GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain.

Extracellular vesicles (EVs) are biological nanoparticles with important roles in intercellular communication, and potential as drug delivery vehicles. Here we demonstrate a role for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in EV assembly and secretion. We observe high levels of GAPDH binding to the outer surface of EVs via a phosphatidylserine binding motif (G58), which promotes extensive EV clustering. Further studies in a Drosophila EV biogenesis model reveal that GAPDH is required for the normal generation of intraluminal vesicles in endosomal compartments, and promotes vesicle clustering. Fusion of the GAPDH-derived G58 peptide to dsRNA-binding motifs enables highly efficient loading of small interfering RNA (siRNA) onto the EV surface. Such vesicles efficiently deliver siRNA to multiple anatomical regions of the brain in a Huntington's disease mouse model after systemic injection, resulting in silencing of the huntingtin gene in different regions of the brain.

Subcellular Organization of the cAMP Signaling Pathway.

The field of cAMP signaling is witnessing exciting developments with the recognition that cAMP is compartmentalized and that spatial regulation of cAMP is critical for faithful signal coding. This realization has changed our understanding of cAMP signaling from a model in which cAMP connects a receptor at the plasma membrane to an intracellular effector in a linear pathway to a model in which cAMP signals propagate within a complex network of alternative branches and the specific functional outcome strictly depends on local regulation of cAMP levels and on selective activation of a limited number of branches within the network. In this review, we cover some of the early studies and summarize more recent evidence supporting the model of compartmentalized cAMP signaling, and we discuss how this knowledge is starting to provide original mechanistic insight into cell physiology and a novel framework for the identification of disease mechanisms that potentially opens new avenues for therapeutic interventions. SIGNIFICANCE STATEMENT: cAMP mediates the intracellular response to multiple hormones and neurotransmitters. Signal fidelity and accurate coordination of a plethora of different cellular functions is achieved via organization of multiprotein signalosomes and cAMP compartmentalization in subcellular nanodomains. Defining the organization and regulation of subcellular cAMP nanocompartments is necessary if we want to understand the complex functional ramifications of pharmacological treatments that target G protein-coupled receptors and for generating a blueprint that can be used to develop precision medicine interventions.

Phosphodiesterase 2A2 regulates mitochondria clearance through Parkin-dependent mitophagy.

Programmed degradation of mitochondria by mitophagy, an essential process to maintain mitochondrial homeostasis, is not completely understood. Here we uncover a regulatory process that controls mitophagy and involves the cAMP-degrading enzyme phosphodiesterase 2A2 (PDE2A2). We find that PDE2A2 is part of a mitochondrial signalosome at the mitochondrial inner membrane where it interacts with the mitochondrial contact site and organizing system (MICOS). As part of this compartmentalised signalling system PDE2A2 regulates PKA-mediated phosphorylation of the MICOS component MIC60, resulting in modulation of Parkin recruitment to the mitochondria and mitophagy. Inhibition of PDE2A2 is sufficient to regulate mitophagy in the absence of other triggers, highlighting the physiological relevance of PDE2A2 in this process. Pharmacological inhibition of PDE2 promotes a 'fat-burning' phenotype to retain thermogenic beige adipocytes, indicating that PDE2A2 may serve as a novel target with potential for developing therapies for metabolic disorders.

Penetrating Trauma To The Axillary Artery.

Axillary artery injuries due to penetrating trauma are relatively uncommon. Management of these injuries is challenging due to the complex local anatomy, rigid chest walls, and associated injuries. Open exposure with direct open vascular repair has been the mainstay of operative management. We report a clinical case of a 51-year-old man victim of penetrating trauma to the axillary artery caused by a chain-saw and repaired by open surgery with a great saphenous vein interposition graft.

Full Rescue of F508del-CFTR Processing and Function by CFTR Modulators Can Be Achieved by Removal of Two Regulatory Regions.

Cystic Fibrosis (CF) is caused by mutations in the CF Transmembrane conductance Regulator (CFTR), the only ATP-binding cassette (ABC) transporter functioning as a channel. Unique to CFTR is a regulatory domain which includes a highly conformationally dynamic region-the regulatory extension (RE). The first nucleotide-binding domain of CFTR contains another dynamic region-regulatory insertion (RI). Removal of RI rescues the trafficking defect of CFTR with F508del, the most common CF-causing mutation. Here we aimed to assess the impact of RE removal (with/without RI or genetic revertants) on F508del-CFTR trafficking and how CFTR modulator drugs VX-809/lumacaftor and VX-770/ivacaftor rescue these variants. We generated cell lines expressing ΔRE and ΔRI CFTR (with/without genetic revertants) and assessed CFTR expression, stability, plasma membrane levels, and channel activity. Our data demonstrated that ΔRI significantly enhanced rescue of F508del-CFTR by VX-809. While the presence of the RI seems to be precluding full rescue of F508del-CFTR processing by VX-809, this region appears essential to rescue its function by VX-770, suggesting some contradictory role in rescue of F508del-CFTR by these two modulators. This negative impact of RI removal on VX-770-stimulated currents on F508del-CFTR can be compensated by deletion of the RE which also leads to the stabilization of this mutant. Despite both regions being conformationally dynamic, RI precludes F508del-CFTR processing while RE affects mostly its stability and channel opening.

Impact of Post-EVAR Graft Limb Kinking in EVAR Limb Occlusion: Aetiology, Early Diagnosis, and Management.

OBJECTIVE/BACKGROUND: Endograft limb occlusion is a potential complication of endovascular aneurysm repair (EVAR), being one of the major causes of secondary interventions and rehospitalisation. The aim of this review is to report on the impact of endograft kinking in endograft limb occlusion, as well as on risk factors, prevention, early diagnosis, and management. METHODS: A systematic review and meta-analysis was conducted according to the recommendations of the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement. RESULTS: After a MEDLINE and Scopus search, 55 articles (27,509 patients) were included in the qualitative analysis and eight in the quantitative analysis. In this meta-analysis, 179 at risk limbs were treated by pre-emptive stenting, which significantly reduced the risk of limb occlusion: not pre-emptively stenting limbs at risk had a negative impact on graft limb patency (odds ratio 4.30, 95% confidence interval 1.45-12.78). Post-operatively, a kink was identified in 422 patients (1.5%), contributing to 42.8% of all limb occlusions. Relevant data support that completion angiography is an inadequate means of diagnosing high risk limbs, proposing cone beam computed tomography and intravascular ultrasound as adjuncts. The post-operative limb occlusion rate ranged from 0% to 10.6%, affecting 984 patients. Several risk factors for limb occlusion have been identified. Regarding treatment, most patients were submitted to femorofemoral bypass (52.3%) or to deployment of a bare metal stent, either alone or associated with catheter directed thrombolysis or mechanical thrombectomy (26.4%). Complications and outcome after re-intervention for limb occlusion are described infrequently in the literature, but single studies have reported on re-occlusion, major amputation, and limb occlusion related mortality rates. CONCLUSION: Pre-EVAR planning should focus on identification of risk factors for kinking. Adjunctive stenting is an effective prophylaxis for selected high risk limbs, yet intra-operative identification remains problematic. Also, it is noteworthy that most limb occlusions occur in the first year after EVAR, emphasising the importance of careful early follow up of high risk patients.

Prediction of Survival after 48 Hours of Intensive Unit Care following Repair of Ruptured Abdominal Aortic Aneurysm-Multicentric Study for External Validation of a New Prediction Score for 30-Day Mortality.

