259804

Outcomes after elective abdominal aortic aneurysm repair in obese versus nonobese patients.

PubMed

Locham, Satinderjit; Rizwan, Muhammad; Dakour-Aridi, Hanaa; Faateh, Muhammad; Nejim, Besma; Malas, Mahmoud

2018-06-07

Obesity is a worldwide epidemic, particularly in Western society. It predisposes surgical patients to an increased risk of adverse outcomes. The aim of our study was to use a nationally representative vascular database and to compare in-hospital outcomes in obese vs nonobese patients undergoing elective open aortic repair (OAR) and endovascular aneurysm repair (EVAR). All patients undergoing elective abdominal aortic aneurysm repair were identified in the Vascular Quality Initiative database (2003-2017). Obesity was defined as body mass index ≥30 kg/m 2 . Univariable (Student t-test and χ 2  test) and multivariable (logistic regression) analyses were implemented to compare in-hospital mortality and any major complications (wound infection, renal failure, and cardiopulmonary failure) in obese vs nonobese patients. We identified a total of 33,082 patients undergoing elective OAR (nonobese, n = 4605 [72.4%]; obese, n = 1754 [27.6%]) and EVAR (nonobese, n = 18,338 [68.6%]; obese, n = 8385 [31.4%]). Obese patients undergoing OAR and EVAR were relatively younger compared with nonobese patients (mean age [standard deviation], 67.55 [8.26] years vs 70.27 [8.30] years and 71.06 [8.22] years vs 74.55 [8.55] years), respectively; (both P < .001). Regardless of approach, obese patients had slightly longer operative time (OAR, 259.02 [109.97] minutes vs 239.37 [99.78] minutes; EVAR, 138.27 [70.64] minutes vs 134.34 [69.98] minutes) and higher blood loss (OAR, 2030 [1823] mL vs 1619 [1642] mL; EVAR, 228 [354] mL vs 207 [312] mL; both P < .001). There was no significant difference in mortality between the two groups undergoing OAR and EVAR (OAR, 2.9% vs 3.2% [P = .50]; EVAR, 0.5% vs 0.6% [P = .76]). On multivariable analysis, obese patients undergoing OAR had 33% higher odds of renal failure (adjusted odds ratio [OR], 1.33; 95% confidence interval [CI], 1.09-1.63; P = .006) and 75% higher odds of wound infections (adjusted OR, 1.75; 95% CI, 1.11-2.76; P = .02) compared with nonobese patients. However, in patients undergoing EVAR, no association was seen between obesity and any major complications. A significant interaction was found between obesity and surgical approach in the event of renal failure, in which obese patients undergoing OAR had significantly higher odds of renal failure compared with those in the EVAR group (OR interaction , 1.36; 95% CI, 1.05-1.75; P = .02). Using a large nationally representative database, we demonstrated an increased risk of renal failure and wound infections in obese patients undergoing OAR compared with nonobese patients. On the other hand, obesity did not seem to increase the odds of major adverse outcomes in patients undergoing EVAR. Further long-term prospective studies are needed to verify the effects of obesity after abdominal aortic aneurysm repair and the implications of these findings in clinical decision-making. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

In vivo topical application of acetyl aspartic acid increases fibrillin-1 and collagen IV deposition leading to a significant improvement of skin firmness.

PubMed

Gillbro, J M; Merinville, E; Cattley, K; Al-Bader, T; Hagforsen, E; Nilsson, M; Mavon, A

2015-10-01

Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A-A was well tolerated. In this study, the aim was to investigate whether A-A-A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. Two separate double-blind vehicle-controlled in vivo studies were conducted using a 1% A-A-A containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of A-A-A on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to A-A-A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. Twelve-day topical application of 1% A-A-A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A-A-A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A-A-A. However, only A-A-A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A-A-A as a skin-firming active ingredient. In this study, we showed the in vivo efficacy of 1% A-A-A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti-ageing 'cosmeceutical' ingredient answering the needs of our key consumer base. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

The Relationship Between Serum Interleukin-1α and Asymptomatic Infrarenal Abdominal Aortic Aneurysm Size, Morphology, and Growth Rates.

PubMed

Ahmad, Mehtab; Kuravi, Sahithi; Hodson, James; Rainger, G Ed; Nash, Gerard B; Vohra, Rajiv K; Bradbury, Andrew W

2018-02-16

In a pilot study, a relationship between abdominal aortic aneurysm (AAA) diameter and serum interleukin (IL)-1α levels was reported, and that endothelial cell (EC) activation in vitro in response to serum from patients with AAA was blocked by anti-IL-1α antibodies. The aim of the present study was to further investigate the relationship between serum IL-1α and asymptomatic infrarenal AAA size, morphology, and growth rates. Serum IL-1α was measured using enzyme linked immunosorbent assay in 101 patients with asymptomatic, infrarenal AAA and related to aneurysm size, morphology, and growth rates. IL-1α was measured in 101 patients. There was no statistically significant difference in mean age between men and women. IL-1α was detectable in 62.4% of patients; median IL-1α titre was 3.26 pg/mL. There was no statistically significant relationship between IL-1α and maximum AAA antero-posterior diameter as measured by ultrasound (p = .649), AAA morphology (aortic length [p = .394], sac [p = .369], and thrombus volume [p = .629]) as measured on computed tomography, absolute increase in AAA diameter (p = .214), or AAA growth rate (p = .230). IL-1α is detectable in the majority of patients with infrarenal AAA, but the cause and clinical significance of this novel observation remains unknown. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition.

PubMed

Cafueri, Giuseppe; Parodi, Federica; Pistorio, Angela; Bertolotto, Maria; Ventura, Francesco; Gambini, Claudio; Bianco, Paolo; Dallegri, Franco; Pistoia, Vito; Pezzolo, Annalisa; Palombo, Domenico

2012-01-01

Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with AAA in comparison with matched controls. TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG). Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed.

Abdominal aortic aneurysm screening program using hand-held ultrasound in primary healthcare

PubMed Central

Kostov, Belchin; Navarro González, Marta; Cararach Salami, Daniel; Pérez Jiménez, Alfonso; Gilabert Solé, Rosa; Bru Saumell, Concepció; Donoso Bach, Lluís; Villalta Martí, Mireia; González-de Paz, Luis; Ruiz Riera, Rafael; Riambau Alonso, Vicenç; Acar-Denizli, Nihan; Farré Almacellas, Marta; Ramos-Casals, Manuel; Benavent Àreu, Jaume

2017-01-01

We determined the feasibility of abdominal aortic aneurysm (AAA) screening program led by family physicians in public primary healthcare setting using hand-held ultrasound device. The potential study population was 11,214 men aged ≥ 60 years attended by three urban, public primary healthcare centers. Participants were recruited by randomly-selected telephone calls. Ultrasound examinations were performed by four trained family physicians with a hand-held ultrasound device (Vscan®). AAA observed were verified by confirmatory imaging using standard ultrasound or computed tomography. Cardiovascular risk factors were determined. The prevalence of AAA was computed as the sum of previously-known aneurysms, aneurysms detected by the screening program and model-based estimated undiagnosed aneurysms. We screened 1,010 men, with mean age of 71.3 (SD 6.9) years; 995 (98.5%) men had normal aortas and 15 (1.5%) had AAA on Vscan®. Eleven out of 14 AAA-cases (78.6%) had AAA on confirmatory imaging (one patient died). The total prevalence of AAA was 2.49% (95%CI 2.20 to 2.78). The median aortic diameter at diagnosis was 3.5 cm in screened patients and 4.7 cm (p<0.001) in patients in whom AAA was diagnosed incidentally. Multivariate logistic regression analysis identified coronary heart disease (OR = 4.6, 95%CI 1.3 to 15.9) as the independent factor with the highest odds ratio. A screening program led by trained family physicians using hand-held ultrasound was a feasible, safe and reliable tool for the early detection of AAA. PMID:28453577

Analysis of the cooperative ATPase cycle of the AAA+ chaperone ClpB from Thermus thermophilus by using ordered heterohexamers with an alternating subunit arrangement.

PubMed

Yamasaki, Takashi; Oohata, Yukiko; Nakamura, Toshiki; Watanabe, Yo-hei

2015-04-10

The ClpB/Hsp104 chaperone solubilizes and reactivates protein aggregates in cooperation with DnaK/Hsp70 and its cofactors. The ClpB/Hsp104 protomer has two AAA+ modules, AAA-1 and AAA-2, and forms a homohexamer. In the hexamer, these modules form a two-tiered ring in which each tier consists of homotypic AAA+ modules. By ATP binding and its hydrolysis at these AAA+ modules, ClpB/Hsp104 exerts the mechanical power required for protein disaggregation. Although ATPase cycle of this chaperone has been studied by several groups, an integrated understanding of this cycle has not been obtained because of the complexity of the mechanism and differences between species. To improve our understanding of the ATPase cycle, we prepared many ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately and measured their nucleotide binding, ATP hydrolysis, and disaggregation abilities. The results indicated that the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring was sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. We also found that cooperative ATP hydrolysis in at least one ring was needed for the disaggregation activity of ClpB. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Safety assessment of a novel active ingredient, acetyl aspartic acid, according to the EU Cosmetics Regulation and the Scientific Committee on Consumer Safety guidelines.

PubMed

Daly, P; Moran, G

2015-10-01

Acetyl aspartic acid (A-A-A) was proposed as a new novel active ingredient for use in cosmetics. The safety of A-A-A was assessed by following an in-house-developed 'New Ingredient Testing Strategy', which was designed in accordance with the Scientific Committee on Consumer Safety (SCCS) notes of guidance and the requirements of Annex I of the EU Cosmetics Regulation. The aim of the project was to determine whether A-A-A was safe for use in cosmetics and to determine a maximum permitted safe level in the formulations. A literature review was conducted, consulting over 40 different information sources. This highlighted a number of gaps which required testing data. A-A-A was tested for phototoxicity according to OECD test guideline 432, skin irritation according to OECD test guideline 439 and eye irritation according to OECD test guideline 437. Dermal absorption of A-A-A was measured according to OECD test guideline 428 and was used to calculate the margin of safety (MoS). Finally, A-A-A was tested in a human repeat insult patch test (HRIPT) and a 14-day in-use tolerance study. A-A-A was non-phototoxic and was non-irritating to skin and eyes in in vitro testing. Dermal absorption was calculated to be 5%. The MoS for A-A-A was 351, at a level of 5%, for all cosmetic product types, indicating no systemic safety toxicity concern. A-A-A at 5% under occlusive patch on a panel of 50 adult volunteers induced no skin irritation or allergic reaction in the HRIPT study. Finally, repeated application of A-A-A to the periocular area, twice per day for 14 days, in 21 female volunteers, demonstrated that 1% A-A-A was well tolerated following dermatological and ophthalmological assessment in a cosmetic formulation. A-A-A was assessed as safe by the cosmetic safety assessor for use in cosmetics at a level of 5% in all cosmetic product types, in line with the requirements of the EU Cosmetics Regulation and in accordance with the SCCS notes of guidance. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Fundamental Characteristics of AAA+ Protein Family Structure and Function.

PubMed

Miller, Justin M; Enemark, Eric J

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

An Evaluation of Parastomal Hernia Repair Using the Americas Hernia Society Quality Collaborative.

PubMed

Fox, Sarah S; Janczyk, Randy; Warren, Jeremy A; Carbonell, Alfredo M; Poulose, Benjamin K; Rosen, Michael J; Hope, William W

2017-08-01

The purpose of this review was to evaluate outcomes relating to parastomal hernia repair. Data from the Americas Hernia Society Quality Collaborative were used to identify patients undergoing parastomal hernia repair from 2013 to 2016. Parastomal hernia repairs were compared with other repairs using Pearson's test and Wilcoxon test with a P value <0.05 considered significant. Parastomal hernia repairs were performed in 311 patients. Techniques of repair include open in 85 per cent and laparoscopic in 15 per cent. Mesh was used in 92 per cent with keyhole in 34 per cent, flat mesh in 33 per cent, and Sugarbaker in 25 per cent. Mesh types were permanent synthetic in 79 per cent, biologic in 13 per cent, absorbable synthetic in 6 per cent, and hybrid synthetic/biologic in 2 per cent. Most common location for mesh was sublay in 84 per cent followed by onlay in 14 per cent and inlay in 2 per cent with 59 per cent of patients undergoing a myofascial release. Ostomy disposition included ostomy left in situ (47%), moved to a new site (18%), taken down (22%), and rematured in same location in (13%). Outcomes related to parastomal hernia repair included 10 per cent surgical site infection, 24 per cent surgical site occurrence, and 12 per cent surgical site occurrences requiring procedural interventions with a 13 per cent readmission rate and 6 per cent reoperation rate. When comparing parastomal hernias with other ventral hernia repairs, parastomal hernias had a significantly higher surgical site infection, surgical site occurrence, surgical site occurrences requiring procedural intervention, readmission, reoperation rate, and length of stay, and were less commonly performed laparoscopically (P < 0.05). Most parastomal hernias are being repaired open with synthetic mesh in the sublay position. Less favorable outcomes of parastomal hernia repair when compared with other ventral hernia repairs are likely related to the complexity of parastomal hernia repair.

Risk Stratification for the Development of Respiratory Adverse Events Following Vascular Surgery Using the Society of Vascular Surgery’s Vascular Quality Initiative

PubMed Central

Genovese, Elizabeth A; Fish, Larry; Chaer, Rabih A; Makaroun, Michel S; Baril, Donald T

2017-01-01

Objective Post-operative respiratory adverse events (RAEs) are associated with high rates of morbidity and mortality in general surgery, however little is known about these complications in the vascular surgery population, a frail subset with multiple comorbidities. The objective of this study was to describe the contemporary incidence of RAEs in vascular surgery patients, the risk factors for this complication and the overall impact of RAEs on patient outcomes. Methods The Vascular Quality Initiative was queried (2003–2014) for patients who underwent endovascular abdominal aortic repair, open abdominal aortic aneurysm (AAA) repair, thoracic endovascular aortic repair (TEVAR), suprainguinal bypass or infrainguinal bypass. A mixed-effects logistic regression model determined the independent risk factors for RAEs. Using a random 85% of the cohort, a risk prediction score for RAEs was created and the score was validated using the remaining 15% of the cohort, comparing the predicted to the actual incidence of RAE and determining the area under the receiver operating characteristic curve. The independent risk of in-hospital mortality and discharge to a nursing facility associated with RAEs was determined using a mixed-effects logistic regression to control for baseline patient characteristics, operative variables and other post-operative adverse events. Results The cohort consisted of 52,562 patients, with a 5.4% incidence of RAEs. The highest rates of RAEs were seen in current smokers (6.1%), recent acute myocardial infarction (10.1%), symptomatic congestive heart failure (CHF) (9.9%), chronic obstructive pulmonary disease (COPD) requiring oxygen therapy (11.0%), urgent and emergent procedures (6.4% and 25.9%, respectively), open AAA repairs (17.6%), in-situ suprainguinal bypasses (9.68%) and TEVARs (9.6%). The variables included in the risk prediction score were age, body mass index, smoking status, CHF severity, COPD severity, degree of renal insufficiency, ambulatory status, transfer status, urgency and operative type. The predicted compared to the actual RAE incidence were highly correlated, with a correlation coefficient of 0.943 (P<.0001) and a c-statistic=0.818. RAEs had a significantly higher rates of in-hospital mortality (25.4% vs. 1.2%, P<.0001, adjusted OR=5.85, P<.0001) and discharge to a nursing facility (57.8% vs. 19.0%, P<.0001, adjusted OR=3.14, P<.0001). Conclusions RAEs are frequent and one of the strongest risk factors for in-hospital mortality and inability to be discharged home. Our risk prediction score accurately stratifies patients based on key demographics, comorbidities, presentation, and operative type that can be used to guide patient counseling, preoperative optimization, and post-operative management. Furthermore, it may be useful in developing quality benchmarks for RAE following major vascular surgery. PMID:27832989

Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men.

PubMed

Wang, Lu; Djousse, Luc; Song, Yiqing; Akinkuolie, Akintunde O; Matsumoto, Chisa; Manson, JoAnn E; Gaziano, J Michael; Sesso, Howard D

2017-01-01

Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (AAA) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no AAA at baseline, 471 reported a newly diagnosed AAA during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) < 25 kg/m 2 , the multivariable hazard ratio (HR [95% CI]) of newly diagnosed AAA was 1.30 [1.06-1.59] for BMI 25-<30 kg/m 2 and 1.69 [1.24-2.30] for BMI ≥ 30 kg/m 2 . The risk of diagnosed AAA was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known AAA risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed AAA (HR = 0.79 [0.57-1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed AAA, particularly over longer follow-up.

Impact of isotropic constitutive descriptions on the predicted peak wall stress in abdominal aortic aneurysms.

