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Biomedical subjects

P L Harris

Publications and source records attributed to P L Harris.

At least 19 recordsLinked to original sources

Impact of renal dysfunction on operative mortality following endovascular abdominal aortic aneurysm surgery.

BACKGROUND: Preoperative renal dysfunction is a significant risk factor for death after open abdominal aortic aneurysm repair. The aim of this study was to determine whether renal dysfunction also affected mortality after endovascular aneurysm repair. METHODS: Patients from the EUROSTAR registry were stratified into two groups: 4198 with normal renal function (creatinine less than 133 micromol/ml) and 969 with renal dysfunction (serum creatinine more than 133 micromol/ml). Patient characteristics and postoperative complications in the two groups were compared and the effect of renal dysfunction on operative mortality was analysed by multivariable regression models. RESULTS: Patients with renal dysfunction had significantly more co-morbidities, including cardiac and pulmonary impairment. Thirty-day mortality was significantly higher in the group with renal dysfunction (6.2 versus 2.0 per cent; P<0.001). A significant increase in mortality (5.5 per cent) was also seen in patients with moderate renal dysfunction (serum creatinine 133-265 micromol/ml). After adjustment for age and other risk factors, renal dysfunction was still an independent risk factor for 30-day mortality (odds ratio 2.3, 95 per cent confidence interval 1.6 to 3.3; P<0.001). CONCLUSION: Renal dysfunction was a significant and independent risk factor for death after endovascular aneurysm repair.

Adult↗

Impact of study design on outcome after endovascular abdominal aortic aneurysm repair. A comparison between the randomized controlled DREAM-trial and the observational EUROSTAR-registry.

BACKGROUND: Patients with abdominal aortic aneurysm (AAA) can be treated by transfemoral endovascular intervention and by conventional open surgery. Level-one evidence of the safety and efficacy of one treatment mode over the other is only provided by a randomised controlled trial (RCT). Results reported by voluntary registries are considered less valid than data from RCTs. On the other hand the outcome of a RCT may not be generalisable to the common practice because of vigorous selection of patients and institutions. PURPOSE: The outcomes reported by the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial were compared with the results of the EURopean collaborators on Stent-graft techniques for AAA Repair (EUROSTAR) registry. METHODS: To obtain comparable study groups with regard to risk factors equal proportions of ASA I, II and III patients as observed in the endovascular arm of the DREAMtrial were selected at random from the EUROSTAR-registry. All patients had an aneurysm of at least 50mm. Only patients, who had been enrolled into the registry from 1999, were selected to avoid the influence of first generation endografts which are not longer in use. Patient characteristics and outcomes of endovascular AAA repair (EVAR) of EUROSTAR and DREAM-trial participants were compared. Differences in early findings between study groups were assessed by Chi-Square tests for discrete variables and by Wilcoxon rank sum tests for continuous variables. Follow-up variables were analysed by Kaplan-Meier and Cox proportional hazard models. RESULTS: Data of 177 patients of the DREAM trial with randomization to EVAR and 856 patients selected in the EUROSTAR-registry were compared. Baseline characteristics were comparable between the EUROSTAR-cohort and EVAR-arm of the DREAM-trial. The 36-month survival-rate was 87.6% for EVAR-arm in the DREAM-trial similar to the 86.8% found in this EUROSTAR-study population. The freedom of secondary procedures reached after 3 years 85.7%, and 86.9% in the DREAM and EUROSTAR-cohort, respectively. CONCLUSION: We found comparable characteristics and outcomes between patients of comparable risk class of the EUROSTAR-registry and the EVAR-cohort of the DREAM-trial. This demonstrates the following: first, the EUROSTAR-data provide reliable information, and further comparisons of registry data with patients treated by conventional AAA surgery may be justified. Secondly, the various outcomes of the randomised DREAM trial appear generalisable, as it agrees with observations in a broad common practice derived database.

Aged↗

Swirling flow pattern in a non-planar model of an interposition vein cuff anastomosis.