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) remains a critical life-threatening condition. We aimed to evaluate rAAA management in our center focusing on predictors of mortality at 48 hr of intensive care unit (ICU) and to develop a new mortality prediction score considering data at 48 hr postprocedure. External validation of the modified score with patient data from independent vascular surgery centers was subsequently pursued. METHODS: Clinical data of all patients admitted in our center from January 2010 to December 2017 with the diagnosis of rAAA were retrospectively reviewed for the development of the mortality prediction score. Subsequently, clinical data from patients admitted at independent centers from January 2010 to December 2017 were reviewed for external validation of the score. Statistical analysis was performed with SPSS Version 25. RESULTS: A total of 78 patients were included in the first part of the study: 21 endovascular aneurysm repairs (EVARs), 56 open repairs (ORs), and 1 case of conservative management. Intraoperative mortality in EVAR and OR groups was 0% vs. 24.6%, respectively (P = 0.012). Thirty-day mortality reached 50% and 33% in the OR and EVAR groups. For patients alive at 48 hr, 30-day mortality diminished to 27.6%. Several preoperative predictors of outcome were identified: smoking (P = 0.004), hemodynamic instability(P = 0.004), and elevated international normalized ratio (P < 0.0001). Dutch Aneurysm Score and Vascular Study Group of New England Score (VSGNE) were also significant predictors of outcome (area under the receiver operating characteristic curve [ROC AUC] 0.89 and 0.79, respectively; P < 0.0001). At 48 hr of ICU stay, high lactate level, high Sequential Organ Failure Assessment score, need for hemodyalitic technique, and hemodynamic instability were significant risk predictors for 30-day mortality (P < 0.05). VSGNE score was modified with the inclusion of 2 variables: hemodynamic instability and lactate level at 48 hr and a new score was attained-Postoperative Aneurysm Score (PAS). Comparing AUC for VSGNE and PAS for patients alive at 48 hr, the latter was significantly better (AUC 0.775 vs. 0.852, P = 0.039). The PAS was applied and validated in 3 independent vascular surgery centers (AUC VSGNE 0.782 vs. AUC PAS 0.820, P = 0.027). CONCLUSIONS: Despite recent evidence on preoperative predictors of survival in an era when both EVAR and OR are available, emergent decision to withhold life-saving treatment will always be extremely difficult. Therefore, the policy in our department is to try surgical repair in all cases. It remains important, however, to identify whether late deaths can be predicted, so that unnecessary prolonged treatment can be avoided. A PAS was delineated predicting 30-day mortality significantly better in patients alive at 48 hr. The score was externally applied and validated in independent centers, corroborating the score's usefulness.

Overview of evidence on risk factors and early management of acute carotid stent thrombosis during the last two decades.

OBJECTIVE: Acute carotid stent thrombosis (ACST) occurring in the first hours after the procedure is an exceedingly rare complication of carotid artery stenting, but it is potentially devastating. This review aimed to evaluate current literature, identifying all reported cases during the last two decades, with the final purpose of reporting predictive factors and early management. METHODS: A systematic review and meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: A total of 464 potentially relevant articles were selected. After review of records at title and abstract level, 29 articles with 60 patients were included. Twelve studies reported on ACST incidence rate in their cohorts, ranging from 0.36% to as high as 33%. In considering etiology, antiplatelet noncompliance or resistance is the most frequently reported risk factor. Emergency procedures seemed to be associated with greater risk for ACST, reaching 5.6% to 33% incidence. Dual-layer stents were also associated with greater risk (45% vs 3.7%; P = .0001; odds ratio, 21.3). Use of an overlapping stent as a bailout procedure because of dissection, malposition, or long lesions was correlated with increased risk (7.3% vs 0.002%), as were long stenotic lesions (22.9 ± 6.83 mm vs 14.2 ± 6.42 mm; P = .0034) and stent length (3.8 ± 0.4 cm vs 2.8 ± 0.86 cm; P = .0055). ACST was associated with neurologic status deterioration in 56.7% of cases. Time to symptoms or ACST diagnosis had a median of 1.5 hours, with 30% occurring intraprocedurally. In asymptomatic ACST, conservative management was unanimous. Endovascular treatment was the most common approach to intraprocedural ACST. Surgical options included carotid endarterectomy with stent explantation (n = 9), which was also a bailout after failed endovascular treatment in two cases. CONCLUSIONS: ACST incidence is higher in emergent, neurologically unstable patients. Antiplatelet noncompliance, antiplatelet resistance, long stenotic lesions, use of more than one stent, and dual-layer stents are also associated with increased risk. The decision as to the best approach depends on whether ACST occurs intraprocedurally or afterward, the development of neurologic status deterioration, and the center's experience. However, additional studies must be undertaken to better define optimal management.

Overview of evidence on emergency carotid stenting in patients with acute ischemic stroke due to tandem occlusions: a systematic review and meta-analysis.

INTRODUCTION: Endovascular intracranial thrombectomy (IT) has established itself as the standard of care in treating large-vessel anterior circulation acute ischemic stroke (AIS). However, internal carotid artery (ICA) stenosis/occlusion hampers distal access and controversy about simultaneous emergency ICA stenting ensues. The purpose of this review was to evaluate the safety of emergency ICA stenting in combination with IT for AIS with tandem occlusions. To our knowledge this is the first meta-analysis to evaluate emergency ICA stenting in tandem occlusions, combining results from studies with a control group. EVIDENCE ACQUISITION: A meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. EVIDENCE SYNTHESIS: A total of 649 potentially relevant articles were initially selected. After reviewing at title or abstract level, 87 articles were read in full and 23 were included. These studies recruited 1000 patients, 220 submitted to IT with no emergency ICA stenting and 780 to IT and emergency ICA stenting. Successful revascularization (Thrombolysis in cerebral infarction scale [TICI] ≥2b) was achieved in 48.6-100%. Good outcome (modified Rankin scale [mRS] ≤2) ranged from 18.2-100%. Symptomatic intracranial hemorrhage (sICH) ranged from 0-45.7% (overall N.=168; 17.2%). Mortality at 90 days ranged from 0-45.4% (overall N.=114; 11.7%). Time to recanalization was significantly longer in the stenting group with an overall mean difference of 1.76 (95% CI: 1.59-1.93). CONCLUSIONS: In this meta-analysis time to recanalization was significantly longer in the emergency ICA stenting group. There was no benefit from emergency stenting in parameters such as successful revascularization (TICI≥2b), clinical outcome (mRS≤2) or 90-day mortality. Data on sICH were scarce. Emergency ICA stenting appears to increase time to revascularization and increase the risk of complications with no demonstrated clinical benefit. Furthermore, no prospective, randomized controlled trials demonstrating relative efficacy and safety of concomitant ICA stenting have been published to date. Additional studies must be undertaken to define the role of angioplasty and stenting of the extracranial carotid arteries in the early management of acute stroke in tandem occlusions. Until then, we recommend that ICA stenting concomitant to thrombectomy in acute stroke patients should be avoided.

Targeting FRET-Based Reporters for cAMP and PKA Activity Using AKAP79.

Fluorescence resonance energy transfer (FRET)-based sensors for 3′⁻5′cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) allow real-time imaging of cAMP levels and kinase activity in intact cells with high spatiotemporal resolution. The development of FRET-based sensors has made it possible to directly demonstrate that cAMP and PKA signals are compartmentalized. These sensors are currently widely used to dissect the organization and physiological function of local cAMP/PKA signaling events in a variety of cell systems. Fusion to targeting domains has been used to direct the sensors to a specific subcellular nanodomain and to monitor cAMP and PKA activity at specific subcellular sites. Here, we investigate the effects of using the A-kinase anchoring protein 79 (AKAP79) as a targeting domain for cAMP and PKA FRET-based reporters. As AKAP79 interacts with PKA itself, when used as a targeting domain, it can potentially impact on the amplitude and kinetics of the signals recorded locally. By using as the targeting domain wild type AKAP79 or a mutant that cannot interact with PKA, we establish that AKAP79 does not affect the amplitude and kinetics of cAMP changes or the level of PKA activity detected by the sensor.

