Predicting iliac limb occlusions after bifurcated aortic stent grafting: Anatomic and device-related causes

AbstractObjective: Graft limb occlusion may complicate endovascular abdominal aortic aneurysm repair. The precise etiologic factors that contribute to the development of these graft limb thromboses have not been defined. We evaluated our experience with bifurcated aortic endografts to determine factors that may predict subsequent limb thrombosis. The management of the thrombosed limbs and the results after treatment were also investigated. Methods: During a 4-year period, 351 patients with aortic aneurysms underwent treatment with bifurcated endografts (702 graft limbs at risk). These 351 bifurcated devices included AneuRx (Medtronic, Minneapolis, Minn; n = 35), Ancure (Guidant, Menlo Park, Calif; n = 8), Gore (W.L. Gore & Associates, Sunnyvale, Calif; n = 25), Talent (World Medical, Sunrise, Fla; n = 255), Teramed (Teramed, Minneapolis, Minn; n = 10), and Vanguard (Boston Scientific Vascular, Natick, Mass; n = 18). Details regarding the type of device, mechanism of deployment, and aortoiliac artery anatomy were collected prospectively and analyzed. Graft limbs were analyzed for diameter, use of additional endograft iliac extensions, deployment in the external iliac artery, and endograft to vessel oversizing. Follow-up included physical examination, duplex ultrasonography, and spiral computed tomographic scans at 1 month, 6 months, and 12 months and annually thereafter. The follow-up period ranged from 2 to 54 months, with a mean follow-up period of 20 months. Results: Twenty-six of 702 limbs (3.7%) had an occlusion develop. The risk of limb thrombosis was associated with a smaller limb diameter. Mean graft limb diameter was 14 mm in the occluded population, and patent limbs had a mean diameter of 16 mm. Thrombosis occurred in 16 of 291 limbs (5.5%) that were 14 mm or less and in 10 of 411 limbs (2.4%) that were greater than 14 mm (P = .03). Extension of a graft to the external iliac artery was performed in 96 of the 702 limbs. Eight of these 96 limbs (8.3%) had thrombosis develop as compared with 18 of 606 (3.0%) that extended to the common iliac artery (P = .01). No significant association was present between limb thrombosis and the contralateral or ipsilateral side of a device, the configuration of the iliac graft limb end (closed web, open web, or bare spring), or the degree of iliac graft limb oversizing. AneuRx, Ancure, Vanguard, and Talent grafts each sustained limb occlusions, with no occlusions seen among the Gore and Teramed devices. No significant increased risk of graft limb thrombosis was observed in unsupported grafts (1/16; 6.3%) versus supported grafts (25/686; 3.6%; P = not significant). Thromboses occurred between 1 day and 23 months after surgery. Thirteen of the 26 thromboses (50%) occurred within 30 days of surgery. Presenting symptoms were mild to moderate claudication in eight patients (30.8%), severe claudication in 16 patient (61.5%), and paresthesia and rest pain in two patients (7.7%). Eighteen of 26 patients (69.2%) eventually needed intervention to reestablish flow to the occluded limb, including thrombolysis and stenting in two patients (7.7%), axillary femoral bypass in one patient (3.8%), femoral-femoral bypass in 13 patients (50.0%), and axillary-bifemoral bypass in two patients (7.7%). All patients with mild to moderate symptoms under observation had improvement in symptoms with no further interventions necessary. All revascularizations were successful in relieving symptoms. Conclusion: Graft limb occlusion is a recognized complication of endovascular treatment of abdominal aortic aneurysms that may be associated with smaller graft limb diameter and extension to the external iliac artery. Occlusions usually necessitate additional intervention for resolution of ischemic symptoms. The use of small diameter grafts should be avoided when possible to reduce the risk of graft limb occlusions. (J Vasc Surg 2002;36:679-84.