One of the main causes of long-term failure of ePTFE grafts is the development of anastomotic intimal hyperplasia which leads to graft thrombosis. Experimental studies with bypass grafts have shown an inverse relationship between mean wall shear stress and intimal hyperplasia. The geometry of the anastomosis has a strong influence on the flow pattern and wall shear stress distribution. The aim of this in vitro study was to investigate the influence of non-planarity in a model of a distal anastomosis with interposition vein cuff, an anastomosis configuration that is increasingly being used because of improved clinical results. Laser Doppler anemometer measurements were carried out in silicone rubber models of interposition vein cuff anastomoses with planar and non-planar inflow. The pulsatile flow waveforms were typical of those found in femoro-infrapopliteal bypass. Axial and radial velocities were measured in the proximal and distal outflow segments. As expected a symmetrical helical flow pattern (Dean flow) was evident in the planar model. The model with non-planar inflow, however, gave rise to swirling flow in both the distal and proximal artery outflow segments for during the systolic phase. In patients, the anastomosis is usually non-planar. Since the configuration depends in part upon the tunnelling of the graft, this may be altered to some extent. Non-planar anastomotic configurations induce a swirling flow pattern, which may normalise wall shear stress, thereby potentially reducing intimal hyperplasia.

Anastomosis, Surgical↗

Endovascular repair of abdominal aortic aneurysms with aortocaval fistula.

OBJECTIVES: To examine the risk of high-flow type II endoleak following endovascular repair of abdominal aortic aneurysm with aortocaval fistula. DESIGN: Case reports. SUBJECTS: Two patients with abdominal aortic aneurysms with aortocaval fistula. METHODS: Both patients had an endovascular repair of their aortic aneurysms. RESULTS: The aneurysms were successfully treated in both patients, without any endoleak on completion angiography. Apart from a transient type II lumbar endoleak in one of the patients, no endoleak was found after 3 and 12 month follow-up. Seven other cases have been published, reporting one type II and one type Ic endoleak. CONCLUSION: We found no evidence that endovascular repair of abdominal aortic aneurysm with aortocaval fistula is associated with a higher incidence of persistent endoleak.

Aged↗

Late complications after ligation and bypass for popliteal aneurysm.

BACKGROUND: Ligation and bypass is standard treatment for popliteal aneurysm. This technique does not abolish collateral circulation to the aneurysm, which may continue to expand and/or rupture. This study assessed whether complete thrombosis of the aneurysm sac occurs after operation and examined the long-term clinical outcome. METHODS: The records of all patients who underwent popliteal aneurysm repair in a university hospital over 10 years were reviewed. Patients who had undergone ligation and bypass were recalled for clinical and ultrasonographic examination to determine the fate of the aneurysm sac. RESULTS: Persistent blood flow in the aneurysm sac was present in 12 of 36 legs a median of 48 months after operation. This was associated with symptomatic enlargement of the aneurysm in six patients. The incidence of sac enlargement was lower in bypassed aneurysms with no intrasac flow on duplex examination. CONCLUSION: Ligation and bypass does not always abolish blood flow in the sac of a popliteal aneurysm. It may be associated with continued expansion and late complications.

Aged↗

Is a type II endoleak after EVAR a harbinger of risk? Causes and outcome of open conversion and aneurysm rupture during follow-up.

OBJECTIVE: There is still debate whether type II endoleaks represent a risk for the patient after EVAR. Treatment policies vary from fairly conservative to active intervention. In this analysis risk factors for type II endoleak and adverse events during follow-up were assessed. In addition, risk factors and causes for conversion to open repair and for rupture post-EVAR were studied. METHODS: The data of 3595 patients, who underwent operation between 1996 and 2002 in 114 European institutions that collaborated in the EUROSTAR Registry, were assessed. To accurately assess the influence of type II endoleaks patients with type I, III and combined endoleaks were excluded from the present study cohort. RESULTS: A combined adverse outcome event consisting of aneurysmal growth, transfemoral reintervention, and transabdominal secondary procedures (including laparoscopic branch vessel clipping) occurred in 55% in patients with type II endoleak at 3 years, compared to 15% in patients without any endoleak (p<0.0001). Conversion to open repair or post-EVAR rupture was not significantly associated with type II endoleaks. An independent association of device migration and expansion of the aneurysm with late conversion was observed. The cumulative incidence of aneurysm rupture at 3 years of follow-up was 1.2% for an annual rate of 0.4%. Variables that significantly and independently correlated with rupture were size of the aneurysm at preoperative measurement and device migration during follow-up. CONCLUSION: Endoleak type II may not be harmless as it was more frequently associated with enlargement of the aneurysm and reinterventions. Large aneurysms and migration of the device were the main risk factors for rupture. The clinical implications of these findings may involve more frequent surveillance visits for patients with type II endoleak. Aneurysm expansion is a clear indication for reintervention. Patients with large aneurysms, 65 mm or larger, may also benefit from a more comprehensive surveillance schedule.

Aortic Aneurysm, Abdominal↗

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts.

