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Moreno R.,Hospital Universitario La Paz | Garcia E.,Hospital Clinico | Teles R.,Hospital de Santa Cruz | Rumoroso J.-R.,Hospital de Galdakao | And 18 more authors.
Circulation: Cardiovascular Interventions | Year: 2013

Background-Patients with coronary total occlusions are at especially high risk for restenosis and new revascularizations. Sirolimus-eluting stents dramatically improved the clinical outcome of this subset of patients in randomized trials, but other drug-eluting stents, mainly the everolimus-eluting stent (currently the most frequently used stent), have not yet been evaluated in patients with coronary total occlusions. The objective was to compare the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent in patients with coronary total occlusions. Methods and Results-A total of 207 patients with coronary total occlusions and estimated time since occlusion >2 weeks were randomized to everolimus- or sirolimus-eluting stent. The primary end point was in-stent late loss at 9-month angiographic follow-up (noninferiority trial). Clinical follow-up was performed at 1 and 12 months. In-stent late loss at 9 months was 0.29±0.60 versus 0.13±0.69 mm in patients allocated to sirolimus- and everolimus-eluting stent, respectively. The observed difference in in-stent late loss between both groups was -0.16 mm (95% confidence interval, 0.04 to -0.36 mm; P for noninferiority <0.01). The rate of binary angiographic restenosis was 10.8% and 9.1% in patients allocated to sirolimus- and everolimus-eluting stent, respectively (P=0.709), whereas the rate of vessel reocclusion was 3.2% and 1.1%, respectively (P=0.339). At 12 months, the rate of major adverse events was 15.9% versus 11.1% with sirolimus- and everolimus-eluting stent, respectively (P=0.335), and probable or definitive stent thrombosis occurred in 3.0% and 0.0% of patients, respectively (P=0.075). Conclusions-In patients with coronary total occlusions, everolimus-eluting stent is as effective as sirolimus-eluting stent. © 2013 American Heart Association, Inc. Source

Bastos Goncalves F.,Erasmus Medical Center | Hoeks S.E.,Erasmus Medical Center | Teijink J.A.,Catharina Hospital | Moll F.L.,University Utrecht | And 4 more authors.
European Journal of Vascular and Endovascular Surgery | Year: 2015

Objective To assess the incidence and risk factors for proximal aneurysm neck related complications with a late generation device for endovascular abdominal aneurysm repair (EVAR). Methods Data were retrieved from a prospective registry (Endurant Stent Graft Natural Selection Global Postmarket Registry) involving 79 institutions worldwide. The risk factors tested were age, gender, surgical risk profile, proximal neck length (<10 mm), diameter (>30 mm), supra- and infrarenal angulation (>60° and 75°), mural thrombus/calcification (>50%) and taper (>10%), and AAA diameter (>65 mm). Two neck related composite endpoints were used, for intra-operative (type-1a endoleak, conversion, deployment/retrieval complication or unintentional renal coverage) and post-operative (type-1a endoleak or migration) adverse events. Independent risk factors were identified using multivariable backwards modeling. Results The study included 1263 patients (mean age 73, 10.3% female) from March 2009 to May 2011. Twenty three (1.8%) intra-operative adverse events occurred. Neck length <10 mm (OR 4.9, 95% CI 1.1-22.6) and neck thrombus/calcification >50% (OR 4.8, 95% CI 1.7-13.5) were risk factors for intra-operative events. The planned 1 year follow up visit was reached for the entire cohort, and the 2 year visit for 431 patients. During this time, 99 (7.8%) events occurred. Female gender (HR 1.9, 95% CI 1.1-3.2), aneurysm diameter >65 mm (HR 2.8, 95% CI 1.9-4.2), and neck length <10 mm (HR 2.8, 95% CI 1.1-6.9) were significant post-operative risk factors. Neck angulation, neck taper, large diameter neck, and presence of thrombus/calcification were not predictors of adverse outcome in this study. Conclusion These results support the adequacy of this device in the face of adverse neck anatomy, and confirm neck length as the most relevant anatomical limitation for EVAR. Additionally, the study confirms the decline in early to mid-term intervention rates with a newer generation device in a large patient sample. Lastly, it suggests that neck related risk factors affect outcome and impact on prognosis in varying degrees. © 2014 European Society for Vascular Surgery. Source

