Biomechanical Assessment Predicts Aneurysm Related Events in Patients with Abdominal Aortic Aneurysm.

OBJECTIVE: To test whether aneurysm biomechanical ratio (ABR; a dimensionless ratio of wall stress and wall strength) can predict aneurysm related events. METHODS: In a prospective multicentre clinical study of 295 patients with an abdominal aortic aneurysm (AAA; diameter ≥ 40 mm), three dimensional reconstruction and computational biomechanical analyses were used to compute ABR at baseline. Participants were followed for at least two years and the primary end point was the composite of aneurysm rupture or repair. RESULTS: The majority were male (87%), current or former smokers (86%), most (72%) had hypertension (mean ± standard deviation [SD] systolic blood pressure 140 ± 22 mmHg), and mean ± SD baseline diameter was 49.0 ± 6.9 mm. Mean ± SD ABR was 0.49 ± 0.27. Participants were followed up for a mean ± SD of 848 ± 379 days and rupture (n = 13) or repair (n = 102) occurred in 115 (39%) cases. The number of repairs increased across tertiles of ABR: low (n = 24), medium (n = 34), and high ABR (n = 44) (p = .010). Rupture or repair occurred more frequently in those with higher ABR (log rank p = .009) and ABR was independently predictive of this outcome after adjusting for diameter and other clinical risk factors, including sex and smoking (hazard ratio 1.41; 95% confidence interval 1.09-1.83 [p = .010]). CONCLUSION: It has been shown that biomechanical ABR is a strong independent predictor of AAA rupture or repair in a model incorporating known risk factors, including diameter. Determining ABR at baseline could help guide the management of patients with AAA.

Validation of a Decision Tree to Streamline Infrainguinal Vein Graft Surveillance.

BACKGROUND: Duplex ultrasound (DU)-based graft surveillance remains controversial. The aim of this study was to assess the ability of a recently proposed decision tree in identifying high-risk grafts which would benefit from DU-based surveillance. MATERIALS AND METHODS: Consecutive patients undergoing infrainguinal vein graft bypass from January 2008 to December 2015 were identified from the National Vascular registry and enrolled in a duplex surveillance program. An early postoperative DU was performed at a median of 6 weeks (range: 4-9 weeks). Grafts were classified into high risk or low risk based on the findings of the earliest postoperative scan and 4 established risk factors for graft failure (diabetes, smoking, infragenicular distal anastomosis, and revision bypass surgery) using a classification and regression tree (CRT). The accuracy of the CRT model was evaluated using area under receiver operator characteristic (AROC) curve. RESULTS: About 278 vein graft bypasses were performed; 29 grafts had occluded by the first surveillance visit; 249 vein grafts were entered into surveillance. Sixty-four (23%) developed critical stenosis. Overall 30-month primary patency, primary-assisted patency, and secondary patency rates were 71.2%, 77.2%, and 80.1%, respectively. AROC for prediction of graft stenosis or occlusion was 83% (95% confidence interval [CI]: 78-87%). The sensitivity and specificity of the CRT model for prediction of graft stenosis or occlusion were 95% (95% CI: 88-98%) and 52.2% (95% CI: 45-60%). CONCLUSIONS: A prediction model based on commonly recorded clinical variables and early postoperative DU scan is accurate at identifying grafts which are at high risk of failure. These high-risk grafts may benefit from DU-based surveillance.

Development of a Decision Tree to Streamline Infrainguinal Vein Graft Surveillance.

BACKGROUND: Duplex ultrasound (DU) remains the gold standard for identification and grading of infrainguinal vein graft stenosis. However, DU-based graft surveillance remains controversial. The aim of this study was to develop a decision tree to identify high-risk grafts which would benefit from DU-based surveillance. METHODS: Consecutive patients undergoing infrainguinal vein graft bypass were enrolled in a DU surveillance program. An early postoperative DU was performed at a median of 6 weeks (range 4-9). Based on the findings of this scan and 4 established risk factors for graft failure (diabetes, smoking, infragenicular distal anastomosis, revision bypass surgery), a classification and regression tree (CART) was created to stratify grafts into grafts which are at high and low risk of developing severe stenosis or occlusion. The accuracy of the CART model was evaluated using area under receiver operator characteristic curve (ROC). RESULTS: Of 796 vein graft bypasses performed (760 patients), 64 grafts were occluded by the first surveillance visit and 732 vein grafts were entered into surveillance program. The CART model stratified 299 grafts (40.8%) as low-risk and 433 (59.2%) as high-risk grafts. One hundred twenty-six (17.2%) developed critical vein graft stenosis. Overall, 30-month primary patency, primary-assisted and secondary patency rates were 76.2%, 83.6%, and 85.3%, respectively. The area under ROC curve for the CART model was 0.88 (95% confidence interval 0.81-0.94). Primary graft patency rates were higher in low-risk versus high-risk grafts (log rank 186, P < 0.0001). Amputation rates were significantly higher in the high-risk grafts compared with low-risk ones (log rank 118, P < 0.0001). CONCLUSION: A clinical decision rule based on readily available clinical data and the findings of significant flow abnormalities on an early postoperative DU scan successfully identifies grafts at high risk of failure and will contribute to safely improving the efficacy of infrainguinal vein graft surveillance services.