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts remains unquantified in vivo, but is likely to influence flow patterns and haemodynamics, thereby impacting upon graft patency. This study measured the ratio of distal to proximal outflow in 30 patients undergoing infrainguinal bypass for lower limb ischaemia, using a flow probe and a transit-time ultrasonic flow meter. The mean outflow distribution was approximately 75% distal to 25% proximal, with above knee anastomoses having a greater proportion of distal flow (84%) compared to below knee grafts (73%). These in vivo flow characteristics differ significantly from those used in theoretical models studying flow phenomena (50:50 and/or 100:0), and should be incorporated into future research.

Aged↗

Rupture of infra-renal aortic aneurysm after endovascular repair: a series from EUROSTAR registry.

OBJECTIVES: Although small, the risk of rupture after EVAR remains a major concern. The aim of this study was to identify mechanisms of late aneurysm rupture after endovascular repair. METHODS: Patients who suffered a proven aneurysm rupture after EVAR were identified from the EUROSTAR (European Collaborators on Stent-graft Techniques for Abdominal Aortic Aneurysm Repair) registry. Complications preceding rupture were studied to identify common patterns and possible mechanisms of late rupture. RESULTS: A rupture was documented in 34 patients resulting in death of 21 (62%). Adverse events documented during previous follow-up in these patients included endoleak (30%), migration (18%), limb occlusion (12%) and kinking (12%). The findings at time of rupture were documented in 24 patients and including endoleak: Type III (10), Type I (9), Type II (1); stent-graft disintegration (2) and migration (3). Aneurysm diameter changes could be ascertained in 24 patients and had increased in only seven. CONCLUSION: The importance of graft-related endoleak, stent-graft disintegration and migration in the causation of aneurysm rupture was confirmed. Poor compliance with follow-up schedule was also identified as a common feature. However, the absence of complications in some patients, who attended regularly for follow-up, highlights the difficulty of predicting rupture after EVAR.

Adult↗

The distaflo graft: a valid alternative to interposition vein?

INTRODUCTION: the rationale behind the Distaflo graft is inhibition of myointimal hyperplasia through optimisation of haemodynamic forces at the distal anastomosis. This prospective study reports our early clinical results. METHOD: patients with critical limb ischaemia, but no autologous vein, underwent infrainguinal bypass using Distaflo. Clinical and Duplex assessment provided prospective data from which one year cumulative patency, limb salvage and survival rates were calculated using Kaplan-Meier analysis. Log rank test enabled comparison with an historical control group of Miller cuff grafts. RESULTS: fifty Distaflo were inserted over 29 months into 46 patients, median age 68.5 years, 27 male (59%), of which 27 (54%) were re-do procedures. Proximal anastomoses were to common femoral arteries in 40 cases (80%); distal anastomoses were to popliteal vessels in 20 (40%), and tibial vessels in 30 (60%). The Distaflo graft had patency, limb salvage and survival rates of 39, 50 and 82% respectively compared to 49, 56 and 85% respectively in the control group, with no statistical difference (p = 0.39; 0.65; 0.67 respectively; log rank). CONCLUSION: in this non-randomised study, the Distaflo has similar one year patency, limb salvage and survival rates to the Miller cuff, potentially justifying its use an alternative in distal prosthetic arterial reconstruction for critical limb ischaemia.

Adult↗

Aortic side branch perfusion alone does not account for high intra-sac pressure after endovascular repair (EVAR) in the absence of graft-related endoleak.

OBJECTIVE: to examine the effect of stent-graft deployment on pressure within an aneurysm sac and to investigate the potential sources of intra-sac pressure. MATERIAL AND METHODS: intra-sac pressure was monitored during and immediately after endovascular repair via an indwelling catheter. Intra-sac pressure was also monitored during conventional open repair and was compared with the pressure measured within patent lumbar and inferior mesenteric side-branches, both before and after restoration of iliac arterial blood flow. Intra-sac and side-branch pressures were recorded and expressed as ratios of simultaneously measured radial artery pressure. RESULTS: in the absence of a graft-related endoleak (23/25 patients), endovascular repair resulted in a significant reduction in intra-sac pulse pressure (median ratio 0.31 IQR 0.10-0.46). There was no corresponding reduction in mean intra-sac pressure (median ratio 0.91; IQR 0.83-1.00). Application of clamps at conventional open repair resulted in a fall in both intra-sac pressure (median ratio 0.39, IQR 0.32-0.64) and pressure within side-branches (median ratio 0.45, IQR 0.33-0.64). Restoration of iliac blood flow resulted in a modest recovery of the side-branch pressure (median ratio 0.63, IQR 0.57-0.81), which nonetheless remained significantly less than the intra-sac pressure recorded after EVAR (p=0.01). CONCLUSION: reperfusion of the aneurysm sac through patent side-branches seems insufficient to account for persistent pressurisation of the aneurysm after endovascular repair. This finding supports the hypothesis that pressure may be transmitted directly through stent-graft fabric.