PubMed

Man, V; Polzer, S; Gasser, T C; Novotny, T; Bursa, J

2018-03-01

Biomechanics-based assessment of Abdominal Aortic Aneurysm (AAA) rupture risk has gained considerable scientific and clinical momentum. However, computation of peak wall stress (PWS) using state-of-the-art finite element models is time demanding. This study investigates which features of the constitutive description of AAA wall are decisive for achieving acceptable stress predictions in it. Influence of five different isotropic constitutive descriptions of AAA wall is tested; models reflect realistic non-linear, artificially stiff non-linear, or artificially stiff pseudo-linear constitutive descriptions of AAA wall. Influence of the AAA wall model is tested on idealized (n=4) and patient-specific (n=16) AAA geometries. Wall stress computations consider a (hypothetical) load-free configuration and include residual stresses homogenizing the stresses across the wall. Wall stress differences amongst the different descriptions were statistically analyzed. When the qualitatively similar non-linear response of the AAA wall with low initial stiffness and subsequent strain stiffening was taken into consideration, wall stress (and PWS) predictions did not change significantly. Keeping this non-linear feature when using an artificially stiff wall can save up to 30% of the computational time, without significant change in PWS. In contrast, a stiff pseudo-linear elastic model may underestimate the PWS and is not reliable for AAA wall stress computations. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms

PubMed Central

Yang, Le; Shen, Lin; Gao, Peixian; Li, Gang; He, Yuxiang; Wang, Maohua; Zhou, Hua; Yuan, Hai; Jin, Xing; Wu, Xuejun

2017-01-01

Background and aims Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). Methods AAA was induced in ApoE−/− mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. Results Phospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model. Conclusions Activation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA. PMID:29190959

Assessment of the accuracy of AortaScan for detection of abdominal aortic aneurysm (AAA).

PubMed

Abbas, A; Smith, A; Cecelja, M; Waltham, M

2012-02-01

AortaScan AMI 9700 is a portable 3D ultrasound device that automatically measures the maximum diameter of the abdominal aorta without the need for a trained sonographer. It is designed to rapidly diagnose or exclude an AAA and may have particular use in screening programs. Our objective was to determine its accuracy to detect AAA. Subjects from our AAA screening and surveillance programs were examined. The aorta was scanned using the AortaScan and computed tomography (CT). Ninety-one subjects underwent imaging (44 AAA on conventional ultrasound surveillance and 47 controls). The largest measurement obtained by AortaScan was compared against the CT-aortic measurement. The mean aortic diameter was 2.8 cm. The CT scan confirmed the diagnosis of AAA in 43 subjects. There was one false positive measurement on conventional ultrasound. AortaScan missed the diagnosis of AAA in eight subjects. There were thirteen false positive measurements. The sensitivity, specificity, positive and negative predictive values were 81%, 72%, 72% and 81% respectively. A device to detect AAA without the need for a trained operator would have potential in a community-based screening programme. The AortaScan, however, lacks adequate sensitivity and significant technical improvement is necessary before it could be considered a replacement for trained screening personnel. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm.

PubMed

Pincemail, J; Defraigne, J O; Cheramy-Bien, J P; Dardenne, N; Donneau, A F; Albert, A; Labropoulos, N; Sakalihasan, N

2012-01-01

Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients. Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤ 50 or > 50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased. The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.

Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Fengxia; Zhang, Minjie; University of Chinese Academy of Sciences, Beijing 100049

2014-10-03

Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage.more » Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.« less

SU-F-T-609: Impact of Dosimetric Variation for Prescription Dose Using Analytical Anisotropic Algorithm (AAA) in Lung SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawai, D; Takahashi, R; Kamima, T

Purpose: Actual irradiated prescription dose to patients cannot be verified. Thus, independent dose verification and second treatment planning system are used as the secondary check. AAA dose calculation engine has contributed to lung SBRT. We conducted a multi-institutional study to assess variation of prescription dose for lung SBRT when using AAA in reference to using Acuros XB and Clarkson algorithm. Methods: Six institutes in Japan participated in this study. All SBRT treatments were planed using AAA in Eclipse and Adaptive Convolve (AC) in Pinnacle3. All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU,more » Triangle Product, Ishikawa, Japan), which implemented a Clarkson-based dose calculation algorithm using CT image dataset. A retrospective analysis for lung SBRT plans (73 patients) was performed to compute the confidence limit (CL, Average±2SD) in dose between the AAA and the SMU. In one of the institutes, a additional analysis was conducted to evaluate the variations between the AAA and the Acuros XB (AXB). Results: The CL for SMU shows larger systematic and random errors of 8.7±9.9 % for AAA than the errors of 5.7±4.2 % for AC. The variations of AAA correlated with the mean CT values in the voxels of PTV (a correlation coefficient : −0.7) . The comparison of AXB vs. AAA shows smaller systematic and random errors of −0.7±1.7%. The correlation between dose variations for AXB and the mean CT values in PTV was weak (0.4). However, there were several plans with more than 2% deviation of AAPM TG114 (Maximum: −3.3 %). Conclusion: In comparison for AC, prescription dose calculated by AAA may be more variable in lung SBRT patient. Even AXB comparison shows unexpected variation. Care should be taken for the use of AAA in lung SBRT. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

A knowledge-based design framework for airplane conceptual and preliminary design

NASA Astrophysics Data System (ADS)

Anemaat, Wilhelmus A. J.

The goal of work described herein is to develop the second generation of Advanced Aircraft Analysis (AAA) into an object-oriented structure which can be used in different environments. One such environment is the third generation of AAA with its own user interface, the other environment with the same AAA methods (i.e. the knowledge) is the AAA-AML program. AAA-AML automates the initial airplane design process using current AAA methods in combination with AMRaven methodologies for dependency tracking and knowledge management, using the TechnoSoft Adaptive Modeling Language (AML). This will lead to the following benefits: (1) Reduced design time: computer aided design methods can reduce design and development time and replace tedious hand calculations. (2) Better product through improved design: more alternative designs can be evaluated in the same time span, which can lead to improved quality. (3) Reduced design cost: due to less training and less calculation errors substantial savings in design time and related cost can be obtained. (4) Improved Efficiency: the design engineer can avoid technically correct but irrelevant calculations on incomplete or out of sync information, particularly if the process enables robust geometry earlier. Although numerous advancements in knowledge based design have been developed for detailed design, currently no such integrated knowledge based conceptual and preliminary airplane design system exists. The third generation AAA methods are tested over a ten year period on many different airplane designs. Using AAA methods will demonstrate significant time savings. The AAA-AML system will be exercised and tested using 27 existing airplanes ranging from single engine propeller, business jets, airliners, UAV's to fighters. Data for the varied sizing methods will be compared with AAA results, to validate these methods. One new design, a Light Sport Aircraft (LSA), will be developed as an exercise to use the tool for designing a new airplane. Using these tools will show an improvement in efficiency over using separate programs due to the automatic recalculation with any change of input data. The direct visual feedback of 3D geometry in the AAA-AML, will lead to quicker resolving of problems as opposed to conventional methods.

Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The Poetic Study.

PubMed

Ungar, Bella; Engel, Tal; Yablecovitch, Doron; Lahat, Adi; Lang, Alon; Avidan, Benjamin; Har-Noy, Ofir; Carter, Dan; Levhar, Nina; Selinger, Limor; Neuman, Sandra; Natour, Ola Haj; Yavzori, Miri; Fudim, Ella; Picard, Orit; Kopylov, Uri; Chowers, Yehuda; Naftali, Timna; Broide, Efrat; Shachar, Eyal; Eliakim, Rami; Ben-Horin, Shomron

2018-06-01

Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively). When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.

Polymorphisms of the interleukin-6 gene promoter and abdominal aortic aneurysm.

PubMed

Smallwood, L; Allcock, R; van Bockxmeer, F; Warrington, N; Palmer, L J; Iacopetta, B; Norman, P E

2008-01-01

Elevated levels of circulating interleukin-6 (IL-6) have been reported in patients with abdominal aortic aneurysms (AAAs). Although this implicates inflammation as a cause of AAAs, there is also evidence that the aneurysmal aorta may secrete IL-6 into the circulation as a result of aortic proteolysis. Genetic association studies are one means of trying to clarify the role of specific mediators in the causal pathway. The aim of the present study was to examine the association between variants of the IL-6 gene and AAAs. An association study involving 677 men with screen-detected AAAs and 656 age-matched controls was performed. Three variants in the IL-6 promoter region were analysed: IL-6-174G>C (rs1800795), IL-6-572G>C (rs1800796) and IL-6-597G>A (rs1800797). Univariate regression of SNP genotype on AAA as a binary outcome was initially performed under a range of genetic models (additive, dominant and recessive). This was followed by multivariate analyses, testing the same models but including risk factors known to be associated with AAAs. All analyses and haplotype estimation were performed under a generalized linear model framework. IL-6-572G>C polymorphism (frequency 1.5% in cases) was identified as an independent risk factor for AAA with an odds ratio (OR) of 6.00 (95%CI: 1.22, 29.41) when applied to the recessive model. No association was seen in the additive or dominant models. In a multivariate analysis using the most common haplotype (h.111, frequency 48.7%) as a reference, h.211 (frequency 4.4%) was an independent risk factor for AAA (OR 1.56, 95%CI: 1.02, 2.39). The IL-6 572G>C polymorphism (and h.211 haplotype) is associated with AAA, however it is too rare to be an important cause of most AAAs. This does not support the concept that the elevated level of IL-6 reported in patients with AAAs is a primary cause of the aneurysmal process.

Adalimumab for Treatment of Noninfectious Uveitis: Immunogenicity and Clinical Relevance of Measuring Serum Drug Levels and Antidrug Antibodies.

PubMed

Cordero-Coma, Miguel; Calleja-Antolín, Sara; Garzo-García, Irene; Nuñez-Garnés, Ana M; Álvarez-Castro, Carolina; Franco-Benito, Manuel; Ruiz de Morales, Jose G

2016-12-01

To evaluate the rate of immunogenicity induced by adalimumab and its relationship with drug serum levels and clinical responses in patients with noninfectious uveitis. Prospective observational study. Consecutive patients from 1 referral center who initiated treatment with adalimumab for active noninfectious uveitis resistant to conventional therapy. All patients received 40 mg adalimumab every other week. Patients were evaluated clinically and immunologically before and after 4, 8, and 24 weeks of treatment. Clinical evaluation included assessment of changes in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and retinal angiographic leakage. Immunologic evaluation included assessment of serum trough adalimumab and antibodies against adalimumab (AAA) levels and class II HLA typing. Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved a complete response and 7 (28%) achieved a partial response. However, 7 of 25 patients (28%) were considered nonresponders. Median trough adalimumab serum levels were higher in responders than in nonresponders (P < 0.001). We observed AAA positivity (AAA+) at least 1 time point in 8 of 25 patients (32%), including 4 with transitory AAA and 4 with permanent AAA. In all patients with permanent AAA+, trough adalimumab levels became undetectable (P < 0.001). However, in patients who demonstrated transitory AAA+, no correlation was observed between AAA titers and adalimumab trough levels (P = 0.2).Concomitant immunosuppression did not show any protective effect on adalimumab immunogenicity in our cohort. An association between the presence of AAA+ and a worse uveitis outcome was observed only in patients with permanent AAA+, which correlated with undetectable adalimumab trough levels (P = 0.014). Treatment of noninfectious uveitis with adalimumab is associated with high rates of favorable clinical response. Overall, adalimumab trough levels were higher in responder patients. Development of permanent AAA was associated with undetectable trough adalimumab levels and worse uveitis outcome. Immunogenicity was more common in patients in whom uveitis was associated with a systemic disease and was not influenced by concomitant immunosuppressors. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Clinical implementation and evaluation of the Acuros dose calculation algorithm.

PubMed

Yan, Chenyu; Combine, Anthony G; Bednarz, Greg; Lalonde, Ronald J; Hu, Bin; Dickens, Kathy; Wynn, Raymond; Pavord, Daniel C; Saiful Huq, M

2017-09-01

The main aim of this study is to validate the Acuros XB dose calculation algorithm for a Varian Clinac iX linac in our clinics, and subsequently compare it with the wildely used AAA algorithm. The source models for both Acuros XB and AAA were configured by importing the same measured beam data into Eclipse treatment planning system. Both algorithms were validated by comparing calculated dose with measured dose on a homogeneous water phantom for field sizes ranging from 6 cm × 6 cm to 40 cm × 40 cm. Central axis and off-axis points with different depths were chosen for the comparison. In addition, the accuracy of Acuros was evaluated for wedge fields with wedge angles from 15 to 60°. Similarly, variable field sizes for an inhomogeneous phantom were chosen to validate the Acuros algorithm. In addition, doses calculated by Acuros and AAA at the center of lung equivalent tissue from three different VMAT plans were compared to the ion chamber measured doses in QUASAR phantom, and the calculated dose distributions by the two algorithms and their differences on patients were compared. Computation time on VMAT plans was also evaluated for Acuros and AAA. Differences between dose-to-water (calculated by AAA and Acuros XB) and dose-to-medium (calculated by Acuros XB) on patient plans were compared and evaluated. For open 6 MV photon beams on the homogeneous water phantom, both Acuros XB and AAA calculations were within 1% of measurements. For 23 MV photon beams, the calculated doses were within 1.5% of measured doses for Acuros XB and 2% for AAA. Testing on the inhomogeneous phantom demonstrated that AAA overestimated doses by up to 8.96% at a point close to lung/solid water interface, while Acuros XB reduced that to 1.64%. The test on QUASAR phantom showed that Acuros achieved better agreement in lung equivalent tissue while AAA underestimated dose for all VMAT plans by up to 2.7%. Acuros XB computation time was about three times faster than AAA for VMAT plans, and computation time for other plans will be discussed at the end. Maximum difference between dose calculated by AAA and dose-to-medium by Acuros XB (Acuros_D m,m ) was 4.3% on patient plans at the isocenter, and maximum difference between D 100 calculated by AAA and by Acuros_D m,m was 11.3%. When calculating the maximum dose to spinal cord on patient plans, differences between dose calculated by AAA and Acuros_D m,m were more than 3%. Compared with AAA, Acuros XB improves accuracy in the presence of inhomogeneity, and also significantly reduces computation time for VMAT plans. Dose differences between AAA and Acuros_D w,m were generally less than the dose differences between AAA and Acuros_D m,m . Clinical practitioners should consider making Acuros XB available in clinics, however, further investigation and clarification is needed about which dose reporting mode (dose-to-water or dose-to-medium) should be used in clinics. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.

PubMed

van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

2016-07-14

Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10(-3)). Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Genetic analysis of abdominal aortic aneurysms (AAA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

St. Jean, P.L.; Hart, B.K.; Zhang, X.C.

1994-09-01

The association between AAA and gender, smoking (SM), hypertension (HTN) and inguinal herniation (IH) was examined in 141 AAA probands and 139 of their 1st degree relatives with aortic exam (36 affected, 103 unaffected). There was no significant difference between age at diagnosis of affecteds and age at exam of unaffecteds. Of 181 males, 142 had AAA; of 99 females, 35 had AAA. Using log-linear modeling AAA was significantly associated at the 5% level with gender, SM and HTN but not IH. The association of AAA with SM and HTN held when males and females were analyzed separately. HTN wasmore » -1.5 times more common in both affected males and females, while SM was 1.5 and 2 times more common in affected males and females, respectively. Tests of association and linkage analyses were performed with relevant candidate genes: 3 COL3A1 polymorphisms (C/T, ALA/THR, AvaII), 2 ELN polymorphisms (SER/GLY, (CA)n), FBN1(TAAA)n, 2 APOB polymorphisms (Xbal,Ins/Del), CLB4B (CA)n, PI and markers D1S243 (CA)n, HPR (CA)n and MFD23(CA)n. The loci were genotyped in > 100 AAA probands and > 95 normal controls. No statistically significant evidence of association at the 5% level was obtained for any of the loci using chi-square test of association. 28 families with 2 or more affecteds were analyzed using the affected pedigree member method (APM) and lod-score analyses. There was no evidence for linkage with any loci using APM. Lod-score analysis under an autosomal recessive model resulted in excluding linkage (lod score < -2) of all loci to AAA at {theta}=0.0. Under an autosomal dominant model, linkage was excluded at {theta}=0.0 to ELN, APOB, CLG4B, D1S243, HPR and MFD23. The various genes previously proposed in AAA pathogenesis are neither associated nor casually related in our study population.« less

Characterization of the mechanical behavior and pathophysiological state of abdominal aortic aneurysms based on 4D ultrasound strain imaging

NASA Astrophysics Data System (ADS)

Wittek, Andreas; Blase, Christopher; Derwich, Wojciech; Schmitz-Rixen, Thomas; Fritzen, Claus-Peter

2017-06-01

Abdominal aortic aneurysms (AAA) are a degenerative disease of the human aortic wall that may lead to weakening and eventually rupture of the wall with high mortality rates. Since the currently established criterion for surgical or endovascular treatment of the disease is imprecise in the individual case and treatment is not free of complications, the need for additional patient-individual biomarkers for short-term AAA rupture risk as basis for improved clinical decision making. Time resolved 3D ultrasound combined with speckle tracking algorithms is a novel non-invasive medical imaging technique that provides full-field displacement and strain measurements of aortic and aneurysmal wall motion. This is patient-individual information that has not been used so far to assess wall strength and rupture risk. The current study uses simple statistical indices of the heterogeneous spatial distribution of in-plane strain components as biomarkers for the pathological state of the aortic and aneurysmal wall. The pathophysiological rationale behind this approach are the known changes in microstructural composition of the aortic wall with progression of AAA development that results in increased stiffening and heterogeneity of the walls mechanical properties and in decreased wall strength. In a comparative analysis of the aortic wall motion of young volunteers without known cardiovascular diseases, aged arteriosclerotic patients without AAA, and AAA patients, mean values of all in-plane strain components were significantly reduced, and the heterogeneity of circumferential strain was significantly increased in the AAA group compared to both other groups. The capacity of the proposed method to differentiate between wall motion of aged, arteriosclerotic patients and AAA patients is a promising step towards a new method for in vivo assessment of AAA wall strength or stratification of AAA rupture risk as basis for improved clinical decision making on surgical or endovascular treatment of AAA.