Outcomes of endovascular treatment of ruptured abdominal aortic aneurysms

IntroductionThe successful application of endovascular techniques for the elective repair of abdominal aortic aneurysms (AAAs) has stimulated a strong interest in their possible use in dealing with a long-standing surgical challenge: the ruptured abdominal aortic aneurysm (RAAA). The use of a conventional open procedure to repair ruptured aneurysms is associated with a high operative mortality of 45% to 50%. In this study, we evaluated the current frequency of endovascular repair of RAAAs in four large states and the impact of this technique on patient outcome.MethodsWe examined discharge data sets from 2000 through 2003 from the four states of California, Florida, New Jersey, and New York, whose combined population represents almost a third of the United States population. Proportions and trends were analyzed by χ2 analysis and continuous variables by the Student’s t test.ResultsWe found that since the year 2000, endovascular repair has begun to emerge as a viable treatment option for RAAAs, accounting for the repair of 6.2% of cases in 2003. During the same period, the use of open procedures for RAAAs declined. The overall mortality rate for the 4-year period was significantly lower for endovascular vs open repair (39.3% vs. 47.7%, P = .005). Moreover, compared with open repair, endovascular repair resulted in a significantly lower rate of pulmonary, renal, and bleeding complications. Survival after endovascular repair correlated with hospital experience, as assessed by the overall volume of elective and nonelective endovascular procedures. For endovascular repairs, mortality ranged from 45.9% for small volume hospitals to 26% for large volume hospitals (P = .0011). Volume was also a determinant of mortality for open repairs, albeit to a much lesser extent (51.5% for small volume hospitals, 44.3% for large volume hospitals; P < .0001).ConclusionWe observed a benefit to using endovascular procedures for RAAAs in institutions with significant endovascular experience; however, the analysis of administrative data cannot rule out selection bias as an explanation of better outcomes. These data strongly endorse the need for prospective studies to clarify to what extent the improved survival in RAAA patients is to be attributed to the endovascular approach rather than the selection of low-risk patients

Computer simulation as a component of catheter-based training

IntroductionComputer simulation has been used in a variety of training programs, ranging from airline piloting to general surgery. In this study we evaluate the use of simulation to train novice and advanced interventionalists in catheter-based techniques.MethodsTwenty-one physicians underwent evaluation in a simulator training program that involved placement of a carotid stent. Five participants were highly experienced in catheter-based techniques (>300 percutaneous cases), including carotid angioplasty and stenting (CAS); the remaining 16 participants were interventional novices (<5 percutaneous cases). The Procedicus VIST simulator, composed of real-time vascular imaging simulation software and a tactile interface coupled to angiographic catheters and guide wires, was used. After didactic instruction regarding CAS and use of the simulator, each participant performed a simulated CAS procedure. The participant's performance was supervised and evaluated by an expert interventionalist on the basis of 50 specific procedural steps with a maximal score of 100. Specific techniques of guide wire and catheter manipulation were subjectively assessed on a scale of 0 to 5 points based on ability. After evaluation of the initial simulated CAS procedure, each participant received a minimum of 2 hours of individualized training by the expert interventionalist, with the VIST simulator. Each participant then performed a second simulated CAS procedure, which was graded with the same scale. After completion, participants assessed the training program and its utility via survey questionnaire.ResultsThe average simulated score for novice participants after the training program improved significantly from 17.8 ± 15.6 to 69.8 ± 9.8 (P < .01), time to complete simulation decreased from 44 ± 10 minutes to 30 ± 8 minutes (P < .01), and fluoroscopy time decreased from 31 ± 7 minutes to 23 ± 7 minutes (P < .01). No statistically significant difference in score, total time, or fluoroscopy time was noted for experienced interventionalists. Improvement was noted in guide wire and catheter manipulation skills in novices.. Analysis of survey data from experienced interventionalists indicated that the simulated clinical scenarios were realistic and that the simulator could be a valuable tool if clinical and tactile feedback were improved. Novices also thought the simulated training was a valuable experience, and desired further training time.ConclusionsAn endovascular training program using the Procedicus VIST haptic simulator resulted in significant improvement in trainee facility with catheter-based techniques in a simulated clinical setting. Novice participants derived the greatest benefit from simulator training in a mentored program, whereas experienced interventionalists did not seem to derive significant benefit

A multicenter experience with the Talent endovascular graft for the treatment of abdominal aortic aneurysms