Lopes Dias J.,Hospital de S. Jose | Lucas R.,Hospital de Santo Antonio dos Capuchos | Magalhaes Pina J.,Hospital de S. Jose | Joao R.,Hospital de S. Jose | And 5 more authors.
Abdominal Imaging | Year: 2015

The use of multiparametric magnetic resonance imaging (mp-MRI) for prostate cancer has increased over recent years, mainly for detection, staging, and active surveillance. However, suspicion of recurrence in the set of biochemical failure is becoming a significant reason for clinicians to request mp-MRI. Radiologists should be able to recognize the normal post-treatment MRI findings. Fibrosis and atrophic remnant seminal vesicles after prostatectomy are often found and must be differentiated from local relapse. Moreover, brachytherapy, external beam radiotherapy, cryosurgery, and hormonal therapy tend to diffusely decrease the signal intensity of the peripheral zone on T2-weighted images (T2WI) due to the loss of water content, consequently mimicking tumor and hemorrhage. The combination of T2WI and functional studies like diffusion-weighted imaging and dynamic contrast-enhanced improves the identification of local relapse. Tumor recurrence tends to restrict on diffusion images and avidly enhances after contrast administration either within or outside the gland. The authors provide a pictorial review of the normal findings and the signs of local tumor relapse after radical prostatectomy, external beam radiotherapy, brachytherapy, cryosurgery, and hormonal therapy. © 2015, Springer Science+Business Media New York. Source

Lopes A.,Hospital Divino Espirito Santo | Cotrim C.,Hospital Garcia de Orta | Martins J.D.F.,Hospital de Santa Marta | Pinto F.,Hospital de Santa Marta
Pediatric Cardiology | Year: 2011

We report the case of a 10-year-old girl with two episodes of light-headedness and chest pain during exercise. She had an unremarkable clinical record, physical examination, ECG, and echocardiogram. Noninvasive ischemia tests were positive, but coronary angiography was normal. Exercise stress echocardiogram revealed an exercise-induced intra-left-ventricular obstruction with a peak gradient of 78 mmHg and replicated her symptoms. After starting beta-blocker therapy her clinical status improved and no residual obstruction was detected. The authors review this unsuspected clinical condition, seldom reported in the adult population and, to our knowledge, never before in a child. © 2011 Springer Science+Business Media, LLC. Source

Moniz S.,National Health Institute Dr Ricardo Jorge | Moniz S.,University of Lisbon | Sousa M.,National Health Institute Dr Ricardo Jorge | Sousa M.,University of Lisbon | And 11 more authors.
ACS Chemical Biology | Year: 2013

Cystic fibrosis (CF), a major life-limiting genetic disease leading to severe respiratory symptoms, is caused by mutations in CF transmembrane conductance regulator (CFTR), a chloride (Cl-) channel expressed at the apical membrane of epithelial cells. Absence of functional CFTR from the surface of respiratory cells reduces mucociliary clearance, promoting airways obstruction, chronic infection, and ultimately lung failure. The most frequent mutation, F508del, causes the channel to misfold, triggering its premature degradation and preventing it from reaching the cell surface. Recently, novel small-molecule correctors rescuing plasma membrane localization of F508del-CFTR underwent clinical trials but with limited success. Plausibly, this may be due to the mutant intrinsic plasma membrane (PM) instability. Herein, we show that restoration of F508del-CFTR PM localization by correctors can be dramatically improved through a novel pathway involving stimulation of signaling by the endogenous small GTPase Rac1 via hepatocyte growth factor (HGF). We first show that CFTR anchors to apical actin cytoskeleton (via Ezrin) upon activation of Rac1 signaling through PIP5K and Arp2/3. We then found that such anchoring retains pharmacologically rescued F508del-CFTR at the cell surface, boosting functional restoration by correctors up to 30% of wild-type channel levels in human airway epithelial cells. Our findings reveal that surface anchoring and retention is a major target pathway for CF pharmacotherapy, namely, to achieve maximal restoration of F508del-CFTR in patients in combination with correctors. Moreover, this approach may also translate to other disorders caused by trafficking-deficient surface proteins. © 2012 American Chemical Society. Source

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