Esophagogastric trauma in Scotland.

BACKGROUND: This study was designed to investigate the incidence of esophageal (ET) and gastric trauma (GT) in Scotland and to identify factors associated with adverse outcome. METHODS: Population-based study of a prospective multicenter database of 52,887 trauma patients, admitted to 25 hospitals from 1992 to 2002. RESULTS: Thirty patients [0.06 %; median age, 32 year (range, 15-79); 86.7 % male] sustained ET [17 (56.7 %) blunt vs. 13 (43.3 %) penetrating]. The most common causes of injury were road traffic accidents (RTAs; n = 11; 36.7 %) and assaults (n = 10; 33.3 %). Most patients (n = 25; 83.3 %) had injury severity scores (ISS) >15, consistent with severe trauma. Fifteen patients (50 %) underwent surgery, of whom 8 (53.3 %) died. Another 13 patients died, yielding an overall mortality rate of 70 %. In contrast, 149 patients [0.29 %; median age, 28 year (range, 13-74); 90.6 % male] sustained GT [124 (83.2 %) penetrating vs. 25 (16.8 %) blunt]. The predominant cause was assault (n = 119; 79.9 %). Most patients (n = 134; 89.9 %) underwent surgery, of which 23 (17.2 %) died. Another 12 patients died, yielding an overall mortality rate of 23.5 %. Factors associated independently with GT mortality included higher ISS, lower Glasgow coma scale (GCS), and hemodynamic compromise. CONCLUSIONS: Esophagogastric trauma occurs predominantly in young males. The incidence of GT, although low, is five times that of ET. Predominant mechanisms of GT are penetrating compared with blunt for ET. Both ET and GT are commonly found in the presence of other multiple injuries, and are associated with high mortality. Operative management of GT is associated with reduced mortality, but outcome is worse for patients with hemodynamic compromise, low GCS, and high ISS.

Low Shear Stress at Baseline Predicts Expansion and Aneurysm-Related Events in Patients With Abdominal Aortic Aneurysm.

BACKGROUND: Low shear stress has been implicated in abdominal aortic aneurysm (AAA) expansion and clinical events. We tested the hypothesis that low shear stress in AAA at baseline is a marker of expansion rate and future aneurysm-related events. METHODS: Patients were imaged with computed tomography angiography at baseline and followed up every 6 months >24 months with ultrasound measurements of maximum diameter. From baseline computed tomography angiography, we reconstructed 3-dimensional models for automated computational fluid dynamics simulations and computed luminal shear stress. The primary composite end point was aneurysm repair and/or rupture, and the secondary end point was aneurysm expansion rate. RESULTS: We included 295 patients with median AAA diameter of 49 mm (interquartile range, 43-54 mm) and median follow-up of 914 (interquartile range, 670-1112) days. There were 114 (39%) aneurysm-related events, with 13 AAA ruptures and 98 repairs (one rupture was repaired). Patients with low shear stress (<0.4 Pa) experienced a higher number of aneurysm-related events (44%) compared with medium (0.4-0.6 Pa; 27%) and high (>0.6 Pa; 29%) shear stress groups (P=0.010). This association was independent of known risk factors (adjusted hazard ratio, 1.72 [95% CI, 1.08-2.73]; P=0.023). Low shear stress was also independently associated with AAA expansion rate (ß=+0.28 mm/y [95% CI, 0.02-0.53]; P=0.037). CONCLUSIONS: We show for the first time that low shear stress (<0.4 Pa) at baseline is associated with both AAA expansion and future aneurysm-related events. Aneurysms within the lowest tertile of shear stress, versus those with higher shear stress, were more likely to rupture or reach thresholds for elective repair. Larger prospective validation trials are needed to confirm these findings and translate them into clinical management.

Greater aortic inflammation and calcification in abdominal aortic aneurysmal disease than atherosclerosis: a prospective matched cohort study.

Objective: Using combined positron emission tomography and CT (PET-CT), we measured aortic inflammation and calcification in patients with abdominal aortic aneurysms (AAA), and compared them with matched controls with atherosclerosis. Methods: We prospectively recruited 63 patients (mean age 76.1±6.8 years) with asymptomatic aneurysm disease (mean size 4.33±0.73 cm) and 19 age-and-sex-matched patients with confirmed atherosclerosis but no aneurysm. Inflammation and calcification were assessed using combined 18F-FDG PET-CT and quantified using tissue-to-background ratios (TBRs) and Agatston scores. Results: In patients with AAA, 18F-FDG uptake was higher within the aneurysm than in other regions of the aorta (mean TBRmax2.23±0.46 vs 2.12±0.46, p=0.02). Compared with atherosclerotic control subjects, both aneurysmal and non-aneurysmal aortae showed higher 18F-FDG accumulation (total aorta mean TBRmax2.16±0.51 vs 1.70±0.22, p=0.001; AAA mean TBRmax2.23±0.45 vs 1.68±0.21, p<0.0001). Aneurysms containing intraluminal thrombus demonstrated lower 18F-FDG uptake within their walls than those without (mean TBRmax2.14±0.43 vs 2.43±0.45, p=0.018), with thrombus itself showing low tracer uptake (mean TBRmax thrombus 1.30±0.48 vs aneurysm wall 2.23±0.46, p<0.0001). Calcification in the aneurysmal segment was higher than both non-aneurysmal segments in patients with aneurysm (Agatston 4918 (2901-8008) vs 1017 (139-2226), p<0.0001) and equivalent regions in control patients (442 (304-920) vs 166 (80-374) Agatston units per cm, p=0.0042). Conclusions: The entire aorta is more inflamed in patients with aneurysm than in those with atherosclerosis, perhaps suggesting a generalised inflammatory aortopathy in patients with aneurysm. Calcification was prominent within the aneurysmal sac, with the remainder of the aorta being relatively spared. The presence of intraluminal thrombus, itself metabolically relatively inert, was associated with lower levels of inflammation in the adjacent aneurysmal wall.

Plasma Desmosine and Abdominal Aortic Aneurysm Disease.

Background It is recognized that factors beyond aortic size are important in predicting outcome in abdominal aortic aneurysm (AAA) disease. AAA is characterized by the breakdown of elastin within the aortic tunica media, leading to aortic dilatation and rupture. The aim of this study was to investigate the association of plasma desmosine (pDES), an elastin-specific degradation product, with disease severity and clinical outcome in patients with AAA. Methods and Results We measured pDES and serum biomarker concentrations in 507 patients with AAAs (94% men; mean age, 72.4±6.1 years; mean AAA diameter, 48±8 mm) and 162 control subjects (100% men; mean age, 71.5±4.4 years) from 2 observational cohort studies. In the longitudinal cohort study (n=239), we explored the incremental prognostic value of pDES on AAA events. pDES was higher in patients with AAA compared with control subjects (mean±SD: 0.46±0.22 versus 0.33±0.16 ng/mL; P<0.001) and had the strongest correlation with AAA diameter (r=0.39; P<0.0001) of any serum biomarker. After adjustment for baseline AAA diameter, pDES was associated with an AAA event (hazard ratio, 2.03 per SD increase [95% CI, 1.02-4.02]; P=0.044). In addition to AAA diameter, pDES provided incremental improvement in risk stratification (continuous net reclassification improvement, 34.4% [95% CI, -10.8% to 57.5%; P=0.09]; integrated discrimination improvement, 0.04 [95% CI, 0.00-0.15; P=0.050]). Conclusions pDES concentrations predict disease severity and clinical outcomes in patients with AAA. Clinical Trial Registration http://www.isrctn.com. Unique identifier: ISRCTN76413758.

18F-Sodium Fluoride Uptake in Abdominal Aortic Aneurysms: The SoFIA3 Study.