AbstractObjective: The Talent endovascular graft has been used in the treatment of abdominal aortic aneurysms (AAAs) in more than 13,000 patients worldwide. However, information regarding the results of its use has been limited. This report describes the experience with 368 patients with AAAs who underwent treatment at four medical centers as part of an investigator-sponsored investigational device exemption trial. Methods: Patients with AAAs were enrolled at four sites during a 32-month period from January 1999 to July 2001. All patients underwent treatment for infrarenal AAA with the Talent endovascular graft. Repair was performed with transrenal stent fixation under epidural (362/368 patients; 98.3%), local (4/368 patients; 1.1%), or general (2/368 patients; 0.5%) anesthesia. The average diameters were: maximum aortic aneurysm, 6.2 ± 1.2 cm; proximal aortic fixation site, 2.6 ± 0.4 cm; and distal iliac fixation site, 1.4 ± 0.6 cm. Bifurcated grafts were used in 276 of 366 patients (75%), aortouniiliac in 57 of 366 patients (16%), and tube aortoaortic in 33 of 366 patients (9%). Multiple comorbid medical conditions were present in all patients (average, 4.7 conditions/patient). The mean age was 75.8 years, and 85% of the patients were male. Follow-up period ranged from 2 to 33 months (mean, 7.3 months). Results: Endovascular graft deployment was accomplished in 366 of 368 patients. In the 263 patients followed for at least 6 months after endovascular repair, AAA diameter decreased by 5 mm or more in 83 patients (32%); diameter remained unchanged (change < 5 mm) in 157 patients (60%) and increased by 5 mm or more in 23 patients (8.7%). Major morbidity occurred in 46 of 368 patients (12.5%), and minor morbidity occurred in 31 of 368 (8.4%). The 30-day mortality rate was 1.9%. Secondary procedures were performed in 32 patients (8.7%). Late rupture occurred in two patients, and late deaths unrelated to AAA occurred in 32 patients (8.7%) during the follow-up period. The primary technical success rate for all patients was 93.4%. The 30-day primary procedural success rate was 73.3%. The 30-day secondary procedural success rate was significantly higher at 85.8%. Computed tomographic scan was performed within 1 month after surgery in 349 patients. An endoleak was present in 43 of 349 patients (12.3%). These endoleaks were comprised of 10 attachment site (type I; 2.9%), 31 retrograde side-branch (type II; 8.9%), and two transgraft (type III; 0.6%). Conclusion: These midterm findings show a high degree of technical and procedural success achieved in a patient population with extensive comorbid medical illnesses with low perioperative morbidity and mortality rates. Further follow-up study will be necessary to determine the effectiveness of the Talent endograft for the long-term treatment of AAA. (J Vasc Surg 2002;35:1123-8.

Temporal Pattern of ICAM-I Mediated Regulatory T Cell Recruitment to Sites of Inflammation in Adoptive Transfer Model of Multiple Sclerosis

Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development

TcOPT3, a Member of Oligopeptide Transporters from the Hyperaccumulator Thlaspi caerulescens, Is a Novel Fe/Zn/Cd/Cu Transporter

BACKGROUND: Thlaspi caerulescens is a natural selected heavy metal hyperaccumulator that can not only tolerate but also accumulate extremely high levels of heavy metals in the shoots. Thus, to identify the transportors involved in metal long-distance transportation is very important for understanding the mechanism of heavy metal accumulation in this hyperaccumulator. METHODOLOGY/PRINCIPAL FINDINGS: We cloned and characterized a novel gene TcOPT3 of OPT family from T. caerulescens. TcOPT3 was pronouncedly expressed in aerial parts, including stem and leaf. Moreover, in situ hybridization analyses showed that TcOPT3 expressed in the plant vascular systems, especially in the pericycle cells that may be involved in the long-distance transportation. The expression of TcOPT3 was highly induced by iron (Fe) and zinc (Zn) deficiency, especially in the stem and leaf. Sub-cellular localization showed that TcOPT3 was a plasma membrane-localized protein. Furthermore, heterogonous expression of TcOPT3 by mutant yeast (Saccharomyces cerevisiae) complementation experiments demonstrated that TcOPT3 could transport Fe(2+) and Zn(2+). Moreover, expression of TcOPT3 in yeast increased metal (Fe, Zn, Cu and Cd) accumulation and resulted in an increased sensitivity to cadmium (Cd) and copper (Cu). CONCLUSIONS: Our data demonstrated that TcOPT3 might encode an Fe/Zn/Cd/Cu influx transporter with broad-substrate. This is the first report showing that TcOPT3 may be involved in metal long-distance transportation and contribute to the heavy metal hyperaccumulation

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome