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1.
  • 2019
  • Journal article (peer-reviewed)
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2.
  • Janko, Matthew R., et al. (author)
  • In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas
  • 2021
  • In: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 73:1, s. 210-221.e1
  • Journal article (peer-reviewed)abstract
    • Objective: The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF. Methods: A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and operative and postoperative variables were recorded. The primary outcome was long-term mortality. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariate analyses were performed. Results: During the study period, 182 patients at 34 institutions from 11 countries presented with SAEF (median age, 72 years; 79% male). The initial aortic procedures that resulted in SAEF were 138 surgical grafts (76%) and 42 endografts (23%), with 2 unknown; 102 of the SAEFs (56%) underwent complete excision of infected aortic graft material, followed by in situ (in-line) bypass (ISB), including antibiotic-soaked prosthetic graft (53), autogenous femoral vein (neoaortoiliac surgery; 17), cryopreserved allograft (28), and untreated prosthetic grafts (4). There were 80 patients (44%) who underwent extra-anatomic bypass (EAB) with infected graft excision. Overall median Kaplan-Meier estimated survival was 319 days (interquartile range, 20-2410 days). Stratified by EAB vs ISB, there was no significant difference in Kaplan-Meier estimated survival (P = .82). In comparing EAB vs ISB, EAB patients were older (74 vs 70 years; P = .01), had less operative hemorrhage (1200 mL vs 2000 mL; P = .04), were more likely to initiate dialysis within 30 days postoperatively (15% vs 5%; P = .02), and were less likely to experience aorta-related hemorrhage within 30 days postoperatively (3% aortic stump dehiscence vs 11% anastomotic rupture; P = .03). There were otherwise no significant differences in presentation, comorbidities, and intraoperative or postoperative variables. Multivariable Cox regression showed that the duration of antibiotic use (hazard ratio, 0.92; 95% confidence interval, 0.86-0.98; P = .01) and rifampin use at time of discharge (hazard ratio, 0.20; 95% confidence interval, 0.05-0.86; P = .03) independently decreased mortality. Conclusions: These data suggest that ISB does not offer a survival advantage compared with EAB and does not decrease the risk of postoperative aorta-related hemorrhage. After repair, <50% of SAEF patients survive 10-months. Each week of antibiotic use decreases mortality by 8%. Further study with risk modeling is imperative for this population. (J Vasc Surg 2021;73:210-21.)
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3.
  • Janko, Matthew R., et al. (author)
  • In-situ bypass is associated with superior infection-free survival compared with extra-anatomic bypass for the management of secondary aortic graft infections without enteric involvement
  • 2022
  • In: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 76:2, s. 546-
  • Journal article (peer-reviewed)abstract
    • Objective: The optimal revascularization modality following complete resection of aortic graft infection (AGI) without enteric involvement remains unclear. The purpose of this investigation is to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients undergoing complete excision of AGI. Methods: A retrospective, multi-institutional study of AGI from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and perioperative variables were recorded. The primary outcome was infection-free survival. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariable analyses were performed. Results: A total of 241 patients at 34 institutions from seven countries presented with AGI during the study period (median age, 68 years; 75% male). The initial aortic procedures that resulted in AGI were 172 surgical grafts (71%), 66 endografts (27%), and three unknown (2%). Of the patients, 172 (71%) underwent complete excision of infected aortic graft material followed by in situ (in-line) bypass (ISB), including antibiotic-treated prosthetic graft (35%), autogenous femoral vein (neo-aortoiliac surgery) (24%), and cryopreserved allograft (41%). Sixty-nine patients (29%) underwent extra-anatomic bypass (EAB). Overall median Kaplan-Meier estimated survival was 5.8 years. Perioperative mortality was 16%. When stratified by ISB vs EAB, there was a significant difference in Kaplan-Meier estimated infection-free survival (2910 days; interquartile range, 391-3771 days vs 180 days; interquartile range, 27-3750 days; P <.001). There were otherwise no significant differences in presentation, comorbidities, or perioperative variables. Multivariable Cox regression showed lower infection-free survival among patients with EAB (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.6-3.6; P <.001), polymicrobial infection (HR, 2.2; 95% CI, 1.4-3.5; P = .001), methicillin-resistant Staphylococcus aureus infection (HR, 1.7; 95% CI, 1.1-2.7; P = .02), as well as the protective effect of omental/muscle flap coverage (HR, 0.59; 95% CI, 0.37-0.92; P = .02). Conclusions: After complete resection of AGI, perioperative mortality is 16% and median overall survival is 5.8 years. EAB is associated with nearly a two and one-half-fold higher reinfection/mortality compared with ISB. Omental and/or muscle flap coverage of the repair appear protective.