BACKGROUND: Fluorine-18-sodium fluoride (18F-NaF) uptake is a marker of active vascular calcification associated with high-risk atherosclerotic plaque. OBJECTIVES: In patients with abdominal aortic aneurysm (AAA), the authors assessed whether 18F-NaF positron emission tomography (PET) and computed tomography (CT) predicts AAA growth and clinical outcomes. METHODS: In prospective case-control (n = 20 per group) and longitudinal cohort (n = 72) studies, patients with AAA (aortic diameter >40 mm) and control subjects (aortic diameter <30 mm) underwent abdominal ultrasound, 18F-NaF PET-CT, CT angiography, and calcium scoring. Clinical endpoints were aneurysm expansion and the composite of AAA repair or rupture. RESULTS: Fluorine-18-NaF uptake was increased in AAA compared with nonaneurysmal regions within the same aorta (p = 0.004) and aortas of control subjects (p = 0.023). Histology and micro-PET-CT demonstrated that 18F-NaF uptake localized to areas of aneurysm disease and active calcification. In 72 patients within the longitudinal cohort study (mean age 73 ± 7 years, 85% men, baseline aneurysm diameter 48.8 ± 7.7 mm), there were 19 aneurysm repairs (26.4%) and 3 ruptures (4.2%) after 510 ± 196 days. Aneurysms in the highest tertile of 18F-NaF uptake expanded 2.5× more rapidly than those in the lowest tertile (3.10 [interquartile range (IQR): 2.34 to 5.92 mm/year] vs. 1.24 [IQR: 0.52 to 2.92 mm/year]; p = 0.008) and were nearly 3× as likely to experience AAA repair or rupture (15.3% vs. 5.6%; log-rank p = 0.043). CONCLUSIONS: Fluorine-18-NaF PET-CT is a novel and promising approach to the identification of disease activity in patients with AAA and is an additive predictor of aneurysm growth and future clinical events. (Sodium Fluoride Imaging of Abdominal Aortic Aneurysms [SoFIA3]; NCT02229006; Magnetic Resonance Imaging [MRI] for Abdominal Aortic Aneurysms to Predict Rupture or Surgery: The MA3RS Trial; ISRCTN76413758).

Follow-up and surveillance of vein grafts: when and how to intervene to prevent complications.

Despite advances in endovascular strategies, surgical infrainguinal lower limb revascularization remains the gold standard treatment for critical lower limb ischemia and disabling claudication. Maintaining patency of infrainguinal vein bypass grafts has been a challenging task for vascular surgeons as they are prone to developing stenoses which may precipitate failure of the bypass. Duplex ultrasound scanning has evolved as the investigation of choice to identify vein graft lesions but graft surveillance programs using this technique remain controversial. The rationale for graft surveillance is that intervention in a patent but failing graft results in improved long-term patency and limb salvage rates compared to rescue of an occluded graft. The six-week postoperative Duplex ultrasound scan is important in identifying flow abnormalities that can predict the natural history of a vein graft and the outlook for the limb in the medium term. There are multiple factors influencing vein graft failure, which means guidelines should be flexible in terms of when and which type of intervention to the graft is optimum. Patency and durability favour open surgical revision over endovascular intervention but this must be counter balanced by the increased morbidity associated with surgical revision.

Exploring the Biological and Mechanical Properties of Abdominal Aortic Aneurysms Using USPIO MRI and Peak Tissue Stress: A Combined Clinical and Finite Element Study.

Inflammation detected through the uptake of ultrasmall superparamagnetic particles of iron oxide (USPIO) on magnetic resonance imaging (MRI) and finite element (FE) modelling of tissue stress both hold potential in the assessment of abdominal aortic aneurysm (AAA) rupture risk. This study aimed to examine the spatial relationship between these two biomarkers. Patients (n = 50) > 40 years with AAA maximum diameters > = 40 mm underwent USPIO-enhanced MRI and computed tomography angiogram (CTA). USPIO uptake was compared with wall stress predictions from CTA-based patient-specific FE models of each aneurysm. Elevated stress was commonly observed in areas vulnerable to rupture (e.g. posterior wall and shoulder). Only 16% of aneurysms exhibited co-localisation of elevated stress and mural USPIO enhancement. Globally, no correlation was observed between stress and other measures of USPIO uptake (i.e. mean or peak). It is suggested that cellular inflammation and stress may represent different but complimentary aspects of AAA disease progression.

Patient-specific modelling of abdominal aortic aneurysms: The influence of wall thickness on predicted clinical outcomes.

Rupture of abdominal aortic aneurysms (AAAs) is linked to aneurysm morphology. This study investigates the influence of patient-specific (PS) AAA wall thickness on predicted clinical outcomes. Eight patients under surveillance for AAAs were selected from the MA(3)RS clinical trial based on the complete absence of intraluminal thrombus. Two finite element (FE) models per patient were constructed; the first incorporated variable wall thickness from CT (PS_wall), and the second employed a 1.9mm uniform wall (Uni_wall). Mean PS wall thickness across all patients was 1.77±0.42mm. Peak wall stress (PWS) for PS_wall and Uni_wall models was 0.6761±0.3406N/mm(2) and 0.4905±0.0850N/mm(2), respectively. In 4 out of 8 patients the Uni_wall underestimated stress by as much as 55%; in the remaining cases it overestimated stress by up to 40%. Rupture risk more than doubled in 3 out of 8 patients when PS_wall was considered. Wall thickness influenced the location and magnitude of PWS as well as its correlation with curvature. Furthermore, the volume of the AAA under elevated stress increased significantly in AAAs with higher rupture risk indices. This highlights the sensitivity of standard rupture risk markers to the specific wall thickness strategy employed.