Aortic Aneurysm↗

Endoleaks during follow-up after endovascular repair of abdominal aortic aneurysm. Are they all dangerous?

AIM: Development of endovascular abdominal aortic aneurysm repair (EVAR) has been accompanied by previously unencoutered complications. The most challenging but least understood of these complications is incomplete seal of the endovascular graft (endoleak), a phenomenon which has a variety of causes. An important consequence of endoleakage may be persistent pressurisation of the aneurysm sac, which may ultimately lead to post-EVAR rupture. METHODS: Data of 110 European centers were recorded in a central database (EUROSTAR). Patient, anatomic characteristics and operative and device details were correlated with the occurrence of different types of endoleaks. Outcome events during follow-up, notably expansion of the aneurysm, incidence of conversion to open repair and post-EVAR rupture were assessed in the different categories of endoleaks and in a group of patients without any endoleak. RESULTS: Type I and III endoleak were associated with an increased frequency of open conversions or risk of rupture of the aneurysm. Device-related endoleaks also correlated with an increased need for secondary interventions. These types of endoleak need to be treated without delay, and when no other possibilities are present, an open conversion to avert the risk of rupture should be considered. Endoleaks type II do not pose an indication for urgent treatment. However, they may not be harmless, as there was a frequent association with enlargement of aneurysm and reinterventions. CONCLUSION: Our findings suggest that more frequent surveillance examinations are indicated than in patients without collateral endoleak. The indication for intervention is primarily dictated by documented expansion of the aneurysm.

Aorta, Abdominal↗

The role of gadolinium-enhanced MR imaging in the preoperative evaluation of inflammatory abdominal aortic aneurysm.

Inflammatory abdominal aortic aneurysm is an uncommon variant of abdominal aortic aneurysms. Thorough preoperative imaging of the extent of the aneurysm and inflammation and the associated complications are crucial in the management of this condition. We report a case of inflammatory abdominal aortic aneurysm where, after the initial contrast-enhanced CT, gadolinium-enhanced MR imaging was used to define the true extent of the inflammation and differentiate inflammation from mural thrombus at the iliac extension of the aneurysm. The imaging appearances are presented and the impact of MR imaging on further surgical management options including endovascular repair are discussed.

Aortic Aneurysm, Abdominal↗

[Endovascular therapy of aneurysms of the abdominal aorta: report of 4,291 patients of the Eurostar Register].

BACKGROUND: The Eurostar project is a multicentred database of the outcome of endovascular repair of infra-renal aortic aneurysms. From 1996 to March, 2002, 113 European centres of vascular surgery have contributed. The purpose of this article is to review the medium term (up to 7 years) results of endovascular aneurysm repair as reported to Eurostar. PATIENTS AND METHODS: Patients intended for endovascular aneurysm repair were notified to the Eurostar Data Registry Centre before treatment in order to eliminate bias due to selective reporting. The following data was collected on all patients: (1) their demographic details and the anatomical characteristics of their aneurysms, (2) details of the endovascular device used, (3) procedural complications and the immediate outcome, (4) results of contrast enhanced CT imaging at 1, 3, 6, 12, 18 and 24 months after operation and at yearly intervals thereafter, (5) all adverse events. Life table analysis was performed to determine the cumulative rates of: (1) death from all causes, (2) secondary intervention. RESULTS: By March 2002, pre- and postoperative data of 4291 patients had been registered. The median duration of follow-up was 12 mo (range 0-96). Successful deployment was achieved in 97.8% of the patients with a perioperative (30 day) mortality of 2.4%. Early conversion to open repair occurred in 1.3%. Late rupture of the aneurysm occurred in 35 patients. The significant factors were endoleaks, graft migration and kinking. Late conversion to open repair occurred at an annual rate of approximately 2%. Risk factors (indications) for late conversion were endoleaks, graft migration and kinking. CONCLUSIONS: Endovascular repair of infra-renal aortic aneurysms using the first and second-generation devices that predominated in this study is associated with a risk of early or late failure of 3% per year, based upon an analysis of observed primary endpoints of rupture and conversion.

Adult↗

The influence of team experience on outcomes of endovascular stenting of abdominal aortic aneurysms.