Abdominal Aortic Aneurysm: Novel Mechanisms and Therapies

PubMed Central

Davis, Frank M.; Rateri, Debra L.; Daugherty, Alan

2015-01-01

Purpose of review Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. Recent Findings An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, MMP3, TGFβR2 and SORT1 loci, are associated with AAA development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β and angiotensin II, are involved in the pathogenesis of AAAs. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Recent preclinical investigations into pharmacological therapies for AAAs have provided intriguing insight for roles of microRNAs to regulate many pathological pathways in AAA development. Several large clinical trials are ongoing seeking to translate preclinical findings into therapeutic options. Summary Recent studies have identified many potential mechanisms involved in AAA pathogenesis that provide insight for the development of a medical treatment for this disease. PMID:26352243

The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders

PubMed Central

Law, Kelsey B.; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O.; Moser, Ann; Brumell, John H.; Braverman, Nancy

2017-01-01

ABSTRACT Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs. PMID:28521612

The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders.

PubMed

Law, Kelsey B; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O; Moser, Ann; Brumell, John H; Braverman, Nancy; Kim, Peter K

2017-05-04

Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs.

The preventive and curative effects of melatonin against abdominal aortic aneurysm in rats.

PubMed

Tekin, Gözde; İsbir, Selim; Şener, Göksel; Çevik, Özge; Çetinel, Şule; Dericioğlu, Okan; Arsan, Sinan; Çobanoğlu, Adnan

2018-05-01

Oxygen free radicals are important components involved in the histopathologic tissue alterations observed during abdominal aortic aneurysms (AAAs). This study examined whether melatonin has protective or therapeutic effects against AAAs. Sprague-Dawley rats were divided into four groups. A CaCl 2 model was used to induce AAA. Starting on the operation day (Mel+AAA+Mel group) or 4 weeks after the operation (AAA+Mel group), the rats received intraperitoneal melatonin (10 mg/kg/day) for 6 and 2 weeks, respectively. The control and AAA groups received vehicle for 2 weeks after the sham operation and AAA induction, respectively. Angiographic measurements were recorded at the beginning, week 4, and week 6 of the study. After decapitation, aorta tissues were taken for the measurement of malondialdehyde, 8-hydroxy-2'-deoxyguanosine, glutathione levels, and myeloperoxidase and caspase-3 activity. Matrix metalloproteinase (MMP)-2, MMP-9, tumor necrosis factor-α, and inducible nitric oxide synthase protein expressions were analyzed by Western blot technique. Aortic tissues were also examined by light microscopy. CaCl 2 caused an inflammatory response and oxidative damage indicated by rises in malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. Myeloperoxidase and caspase-3 activities were increased, but glutathione levels were reduced. On the one hand, MMP-2, MMP-9, tumor necrosis factor-α, and inducible nitric oxide synthase protein expressions were increased in the vehicle-treated AAA group. On the other hand, melatonin treatment reversed all of these biochemical indices and histopathologic alterations. According to the data, although melatonin tended to reverse the biochemical parameters given on week 4, the preventive effect is more pronounced when given concomitantly with AAA induction because values were closer to the control levels. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Ultraviolet B Exposure Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Expanding CD4+Foxp3+ Regulatory T Cells.

PubMed

Hayashi, Tomohiro; Sasaki, Naoto; Yamashita, Tomoya; Mizoguchi, Taiji; Emoto, Takuo; Amin, Hilman Zulkifli; Yodoi, Keiko; Matsumoto, Takuya; Kasahara, Kazuyuki; Yoshida, Naofumi; Tabata, Tokiko; Kitano, Naoki; Fukunaga, Atsushi; Nishigori, Chikako; Rikitake, Yoshiyuki; Hirata, Ken-Ichi

2017-08-31

Pathogenic immune responses are known to play an important role in abdominal aortic aneurysm (AAA) development. Ultraviolet B (UVB) irradiation has been demonstrated to have therapeutic potential not only for cutaneous diseases but also for systemic inflammatory diseases in mice by suppressing immunoinflammatory responses. We investigated the effect of UVB irradiation on experimental AAA. We used an angiotensin II-induced AAA model in apolipoprotein E-deficient mice fed a high-cholesterol diet. Mice aged 10 weeks were irradiated with 5 kJ/m 2 UVB once weekly for 6 weeks (UVB-irradiated, n=38; nonirradiated, n=42) and were euthanized for evaluation of AAA formation at 16 weeks. Overall, 93% of angiotensin II-infused mice developed AAA, with 60% mortality possibly because of aneurysm rupture. UVB irradiation significantly decreased the incidence (66%) and mortality (29%) of AAA ( P =0.004 and P =0.006, respectively). UVB-irradiated mice had significantly smaller diameter AAA ( P =0.008) and fewer inflammatory cells in the aortic aneurysm tissue than nonirradiated mice, along with systemic expansion of CD4 + Foxp3 + regulatory T cells and decreased effector CD4 + CD44 high CD62L low T cells in para-aortic lymph nodes. Genetic depletion of regulatory T cells abrogated these beneficial effects of UVB treatment, demonstrating a critical role of regulatory T cells. Our data suggest that UVB-dependent expansion of regulatory T cells has beneficial effects on experimental AAA and may provide a novel strategy for the treatment of AAA. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Electron cryomicroscopy structure of a membrane-anchored mitochondrial AAA protease.

PubMed

Lee, Sukyeong; Augustin, Steffen; Tatsuta, Takashi; Gerdes, Florian; Langer, Thomas; Tsai, Francis T F

2011-02-11

FtsH-related AAA proteases are conserved membrane-anchored, ATP-dependent molecular machines, which mediate the processing and turnover of soluble and membrane-embedded proteins in eubacteria, mitochondria, and chloroplasts. Homo- and hetero-oligomeric proteolytic complexes exist, which are composed of homologous subunits harboring an ATPase domain of the AAA family and an H41 metallopeptidase domain. Mutations in subunits of mitochondrial m-AAA proteases have been associated with different neurodegenerative disorders in human, raising questions on the functional differences between homo- and hetero-oligomeric AAA proteases. Here, we have analyzed the hetero-oligomeric yeast m-AAA protease composed of homologous Yta10 and Yta12 subunits. We combined genetic and structural approaches to define the molecular determinants for oligomer assembly and to assess functional similarities between Yta10 and Yta12. We demonstrate that replacement of only two amino acid residues within the metallopeptidase domain of Yta12 allows its assembly into homo-oligomeric complexes. To provide a molecular explanation, we determined the 12 Å resolution structure of the intact yeast m-AAA protease with its transmembrane domains by electron cryomicroscopy (cryo-EM) and atomic structure fitting. The full-length m-AAA protease has a bipartite structure and is a hexamer in solution. We found that residues in Yta12, which facilitate homo-oligomerization when mutated, are located at the interface between neighboring protomers in the hexamer ring. Notably, the transmembrane and intermembrane space domains are separated from the main body, creating a passage on the matrix side, which is wide enough to accommodate unfolded but not folded polypeptides. These results suggest a mechanism regarding how proteins are recognized and degraded by m-AAA proteases.

Oxidative Stress in Aortas of Patients with Advanced Occlusive and Aneurysmal Diseases.

PubMed

Lucas, Márcio L; Carraro, Cristina C; Belló-Klein, Adriane; Kalil, Antônio N; Aerts, Newton R; Carvalho, Fabiano B; Fernandes, Marilda C; Zettler, Claudio G

2018-06-06

Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA. Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or AAA (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas. There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05). Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease-Associated Abdominal Aortic Aneurysm.

PubMed

Wakita, Daiko; Kurashima, Yosuke; Crother, Timothy R; Noval Rivas, Magali; Lee, Youngho; Chen, Shuang; Fury, Wen; Bai, Yu; Wagner, Shawn; Li, Debiao; Lehman, Thomas; Fishbein, Michael C; Hoffman, Hal M; Shah, Prediman K; Shimada, Kenichi; Arditi, Moshe

2016-05-01

Kawasaki disease (KD) is the most common cause of acquired cardiac disease in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated the development of systemic arterial dilatation and aneurysms, including abdominal aortic aneurysm (AAA) in the Lactobacillus casei cell-wall extract (LCWE)-induced KD vasculitis mouse model. We discovered that in addition to aortitis, coronary arteritis and myocarditis, the LCWE-induced KD mouse model is also associated with abdominal aorta dilatation and AAA, as well as renal and iliac artery aneurysms. AAA induced in KD mice was exclusively infrarenal, both fusiform and saccular, with intimal proliferation, myofibroblastic proliferation, break in the elastin layer, vascular smooth muscle cell loss, and inflammatory cell accumulation in the media and adventitia. Il1r(-/-), Il1a(-/-), and Il1b(-/-) mice were protected from KD associated AAA. Infiltrating CD11c(+) macrophages produced active caspase-1, and caspase-1 or NLRP3 deficiency inhibited AAA formation. Treatment with interleukin (IL)-1R antagonist (Anakinra), anti-IL-1α, or anti-IL-1β mAb blocked LCWE-induced AAA formation. Similar to clinical KD, the LCWE-induced KD vasculitis mouse model can also be accompanied by AAA formation. Both IL-1α and IL-1β play a key role, and use of an IL-1R blocking agent that inhibits both pathways may be a promising therapeutic target not only for KD coronary arteritis, but also for the other systemic arterial aneurysms including AAA that maybe seen in severe cases of KD. The LCWE-induced vasculitis model may also represent an alternative model for AAA disease. © 2016 American Heart Association, Inc.

Evaluation of the relationship between plasma lipids and abdominal aortic aneurysm: A Mendelian randomization study.

PubMed

Weng, Lu-Chen; Roetker, Nicholas S; Lutsey, Pamela L; Alonso, Alvaro; Guan, Weihua; Pankow, James S; Folsom, Aaron R; Steffen, Lyn M; Pankratz, Nathan; Tang, Weihong

2018-01-01

Studies have reported that higher circulating levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and lower of high-density lipoprotein (HDL) cholesterol may be associated with increased risk of abdominal aortic aneurysm (AAA). Whether dyslipidemia causes AAA is still unclear and is potentially testable using a Mendelian randomization (MR) approach. We investigated the associations between blood lipids and AAA using two-sample MR analysis with SNP-lipids association estimates from a published genome-wide association study of blood lipids (n = 188,577) and SNP-AAA association estimates from European Americans (EAs) of the Atherosclerosis Risk in Communities (ARIC) study (n = 8,793). We used inverse variance weighted (IVW) MR as the primary method and MR-Egger regression and weighted median MR estimation as sensitivity analyses. Over a median of 22.7 years of follow-up, 338 of 8,793 ARIC participants experienced incident clinical AAA. Using the IVW method, we observed positive associations of plasma LDL cholesterol and TC with the risk of AAA (odds ratio (OR) = 1.55, P = 0.02 for LDL cholesterol and OR = 1.61, P = 0.01 for TC per 1 standard deviation of lipid increment). Using the MR-Egger regression and weighted median methods, we were able to validate the association of AAA risk with TC, although the associations were less consistent for LDL cholesterol due to wider confidence intervals. Triglycerides and HDL cholesterol were not associated with AAA in any of the MR methods. Assuming instrumental variable assumptions are satisfied, our finding suggests that higher plasma TC and LDL cholesterol are causally associated with the increased risk of AAA in EAs.

Place of endovascular repair in the treatment of abdominal aortic aneurysm.

PubMed

BenHammamia, Mohamed; Kaouel, Karim; Ben Mrad, Malek; Ziadi, Jalel; Derbel, Bilel; Ghedira, Faker; Denguir, Raouf

2017-01-01

Open repair for abdominal aortic aneurysm (AAA) has a significant morbidity and mortality. Since the introduction of endovascular techniques, much progress has been made. The aim of this study is to clarify the feasibility and the results of endovascular aneurysm repair (EVAR) in short and middle terms. Between 2008 and 2015, 14 patients underwent EVAR. The average age was 65 years. Comorbidities were found in 7 patients. It was coronary artery disease in 3 cases and severe respiratory failure in 4 cases. The aneurysm was atherosclerotic in 12 cases and inflammatory in 2 cases. The average length of the proximal neck was 29 mm. The mean aneurysm diameter was 65mm. A bifurcated stent graft has been deployed in 12 cases and an aorto-mono-iliac stent graft was deployed in 2 cases. Immediate technical success was achieved in 13 patients. Immediate surgical conversion was performed in 1 case. The average hospital stay was 5 days. We haven't deployed any early death. After a mean follow-up of 3 years, we deployed 3 late deaths; two deaths were not related to the aneurysm and one death was secondary to rupture of the aneurysm caused by a proximal stent graft migration. EVAR is actually a therapeutic increasingly used. Its results, especially late, are still being evaluated. Meanwhile, its indications must be selective.

Technology penetration of endovascular aortic aneurysm repair in southern California.

PubMed

Shah, Haimesh; Kumar, S Ram; Major, Kevin; Hood, Douglas; Rowe, Vincent; Weaver, Fred A

2006-11-01

Our objective was to investigate the penetration of endovascular abdominal aortic aneurysm repair (EVAR) in the large, diverse health-care market of southern California over 3 years and to study variability in the pattern of distribution of EVAR in southern California counties by analyzing available demographic, geographic, and socioeconomic data from California state health-care databases. Information abstracted from the inpatient hospital discharge data for patients undergoing AAA repair for the years 2001, 2002, and 2003, derived from the Office of Statewide Health Planning and Development, included age, gender, race, hospitals performing EVAR, and payors for the service. Per-capita income (PCI) for the year 1999 and the population size of each county for the respective years were obtained from the U.S. Census Bureau. Data pertaining to members of the Southern California Vascular Surgical Society (SCVSS) serving the southern California region were obtained from the SCVSS membership directory. Data were categorized based on 10 counties in southern California. All the above variables were analyzed using the chi-squared test, with p < 0.05 considered significant. The proportions of EVAR for the years 2001, 2002, and 2003 were 15.4% (n = 409), 20.2% (n = 492), and 25.9% (n = 566), respectively. This is a 67.8% (p < 0.0001) increase in EVAR application in southern California since 2001. However, the proportion of EVAR varied among counties (p < 0.0001), with 457 EVARs performed in Los Angeles County and eight in Imperial County during the study period. EVAR proportion was higher in patients aged > or =65 years (p < 0.0001) and male patients (p < 0.0001). The proportion of EVAR was significantly higher in counties with more than 20 vascular surgeons available (p < 0.0001) and PCI >21,000 US$ (p < 0.0001) and in Medicare, health maintenance organization, preferred provider organization, and private insurance holders (p < 0.0001). There was a trend toward increased EVARs in counties with more than eight hospitals that performed EVAR (p = 0.0545). However, no significant difference in EVAR proportion was observed among subgroups based on race (p = 0.535) and population size (p = 0.84). Although the number and proportion of EVAR increased significantly in southern California over 3 years, the penetration of the procedure varied among counties. County affluence, payor mix, and the number of vascular surgeons/county influenced the variability. These observations suggest that economic barriers may limit access to new biomedical technology. This has implications for health-care public policy directed toward providing equal access to medical care without regard to economic status.

Abdominal aortic aneurysms: an autoimmune disease?

PubMed

Jagadesham, Vamshi P; Scott, D Julian A; Carding, Simon R

2008-12-01

Abdominal aortic aneurysms (AAAs) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation of the inflammatory response in aortic tissue. AAAs share many features of autoimmune disease, including genetic predisposition, organ specificity and chronic inflammation. Here, this evidence is used to propose that the chronic inflammation observed in AAAs is a consequence of a dysregulated autoimmune response against autologous components of the aortic wall that persists inappropriately. Identification of the molecular and cellular targets involved in AAA formation will allow the development of therapeutic agents for the treatment of AAA.

Fundamental Characteristics of AAA+ Protein Family Structure and Function

PubMed Central

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins. PMID:27703410

Ultrasound use in Australasian emergency departments: a survey of Australasian College for Emergency Medicine Fellows and Trainees.

PubMed

Craig, Simon; Egerton-Warburton, Diana; Mellett, Tanya

2014-06-01

To describe current practice of EDUS by ACEM Trainees and Fellows; to describe potential barriers to US use in the Australasian setting; to determine compliance with current college guidelines regarding US credentialing. Data were collected by a cross-sectional online survey. Respondents were Trainees and Fellows of the ACEM. Outcome measures included the percentage of respondents currently undergoing or that had completed US credentialing for Focused Assessment with Sonography for Trauma (FAST) and assessment of abdominal aortic aneurysm (AAA) scans. The perceived barriers to use of emergency US were explored. There were 512 survey respondents, giving an overall response rate of 15%. Fellows were more likely to be credentialed compared with Trainees. There were 61% of respondents not credentialed for FAST and assessment of AAA scans. However, a significant proportion performed these scans regularly, and did not routinely seek independent confirmation of their findings. Barriers to credentialing included limited time and no credentialing programme at the individual's hospital. The present study showed that only a minority of ACEM Trainees and Fellows are credentialed to perform routine ED scans. Many non-credentialed ACEM Trainees and Fellows are performing scans, many without independent confirmation of their findings. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase.