MRI using ultrasmall superparamagnetic particles of iron oxide in patients under surveillance for abdominal aortic aneurysms to predict rupture or surgical repair: MRI for abdominal aortic aneurysms to predict rupture or surgery-the MA(3)RS study.

INTRODUCTION: Population screening for abdominal aortic aneurysms (AAA) halves the associated mortality and has led to the establishment of national screening programmes. Prediction of aneurysm growth and rupture is challenging and currently relies on serial diameter measurements with ultrasound. Recently, a novel MRI-based technique using ultrasmall superparamagnetic particles of iron oxide (USPIO) has demonstrated considerable promise as a method of identifying aneurysm inflammation and expansion. METHODS AND ANALYSIS: The MA(3)RS study is a prospective observational multicentre cohort study of 350 patients with AAA in three centres across Scotland. All participants will undergo MRI with USPIO and aneurysm expansion will be measured over 2 years with CT in addition to standard clinical ultrasound surveillance. The relationship between mural USPIO uptake and subsequent clinical outcomes, including expansion, rupture and repair, will be evaluated and used to determine whether the technique augments standard risk prediction markers. To ensure adequate sensitivity to answer the primary question, we need to observe 130 events (composite of rupture or repair) with an estimated event rate of 41% over 2 years of follow-up. The MA(3)RS study is currently recruiting and expects to report in 2017. DISCUSSION: This is the first study to evaluate the use of USPIO-enhanced MRI to provide additional information to aid risk prediction models in patients with AAA. If successful, this study will lay the foundation for a large randomised controlled trial targeted at applying this technique to determine clinical management. TRIAL REGISTRATION NUMBER: Current Controlled Trials: ISRCTN76413758.

Does blood transfusion increase the chance of recurrence in patients undergoing surgery for lung cancer?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether blood transfusion increases the chance of recurrence in patients undergoing surgery for lung cancer. Altogether 468 papers were found using the reported search, of which 21 represented the best evidence to answer the clinical question. The authors, journal date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Nineteen cohort studies (two of which examined the same or similar data sets as two other studies already included), one comment article and one meta-analysis were identified. In total, the outcomes of 5378 patients undergoing surgical resection for lung cancer were analysed. The transfusion rate varied between 15 and 67%. The primary endpoints in all 21 papers were recurrence, survival or disease-free survival. We conclude that the research undertaken to examine the relationship between blood transfusion and lung cancer recurrence, survival and disease-free survival comes to no definite conclusion. Half of the papers relating to recurrence state that there is no significantly increased risk of recurrence with transfusion, whereas the other half state that there is. However, four of the five papers examining disease-free survival demonstrate a significant adverse relationship between this primary outcome and blood transfusion. With regard to survival, five of the papers reviewed showed no effect of blood transfusion, whereas five showed some form of adverse effect. Although there is no overwhelming agreement among the presented evidence, there is a slightly larger body of evidence supporting the theory that blood transfusions are associated with poorer outcomes in patients undergoing resection for lung cancer. However, whether this is a direct effect, or a surrogate marker for other factors such as anaemia, is unclear.

Cavitating mesenteric lymph node syndrome in association with coeliac disease and enteropathy associated T-cell lymphoma: a case report and review of the literature.

Cavitating mesenteric lymph node syndrome (CMLNS) is a rare and poorly understood complication of coeliac disease (CD), with only 37 cases reported in the literature. CD is an immune-mediated enteropathy, with alterations seen in the small bowel architecture on exposure to ingested gluten. Those who fail to respond to a strict gluten-free diet are termed to have refractory coeliac disease (RCD). This is associated with serious complications such as enteropathy-associated T-cell lymphoma (EATL). We present the case of a 71-year-old female investigated for weight loss and a palpable intraabdominal mass. Abdominal computed tomographic (CT) scan showed multiple necrotic mesenteric lymph nodes. At operation, multiple cavitating mesenteric lymph nodes, containing milky fluid, were found. An incidental EATL was found at the terminal ileum, which was resected. The patient subsequently tested positive for CD. This is the second case report to document an association between CMLNS and EATL. This paper highlights the varied presentation of CD. In this case, the diagnosis of CD was made retrospectively after the complications were dealt with. This paper is followed by a review of relevant literature.