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4.
  • Abdelhalim, Mohamed A., et al. (author)
  • Multicenter trans-Atlantic experience with fenestrated-branched endovascular aortic repair of chronic post-dissection thoracoabdominal aortic aneurysms
  • 2023
  • In: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 78:4, s. 854-862.e1
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: This multicenter international study aimed to describe outcomes of fenestrated-branched endovascular aortic repairs (FB-EVAR) in a cohort of patients treated for chronic post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs).METHODS: We reviewed the clinical data of all consecutive patients treated by FB-EVAR for repair of extent I to III PD-TAAAs in 16 centers from the United States and Europe (2008-2021). Data were extracted from institutional prospectively maintained databases and electronic patient records. All patients received off-the-shelf or patient-specific manufactured fenestrated-branched stent grafts. Endpoints were any cause mortality and major adverse events at 30 days, technical success, target artery (TA) patency, freedom from TA instability, minor (endovascular with <12 Fr sheath) and major (open or ≥12 Fr sheath) secondary interventions, patient survival, and freedom from aortic-related mortality (ARM).RESULTS: A total of 246 patients (76% male; median age, 67 years [interquartile range, 61-73 years]) were treated for extent I (7%), extent II (55%), and extent III (35%) PD-TAAAs by FB-EVAR. The median aneurysm diameter was 65 mm (interquartile range, 59-73 mm). Eighteen patients (7%) were octogenarians, 212 (86%) were American Society of Anesthesiologists class ≥3, and 21 (9%) presented with contained ruptured or symptomatic aneurysms. There were 917 renal-mesenteric vessels targeted by 581 fenestrations (63%) and 336 directional branches (37%), with a mean of 3.7 vessels per patient. Technical success was 96%. Mortality and rate of major adverse events at 30 days was 3% and 28%, including disabling complications such as new onset dialysis in 1%, major stroke in 1%, and permanent paraplegia in 2%. Mean follow-up was 24 months. Kaplan-Meier (KM) estimated patient survival at 3 and 5 years was 79% ± 6% and 65% ± 10%. KM estimated freedom from ARM was 95% ± 3% and 93% ± 5% at the same intervals. Unplanned secondary interventions were needed in 94 patients (38%), including minor procedures in 64 (25%) and major procedures in 30 (12%). There was one conversion to open surgical repair (<1%). KM estimated freedom from any secondary intervention was 44% ± 9% at 5 years. KM estimated primary and secondary TA patency were 93% ± 2% and 96% ± 1% at 5 years, respectively.CONCLUSIONS: FB-EVAR for chronic PD-TAAAs was associated with high technical success and a low rate of mortality (3%) and disabling complications at 30 days. Although the procedure is effective in the prevention of ARM, patient survival was low at 5 years (65%), likely due to the significant comorbidities in this cohort of patients. Freedom from secondary interventions at 5 years was 44%, although most procedures were minor. The significant rate of reinterventions highlights the need for continued patient surveillance.
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5.