PubMed

Deville, Célia; Carroni, Marta; Franke, Kamila B; Topf, Maya; Bukau, Bernd; Mogk, Axel; Saibil, Helen R

2017-08-01

Refolding aggregated proteins is essential in combating cellular proteotoxic stress. Together with Hsp70, Hsp100 chaperones, including Escherichia coli ClpB, form a powerful disaggregation machine that threads aggregated polypeptides through the central pore of tandem adenosine triphosphatase (ATPase) rings. To visualize protein disaggregation, we determined cryo-electron microscopy structures of inactive and substrate-bound ClpB in the presence of adenosine 5'- O -(3-thiotriphosphate), revealing closed AAA+ rings with a pronounced seam. In the substrate-free state, a marked gradient of resolution, likely corresponding to mobility, spans across the AAA+ rings with a dynamic hotspot at the seam. On the seam side, the coiled-coil regulatory domains are locked in a horizontal, inactive orientation. On the opposite side, the regulatory domains are accessible for Hsp70 binding, substrate targeting, and activation. In the presence of the model substrate casein, the polypeptide threads through the entire pore channel and increased nucleotide occupancy correlates with higher ATPase activity. Substrate-induced domain displacements indicate a pathway of regulated substrate transfer from Hsp70 to the ClpB pore, inside which a spiral of loops contacts the substrate. The seam pore loops undergo marked displacements, along with ordering of the regulatory domains. These asymmetric movements suggest a mechanism for ATPase activation and substrate threading during disaggregation.

Structural Basis for Disassembly of Katanin Heterododecamers.

PubMed

Nithianantham, Stanley; McNally, Francis J; Al-Bassam, Jawdat

2018-05-11

The reorganization of microtubules in mitosis, meiosis and development requires the microtubule-severing activity of katanin.  Katanin is a heterodimer composed of an ATPase Associated with diverse cellular Activities (AAA) subunit and a regulatory subunit. Microtubule severing requires ATP hydrolysis by katanin's conserved AAA ATPase domains. Whereas other AAA ATPases form stable hexamers, we show that katanin only forms monomer or dimers of heterodimers in solution.  Katanin oligomers consistent with hexamers of heterodimers or heterododecamers were only observed for an ATP hydrolysis deficient mutant in the presence of ATP.  X-ray structures of katanin's AAA ATPase in monomeric nucleotide-free and pseudo-oligomeric ADP-bound states reveal conformational changes in AAA subdomains that explained the structural basis for instability of katanin heterododecamer.  We propose that the rapid dissociation of katanin AAA oligomers may lead to an auto-inhibited state that prevents inappropriate microtubule severing, or that cyclical disassembly into heterodimers may critically contribute to the microtubule-severing mechanism. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

A Non-Competitive Inhibitor of VCP/p97 and VPS4 Reveals Conserved Allosteric Circuits in Type I and II AAA ATPases.

PubMed

Pöhler, Robert; Krahn, Jan H; van den Boom, Johannes; Dobrynin, Grzegorz; Kaschani, Farnusch; Eggenweiler, Hans-Michael; Zenke, Frank T; Kaiser, Markus; Meyer, Hemmo

2018-02-05

AAA ATPases have pivotal functions in diverse cellular processes essential for survival and proliferation. Revealing strategies for chemical inhibition of this class of enzymes is therefore of great interest for the development of novel chemotherapies or chemical tools. Here, we characterize the compound MSC1094308 as a reversible, allosteric inhibitor of the type II AAA ATPase human ubiquitin-directed unfoldase (VCP)/p97 and the type I AAA ATPase VPS4B. Subsequent proteomic, genetic and biochemical studies indicate that MSC1094308 binds to a previously characterized drugable hotspot of p97, thereby inhibiting the D2 ATPase activity. Our results furthermore indicate that a similar allosteric site exists in VPS4B, suggesting conserved allosteric circuits and drugable sites in both type I and II AAA ATPases. Our results may thus guide future chemical tool and drug discovery efforts for the biomedically relevant AAA ATPases. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pathophysiology of AAA: heredity vs environment.

PubMed

Björck, Martin; Wanhainen, Anders

2013-01-01

Abdominal aortic aneurysm (AAA) has a complex pathophysiology, in which both environmental and genetic factors play important roles, the most important being smoking. The recently reported falling prevalence rates of AAA in northern Europe and Australia/New Zeeland are largely explained by healthier smoking habits. Dietary factors and obesity, in particular abdominal obesity, are also of importance. A family history of AAA among first-degree relatives is present in approximately 13% of incident cases. The probability that a monozygotic twin of a person with an AAA has the disease is 24%, 71 times higher than that for a monozygotic twin of a person without AAA. Approximately 1000 SNPs in 100 candidate genes have been studied, and three genome-wide association studies were published, identifying different diverse weak associations. An example of interaction between environmental and genetic factors is the effect of cholesterol, where genetic and dietary factors affect levels of both HDL and LDL. True epigenetic studies have not yet been published. Copyright © 2013 Elsevier Inc. All rights reserved.

40 CFR 90.1207 - Entry and access.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the following places: (1) Any facility where engines undergo or are undergoing aging, maintenance, repair, preparation for aging, selection for aging or emission testing. (2) Any facility where records or... (b) and also to inspect and make copies of records related to engine aging (service accumulation) and...

40 CFR 90.1207 - Entry and access.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the following places: (1) Any facility where engines undergo or are undergoing aging, maintenance, repair, preparation for aging, selection for aging or emission testing. (2) Any facility where records or... (b) and also to inspect and make copies of records related to engine aging (service accumulation) and...

40 CFR 90.1207 - Entry and access.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the following places: (1) Any facility where engines undergo or are undergoing aging, maintenance, repair, preparation for aging, selection for aging or emission testing. (2) Any facility where records or... (b) and also to inspect and make copies of records related to engine aging (service accumulation) and...

40 CFR 90.1207 - Entry and access.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the following places: (1) Any facility where engines undergo or are undergoing aging, maintenance, repair, preparation for aging, selection for aging or emission testing. (2) Any facility where records or... (b) and also to inspect and make copies of records related to engine aging (service accumulation) and...

40 CFR 90.1207 - Entry and access.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the following places: (1) Any facility where engines undergo or are undergoing aging, maintenance, repair, preparation for aging, selection for aging or emission testing. (2) Any facility where records or... (b) and also to inspect and make copies of records related to engine aging (service accumulation) and...

Functional characterization of T cells in abdominal aortic aneurysms.

PubMed

Forester, Nerys D; Cruickshank, Sheena M; Scott, D Julian A; Carding, Simon R

2005-06-01

Abdominal aortic aneurysms (AAA) exhibit features of a chronic inflammatory disorder. The functional attributes of the T cells in AAA tissue are unclear, with little quantitative or functional data. Using a novel, non-enzymatic method to isolate viable cells from AAA tissue, functional properties of AAA T cells were investigated for the first time. Composition and phenotype of AAA T cells was determined by flow cytometry and verified by immunohistochemistry. Tissue mononuclear cells (MNCs) were cultured in the presence of T-cell mitogens, and cell cycle analysis and cytokine production assessed. Typical cell yield was 4.5 x 10(6) cells per gram of AAA tissue. The majority (58.1+/-5.3%) of haematopoietic (CD45+) cells recovered were CD3+ T cells, B cells comprised 41.1+/-5.7%, natural killer cells 7.3+/-2.5%, and macrophages 2%. Freshly isolated T cells were in resting (G1) state, with 25% expressing the activation-associated cell surface antigens major histocompatibility complex II and CD25. When stimulated in vitro, a significant proportion entered S and G2 phase of the cell cycle, up-regulated CD25, and secreted tumour necrosis factor-alpha, interferon-gamma, interleukin (IL)-5 and IL-6. Despite patient differences, the composition of the AAA inflammatory infiltrate was remarkably consistent, and when re-stimulated ex-vivo T cells produced a stereotypical cytokine response, consistent with the hypothesis that AAA T cells can promote tissue inflammation by secretion of proinflammatory cytokines, and in addition provide signals for B-cell help.

Distinct Effect of Benzalkonium Chloride on the Esterase and Aryl Acylamidase Activities of Butyrylcholinesterase.

PubMed

Jaganathan; Boopathy

2000-08-01

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) from vertebrates, other than their predominant acylcholine hydrolase (esterase) activity, display a genuine aryl acylamidase activity (AAA) capable of hydrolyzing the synthetic substrate o-nitroacetanilide to o-nitroaniline. This AAA activity is strongly inhibited by classical cholinesterase (ChE) inhibitors. In the present study, benzalkonium chloride (BAC), a cationic detergent widely used as a preservative in pharmaceutical preparations, has been shown to distinctly modulate the esterase and AAA activities of BChEs. The detergent BAC was able to inhibit the esterase activity of human serum and horse serum BChEs and AChEs from electric eel and human erythrocyte. The remarkable property of BAC was its ability to profoundly activate the AAA activity of human serum and horse serum BChEs but not the AAA activity of AChEs. Thus BAC seem to preferentially activate the AAA activity of BChEs alone. Results of the study using the ChE active site-specific inhibitor diisopropyl phosphorofluoridate indicated that BAC binds to the active site of ChEs. Furthermore, studies using a structural homolog of BAC indicated that the alkyl group of BAC is essential not only for its interaction with ChEs but also for its distinct effect on the esterase and AAA activities of BChEs. This is the first report of a compound that inhibits the esterase activity, while simultaneously activating the AAA activity, of BChEs. Copyright 2000 Academic Press.

Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression.

PubMed

Iida, Yasunori; Xu, Baohui; Xuan, Haojun; Glover, Keith J; Tanaka, Hiroki; Hu, Xiaolei; Fujimura, Naoki; Wang, Wei; Schultz, Joshua R; Turner, Court R; Dalman, Ronald L

2013-04-01

Macrophages are critical contributors to abdominal aortic aneurysm (AAA) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4-CCL5 interaction, to influence AAA progression in murine models. AAAs were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed AAAs, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase infusion also stabilized or reduced enlargement of existing AAAs. Finally, MKEY treatment was effective in limiting AAA formation after angiotensin II infusion in apolipoprotein E-deficient mice. MKEY suppresses AAA formation and progression in 2 complementary experimental models. Peptide inhibition of CXCL4-CCL5 interactions may represent a viable translational strategy to limit progression of human AAA disease.

SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamichhane, N; Studenski, M

2016-06-15

Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobendmore » block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.« less

Histopathological analysis of cellular localization of cathepsins in abdominal aortic aneurysm wall.

PubMed

Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Zimmermann, Alexander; Ockert, Stefan; Eckstein, Hans-Henning; Pelisek, Jaroslav

2012-08-01

An important feature of abdominal aortic aneurysm (AAA) is the destruction of vessel wall, especially elastin and collagen. Besides matrix metalloproteinases, cathepsins are the most potent elastolytic enzymes. The expression of cathepsins with known elastolytic and collagenolytic activities in the individual cells within AAA has not yet been determined. The vessel wall of 32 AAA patients and 10 organ donors was analysed by immunohistochemistry for expression of cathepsins B, D, K, L and S, and cystatin C in all cells localized within AAA. Luminal endothelial cells (ECs) of AAA were positive for cathepsin D and partially for cathepsins B, K and S. Endothelial cells of the neovessels and smooth muscle cells in the media were positive for all cathepsins tested, especially for cathepsin B. In the inflammatory infiltrate all cathepsins were expressed in the following pattern: B > D = S > K = L. Macrophages showed the highest staining intensity for all cathepsins. Furthermore, weak overall expression of cystatin C was observed in all the cells localized in the AAA with the exception of the ECs. There is markedly increased expression of the various cathepsins within the AAA wall compared to healthy aorta. Our data are broadly consistent with a role for cathepsins in AAA; and demonstrate expression of cathepsins D, B and S in phagocytic cells in the inflammatory infiltrate; and also may reveal a role for cathepsin B in lymphocytes. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men

PubMed Central

Djousse, Luc; Song, Yiqing; Akinkuolie, Akintunde O.; Matsumoto, Chisa; Manson, JoAnn E.; Gaziano, J. Michael; Sesso, Howard D.

2017-01-01

Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (AAA) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no AAA at baseline, 471 reported a newly diagnosed AAA during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) < 25 kg/m2, the multivariable hazard ratio (HR [95% CI]) of newly diagnosed AAA was 1.30 [1.06–1.59] for BMI 25–<30 kg/m2 and 1.69 [1.24–2.30] for BMI ≥ 30 kg/m2. The risk of diagnosed AAA was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known AAA risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed AAA (HR = 0.79 [0.57–1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed AAA, particularly over longer follow-up. PMID:28326193

Inguinal hernia repair in women: is the laparoscopic approach superior?

PubMed

Ashfaq, A; McGhan, L J; Chapital, A B; Harold, K L; Johnson, D J

2014-06-01

Laparoscopic inguinal hernia repair is associated with reduced post-operative pain and earlier return to work in men. However, the role of laparoscopic hernia repair in women is not well reported. The aim of this study was to review the outcomes of the laparoscopic versus open repair of inguinal hernias in women and to discuss patients' considerations when choosing the approach. A retrospective chart review of all consecutive patients undergoing inguinal hernia repair from January 2005 to December 2009 at a single institution was conducted. Presentation characteristics and outcome measures including recurrence rates, post-operative pain and complications were compared in women undergoing laparoscopic versus open hernia repair. A total of 1,133 patients had an inguinal herniorrhaphy. Of these, 101 patients were female (9 %), with a total of 111 hernias. A laparoscopic approach was chosen in 44 % of patients. The majority of women (56 %) presented with groin pain as the primary symptom. Neither the mode of presentation nor the presenting symptoms significantly influenced the surgical approach. There were no statistically significant differences in hernia recurrence, post-operative neuralgia, seroma/hematoma formation or urinary retention between the two approaches (p < 0.05). A greater proportion of patients with bilateral hernias had a laparoscopic approach rather than an open technique (12 vs. 2 %, p = 0.042). Laparoscopic herniorrhaphy is as safe and efficacious as open repair in women, and should be considered when the diagnosis is in question, for management of bilateral hernias or when concomitant abdominal pathology is being addressed.

Bio-enhanced repair of the anterior cruciate ligament

PubMed Central

Proffen, Benedikt L.; Sieker, Jakob T.; Murray, Martha

2015-01-01

Suture repair of the ACL has been widely abandoned in favor of ACL reconstruction, largely due to the high rates of failure and unreliability of the outcomes following suture repair. However, there have been recent basic science studies which suggest that combining a suture repair with a biologic adjunct may improve the results of suture repair of the ACL, with several studies in large animal models showing equivalent strength of an ACL treated with bio-enhanced repaired with that of an ACL graft at 3, 6 and 12 months after surgery. In addition, the groups treated with bio-enhanced repair had significantly less osteoarthritis when compared with the animals undergoing ACL reconstruction. These findings have led to a renewed interest in bio-enhanced primary repair as a way to make repair of the ACL a viable option for a select group of patients in the future. PMID:25595694

Urinary function after Snodgrass repair of distal hypospadias: comparison with the Mathieu repair.

PubMed

Scarpa, Maria Grazia; Castagnetti, Marco; Berrettini, Alfredo; Rigamonti, Waifro; Musi, Luciano

2010-05-01

To evaluate urinary function in patients with distal hypospadias undergoing repair by the tubularized incised-plate urethroplasty (TIP or Snodgrass), compare the results with those in patients treated by the Mathieu technique, and show the potential issues inherent to the evaluation of such results. A cross-sectional assessment was performed of uncomplicated distal hypospadias operated on during a 3-year period, already toilet trained, and able to void volitionally. Evaluation included clinical assessment urinary symptoms and urinary stream, and uroflowmetry. Out of 83 patients operated on during the study period, 10 (12%) developed complication and 32 were not toilet trained or refused to participate in the study. Median follow-up in the remaining 41 patients included in the study was 20 (3-36) months. None of these patients presented voiding symptoms or urinary stream abnormalities. Uroflowmetry was normal in 30 cases and obstructive in 11 (27%). An obstructive flow pattern was more common in patients undergoing TIP versus Mathieu repair, 8 of 19 (42%) versus 3 of 22 (14%), respectively (P = 0.07). Four TIP cases with an obstructive uroflow pattern were managed conservatively. Although both the TIP and the Mathieu repair allow good results in terms of urinary function after distal hypospadias repairs, the TIP technique seems more likely to be associated with urine flow pattern abnormalities. The actual clinical relevance of this finding remains ill defined.

Advanced Oxidation Protein Products and Carbonylated Proteins as Biomarkers of Oxidative Stress in Selected Atherosclerosis-Mediated Diseases.

PubMed

Gryszczyńska, Bogna; Formanowicz, Dorota; Budzyń, Magdalena; Wanic-Kossowska, Maria; Pawliczak, Elżbieta; Formanowicz, Piotr; Majewski, Wacław; Strzyżewski, Krzysztof Wojciech; Kasprzak, Magdalena P; Iskra, Maria

2017-01-01

The main question of this study was to evaluate the intensity of oxidative protein modification shown as advanced oxidation protein products (AOPP) and carbonylated proteins, expressed as protein carbonyl content (C=O) in abdominal aortic aneurysms (AAA), aortoiliac occlusive disease (AIOD), and chronic kidney disease (CKD). The study was carried out in a group of 35 AAA patients and 13 AIOD patients. However, CKD patients were divided into two groups: predialysis (PRE) included 50 patients or hemodialysis (HD) consisted of 34 patients. AOPP and C=O were measured using colorimetric assay kit, while C-reactive protein concentration was measured by high-sensitivity assay (hsCRP). The concentration of AOPP in both AAA and AIOD groups was higher than in PRE and HD groups according to descending order: AAA~AIOD > HD > PRE. The content of C=O was higher in the PRE group in comparison to AIOD and AAA according to the descending order: PRE~HD > AAA~AIOD. AAA, AIOD, and CKD-related atherosclerosis (PRE and HD) contribute to the changes in the formation of AOPP and C=O. They may promote modification of proteins in a different way, probably due to the various factors that influence oxidative stress here.

CFD modelling of abdominal aortic aneurysm on hemodynamic loads using a realistic geometry with CT.