Ilio-Iliac Arteriovenous Fistulae-An Unusual Diagnosis with an Even More Unusual Clinical Presentation.

BACKGROUND: Major pelvic ilio-iliac arteriovenous fistula (AVF) is an exceedingly rare diagnosis with only a few described cases in the literature, most of them related to congenital defects or trauma. In this case report, we aim to present a case of an ilio-iliac AVF with an atypical clinical presentation. METHODS: Relevant medical data were collected from hospital database. RESULTS: The patient is a 77-year-old woman, with a relevant medical history of a temporally remote hysterectomy. She developed an exuberant unilateral right leg edema and was diagnosed with a femoro-iliac deep vein thrombosis (DVT) and started on anticoagulation and daily use of elastic compression stockings. No improvement in leg edema was evident, and she reported painful complaints refractory to medication. She also progressively developed right foot numbness and foot drop. A computed tomography angiography (CTA) was performed to exclude any compressive or paraneoplastic syndrome, with no remarkable findings other than common iliac vein (CIV) occlusion. As the patient's symptoms continued to worsen, a new CTA was performed 5 months later, which revealed an ilio-iliac AVF that was confirmed by angiography. After 2 ineffective attempts to embolize AVF afferents, we chose to completely embolize the arterial component of the AVF with Helix EV3 coils and Onyx glue (Covidien, Irvine, CA, USA). CIV recanalization and deployment of a Venovo stent (Bard Inc, Tempe, AZ, USA) was also performed. The final angiograms showed exclusion of the AVF and rapid venous flow through the stent. There was progressive improvement of edema and pain but little improvement of foot drop. CONCLUSION: AVF etiology and mechanism of neurologic deficits are controversial, with multiple possible explanations. Endovascular treatment modalities are promising a safer and more efficient approach when compared with open surgery. Our experience in this case was encouraging, but long-term results are currently lacking.

PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling.

cAMP/PKA signalling is compartmentalised with tight spatial and temporal control of signal propagation underpinning specificity of response. The cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within which they control local cAMP levels and are key regulators of signal compartmentalisation. Several components of the cAMP/PKA cascade are located to different mitochondrial sub-compartments, suggesting the presence of multiple cAMP/PKA signalling domains within the organelle. The function and regulation of these domains remain largely unknown. Here, we describe a novel cAMP/PKA signalling domain localised at mitochondrial membranes and regulated by PDE2A2. Using pharmacological and genetic approaches combined with real-time FRET imaging and high resolution microscopy, we demonstrate that in rat cardiac myocytes and other cell types mitochondrial PDE2A2 regulates local cAMP levels and PKA-dependent phosphorylation of Drp1. We further demonstrate that inhibition of PDE2A, by enhancing the hormone-dependent cAMP response locally, affects mitochondria dynamics and protects from apoptotic cell death.

EPAC1 activation by cAMP stabilizes CFTR at the membrane by promoting its interaction with NHERF1.

Cyclic AMP (cAMP) activates protein kinase A (PKA) but also the guanine nucleotide exchange factor 'exchange protein directly activated by cAMP' (EPAC1; also known as RAPGEF3). Although phosphorylation by PKA is known to regulate CFTR channel gating - the protein defective in cystic fibrosis - the contribution of EPAC1 to CFTR regulation remains largely undefined. Here, we demonstrate that in human airway epithelial cells, cAMP signaling through EPAC1 promotes CFTR stabilization at the plasma membrane by attenuating its endocytosis, independently of PKA activation. EPAC1 and CFTR colocalize and interact through protein adaptor NHERF1 (also known as SLC9A3R1). This interaction is promoted by EPAC1 activation, triggering its translocation to the plasma membrane and binding to NHERF1. Our findings identify a new CFTR-interacting protein and demonstrate that cAMP activates CFTR through two different but complementary pathways - the well-known PKA-dependent channel gating pathway and a new mechanism regulating endocytosis that involves EPAC1. The latter might constitute a novel therapeutic target for treatment of cystic fibrosis.