  • Dias, N., et al. (author)
  • Outcomes of Elective and Non-elective Fenestrated-branched Endovascular Aortic Repair for Treatment of Thoracoabdominal Aortic Aneurysms
  • 2023
  • In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 278:4, s. 568-577, s. 568-577
  • Journal article (peer-reviewed)abstract
    • Objective: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs).Background: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described.Methods: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006-2021) were reviewed. Endpoints including early mortality and major adverse events (MAEs), all-cause mortality, and aortic-related mortality (ARM), were analyzed and compared in patients who had non-elective versus elective repair.Results: A total of 2603 patients (69% males; mean age 72 +/- 10 year old) underwent FB-EVAR for TAAAs. Elective repair was performed in 2187 patients (84%) and non-elective repair in 416 patients [16%; 268 (64%) symptomatic, 148 (36%) ruptured]. Non-elective FB-EVAR was associated with higher early mortality (17% vs 5%, P < 0.001) and rates of MAEs (34% vs 20%, P < 0.001). Median follow-up was 15 months ( interquartile range, 7-37 months). Survival and cumulative incidence of ARM at 3 years were both lower for non-elective versus elective patients (50 +/- 4% vs 70 +/- 1% and 21 +/- 3% vs 7 +/- 1%, P < 0.001). On multivariable analysis, non-elective repair was associated with increased risk of all-cause mortality ( hazard ratio, 1.92; 95% CI] 1.50-2.44; P < 0.001) and ARM (hazard ratio, 2.43; 95% CI, 1.63-3.62; P < 0.001).Conclusions: Non-elective FB-EVAR of symptomatic or ruptured TAAAs is feasible, but carries higher incidence of early MAEs and increased all-cause mortality and ARM than elective repair. Long-term follow-up is warranted to justify the treatment.
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6.
  • Dias-Neto, Marina, et al. (author)
  • Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms
  • 2023
  • In: Journal of Vascular Surgery. - : MOSBY-ELSEVIER. - 0741-5214 .- 1097-6809. ; 77:6, s. 1588-1597
  • Journal article (peer-reviewed)abstract
    • Objective: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs).Methods: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single-or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality.Results: A total of 1947 patients (65% male; mean age, 71 +/- 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9 +/- 1.3% vs 79.6 +/- 1.7%) and 3 years (72.7 +/- 2.1% vs 64.2 +/- 2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach.Conclusions: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years.
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7.
  • D'Oria, Mario, et al. (author)
  • Outcomes of "Anterior Versus Posterior Divisional Branches of the Hypogastric Artery as Distal Landing Zone for Iliac Branch Devices" : The International Multicentric R3OYAL Registry
  • 2024
  • In: Journal of Endovascular Therapy. - : Sage Publications. - 1526-6028 .- 1545-1550. ; 31:2, s. 282-294
  • Journal article (peer-reviewed)abstract
    • Objective: The aim of this multicentric registry was to assess the outcomes of "anteRior versus posteRior divisional bRanches Of the hYpogastric artery as distAl landing zone for iLiac branch devices (R3OYAL)."Methods: The main exposure of interest for the purpose of this study was the internal iliac artery (IIA) divisional branch (anterior vs posterior) that was used as distal landing zone. Early endpoints included technical success and adverse events. Late endpoints included survival, primary/secondary IIA patency, and IIA branch instability.Results: A total of 171 patients were included in the study, of which 50 received bilateral implantation of iliac branch devices (IBDs). This resulted in a total of 221 incorporated IIAs included in the final analysis, of which 40 were anterior divisional branches and 181 were posterior divisional branches. Technical success was high in both groups (anterior division: 98% vs posterior division: 100%, P = .18). Occurrence of any adverse event was noted in 14% of patients in both groups (P = 1.0). The overall rate of freedom from the composite IBD branch instability did not show significant differences between patients receiving distal landing in the anterior or posterior division of the IIA at 3 years (79% vs 87%, log-rank test = .215). The 3-year estimates of IBD patency were significantly lower in patients who received distal landing in the anterior divisional branch than those who received distal landing in the posterior divisional branch (primary patency: 81% vs 96%, log-rank test = .009; secondary patency: 81% vs 97%, log-rank test < .001).Conclusions: The use of the anterior or posterior divisional branches of the IIA as distal landing zone for IBD implantation shows comparable profiles in terms of immediate technical success, perioperative safety, and side-branch instability up to 3 years. However, IBD patency at 3 years was higher when the distal landing zone was achieved within the posterior divisional branch of the IIA.Clinical Impact: The results from this large multicentric registry confirm that use of the anterior or posterior divisional branches of the internal iliac artery (IIA) as distal landing zone for implantation of iliac branch devices (IBD) shows comparable profiles of safety and feasibility, thereby allowing to extend the indications for endovascular repair of aorto-iliac aneurysms to cases with unsuitable anatomy within the IIA main trunk. Although mid-term rates of device durability and branch instability seem to be similar, the rates of primary and secondary IBD patency at three years was favored when the distal landing zone was achieved in the posterior divisional branch of the IIA.