PubMed

Soudah, Eduardo; Ng, E Y K; Loong, T H; Bordone, Maurizio; Pua, Uei; Narayanan, Sriram

2013-01-01

The objective of this study is to find a correlation between the abdominal aortic aneurysm (AAA) geometric parameters, wall stress shear (WSS), abdominal flow patterns, intraluminal thrombus (ILT), and AAA arterial wall rupture using computational fluid dynamics (CFD). Real AAA 3D models were created by three-dimensional (3D) reconstruction of in vivo acquired computed tomography (CT) images from 5 patients. Based on 3D AAA models, high quality volume meshes were created using an optimal tetrahedral aspect ratio for the whole domain. In order to quantify the WSS and the recirculation inside the AAA, a 3D CFD using finite elements analysis was used. The CFD computation was performed assuming that the arterial wall is rigid and the blood is considered a homogeneous Newtonian fluid with a density of 1050 kg/m(3) and a kinematic viscosity of 4 × 10(-3) Pa·s. Parallelization procedures were used in order to increase the performance of the CFD calculations. A relation between AAA geometric parameters (asymmetry index ( β ), saccular index ( γ ), deformation diameter ratio ( χ ), and tortuosity index ( ε )) and hemodynamic loads was observed, and it could be used as a potential predictor of AAA arterial wall rupture and potential ILT formation.

Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats

PubMed Central

Delbosc, Sandrine; Alsac, Jean-Marc; Journe, Clement; Louedec, Liliane; Castier, Yves; Bonnaure-Mallet, Martine; Ruimy, Raymond; Rossignol, Patrick; Bouchard, Philippe; Michel, Jean-Baptiste; Meilhac, Olivier

2011-01-01

Background Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia. Methods and Findings Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. Conclusions Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression. PMID:21533243

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

PubMed Central

Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.

2017-01-01

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403

Hyperhomocysteinaemia is an independent risk factor of abdominal aortic aneurysm in a Chinese Han population

PubMed Central

Liu, Jie; Wei Zuo, Shang; Li, Yue; Jia, Xin; Jia, Sen Hao; Zhang, Tao; Xiang Song, Yu; Qi Wei, Ying; Xiong, Jiang; Hua Hu, Yong; Guo, Wei

2016-01-01

The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships PMID:26865327

Management of Iatrogenic Pseudoaneurysms in Patients Undergoing Coronary Artery Bypass Grafting.

PubMed

Stone, Patrick A; Thompson, Stephanie N; Hanson, Brent; Masinter, David

2016-05-01

A plethora of papers have been written regarding postcatheterization femoral pseudoaneurysms. However, literature is lacking on pseudoaneurysmal management in patients undergoing coronary artery bypass grafting (CABG). Thus, we examined if pseudoaneurysms with subsequent CABG can be managed with the same strategies as those not exposed to the intense anticoagulation accompanying CABGs. During a 14-year study period, we retrospectively examined femoral iatrogenic pseudoaneurysms (IPSAs) diagnosed postheart catheterization in patients having a subsequent CABG. Patient information was obtained from electronic medical records and included pseudoaneurysm characteristics, treatment, and resolution. Outcomes of interest included the occurrence of IPSA treatment failures and complications. In the 66 patients (mean age, 66 ± 11 years, 46% male) meeting inclusion criteria, mean dose of heparin received during the CABG procedure was 34 000 ± 23 000 units. The IPSA size distribution was the following: 17% of IPSAs measured <1 cm, 55% between 1 and 3 cm, and 21% measured >3 cm. Pseudoaneurysms were managed with compression, duplex-guided thrombin injection, and surgical repair (1%, 27%, and 26% of cases, respectively). Thrombin injection and surgical repair were 100% effective at treating pseudoaneurysms, with 1 patient experiencing a surgical site infection postsurgical repair. Observation-only management was employed in 30 (45%) patients. Nine of 30 patients with no intervention beyond observation had duplex documented resolution/thrombosis during follow-up. One patient initially managed by observation required readmission and surgical repair of an enlarging pseudoaneurysm (6 cm growth) following CABG. Management of pseudoaneurysms in patients prior to CABG should be similar to those patients not undergoing intense anticoagulation. In appropriate cases, small aneurysms can be safely observed, while thrombin injections are effective and safe as well. Thus, routine open surgical repair is not routinely required in patients with femoral pseudoaneurysms at time of CABG. © The Author(s) 2016.

Infection Rates in Arthroscopic Versus Open Rotator Cuff Repair.

PubMed

Hughes, Jonathan D; Hughes, Jessica L; Bartley, Justin H; Hamilton, William P; Brennan, Kindyle L

2017-07-01

The prevalence of rotator cuff repair continues to rise, with a noted transition from open to arthroscopic techniques in recent years. One reported advantage of arthroscopic repair is a lower infection rate. However, to date, the infection rates of these 2 techniques have not been directly compared with large samples at a single institution with fully integrated medical records. To retrospectively compare postoperative infection rates between arthroscopic and open rotator cuff repair. Cohort study; Level of evidence, 3. From January 2003 until May 2011, a total of 1556 patients underwent rotator cuff repair at a single institution. These patients were divided into an arthroscopic repair group and an open group. A Pearson chi-square test and Fisher exact test were used, with a subgroup analysis to segment the open repair group into mini-open and open procedures. The odds ratio and 95% CI of developing a postoperative infection was calculated for the 2 groups. A multiple-regressions model was then utilized to identify predictors of the presence of infection. Infection was defined as only those treated with surgical intervention, thus excluding superficial infections treated with antibiotics alone. A total of 903 patients had an arthroscopic repair, while 653 had open repairs (600 mini-open, 53 open). There were 4 confirmed infections in the arthroscopic group and 16 in the open group (15 mini-open, 1 open), resulting in postoperative infection rates of 0.44% and 2.45%, respectively. Subgroup analysis of the mini-open and open groups demonstrated a postoperative infection rate of 2.50% and 1.89%, respectively. The open group had an odds ratio of 5.645 (95% CI, 1.9-17.0) to develop a postoperative infection compared with the arthroscopic group. Patients undergoing open rotator cuff repair had a significantly higher rate of postoperative infection compared with those undergoing arthroscopic rotator cuff repair.

Suture repair of umbilical hernia during caesarean section: a case-control study.

PubMed

Steinemann, D C; Limani, P; Ochsenbein, N; Krähenmann, F; Clavien, P-A; Zimmermann, R; Hahnloser, D

2013-08-01

The objective of this study was to investigate the additional burdens in terms of pain, prolongation of surgery and morbidity which is added to elective caesarean section if umbilical hernia suture repair is performed simultaneously. Secondly, patient's satisfaction and hernia recurrence rate were assessed. Consecutive women with symptomatic umbilical hernia undergoing internal or external suture repair during elective caesarean were included in this retrospective cohort-control study. Data on post-operative pain, duration of surgery and morbidity of a combined procedure were collected. These patients were matched 1:10 to women undergoing caesarean section only. Additionally, two subgroups were assessed separately: external and internal suture hernia repair. These subgroups were compared for patient's satisfaction, cosmesis, body image and recurrence rate. Fourteen patients with a mean age of 37 years were analysed. Internal suture repair (n = 7) prolonged caesarean section by 20 min (p = 0.001) and external suture repair (n = 7) by 34 min (p < 0.0001). Suture repair did not increase morphine use (0.38 ± 0.2 vs. 0.4 ± 02 mg/kg body weight), had no procedure-related morbidity and prolonged hospitalization by 0.5 days (p = 0.01). At a median follow-up of 37 (5-125) months, two recurrences in each surgical technique, internal and external suture repair, occurred (28 %). Body image and cosmesis score showed a higher level of functioning in internal suture repair (p = 0.02; p = 0.04). Despite a high recurrence rate, internal suture repair of a symptomatic umbilical hernia during elective caesarean section should be offered to women if requested. No additional morbidity or scar is added to caesarean section. Internal repair is faster, and cosmetic results are better, additional skin or fascia dissection is avoided, and it seems to be as effective as an external approach. Yet, women must be informed on the high recurrence rate.

The association between caudal anesthesia and increased risk of postoperative surgical complications in boys undergoing hypospadias repair.

PubMed

Taicher, Brad M; Routh, Jonathan C; Eck, John B; Ross, Sherry S; Wiener, John S; Ross, Allison K

2017-07-01

Recent reports have suggested that caudal anesthesia may be associated with an increased risk of postoperative surgical complications. We examined our experience with caudal anesthesia in hypospadias repair to evaluate for increased risk of urethrocutaneous fistula or glanular dehiscence. All hypospadias repairs performed by a single surgeon in 2001-2014 were reviewed. Staged or revision surgeries were excluded. Patient age, weight, hypospadias severity, surgery duration, month and year of surgery, caudal anesthesia use, and postoperative complications were recorded. Bivariate and multivariate statistical analyses were performed. We identified 395 single-stage primary hypospadias repairs. Mean age was 15.6 months; 326 patients had distal (83%) and 69 had proximal (17%) hypospadias. Caudal anesthetics were used in 230 (58%) cases; 165 patients (42%) underwent local penile block at the discretion of the surgeon and/or anesthesiologist. Complications of urethrocutaneous fistula or glanular deshiscence occurred in 22 patients (5.6%) and were associated with caudal anesthetic use (OR 16.5, 95% CI 2.2-123.8, P = 0.007), proximal hypospadias (OR 8.2, 95% CI 3.3-20.0, P < 0.001), increased surgical duration (OR 1.01, 95% CI 1.01-1.02, P < 0.001), and earlier year of practice (OR 3.0, 95% CI 1.2-7.9, P = 0.03 for trend). After adjusting for confounding variables via multivariable logistic regression, both caudal anesthetic use (OR 13.4, 95% CI 1.8-101.8, P = 0.01) and proximal hypospadias (OR 6.8, 95% CI 2.7-16.9, P < 0.001) remained highly associated with postoperative complications. In our experience, caudal anesthesia was associated with an over 13-fold increase in the odds of developing postoperative surgical complications in boys undergoing hypospadias repair even after adjusting for urethral meatus location. Until further investigation occurs, clinicians should carefully consider the use of caudal anesthesia for children undergoing hypospadias repair. © 2017 John Wiley & Sons Ltd.

NASA Airborne Astronomy Ambassadors (AAA)

NASA Astrophysics Data System (ADS)

Backman, D. E.; Harman, P. K.; Clark, C.

2016-12-01

NASA's Airborne Astronomy Ambassadors (AAA) is a three-part professional development (PD) program for high school physics and astronomy teachers. The AAA experience consists of: (1) blended-learning professional development composed of webinars, asynchronous content learning, and a series of hands-on workshops (2) a STEM immersion experience at NASA Armstrong Flight Research Center's B703 science research aircraft facility in Palmdale, California, and (3) ongoing participation in the AAA community of practice (CoP) connecting participants with astrophysics and planetary science Subject Matter Experts (SMEs). The SETI Institute (SI) is partnering with school districts in Santa Clara and Los Angeles Counties during the AAA program's "incubation" period, calendar years 2016 through 2018. AAAs will be selected by the school districts based on criteria developed during spring 2016 focus group meetings led by the program's external evaluator, WestEd.. Teachers with 3+ years teaching experience who are assigned to teach at least 2 sections in any combination of the high school courses Physics (non-AP), Physics of the Universe (California integrated model), Astronomy, or Earth & Space Sciences are eligible. Partner districts will select at least 48 eligible applicants with SI oversight. WestEd will randomly assign selected AAAs to group A or group B. Group A will complete PD in January - June of 2017 and then participate in SOFIA science flights during fall 2017 (SOFIA Cycle 5). Group B will act as a control during the 2017-18 school year. Group B will then complete PD in January - June of 2018 and participate in SOFIA science flights in fall 2018 (Cycle 6). Under the current plan, opportunities for additional districts to seek AAA partnerships with SI will be offered in 2018 or 2019. A nominal two-week AAA curriculum component will be developed by SI for classroom delivery that will be aligned with selected California Draft Science Framework Disciplinary Core Ideas, Crosscutting Concepts, and Science and Engineering Practices. (The California Draft Framework in turn is aligned with NGSS). The AAA program will demonstrate student gains in standards-based student learning, measure changes in student attitudes towards STEM, and observe & record Ambassadors' implementation of curricular changes.

Does specialization improve outcome in abdominal aortic aneurysm surgery?

PubMed

Rosenthal, Rachel; von Känel, Oliver; Eugster, Thomas; Stierli, Peter; Gürke, Lorenz

2005-01-01

Specialization and high volume are reported to be related to a better outcome after abdominal aortic aneurysm repair. The aim of this study was to compare, in patients undergoing abdominal aortic aneurysm repair, the outcomes of those whose surgery was done by general surgeons with the outcomes of those whose surgery was done by specialist vascular surgeons. All patients undergoing abdominal aortic aneurysm repair at the Basel University Hospital (referral center) from January 1990 to December 2000 were included. Patients with endovascular treatment were excluded. Operations in group A (n = 189), between January 1990 and May 1995, were done by general surgeons. Operations in group B (n = 291), between June 1995 and December 2000, were done by vascular surgeons. In-hospital mortality and local and systemic complications were assessed. In-hospital mortality rates were significantly lower for group B (with specialist surgeons) than for group A, both overall (group B, 11.7%; group A, 21.7%; p = .003) and for emergency interventions (group B, 28.1%; group A, 41.9%; p = .042). The reduction in mortality for elective surgery in group B was not statistically significant (group B, 1.1%; group A, 4.9%; p = .054). There were significantly fewer pulmonary complications in group B compared with group A (p = .000). We conclude that in patients undergoing abdominal aortic aneurysm repair, those whose surgery is done by a specialized team have a significantly better outcome than those whose surgery is done by general surgeons.

Compressive cryotherapy versus ice-a prospective, randomized study on postoperative pain in patients undergoing arthroscopic rotator cuff repair or subacromial decompression.

PubMed

Kraeutler, Matthew J; Reynolds, Kirk A; Long, Cyndi; McCarty, Eric C

2015-06-01

The purpose of this study was to compare the effect of compressive cryotherapy (CC) vs. ice on postoperative pain in patients undergoing shoulder arthroscopy for rotator cuff repair or subacromial decompression. A commercial device was used for postoperative CC. A standard ice wrap (IW) was used for postoperative cryotherapy alone. Patients scheduled for rotator cuff repair or subacromial decompression were consented and randomized to 1 of 2 groups; patients were randomized to use either CC or a standard IW for the first postoperative week. All patients were asked to complete a "diary" each day, which included visual analog scale scores based on average daily pain and worst daily pain as well as total pain medication usage. Pain medications were then converted to a morphine equivalent dosage. Forty-six patients completed the study and were available for analysis; 25 patients were randomized to CC and 21 patients were randomized to standard IW. No significant differences were found in average pain, worst pain, or morphine equivalent dosage on any day. There does not appear to be a significant benefit to use of CC over standard IW in patients undergoing shoulder arthroscopy for rotator cuff repair or subacromial decompression. Further study is needed to determine if CC devices are a cost-effective option for postoperative pain management in this population of patients. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Diabetes mellitus increases the risk of ruptured abdominal aortic aneurysms.

PubMed

Wierzba, Waldemar; Sliwczynski, Andrzej; Pinkas, Jaroslaw; Jawien, Arkadiusz; Karnafel, Waldemar

2017-09-01

The publication is a polemical response to reports that present data that diabetes reduces the risk of rupture of abdominal aortic aneurysm (AAA). The study analyzed all cases of developing AAA in patients with and without diabetes in 2012 in Poland. Data for the analysis were obtained with a unique and complete resources of the National Health Fund (NFZ) and population data from the Central Statistical Office (GUS). In Poland during 2012 2,227,453 patients with diabetes were treated, 975,364 males and 1,252,089 females. The incidence of AAA without rupture in patients without diabetes calculated per 100,000 of the non-diabetes general population was 25.0 +/- 9.0 in males and 5.6 +/- 2.3 in females. The incidence of ruptured AAA in the general population without diabetes was 3.6 +/- 0.9 in males, and 0.6 +/- 0.3 in females calculated per 100,000 of inhabitants without diabetes. The incidence of AAA without rupture in patients with diabetes was 184.897 +/- 70.653 in males and 35.364 +/- 24.925 in females calculated per 100,000 of patients diagnosed with diabetes. The incidence of ruptured AAA in patients with diabetes was 21.090 +/- 6.050 in males and 5.170 +/- 3.053 in females calculated per 100,000 of patients diagnosed with diabetes. The incidence rate for ruptured AAA in 2012 in Poland is statistically higher both in females and males in the population with diabetes. The incidence rate for AAA without rupture in 2012 in Poland is statistically higher in patients diagnosed with diabetes.

Functional characterization of T cells in abdominal aortic aneurysms

PubMed Central

Forester, Nerys D; Cruickshank, Sheena M; Scott, D Julian A; Carding, Simon R

2005-01-01

Abdominal aortic aneurysms (AAA) exhibit features of a chronic inflammatory disorder. The functional attributes of the T cells in AAA tissue are unclear, with little quantitative or functional data. Using a novel, non-enzymatic method to isolate viable cells from AAA tissue, functional properties of AAA T cells were investigated for the first time. Composition and phenotype of AAA T cells was determined by flow cytometry and verified by immunohistochemistry. Tissue mononuclear cells (MNCs) were cultured in the presence of T-cell mitogens, and cell cycle analysis and cytokine production assessed. Typical cell yield was 4·5 × 106 cells per gram of AAA tissue. The majority (58·1 ± 5·3%) of haematopoietic (CD45+) cells recovered were CD3+ T cells, B cells comprised 41·1 ± 5·7%, natural killer cells 7·3 ± 2·5%, and macrophages 2%. Freshly isolated T cells were in resting (G1) state, with 25% expressing the activation-associated cell surface antigens major histocompatibility complex II and CD25. When stimulated in vitro, a significant proportion entered S and G2 phase of the cell cycle, up-regulated CD25, and secreted tumour necrosis factor-α, interferon-γ, interleukin (IL)-5 and IL-6. Despite patient differences, the composition of the AAA inflammatory infiltrate was remarkably consistent, and when re-stimulated ex-vivo T cells produced a stereotypical cytokine response, consistent with the hypothesis that AAA T cells can promote tissue inflammation by secretion of proinflammatory cytokines, and in addition provide signals for B-cell help. PMID:15885133

Atmospheric Pressure and Abdominal Aortic Aneurysm Rupture: Results From a Time Series Analysis and Case-Crossover Study.