Endoleak type II post-EVAR - predictive factors and therapeutic intervention - single centre experience in 100 EVAR procedures.

INTRODUCTION: Endovascular aortic repair (EVAR) has significantly altered the therapeutic strategy for abdominal aortic aneurysm (AAA), due to less invasiveness and lower perioperative morbi-mortality. However, specific complications such as persistent type 2 endoleak (pT2E, present > 6 months after EVAR) have been associated with adverse outcomes. However conflicting results from heterogeneous studies, failed to support an optimal threshold for intervention. The purpose of this study was to identify predictive factors associated with pT2E. METHODS: The clinical data of the last 100 patients admitted for EVAR in our hospital until April 2016 were retrospec- tively reviewed. Statistical analysis was performed using SPSS V.22. RESULTS: We analyzed 100 cases of EVAR, performed with a branched stentgraft for AAA or aorto-iliac aneurysms. Most cases (n=83) were performed electively but 17 were performed for ruptured AAA. No pre-operative inferior mesen- teric artery (IMA) coil embolization was performed. A pT2E was observed by Computed Tomography Angiography (CTA) in 21 cases (21%). Univariate analysis of risk factors for pT2E revealed that the number of patent lumbar arteries, patent IMA, platelet antiaggregants, absence of thoracic aortic aneurysm, and ruptured AAA were risk factors for pT2E (p<0.05). Binary logistic regression concluded platelet antiaggregants and increasing number of patent lumbars were independent risk factors for pT2E (p<0.05). DISCUSSION: Recently, pT2E that persists over a long period of time following EVAR has been reported to be involved in aneurysm sac growth, open conversion and rupture. Identification of pT2E predictive factors is crucial to prevent compli- cations and to consider measures such as pre-operative IMA coil embolization. We identified the number of patent lumbar arteries, the presence of patent IMA, platelet antiaggregants, absence of thoracic aortic aneurysm and ruptured AAA as sta- tistically significant risk factors for pT2E (p<0.05).

Introdução: A reparação endovascular de aneurisma da aorta abdominal (EVAR) alterou progressivamente a estratégia terapêutica devido à menor morbi-mortalidade peri-operatória associada. No entanto existem complicações específicas associa- das, como o endoleak tipo 2 persistente (pT2E, presente> 6 meses após EVAR). O principal objetivo deste estudo foi a identifi- cação de fatores preditivos associados a pT2E. Métodos: Os dados clínicos dos últimos 100 doentes admitidos para EVAR no nosso centro até abril de 2016 foram retrospetivamente analisados. O estudo estatístico foi realizado utilizando o SPSS V.22. Resultados: Foram analisados 100 casos de EVAR, realizados com endoprótese ramificada para aneurisma da aorta abdominal (AAA) ou aneurismas aorto-ilíacos. A maioria dos casos (n=83) foram realizados eletivamente, mas 17 foram reali- zados por rotura de AAA. Não houve nenhum caso de embolização pré-operatória da artéria mesentérica inferior (AMI). pT2E foi diagnosticado por Angio-Tomografia Computadorizada (AngioTC) em 21 casos (21%). A análise univariada dos fatores de risco para pT2E revelou que o número de artérias lombares (AL) permeáveis, permeabilidade da AMI, antiagregação plaquetária, ausência de aneurisma aórtico torácico e rotura de AAA são fatores de risco para pT2E (p<0,05). Uma regressão logística binária foi realizada e permitiu concluir que a antiagregação plaquetária e o número crescente de AL permeáveis são fatores de risco independentes para pT2E (p<0,05). Discussão: Atualmente, o pT2E tem sido cada vez mais associado a outcomes adversos como o crescimento do saco aneurismático, re-intervenção endovascular, conversão aberta e rotura. No entanto, a discrepância de dados na literatura condu- zem à ausência de um limiar consensual para tratamento. A identificação dos fatores preditivos de pT2E é crucial para prevenir complicações e considerar medidas como a embolização pré-operatória da AMI. Identificamos o número de AL permeáveis, AMI permeável, antiagregação plaquetária, ausência de aneurisma aórtico torácico e rotura de AAA como fatores de risco estatistica- mente significativos para pT2E (p<0,05).