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8.
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9.
  • Onengut-Gumuscu, Suna, et al. (author)
  • Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.
  • 2015
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47:4, s. 381-386
  • Journal article (peer-reviewed)abstract
    • Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10(-8)). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal.
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10.
  • Tenorio, Emanuel R, et al. (author)
  • Multicenter global early feasibility study to evaluate total endovascular arch repair using three-vessel inner branch stent-grafts for aneurysms and dissections
  • 2021
  • In: Journal of Vascular Surgery. - : Elsevier BV. - 1097-6809 .- 0741-5214. ; 74:4, s. 4-1065
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To evaluate the outcomes of total endovascular aortic arch repair using three-vessel inner branch stent-grafts for aneurysms and chronic dissections.METHODS: We reviewed the clinical data and outcomes of consecutive patients treated by total endovascular aortic arch repair at eight academic centers using three-vessel inner branch stent-grafts (William Cook Europe, Bjaeverskov, Denmark) between 2016 to 2019. All patients received three vessel designs with two antegrade and one retrograde inner branch, which was used to incorporate the innominate (IA), left common carotid (LCCA) and left subclavian arteries (LSA). The antegrade inner branches were accessed via carotid or upper extremity access. A preloaded catheter was used for access to the retrograde LSA branch via trans-femoral approach. End-points were technical success, mortality, major adverse events (MAEs), any stroke (minor or major) or transient ischemia attack (TIA), secondary interventions, target vessel patency, target vessel instability, aneurysm-related mortality and patient survival.RESULTS: There were 39 patients (31 male patients [79%], mean age 70±7) treated for 14 (36%) degenerative and 25 (64%) chronic post-dissection arch aneurysms. Clinical characteristics included American Society of Anesthesiologist (ASA) classification > 3 in 28 patients (95%) and prior median sternotomy for ascending aortic repair in 28 patients (72%). Technical success rate was 100%. There were two in-hospital or 30-day deaths (5%) and two strokes (one minor). Combined mortality/any stroke rate was 8% (n=3). MAEs occurred in 10 patients (26%), including respiratory failure in four patients (10%) and estimated blood loss >1L, myocardial infarction and acute kidney injury in two patients each (5%). Median follow up was 3.2 months (IQR, 1 to 14). Twelve patients (31%) required secondary interventions to treat vascular access complications in five patients, endoleak in six patients (three type II, one type IC, one type IA/IB, one type IIIA) and target vessel stenosis in one patient. At 1-year, primary and secondary patency rates and freedom from target vessel instability were 95%±5%, 100% and 91%±5%. Freedom from aortic-related mortality and patient survival were 94%±4% and 90%±6%, respectively.CONCLUSION: This multicenter global experience demonstrates the technical feasibility and safety of total endovascular aortic arch repair for aneurysms and chronic dissections using three-vessel inner branch stent-grafts. Mortality and stroke rates compare favorably to open surgical repair in a higher risk group of patients. Rate of secondary interventions was high (31%), emphasizing need for larger experience and longer follow-up.
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