PubMed

Penning de Vries, Bas B L; Kolkert, Joé L P; Meerwaldt, Robbert; Groenwold, Rolf H H

2017-10-01

Associations between atmospheric pressure and abdominal aortic aneurysm (AAA) rupture risk have been reported, but empirical evidence is inconclusive and largely derived from studies that did not account for possible nonlinearity, seasonality, and confounding by temperature. Associations between atmospheric pressure and AAA rupture risk were investigated using local meteorological data and a case series of 358 patients admitted to hospital for ruptured AAA during the study period, January 2002 to December 2012. Two analyses were performed-a time series analysis and a case-crossover study. Results from the 2 analyses were similar; neither the time series analysis nor the case-crossover study showed a significant association between atmospheric pressure ( P = .627 and P = .625, respectively, for mean daily atmospheric pressure) or atmospheric pressure variation ( P = .464 and P = .816, respectively, for 24-hour change in mean daily atmospheric pressure) and AAA rupture risk. This study failed to support claims that atmospheric pressure causally affects AAA rupture risk. In interpreting our results, one should be aware that the range of atmospheric pressure observed in this study is not representative of the atmospheric pressure to which patients with AAA may be exposed, for example, during air travel or travel to high altitudes in the mountains. Making firm claims regarding these conditions in relation to AAA rupture risk is difficult at best. Furthermore, despite the fact that we used one of the largest case series to date to investigate the effect of atmospheric pressure on AAA rupture risk, it is possible that this study is simply too small to demonstrate a causal link.

Animal-assisted activity and emotional status of patients with Alzheimer's disease in day care.

PubMed

Mossello, Enrico; Ridolfi, Alessandro; Mello, Anna Maria; Lorenzini, Giulia; Mugnai, Francesca; Piccini, Carolina; Barone, Domenico; Peruzzi, Anna; Masotti, Giulio; Marchionni, Niccolò

2011-08-01

Preliminary studies suggest beneficial effects of animal-assisted activities (AAA) on behavioral and psychological symptoms of dementia (BPSD), but data are inconsistent. This study aimed to assess the effect of AAA with dogs on cognition, BPSD, emotional status and motor activity in severe Alzheimer's disease (AD). Ten patients attending an Alzheimer Day Care Center (ADCC) participated in a repeated measures study, which included: two weeks' pre-intervention, three weeks' control activity with plush dogs (CA), and three weeks' AAA. Cognitive function (Severe Impairment Battery), mood (Cornell Scale for Depression in Dementia; CSDD), BPSD (Neuropsychiatric Inventory; NPI) and agitation (Cohen-Mansfield Agitation Inventory; CMAI) were assessed at baseline and after each period. Observed Emotion Rating Scale (OERS) for emotional status, Agitated Behavior Mapping Instrument (ABMI) and a checklist for motor activity were completed across the study periods, both during intervention sessions and after three hours. Cognition and NPI were unchanged across the study. Declines in the CMAI and CSDD scores after AAA were not significant, while the NPI anxiety item score decreased in comparison with CA (CA 3.1±2.3, AAA 1.5±2.7, p = 0.04). OERS "sadness" decreased (p = 0.002), while "pleasure" (p = 0.016) and "general alertness" (p = 0.003) increased during AAA compared with CA sessions, and observed sadness remained lower after three hours (p = 0.002). Motor activity increased significantly during AAA. In this sample of severe AD patients in ADCC, AAA was associated with a decrease in anxiety and sadness and an increase in positive emotions and motor activity in comparison with a control activity.

Characterization of the binding specificity of Anguilla anguilla agglutinin (AAA) in comparison to Ulex europaeus agglutinin I (UEA-I).

PubMed

Baldus, S E; Thiele, J; Park, Y O; Hanisch, F G; Bara, J; Fischer, R

1996-08-01

Using immunochemical and immunohistochemical methods, the binding site of Anguilla anguilla agglutinin (AAA) was characterized and compared with the related fucose-specific lectin from Ulex europaeus (UEA-I). In solid-phase enzyme-linked immunoassays, the two lectins recognized Fuc alpha 1-2Gal beta-HSA. AAA additionally cross-reacted with neoglycolipids bearing lacto-N-fucopentaose (LNFP) I [H type 1] and II [Le(a)] and lactodifucotetraose (LDFT) as glycan moieties. UEA-I, on the other hand, bound to a LDFT-derived neoglycolipid but not to the other neoglycolipids tested. Binding of AAA to gastric mucin was competitively neutralized by Le(a)-specific monoclonal antibodies. UEA-I binding, on the other hand, was reduced after co-incubation with H type 2- and Le(y)-specific monoclonal antibodies. According to our results, AAA reacts with fucosylated type 1 chain antigens, whereas UEA-I binds only to the alpha 1-2-fucosylated LDFT-derived neoglycolipid. In immunohistochemical studies, the reactivity of AAA and UEA-I in normal pyloric mucosa from individuals with known Lewis and secretor status was analysed. AAA showed a broad reaction in the superficial pyloric mucosa from secretors and non-secretors, but AAA reactivity was more pronounced in Le(a+b-) individuals. On the other hand, UEA-I stained the superficial pyloric mucosa only from secretor individuals. A staining of deep mucous glands by the lectins was found in all specimens. Both reacted with most human carcinomas of different origin. Slight differences in their binding pattern were observed and may be explained by the different fine-specificities of the lectins.

Molecular insights into the m-AAA protease-mediated dislocation of transmembrane helices in the mitochondrial inner membrane.

PubMed

Lee, Seoeun; Lee, Hunsang; Yoo, Suji; Kim, Hyun

2017-12-08

Protein complexes involved in respiration, ATP synthesis, and protein import reside in the mitochondrial inner membrane; thus, proper regulation of these proteins is essential for cell viability. The m -AAA protease, a conserved hetero-hexameric AAA (ATPase associated with diverse cellular activities) protease, composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates the dislocation of membrane-embedded substrates, including foreign transmembrane (TM) segments, but the molecular mechanism involved in these processes remains elusive. This study investigated the role of the TM domains in the m -AAA protease by systematic replacement of one TM domain at a time in yeast. Our data indicated that replacement of the Yta10 TM2 domain abolishes membrane dislocation for only a subset of substrates, whereas replacement of the Yta12 TM2 domain impairs membrane dislocation for all tested substrates, suggesting different roles of the TM domains in each m -AAA protease subunit. Furthermore, m -AAA protease-mediated membrane dislocation was impaired in the presence of a large downstream hydrophilic moiety in a membrane substrate. This finding suggested that the m -AAA protease cannot dislocate large hydrophilic domains across the membrane, indicating that the membrane dislocation probably occurs in a lipid environment. In summary, this study highlights previously underappreciated biological roles of TM domains of the m -AAA proteases in mediating the recognition and dislocation of membrane-embedded substrates. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Early Impact of Medicare Accountable Care Organizations on Inpatient Surgical Spending.

PubMed

Nathan, Hari; Thumma, Jyothi R; Ryan, Andrew M; Dimick, Justin B

2018-05-16

To evaluate whether hospital participation in accountable care organizations (ACOs) is associated with reduced Medicare spending for inpatient surgery. ACOs have proliferated rapidly and now cover more than 32 million Americans. Medicare Shared Savings Program (MSSP) ACOs have shown modest success in reducing medical spending. Whether they have reduced surgical spending remains unknown. We used 100% Medicare claims from 2010 to 2014 for patients aged 65 to 99 years undergoing 6 common elective surgical procedures [abdominal aortic aneurysm (AAA) repair, colectomy, coronary artery bypass grafting (CABG), hip or knee replacement, or lung resection]. We compared total Medicare payments for 30-day surgical episodes, payments for individual components of care (index hospitalization, readmissions, physician services, and postacute care), and clinical outcomes for patients treated at MSSP ACO hospitals versus matched controls at non-ACO hospitals. We accounted for preexisting trends independent of ACO participation using a difference-in-differences approach. Among 341,675 patients at 427 ACO hospitals and 1,024,090 matched controls at 1531 non-ACO hospitals, patient and hospital characteristics were well-balanced. Average baseline payments were similar at ACO versus non-ACO hospitals. ACO participation was not associated with reductions in total Medicare payments [difference-in-differences estimate=-$72, confidence interval (CI95%): -$228 to +$84] or individual components of payments. ACO participation was also not associated with clinical outcomes. Duration of ACO participation did not affect our estimates. Although Medicare ACOs have had success reducing spending for medical care, they have not had similar success with surgical spending. Given that surgical care accounts for 30% of total health care costs, ACOs and policymakers must pay greater attention to reducing surgical expenditures.

Enhanced cartilage repair in 'healer' mice-New leads in the search for better clinical options for cartilage repair.

PubMed

Fitzgerald, Jamie

2017-02-01

Adult articular cartilage has a poor capacity to undergo intrinsic repair. Current strategies for the repair of large cartilage defects are generally unsatisfactory because the restored cartilage does not have the same resistance to biomechanical loading as authentic articular cartilage and degrades over time. Recently, an exciting new research direction, focused on intrinsic cartilage regeneration rather than fibrous repair by external means, has emerged. This review explores the new findings in this rapidly moving field as they relate to the clinical goal of restoration of structurally robust, stable and non-fibrous articular cartilage following injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

Strategies for the evaluation of DNA damage and repair mechanisms in cancer.

PubMed

Figueroa-González, Gabriela; Pérez-Plasencia, Carlos

2017-06-01

DNA lesions and the repair mechanisms that maintain the integrity of genomic DNA are important in preventing carcinogenesis and its progression. Notably, mutations in DNA repair mechanisms are associated with cancer predisposition syndromes. Additionally, these mechanisms maintain the genomic integrity of cancer cells. The majority of therapies established to treat cancer are genotoxic agents that induce DNA damage, promoting cancer cells to undergo apoptotic death. Effective methods currently exist to evaluate the diverse effects of genotoxic agents and the underlying molecular mechanisms that repair DNA lesions. The current study provides an overview of a number of methods that are available for the detection, analysis and quantification of underlying DNA repair mechanisms.

Temporal trends and geographical variation in the use of subacromial decompression and rotator cuff repair of the shoulder in England.

PubMed

Judge, A; Murphy, R J; Maxwell, R; Arden, N K; Carr, A J

2014-01-01

We explored the trends over time and the geographical variation in the use of subacromial decompression and rotator cuff repair in 152 local health areas (Primary Care Trusts) across England. The diagnostic and procedure codes of patients undergoing certain elective shoulder operations between 2000/2001 and 2009/2010 were extracted from the Hospital Episode Statistics database. They were grouped as 1) subacromial decompression only, 2) subacromial decompression with rotator cuff repair, and 3) rotator cuff repair only. The number of patients undergoing subacromial decompression alone rose by 746.4% from 2523 in 2000/2001 (5.2/100 000 (95% confidence interval (CI) 5.0 to 5.4) to 21 355 in 2009/2010 (40.2/100 000 (95% CI 39.7 to 40.8)). Operations for rotator cuff repair alone peaked in 2008/2009 (4.7/100 000 (95% CI 4.5 to 4.8)) and declined considerably in 2009/2010 (2.6/100 000 (95% CI 2.5 to 2.7)). Given the lack of evidence for the effectiveness of these operations and the significant increase in the number of procedures being performed in England and elsewhere, there is an urgent need for well-designed clinical trials to determine evidence of clinical effectiveness.

Clinical and Radiographic Outcomes of Meniscus Surgery and Future Targets for Biologic Intervention: A review of data from the MOON Group

PubMed Central

Westermann, Robert W.; Jones, Morgan; Wasserstein, David; Spindler, Kurt P.

2017-01-01

Meniscus injury and treatment occurred with the majority of anterior cruciate ligament reconstructions (ACLR) in the multicenter orthopaedic outcomes (MOON) cohort. We describe the patient reported outcomes, radiographic outcomes and predictors of pain from meniscus injuries and treatment in the setting of ACLR. Patient reported outcomes improve significantly following meniscus repair with ACLR, but differences exist based on the meniscus injury laterally (medial or lateral). Patients undergoing medial meniscus repair have worse patient-reported outcomes and more pain compared to those with uninjured menisci. However, lateral meniscal tears can be repaired with similar outcomes as uninjured menisci. Medial meniscal treatment (meniscectomy or repair) results in a significant loss of joint space at 2 years compared to uninjured menisci. Menisci treated with excision had a greater degree of joint space loss compared to those treated with repair. Clinically significant knee pain is more common following injuries to the medial meniscus and increased in patients who undergo early re-operation after initial ACLR. Future research efforts aimed at improving outcomes after combined ACLR and meniscus treatment should focus on optimizing biologic and mechanical environments that promote healing of medial meniscal tears sustained during ACL injury. PMID:28282214

77 FR 13608 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-07

... Against AIDS (AAA) in 2009, a 5-year, multifaceted communication campaign consisting of several campaigns targeting various high-risk populations. The overall goals of AAA are to increase HIV/AIDS awareness and reduce HIV incidence in the United States. Each AAA campaign uses mass media and direct-to-consumer...

Advanced, Analytic, Automated (AAA) Measurement of Engagement during Learning

ERIC Educational Resources Information Center

D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

2017-01-01

It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in…

Common iliac artery aneurysms in patients with abdominal aortic aneurysms.

PubMed

Armon, M P; Wenham, P W; Whitaker, S C; Gregson, R H; Hopkinson, B R

1998-03-01

To determine the incidence of common iliac artery (CIA) aneurysms in patients with abdominal aortic aneurysms (AAA) and to evaluate the relationship between AAA and CIA diameter. Spiral CT angiography was used to measure the maximum diameters of the abdominal aorta and the common iliac arteries of 215 patients with AAA. The median CIA diameter was 1.7 cm--significantly greater than the published mean of 1.25 (2 S.D. = 0.85-1.65) cm of an age-matched, non-vascular population. Thirty-four patients (16%) had unilateral and 26 patients (12%) bilateral CIA aneurysms > or = 2.4 cm diameter. Eight-six vessels (20%) were affected. Right CIA diameters were wider than left CIA diameters (p < 0.0001, Wilcoxon matched-pairs signed rank test). The correlation between AAA size and CIA diameter was weak. The AAA population has abnormally dilated common iliac arteries. In this population, common iliac artery aneurysms should be defined as those greater than 2.4 cm diameter. 20% of CIAs in patients with AAA are aneurysmal according to this definition.

AAA (2010) CAPD clinical practice guidelines: need for an update.

PubMed

DeBonis, David A

2017-09-01

Review and critique of the clinical value of the AAA CAPD guidance document in light of criteria for credible and useful guidance documents, as discussed by Field and Lohr. A qualitative review of the of the AAA CAPD guidelines using a framework by Field and Lohr to assess their relative value in supporting the assessment and management of CAPD referrals. Relevant literature available through electronic search tools and published texts were used along with the AAA CAPD guidance document and the chapter by Field and Lohr. The AAA document does not meet many of the key requirements discussed by Field and Lohr. It does not reflect the current literature, fails to help clinicians understand for whom auditory processing testing and intervention would be most useful, includes contradictory suggestions which reduce clarity and appears to avoid conclusions that might cast the CAPD construct in a negative light. It also does not include input from diverse affected groups. All of these reduce the document's credibility. The AAA CAPD guidance document will need to be updated and re-conceptualised in order to provide meaningful guidance for clinicians.

Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

PubMed

Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

2018-01-15

Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Epidemiology of abdominal aortic aneurysms in the Asian community.

PubMed

Spark, J I; Baker, J L; Vowden, P; Wilkinson, D

2001-03-01

Studies relating to the ethnic origin of patients with an abdominal aortic aneurysm (AAA) are few and are mainly concerned with the differences between black and white Americans. The purpose of this study was to determine whether the incidence of AAA among the Asian population of Bradford is different from that in the Caucasian population. A retrospective study of patients with an AAA was carried out between 1990 and 1997 using data collected by the Patient Administrative Service, personal databases of the vascular consultants and theatre records. Information about the ethnic composition of the population of Bradford was obtained from the 1991 national census. Demographic data, including ethnic origin and clinical details, were obtained from patient notes. Two hundred and thirty-three patients with an AAA were identified during the study interval. The Asian population comprised 14.0 per cent of the total population of Bradford. Twenty-eight AAAs would be expected per year. All of the aneurysms identified occurred in the Caucasian population and none in the Asian community. These early results suggest that AAA is rare among the Asian population.

[Ultrasound screening of abdominal aortic aneurysm: Lessons from Vesale 2013].