OBJECTIVE: To determine whether the experience of the specialist team was associated with adverse events following endovascular treatment of abdominal aortic aneurysms. METHODS: The EUROSTAR database is a voluntary registry of 2863 patients admitted to 93 hospitals in Europe with an abdominal aortic aneurysm treated with endovascular stenting. Mortality, rupture and the need for secondary interventions were the main outcomes. RESULTS: In patients who underwent endovascular stenting by the most experienced specialist teams the mortality rate was 40% lower than in those treated by the least experienced teams (adjusted hazard ratio 0.60, 95% confidence interval: 0.4-1.0; p = 0.05). Also patients treated by the most experienced specialist teams were 68% less likely to have adverse events necessitating a secondary intervention than those treated by the least experienced teams (adjusted hazard ratio 0.32, 95% confidence interval: 0.2-0.5; p < 0.001). The crude rupture rate was 0.1% among patients treated by the most experienced specialist teams and 0.8% among those treated by the least experienced teams (p = 0.74). CONCLUSIONS: Specialist teams with a high level of experience of endovascular abdominal aortic aneurysm stenting encounter lower mortality rates and fewer adverse events leading to secondary interventions.

Adult↗

Experimental evaluation of flow patterns in interposition vein cuff anastomosis. The influence of non-planarity of the inflow.

Clinical evidence suggests that the development of myointimal hyperplasia in prosthetic femorodistal bypass grafts may be reduced by the interposition of a cuff of autologous vein between the graft and the recipient artery. Previous experimental work has shown that some of the benefits may be attributed to the geometry of the cuffed anastomosis. Since the distal anastomosis in vivo is often non-planar we have carried out a preliminary study in a model where the graft is at an angle of 45 degrees to the anterior-posterior plane of the anastomosis. This out-of-plane angulation produces highly asymmetric flow patterns in the anastomosis with significant flow separation on the ipsilateral side of the cuff. In the proximal and distal outflow, however, the velocity vectors show significant helical motion with temporal instability in the distal outflow.

Anastomosis, Surgical↗

Active glycation in neurofibrillary pathology of Alzheimer disease: N(epsilon)-(carboxymethyl) lysine and hexitol-lysine.

Advanced glycation end products are a diverse class of posttranslational modifications, stemming from reactive aldehyde reactions, that have been implicated in the pathogenesis of a number of degenerative diseases. Because advanced glycation end products are accelerated by, and result in formation of, oxygen-derived free radicals, they represent an important component of the oxidative stress hypothesis of Alzheimer disease (AD). In this study, we used in situ techniques to assess N(epsilon)-(Carboxymethyl)lysine (CML), the predominant advanced glycation end product that accumulates in vivo, along with its glycation-specific precursor hexitol-lysine, in patients with AD as well as in young and aged-matched control cases. Both CML and hexitol-lysine were increased in neurons, especially those containing intracellular neurofibrillary pathology in cases of AD. The increase in hexitol-lysine and CML in AD suggests that glycation is an early event in disease pathogenesis. In addition, because CML can result from either lipid peroxidation or advanced glycation, while hexitol-lysine is solely a product of glycation, this study, together with studies demonstrating the presence of 4-hydroxy-2-nonenal adducts and pentosidine, provides evidence of two distinct oxidative processes acting in concert in AD neuropathology. Our findings support the notion that aldehyde-mediated modifications, together with oxyradical-mediated modifications, are critical pathogenic factors in AD.

Adult↗

Melatonin acts as antioxidant and pro-oxidant in an organotypic slice culture model of Alzheimer's disease.

An organotypic mouse brain slice culture system of Alzheimer's disease (AD) under low oxygen partial pressures was developed to determine the antioxidant properties of the pineal hormone melatonin in vitro. Assays for biochemical markers of oxidative stress including redox active iron assay, heme-oxygenase-1 and 8-hydroxyguanosine inmunoreactivity were performed along with morphological analysis for stressed tissue following amyloid-beta (A beta) 1-40 insult. Melatonin (100 microM) significantly reduced the appearance of condensed chromatin, redox active iron, heme-oxygenase-1 induction and 8-hydroxyguanosine immunoreactivity caused by 50 microM A beta. Melatonin also prevented A beta-induced morphological signs of oxidative stress in tissue ultrastructure, including edema and dark degenerating profiles as visualized under electron microscope. At elevated concentrations (1 mM), melatonin induced redox active iron and heme-oxgenase-1 immunoreactivity. Thus, while melatonin may be a potential therapeutic agent in the prevention of oxidative stress associated with A beta and AD, it can also induce markers of oxidative stress at millimolar concentrations.

Alzheimer Disease↗