Guía española de la EPOC (GesEPOC). Actualización 2014 / Spanish Guideline for COPD (GesEPOC). Update 2014

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[Unruptured symptomatic abdominal aortic aneurysms]. / Aneurismas da aorta abdominal sintomáticos não rotos.

OBJECTIVES: The authors aim to present a case series of patients with unruptured symptomatic abdominal aortic aneurysms with atypical presentation or clinical manifestations. METHODS: A retrospective analysis from 2010 to 2013 of unruptured symptomatic abdominal aortic aneurysms was made in a Vascular Surgery department. RESULTS: 4 clinical cases were selected, all male, mean age of 72.2 years, with a history of smoking (75 %), hypertension (50 %), dyslipidemia (25 %) , DM (25 %) and CRI (25 %). Abdominal aortic aneurysms were diagnosed with unusual forms of presentation, from those associated to local events (venous or spinal compression), to infectious processes "in situ", complete thrombosis of the aneurysmal sac, to those with remotely manifestations (peripheral embolization). Medical and surgical treatments are described in this paper, taking into account the particularities of each patient. CONCLUSION: Rupture is the most common manifestation of abdominal aortic aneurysms. Although more rare, symptomatic unruptured AAA require a higher degree of suspicion, with some specific features to be considered, as we intend to demonstrate.

[Endovascular management of a thoracoabdominal aortic aneurysm in a chronic contained rupture using the "Sandwich technique"]. / Tratamento Endovascular de um Aneurisma da Aorta Toracoabdominal em Rotura Contida, Utilizando a Técnica de "Sandwich"

OBJECTIVE: The authors report the prompt diagnosis and endovascular treatment with the "Sandwich" technique of a chronic contained rupture of a thoracoabdominal aortic aneurysm in an unfit patient for open surgery. METHODS: A 57-year-old male patient with severe pulmonar and cardiac comorbilities presented at the emergency department with a contained rupture of a type V thoracoabdominal aneurysm, involving the celiac axis. A "Sandwich" technique was performed deploying a ViaBahn graft through a transbrachial access interlayed by two Gore TAG endoprothesis. RESULTS: At the term of the 1st month of follow-up, no endoleaks were observed. DISCUSSION: An impending ruptured thoracoabdominal aortic aneurysm was successfully excluded using the "Sandwich" technique, in a patient unfit for the conventional open correction.

Competent jerks, lovable fools, and the formation of social networks.

When looking for help with a task at work, people turn to those best able to do the job. Right? Wrong. New research shows that work partners tend to be chosen not for ability but for likability. Drawing from their study encompassing 10,000 work relationships in five organizations, the authors have classified work partners into four archetypes: the competent jerk, who knows a lot but is unpleasant; the lovable fool, who doesn't know much but is a delight; the lovable star, who's both smart and likable; and the incompetent jerk, who.. .well, that's self-explanatory. Of course, everybody wants to work with the lovable star, and nobody wants to work with the incompetent jerk. More interesting is that people prefer the lovable fool over the competent jerk. That has big implications for every organization, as both of these types often represent missed opportunities. Because they are liked by a disproportionate number of people, lovable fools can bridge gaps between diverse groups that might not otherwise interact. But their networking skills are often developed at the expense of job performance, which can make these employees underappreciated and vulnerable to downsizing. To get the most out of them, managers need to protect them and put them in positions that don't waste their bridge-building talents. As for the competent jerks, too often their expertise goes untapped by people who just can't put up with them. But many can be socialized through coaching or by being made accountable for bad behavior. Others may need to display their competence in more isolated settings. Intriguingly, managers aren't limited to leveraging people that others like and changing those that others loathe. They also can create situations in which people are more apt to like one another, whatever their individual qualities.