PubMed

Laroche, J P; Becker, F; Baud, J M; Miserey, G; Jaussent, A; Picot, M C; Bura-Rivière, A; Quéré, I

2015-12-01

Although aneurysm of the abdominal infra-renal aorta (AAA) meets criteria warranting B mode ultrasound screening, the advantages of mass screening versus selective targeted opportunistic screening remain a subject of debate. In France, the French Society of Vascular Medicine (SFMV) and the Health Authority (HAS) published recommendations for targeted opportunistic screening in 2006 and 2013 respectively. The SFMV held a mainstream communication day on November 21, 2013 in France involving participants from metropolitan France and overseas departments that led to a proposal for free AAA ultrasound screening: the Vesalius operation. Being a consumer operation, the selection criteria were limited to age (men and women between 60 and 75 years); the age limit was lowered to 50 years in case of direct family history of AAA. More than 7000 people (as many women as men) were screened in 83 centers with a 1.70% prevalence of AAA in the age-based target population (3.12% for men, 0.27% for women). The median diameter of detected AAA was 33 mm (range 20 to 74 mm). The prevalence of AAA was 1.7% in this population. Vesalius data are consistent with those of the literature both in terms of prevalence and for cardiovascular risk factors with the important role of smoking. Lessons from Vesalius to take into consideration are: screening is warranted in men 60 years and over, especially smokers, and in female smokers. Screening beyond 75 years should be discussed. Given the importance of screening, the SFMV set up a year of national screening for AAA (Vesalius operation 2014/2015) in order to increase public and physician awareness about AAA detection, therapeutic management, and monitoring. AAA is a serious, common, disease that kills 6000 people each year. The goal of screening is cost-effective reduction in the death toll. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Combination Therapy with Atorvastatin and Amlodipine Suppresses Angiotensin II-Induced Aortic Aneurysm Formation

PubMed Central

Takahashi, Kikuyo; Matsumoto, Yasuharu; Do.e, Zhulanqiqige; Kanazawa, Masanori; Satoh, Kimio; Shimizu, Takuya; Sato, Akira; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

2013-01-01

Background Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease. It is controversial whether statin and calcium channel blockers (CCBs) has an inhibitory effect on the expansion of AAA. Some studies reported that CCBs have an inhibitory effect on Rho-kinase activity. Rho-kinase plays an important role in the pathogenesis of various cardiovascular diseases. However, there is no study reporting of the association between Rho-kinase and human AAAs. Methods and Results Experimental AAA was induced in Apolipoprotein E-deficient (ApoE-/-) mice infused with angiotensin II (AngII) for 28 days. They were randomly divided into the following 5 groups; saline infusion alone (sham), AngII infusion alone, AngII infusion plus atorvastatin (10 mg/kg/day), AngII infusion plus amlodipine (1 mg/kg/day), and AngII infusion plus combination therapy with atorvastatin (10 mg/kg/day) and amlodipine (1 mg/kg/day). The combination therapy significantly suppressed AngII-induced increase in maximal aortic diameter as compared with sham, whereas each monotherapy had no inhibitory effects. The combination therapy significantly reduced AngII-induced apoptosis and elastin degradation at the AAA lesion, whereas each monotherapy did not. Moreover, Rho-kinase activity, as evaluated by the extent of phosphorylation of myosin-binding subunit (a substrate of Rho-kinase) and matrix metalloproteinase activity were significantly increased in the AngII-induced AAA lesion as compared with sham, both of which were again significantly suppressed by the combination therapy. In human aortic samples, immunohistochemistory revealed that the activity and expression of Rho-kinase was up-regulated in AAA lesion as compared with abdominal aorta from control subjects. Conclusions Rho-kinase is up-regulated in the aortic wall of human AAA. The combination therapy with amlodipine and Atorvastatin, but not each monotherapy, suppresses AngII-induced AAA formation in mice in vivo, for which Rho-kinase inhibition may be involved. PMID:23967318

Human serum cholinesterase from liver pathological samples exhibit highly elevated aryl acylamidase activity.

PubMed

Boopathy, Rathanam; Rajesh, Ramanna Valmiki; Darvesh, Sultan; Layer, Paul G

2007-05-01

Although aspartate aminotransferase (AST) and gamma-glutamyltransferase (gamma GT) enzymes are widely used as markers for liver disorders, the ubiquitous enzyme butyrylcholinesterase (BChE), synthesized in liver is also used as marker in the assessment of liver pathophysiology. This BChE enzyme in addition to its esterase activity has yet another enzymatic function designated as aryl acylamidase (AAA) activity. It is determined in in vitro based on the hydrolysis of the synthetic substrate o-nitroacetanilide. In the present study, human serum cholinesterase (BChE) activity was studied with respect to its AAA activity on the BChE protein (AAA(BChE)) in patients with liver disorders. AST and gamma GT values were taken into account in this study as known markers for liver disorders. Blood samples were grouped into 3 based on esterase activity associated with BChE protein. They are normal, low, and very low BChE activity but with markedly increased AST and gamma GT levels. These samples were tested for their respective AAA function. Association of AAA with BChE from samples was proved using BChE monoclonal antibody precipitation experiment. The absolute levels of AAA were increased as BChE activity decreased while deviating from normal samples and such deviation was directly proportional to the severity of the liver disorder. Differences between these groups became prominent after determining the ratios of AAA(BChE) to BChE activities. Samples showing very high AAA(BChE) to BChE ratio were also showing high to very high gamma GT values. These findings establish AAA(BChE) as an independently regulated enzymatic activity on BChE especially in liver disorders. Moreover, since neither the low esterase activity of BChE by itself nor increased levels of AST/gamma GT are sufficient pathological indicators, this pilot study merits replication with large sample numbers.

Angiotensin-Induced Abdominal Aortic Aneurysms in Hypercholesterolemic Mice: Role of Serum Cholesterol and Temporal Effects of Exposure

PubMed Central

Prins, Petra A.; Hill, Michael F.; Airey, David; Nwosu, Sam; Perati, Prudhvidhar R.; Tavori, Hagai; F. Linton, MacRae; Kon, Valentina; Fazio, Sergio; Sampson, Uchechukwu K.

2014-01-01

Objective Understanding variations in size and pattern of development of angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) may inform translational research strategies. Thus, we sought insight into the temporal evolution of AAA in apolipoprotein (apo)E−/− mice. Approach A cohort of mice underwent a 4-week pump-mediated infusion of saline (n = 23) or 1500 ng/kg/min of Ang II (n = 85) and AAA development was tracked via in vivo ultrasound imaging. We adjusted for hemodynamic covariates in the regression models for AAA occurrence in relation to time. Results The overall effect of time was statistically significant (p<0.001). Compared to day 7 of AngII infusion, there was no decrease in the log odds of AAA occurrence by day 14 (−0.234, p = 0.65), but compared to day 21 and 28, the log odds decreased by 9.07 (p<0.001) and 2.35 (p = 0.04), respectively. Hemodynamic parameters were not predictive of change in aortic diameter (Δ) (SBP, p = 0.66; DBP, p = 0.66). Mean total cholesterol (TC) was higher among mice with large versus small AAA (601 vs. 422 mg/ml, p<0.0001), and the difference was due to LDL. AngII exposure was associated with 0.43 mm (95% CI, 0.27 to 0.61, p<0.0001) increase in aortic diameter; and a 100 mg/dl increase in mean final cholesterol level was associated with a 12% (95% CI, 5.68 to 18.23, p<0.0001) increase in aortic diameter. Baseline cholesterol was not associated with change in aortic diameter (p = 0.86). Conclusions These are the first formal estimates of a consistent pattern of Ang II-induced AAA development. The odds of AAA occurrence diminish after the second week of Ang II infusion, and TC is independently associated with AAA size. PMID:24465413

Increased 18F-FDG Uptake Is Predictive of Rupture in a Novel Rat Abdominal Aortic Aneurysm Rupture Model

PubMed Central

English, Sean J.; Piert, Morand R.; Diaz, Jose A.; Gordon, David; Ghosh, Abhijit; D'Alecy, Louis G.; Whitesall, Steven E.; Sharma, Ashish K.; DeRoo, Elise P.; Watt, Tessa; Su, Gang; Henke, Peter K.; Eliason, Jonathan L.; Ailawadi, Gorav; Upchurch, Gilbert R.

2015-01-01

Objective To determine whether 18F-fluorodeoxyglucose (18F-FDG) micro–positron emission tomography (micro-PET) can predict abdominal aortic aneurysm (AAA) rupture. Background An infrarenal AAA model is needed to study inflammatory mechanisms that drive rupture. 18F-FDG PET can detect vascular inflammation in animal models and patients. Methods After exposing Sprague-Dawley rats to intra-aortic porcine pancreatic elastase (PPE) (12 U/mL), AAA rupture was induced by daily, subcutaneous, β-aminopropionitrile (BAPN, 300 mg/kg, N = 24) administration. Negative control AAA animals (N = 15) underwent daily saline subcutaneous injection after PPE exposure. BAPN-exposed animals that did not rupture served as positive controls [nonruptured AAA (NRAAA) 14d, N = 9]. Rupture was witnessed using radiotelemetry. Maximum standard uptakes for 18F-FDG micro-PET studies were determined. Aortic wall PAI-1, uPA, and tPA concentrations were determined by western blot analyses. Interleukin (IL)-1β, IL-6, IL-10, and MIP-2 were determined by Bio-Plex bead array. Neutrophil and macrophage populations per high-power field were quantified. Matrix metalloproteinase (MMP) activities were determined by zymography. Results When comparing ruptured AAA (RAAA) to NRAAA 14d animals, increased focal 18F-FDG uptakes were detected at subsequent sites of rupture (P = 0.03). PAI-1 expression was significantly less in RAAA tissue (P = 0.01), with comparable uPA and decreased tPA levels (P = 0.02). IL-1β (P = 0.04), IL-6 (P = 0.001), IL-10 (P = 0.04), and MIP-2 (P = 0.02)expression, neutrophil (P = 0.02) and macrophage presence (P = 0.002), and MMP9 (P < 0.0001) activity were increased in RAAA tissue. Conclusions With this AAA rupture model, increased prerupture 18F-FDG uptake on micro-PET imaging was associated with increased inflammation in the ruptured AAA wall. 18F-FDG PET imaging may be used to monitor inflammatory changes before AAA rupture. PMID:24651130

Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

PubMed

Ong, Chloe C H; Ang, Khong Wei; Soh, Roger C X; Tin, Kah Ming; Yap, Jerome H H; Lee, James C L; Bragg, Christopher M

2017-01-01

There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-E-T-538: Evaluation of IMRT Dose Calculation Based on Pencil-Beam and AAA Algorithms.

PubMed

Yuan, Y; Duan, J; Popple, R; Brezovich, I

2012-06-01

To evaluate the accuracy of dose calculation for intensity modulated radiation therapy (IMRT) based on Pencil Beam (PB) and Analytical Anisotropic Algorithm (AAA) computation algorithms. IMRT plans of twelve patients with different treatment sites, including head/neck, lung and pelvis, were investigated. For each patient, dose calculation with PB and AAA algorithms using dose grid sizes of 0.5 mm, 0.25 mm, and 0.125 mm, were compared with composite-beam ion chamber and film measurements in patient specific QA. Discrepancies between the calculation and the measurement were evaluated by percentage error for ion chamber dose and γ〉l failure rate in gamma analysis (3%/3mm) for film dosimetry. For 9 patients, ion chamber dose calculated with AAA-algorithms is closer to ion chamber measurement than that calculated with PB algorithm with grid size of 2.5 mm, though all calculated ion chamber doses are within 3% of the measurements. For head/neck patients and other patients with large treatment volumes, γ〉l failure rate is significantly reduced (within 5%) with AAA-based treatment planning compared to generally more than 10% with PB-based treatment planning (grid size=2.5 mm). For lung and brain cancer patients with medium and small treatment volumes, γ〉l failure rates are typically within 5% for both AAA and PB-based treatment planning (grid size=2.5 mm). For both PB and AAA-based treatment planning, improvements of dose calculation accuracy with finer dose grids were observed in film dosimetry of 11 patients and in ion chamber measurements for 3 patients. AAA-based treatment planning provides more accurate dose calculation for head/neck patients and other patients with large treatment volumes. Compared with film dosimetry, a γ〉l failure rate within 5% can be achieved for AAA-based treatment planning. © 2012 American Association of Physicists in Medicine.

Association of high sensitivity C-reactive protein and abdominal aortic aneurysm: a meta-analysis and systematic review.

PubMed

Wang, Yunpeng; Shen, Guanghui; Wang, Haiyang; Yao, Ye; Sun, Qingfeng; Jing, Bao; Liu, Gaoyan; Wu, Jia; Yuan, Chao; Liu, Siqi; Liu, Xinyu; Li, Shiyong; Li, Haocheng

2017-12-01

To evaluate the association of high sensitivity C-reactive protein (hsCRP) with the presence of abdominal aortic aneurysm (AAA). Medline, Cochrane, Embase, and Google Scholar databases were searched until 22 June 2016 using the keywords predictive factors, biomarkers, abdominal aortic aneurysm, prediction, high sensitivity C-reactive protein, and hsCRP. Prospective studies, retrospective studies, and cohort studies were included. Twelve case-control studies were included in the meta-analysis with a total of 8345 patients (1977 in the AAA group and 6368 in the control group). The pooled results showed that AAA patients had higher hsCRP value than the control group (difference in means = 1.827, 95% CI = 0.010 to 3.645, p = .049). Subgroup analysis found AAA patients with medium or small aortic diameter (<50 mm) had higher hsCRP plasma levels than the control group (difference in means = 1.301, 95% CI = 0.821 to 1.781, p < .001). In patients with large aortic diameter (≥50 mm), no difference was observed in hsCRP levels between the AAA and control groups (difference in means = 1.769, 95% CI = -1.387 to 4.925, p = .272). Multi-regression analysis found the difference in means of hsCRP plasma levels between AAA and control groups decreased as aortic diameter increased (slope = -0.04, p < .001), suggesting that hsCRP levels may be inversely associated with increasing aneurysm size. Our findings suggest that hsCRP levels may possibly be used as a diagnostic biomarker for AAA patients with medium or small aortic diameter but not for AAA patients with large aortic diameter. The correlation between serum hsCRP level and AAA aneurysm is not conclusive due to the small number of included articles and between-study heterogeneity.

The Impact of Individual In Vivo Repair of DNA Double-Strand Breaks on Oral Mucositis in Adjuvant Radiotherapy of Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fleckenstein, Jochen, E-mail: rajfle@uks.eu; Kuehne, Martin; Seegmueller, Katharina

2011-12-01

Purpose: To evaluate the impact of individual in vivo DNA double-strand break (DSB) repair capacity on the incidence of severe oral mucositis in patients with head-and-neck cancer undergoing adjuvant radiotherapy (RT) or radiochemotherapy (RCT). Patients and Methods: Thirty-one patients with resected head-and-neck cancer undergoing adjuvant RT or RCT were examined. Patients underwent RT of the primary tumor site and locoregional lymph nodes with a total dose of 60-66 Gy (single dose 2 Gy, five fractions per week). Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. To assess DSB repair, {gamma}-H2AX foci in blood lymphocytes were quantified before and 0.5more » h, 2.5 h, 5 h, and 24 h after in vivo radiation exposure (the first fraction of RT). World Health Organization scores for oral mucositis were documented weekly and correlated with DSB repair. Results: Sixteen patients received RT alone; 15 patients received RCT. In patients who developed Grade {>=} 3 mucositis (n = 18) the amount of unrepaired DSBs 24 h after radiation exposure and DSB repair half-times did not differ significantly from patients with Grade {<=}2 mucositis (n = 13). Patients with a proportion of unrepaired DSBs after 24 h higher than the mean value + one standard deviation had an increased incidence of severe oral mucositis. Conclusions: Evaluation of in vivo DSB repair by determination of {gamma}-H2AX foci loss is feasible in clinical practice and allows identification of patients with impaired DSB repair. The incidence of oral mucositis is not closely correlated with DSB repair under the evaluated conditions.« less

Valve Repair Is Superior to Replacement in Most Patients With Coexisting Degenerative Mitral Valve and Coronary Artery Diseases.

PubMed

Javadikasgari, Hoda; Gillinov, A Marc; Idrees, Jay J; Mihaljevic, Tomislav; Suri, Rakesh M; Raza, Sajjad; Houghtaling, Penny L; Svensson, Lars G; Navia, José L; Mick, Stephanie L; Desai, Milind Y; Sabik, Joseph F; Blackstone, Eugene H

2017-06-01

For mitral regurgitation (MR) from degenerative mitral disease in patients with coexisting coronary artery disease, the appropriate surgical strategy remains controversial. From 1985 to 2011, 1,071 adults (age 70 ± 9.3 years, 77% men) underwent combined coronary artery bypass grafting and either mitral valve repair (n = 872, 81%) or replacement (n=199, 19%) for degenerative MR. Propensity matching (177 patient pairs, 89% of possible matches) was used to compare early outcomes and time-related recurrence of MR after mitral valve repair, mitral valve reoperation, and mortality. Risk factors for death were identified with multivariable, multiphase hazard-function analysis. Patients undergoing valve replacement were older, with more valve calcification and a higher prevalence of preoperative atrial fibrillation and heart failure (all p < .0001). Among matched pairs, mitral replacement versus repair was associated with higher hospital mortality (5.0% vs 1.0%, p = .0001) and more postoperative renal failure (7.0% vs 3.2%, p = .01), reexplorations for bleeding (6.0% vs 3.1%, p = .05), and respiratory failure (14% vs 4.7%, p < .0001). Of matched patients undergoing repair, 18% had MR above 3+ by 5 years. Mitral valve durability was similar between matched groups, but survival at 15 years was 18% after replacement versus 52% after repair. Nomograms from the multivariable equation revealed that in 94% of cases, 10-year survival was calculated to be higher after repair than after replacement. In patients with coexisting degenerative mitral valve and coronary artery diseases, mitral valve repair is expected to confer a long-term survival advantage over replacement despite some recurrence of MR. When feasible, it is the procedure of choice for these patients. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

3D analysis of vortical structures in an abdominal aortic aneurysm by stereoscopic PIV

NASA Astrophysics Data System (ADS)

Deplano, Valérie; Guivier-Curien, Carine; Bertrand, Eric

2016-11-01

The present work presents an experimental in vitro three-dimensional analysis of the flow dynamics in an abdominal aortic aneurysm (AAA) through stereoscopic particle image velocimetry (SPIV) measurements. The experimental set-up mimics the pathophysiological context involving a shear thinning blood analogue fluid, compliant AAA and aorto-iliac bifurcation walls and controlled inlet and outlet flow rate and pressure waveforms as well as working fluid temperature. SPIV was carefully calibrated and conducted to assess the three velocity components in the AAA volume. For the first time in the literature, the 3D vortex ring genesis, propagation, and vanishing in the AAA bulge are experimentally described and quantified. In comparison with classical 2-component PIV measurements (2C PIV), the third component of the velocity vector was shown to be of importance in such a geometry, especially, during the deceleration phase of the flow rate. The 3D velocity magnitude reached up more than 20 % of the 2D one showing that 2C PIV are definitively not accurate enough to provide a complete description of flow behaviour in an AAA. In addition to potential clinical implications of a full 3D vortex ring description in AAA evolution, the 3D in vitro experimental quantification of the flow dynamics carried out in the present study offers an interesting tool for the validation of fluid-structure interaction numerical studies dealing with AAA.

Abdominal aorta aneurysm (AAA): Is there a role for prevention and therapy using antioxidants?

PubMed

Pincemail, Joël; Defraigne, Jean-Olivier; Courtois, Audrey; Albert, Adelin; Cheramy-Bien, Jean-Paul; Sakalihasan, Natzi

2017-09-18

Abdominal aortic aneurysm (AAA) is a degenerative disease that cause mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seems to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin. Reducing oxidative stress by antioxidants has been shown to be a potential strategy for limiting AAA development. Human studies confirmed that oxidative stress and endothelial dysfunction are well associated with AAA development. Unfortunately, there is currently no evidence showing that strategies using low molecular weight antioxidants (vitamins C and E, β-carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function but also their capacity to stimulate enzymatic antioxidants trough activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression. Clinical studies are therefore urgently necessary to confirm such a suggestion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying.

PubMed

Wang, Shuaiyu; Jacquemyn, Julie; Murru, Sara; Martinelli, Paola; Barth, Esther; Langer, Thomas; Niessen, Carien M; Rugarli, Elena I

2016-12-01

The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the m-AAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency.

Polymorphisms of the matrix metalloproteinase 9 gene and abdominal aortic aneurysm.

PubMed

Smallwood, L; Allcock, R; van Bockxmeer, F; Warrington, N; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

2008-10-01

Increased matrix metalloproteinase (MMP) 9 activity has been implicated in the formation of abdominal aortic aneurysm (AAA). The aim was to explore the association between potentially functional variants of the MMP-9 gene and AAA. The -1562C > T and -1811A > T variants of the MMP-9 gene were genotyped in 678 men with an AAA (at least 30 mm in diameter) and 659 control subjects (aortic diameter 19-22 mm) recruited from a population-based trial of screening for AAA. Levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed by multivariable logistic regression. There was no association between the MMP-9-1562C > T (odds ratio (OR) 0.70 (95 per cent confidence interval (c.i.) 0.27 to 1.82)) or -1811A > T (OR 0.71 (95 per cent c.i. 0.28 to 1.85)) genotypes, or the most common haplotype (OR 0.81 (95 per cent c.i. 0.62 to 1.05)) and AAA. The serum MMP-9 concentration was higher in cases than controls, and in minor allele carriers in cases and controls, although the differences were not statistically significant. In this study, the genetic tendency to higher levels of circulating MMP-9 was not associated with AAA.

Polymorphisms of the MMP-9 gene and abdominal aortic aneurysm

PubMed Central

Smallwood, Linda; Allcock, Richard; van Bockxmeer, Frank; Warrington, Nicole; Palmer, Lyle J; Iacopetta, Barry; Golledge, Jonathan; Norman, Paul E

2008-01-01

Background Increased matrix metalloproteinase-9 (MMP-9) activity has been implicated in the formation of abdominal aortic aneurysms (AAAs). The aim of the present study was to explore the association between potentially functional variants of the MMP-9 gene and AAA. Method The −1562C>T and −1811A>T variants of the MMP-9 gene were genotyped in 678 men with AAAs (>30mm in diameter) and 659 controls (aortic diameter 19−22mm) recruited from a population-based trial of screening for AAAs. The levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed using multivariate logistic regression. Results There was no association between the MMP-9 −1562C>T (OR 0.70 95%CI 0.27, 1.82) or −1811A>T (OR 0.71, 95%CI 0.28, 1.85) genotypes, or the most common haplotype (OR 0.81 95%CI 0.62, 1.05), and AAA. The serum MMP-9 concentration (ng/mL) was higher in cases than controls and in minor allele carriers in cases and controls although the differences were not statistically significant. Conclusion The results suggest that a genetic tendency to have higher levels of circulating MMP-9 is not associated with AAAs. PMID:18763261

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun Zhonghua, E-mail: z.sun@curtin.edu.a; Chaichana, Thanapong

The purpose of the study was to investigate the hemodynamic effect of stent struts (wires) on renal arteries in patients with abdominal aortic aneurysms (AAAs) treated with suprarenal stent-grafts. Two sample patients with AAA undergoing multislice CT angiography pre- and postsuprarenal fixation of stent-grafts were selected for inclusion in the study. Eight juxtarenal models focusing on the renal arteries were generated from the multislice CT datasets. Four types of configurations of stent wires crossing the renal artery ostium were simulated in the segmented aorta models: a single wire crossing centrally, a single wire crossing peripherally, a V-shaped wire crossing centrally,more » and multiple wires crossing peripherally. The blood flow pattern, flow velocity, wall pressure, and wall shear stress at the renal arteries pre- and post-stent-grafting were analyzed and compared using a two-way fluid structure interaction analysis. The stent wire thickness was simulated with a diameter of 0.4, 1.0, and 2.0 mm, and hemodynamic analysis was performed at different cardiac cycles. The interference of stent wires with renal blood flow was mainly determined by the thickness of stent wires and the type of configuration of stent wires crossing the renal ostium. The flow velocity was reduced by 20-30% in most of the situations when the stent wire thickness increased to 1.0 and 2.0 mm. Of the four types of configuration, the single wire crossing centrally resulted in the highest reduction of flow velocity, ranging from 21% to 28.9% among three different wire thicknesses. Wall shear stress was also dependent on the wire thickness, which decreased significantly when the wire thickness reached 1.0 and 2.0 mm. In conclusion, our preliminary study showed that the hemodynamic effect of suprarenal stent wires in patients with AAA treated with suprarenal stent-grafts was determined by the thickness of suprarenal stent wires. Research findings in our study are useful for follow-up of patients treated with suprarenal stent-grafts to ensure long-term safety of the suprarenal fixation.« less

Association of branched-chain amino acids with carotid intima-media thickness and coronary artery disease risk factors.

PubMed

Yang, Ruiyue; Dong, Jun; Zhao, Haijian; Li, Hongxia; Guo, Hanbang; Wang, Shu; Zhang, Chuanbao; Wang, Siming; Wang, Mo; Yu, Songlin; Chen, Wenxiang

2014-01-01

Recent studies have determined that branched-chain (BCAAs) and aromatic (AAAs) amino acids are strongly correlated with obesity and atherogenic dyslipidemia and are strong predictors of diabetes. However, it is not clear if these amino acids are capable of identifying subjects with coronary artery disease (CAD), particularly with subclinical atherosclerosis who are at risk of developing CAD. Four hundred and seventy two Chinese subjects (272 males and 200 females, 42-97 y of age) undergoing physical exams were recruited at random for participation in the cross-sectional study. Serum BCAAs and AAAs were measured using our previously reported isotope dilution liquid chromatography tandem mass spectrometry method. Bilateral B-mode carotid artery images for carotid intima-media thickness (cIMT) were acquired at end diastole and cIMT values more than 0.9 mm were categorized as increased. Correlations of BCAAs with cIMT and other CAD risk factors were analyzed. BCAAs and AAAs were significantly and positively associated with risk factors of CAD, e.g., cIMT, BMI, waist circumference, blood pressure, fasting blood glucose, TG, apoB, apoB/apoAI ratio, apoCII, apoCIII and hsCRP, and were significantly and negatively associated with HDL-C and apoAI. Stepwise multiple linear regression analysis revealed that age (β = 0.175, P<0.001), log BCAA (β = 0.147, P<0.001) and systolic blood pressure (β = 0.141, P = 0.012) were positively and independently associated with cIMT. In the logistic regression model, the most and only powerful laboratory factor correlated with increased cIMT was BCAA (the odds ratio of the fourth quartile compared to the first quartile was 2.679; P = 0.009). BCAAs are independently correlated with increased cIMT. This correlation would open a new field of research in the mechanistic understanding and risk assessment of CAD.

Anti-TNF Therapeutic Drug Monitoring in Postoperative Crohn's Disease.

PubMed

Wright, Emily K; Kamm, Michael A; De Cruz, Peter; Hamilton, Amy L; Selvaraj, Fabiyola; Princen, Fred; Gorelik, Alexandra; Liew, Danny; Prideaux, Lani; Lawrance, Ian C; Andrews, Jane M; Bampton, Peter A; Jakobovits, Simon L; Florin, Timothy H; Gibson, Peter R; Debinski, Henry; Macrae, Finlay A; Samuel, Douglas; Kronborg, Ian; Radford-Smith, Graham; Gearry, Richard B; Selby, Warwick; Bell, Sally J; Brown, Steven J; Connell, William R

2018-05-25

Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts ≥ i2] [9.98µg/mL vs 8.43 µg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 µg/mL] than patients on combination therapy [11.725 µg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 µg/mL vs 12.0 µg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.

Simple versus complex degenerative mitral valve disease.

PubMed

Javadikasgari, Hoda; Mihaljevic, Tomislav; Suri, Rakesh M; Svensson, Lars G; Navia, Jose L; Wang, Robert Z; Tappuni, Bassman; Lowry, Ashley M; McCurry, Kenneth R; Blackstone, Eugene H; Desai, Milind Y; Mick, Stephanie L; Gillinov, A Marc

2018-07-01

At a center where surgeons favor mitral valve (MV) repair for all subsets of leaflet prolapse, we compared results of patients undergoing repair for simple versus complex degenerative MV disease. From January 1985 to January 2016, 6153 patients underwent primary isolated MV repair for degenerative disease, 3101 patients underwent primary isolated MV repair for simple disease (posterior prolapse), and 3052 patients underwent primary isolated MV repair for complex disease (anterior or bileaflet prolapse), based on preoperative echocardiographic images. Logistic regression analysis was used to generate propensity scores for risk-adjusted comparisons (n = 2065 matched pairs). Durability was assessed by longitudinal recurrence of mitral regurgitation and reoperation. Compared with patients with simple disease, those undergoing repair of complex pathology were more likely to be younger and female (both P values < .0001) but with similar symptoms (P = .3). The most common repair technique was ring/band annuloplasty (3055/99% simple vs 3000/98% complex; P = .5), followed by leaflet resection (2802/90% simple vs 2249/74% complex; P < .0001). Among propensity-matched patients, recurrence of severe mitral regurgitation 10 years after repair was 6.2% for simple pathology versus 11% for complex pathology (P = .007), reoperation at 18 years was 6.3% for simple pathology versus 11% for complex pathology, and 20-year survival was 62% for simple pathology versus 61% for complex pathology (P = .6). Early surgical intervention has become more common in patients with degenerative MV disease, regardless of valve prolapse complexity or symptom status. Valve repair was associated with similarly low operative risk and time-related survival but less durability in complex disease. Lifelong annual echocardiographic surveillance after MV repair is recommended, particularly in patients with complex disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Comparison of endovascular repair with branched stent graft and open repair for aortic arch aneurysm.

PubMed

Kawatou, Masahide; Minakata, Kenji; Sakamoto, Kazuhisa; Nakatsu, Taro; Tazaki, Junichi; Higami, Hirooki; Uehara, Kyokun; Yamazaki, Kazuhiro; Inoue, Kanji; Kimura, Takeshi; Sakata, Ryuzo

2017-08-01

Although conventional open repair is our preference for patients with aortic arch aneurysms, we have often chosen thoracic endovascular aneurysm repair (TEVAR) with a handmade branched stent graft (bTEVAR) in high-risk patients. The aim of this study was to compare the midterm clinical outcomes of our bTEVAR technique to those of the open repair. Between January 2007 and December 2014, we treated 129 patients with aortic arch aneurysm by means of either conventional open repair (OPEN, n = 61) or bTEVAR (n = 68) at our institution. The mean ages were 70.5 ± 12.7 years in the OPEN group and 72.7 ± 12.5 years in the bTEVAR group (P = 0.32). The aetiologies included true aneurysm in 101 patients (78.3%) and chronic dissection in 26 (20.1%). There were 2 (3.3%) in-hospital deaths in the OPEN group and 3 (4.4%) in the bTEVAR group. The mean follow-up duration was 3.0 ± 2.1 years (2.4 ± 1.9 years in the OPEN group and 3.6 ± 2.3 years in the bTEVAR group). There was no difference in 5-year aneurysm-related mortality between groups (10.7% in OPEN vs 12.8% in bTEVAR, P = 0.50). In terms of late additional procedures, however, none were required in the OPEN group, whereas 10 (15.4%) additional endovascular repairs and 4 (6.2%) open repairs were required in the bTEVAR group. Our bTEVAR could be performed with low early mortality, and it yielded similar midterm aneurysm-related mortality to that of conventional open repair. However, these patients undergoing this technique required more late additional procedures than those undergoing conventional open repair. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Analysis of a Typical Chinese High School Biology Textbook Using the AAAS Textbook Standards

ERIC Educational Resources Information Center

Liang, Ye; Cobern, William W.

2013-01-01

The purpose of this study was to evaluate a typical Chinese high school biology textbook using the textbook standards of the American Association for the Advancement of Science (AAAS). The data were composed of three chapters selected from the textbook. Each chapter was analyzed and rated using the AAAS textbook standards. Pearson correlations…

40 CFR 78.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., subparts AAA through III of part 96 of this chapter or State regulations approved under § 51.124(o)(1) or... HHHH of part 60 of this chapter, subparts AA through II of part 96 of this chapter, subparts AAA... chapter. (8) Under subparts AAA through III of part 96 of this chapter, (i) The decision on the deduction...

40 CFR 280.104 - Local government bond rating test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... million or more, excluding refunded obligations, with a Moody's rating of Aaa, Aa, A, or Baa, or a Standard & Poor's rating of AAA, AA, A, or BBB. Where a local government has multiple outstanding issues... bonds of $1 million or more, excluding refunded issues and by also having a Moody's rating of Aaa, A, A...

Does continuous trusted adult support in childhood impart life-course resilience against adverse childhood experiences - a retrospective study on adult health-harming behaviours and mental well-being.

PubMed

Bellis, Mark A; Hardcastle, Katie; Ford, Kat; Hughes, Karen; Ashton, Kathryn; Quigg, Zara; Butler, Nadia

2017-03-23

Adverse childhood experiences (ACEs) including child abuse and household problems (e.g. domestic violence) increase risks of poor health and mental well-being in adulthood. Factors such as having access to a trusted adult as a child may impart resilience against developing such negative outcomes. How much childhood adversity is mitigated by such resilience is poorly quantified. Here we test if access to a trusted adult in childhood is associated with reduced impacts of ACEs on adoption of health-harming behaviours and lower mental well-being in adults. Cross-sectional, face-to-face household surveys (aged 18-69 years, February-September 2015) examining ACEs suffered, always available adult (AAA) support from someone you trust in childhood and current diet, smoking, alcohol consumption and mental well-being were undertaken in four UK regions. Sampling used stratified random probability methods (n = 7,047). Analyses used chi squared, binary and multinomial logistic regression. Adult prevalence of poor diet, daily smoking and heavier alcohol consumption increased with ACE count and decreased with AAA support in childhood. Prevalence of having any two such behaviours increased from 1.8% (0 ACEs, AAA support, most affluent quintile of residence) to 21.5% (≥4 ACEs, lacking AAA support, most deprived quintile). However, the increase was reduced to 7.1% with AAA support (≥4 ACEs, most deprived quintile). Lower mental well-being was 3.27 (95% CIs, 2.16-4.96) times more likely with ≥4 ACEs and AAA support from someone you trust in childhood (vs. 0 ACE, with AAA support) increasing to 8.32 (95% CIs, 6.53-10.61) times more likely with ≥4 ACEs but without AAA support in childhood. Multiple health-harming behaviours combined with lower mental well-being rose dramatically with ACE count and lack of AAA support in childhood (adjusted odds ratio 32.01, 95% CIs 18.31-55.98, ≥4 ACEs, without AAA support vs. 0 ACEs, with AAA support). Adverse childhood experiences negatively impact mental and physical health across the life-course. Such impacts may be substantively mitigated by always having support from an adult you trust in childhood. Developing resilience in children as well as reducing childhood adversity are critical if low mental well-being, health-harming behaviours and their combined contribution to non-communicable disease are to be reduced.