Zika virus infection impairs synaptogenesis, induces neuroinflammation, and could be an environmental risk factor for autism spectrum disorder outcome.

Zika virus (ZIKV) infection was first associated with Central Nervous System (CNS) infections in Brazil in 2015, correlated with an increased number of newborns with microcephaly, which ended up characterizing the Congenital Zika Syndrome (CZS). Here, we investigated the impact of ZIKV infection on the functionality of iPSC-derived astrocytes. Besides, we extrapolated our findings to a Brazilian cohort of 136 CZS children and validated our results using a mouse model. Interestingly, ZIKV infection in neuroprogenitor cells compromises cell migration and causes apoptosis but does not interfere in astrocyte generation. Moreover, infected astrocytes lost their ability to uptake glutamate while expressing more glutamate transporters and secreted higher levels of IL-6. Besides, infected astrocytes secreted factors that impaired neuronal synaptogenesis. Since these biological endophenotypes were already related to Autism Spectrum Disorder (ASD), we extrapolated these results to a cohort of children, now 6-7 years old, and found seven children with ASD diagnosis (5.14 %). Additionally, mice infected by ZIKV revealed autistic-like behaviors, with a significant increase of IL-6 mRNA levels in the brain. Considering these evidence, we inferred that ZIKV infection during pregnancy might lead to synaptogenesis impairment and neuroinflammation, which could increase the risk for ASD.

Fundamental neurochemistry review: Glutamatergic dysfunction as a central mechanism underlying flavivirus-induced neurological damage.

The Flaviviridae family comprises positive-sense single-strand RNA viruses mainly transmitted by arthropods. Many of these pathogens are especially deleterious to the nervous system, and a myriad of neurological symptoms have been associated with infections by Zika virus (ZIKV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) in humans. Studies suggest that viral replication in neural cells and the massive release of pro-inflammatory mediators lead to morphological alterations of synaptic spine structure and changes in the balance of excitatory/inhibitory neurotransmitters and receptors. Glutamate is the predominant excitatory neurotransmitter in the brain, and studies propose that either enhanced release or impaired uptake of this amino acid contributes to brain damage in several conditions. Here, we review existing evidence suggesting that glutamatergic dysfunction-induced by flaviviruses is a central mechanism for neurological damage and clinical outcomes of infection. We also discuss current data suggesting that pharmacological approaches that counteract glutamatergic dysfunction show benefits in animal models of such viral diseases.

Predictors of adverse events in uncomplicated type B aortic dissection: a systematic review with meta-analysis.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) has been selectively used for uncomplicated acute type B aortic dissection (TBAD); however, not all cases will benefit from TEVAR. A search for high risk clinical and radiographic predictors for complications is ongoing. This systematic review and meta-analysis aimed to identify predictors of major adverse events during follow-up of uncomplicated TBAD, in order to identify who might benefit from elective TEVAR. EVIDENCE ACQUISITION: A systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) Statement. EVIDENCE SYNTHESIS: 16 studies were included in a qualitative synthesis and 10 in the meta-analysis. Several risk factors associated to major adverse events have been described, including: 1) aortic diameter ≥40 mm; 2) greater false lumen diameter (>22 mm); 3) patent false lumen; 4) primary entry tear >10 mm; and 5) greater number of false lumen vessels origin. Quantitative synthesis identified an aortic diameter ≥40 mm significantly associated with major adverse events (HR=3.56; P<0.00001). Reporting of false lumen status, aortic diameters and growth, and demographic data was not always congruent with the most recent recommendations by Society for Vascular Surgery and Society of Thoracic Surgeons, published in 2020. CONCLUSIONS: Acute and subacute patients with uncomplicated TBAD presenting with an aortic diameter ≥40 mm and solely treated with BMT have an increased hazard of developing major adverse events (HR), making them potential candidates for TEVAR. Remaining risk factors analysed have weaker evidence.

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.

Rare Condition, Unusual Anatomy, Elegant Solution - an Uncommon Manifestation of Kawasaki Disease.

INTRODUCTION: Peripheral artery aneurysms are a rare manifestation of Kawasaki disease (KD), with an estimated incidence of approximately 2% of all KD patients. The case of a 14-year-old girl with past clinical history suggestive of KD is reported; she presented with an aneurysm located in the brachial part of a superficial brachioulnoradial artery, still with the genuine brachial artery in place (an anatomical variation with a reported incidence of 0.14-1.3% in general population). Relevant medical data were collected from the hospital database. REPORT: This is a report of a case of a symptomatic superficial brachioulnoradial artery aneurysm, secondary to KD, treated with aneurysm exclusion and superficial brachioulnoradial to the genuine brachial artery transposition. Uneventful intra- and postoperative course with symptom resolution is reported. DISCUSSION: The coexistence of a rare manifestation of KD (peripheral aneurysm) with an even rarer brachial artery variation allowed a simple but elegant solution, making this a unique case.

Management of a rapidly expanding celiac artery aneurysm with the chimney technique.

Infective celiac artery aneurysm is an extremely rare diagnosis, with few reported cases in the literature. We present the case of a rapidly expanding celiac artery aneurysm involving the ostia, probably infectious, successfully treated in an urgent setting by aneurysm exclusion resorting to the chimney technique. On follow-up, computed tomography angiography revealed complete aneurysm thrombosis and patent celiac artery. Previous reports of endovascular treatment of infective celiac artery aneurysm involved its embolization. This is the first reported case of chimney technique used to exclude a celiac artery aneurysm, with a clinical suspicion of infectious etiology, preserving celiac artery patency. Short-term results are encouraging, but implantation of prosthetic material in an infected environment is a concern.

Acute and chronic neurological consequences of early-life Zika virus infection in mice.

Although congenital Zika virus (ZIKV) exposure has been associated with microcephaly and other neurodevelopmental disorders, long-term consequences of perinatal infection are largely unknown. We evaluated short- and long-term neuropathological and behavioral consequences of neonatal ZIKV infection in mice. ZIKV showed brain tropism, causing postnatal-onset microcephaly and several behavioral deficits in adulthood. During the acute phase of infection, mice developed frequent seizures, which were reduced by tumor necrosis factor-α (TNF-α) inhibition. During adulthood, ZIKV replication persisted in neonatally infected mice, and the animals showed increased susceptibility to chemically induced seizures, neurodegeneration, and brain calcifications. Altogether, the results show that neonatal ZIKV infection has long-term neuropathological and behavioral complications in mice and suggest that early inhibition of TNF-α-mediated neuroinflammation might be an effective therapeutic strategy to prevent the development of chronic neurological abnormalities.

Two-Stage Basilic Vein Transposition: Second Stage Results.

The increasing survival of hemodialysis patients results in the depletion of superficial venous capital justifying the use of the basilic vein. Many groups still prefer an arteriovenous graft due to transposition complexity and the time needed to achieve maturation. In this work we review the results of our series of basilic vein transpositions (BVT). BVTs were performed in two stages: first, creation of the fistula; second, transposition of the vein using three small incisions in the arm. All patients had to have direct arterialization of the basilic vein, therefore, patients with previous ipsilateral wrist fistulas also followed a two-stage protocol. Data were retrospectively revised from all transposition procedures made between September 2005 and November 2012. Patency and complication rates were the primary outcomes evaluated. A total of 276 basilic veins were transposed. Usage rate was 82.2%. 8% (N = 22) of the fistulas were never used due to thrombosis. Secondary patency rates at 1 and 2 years were, respectively, 84% and 66.3%. Complications occurred in 61.6% (N = 170) of fistulas and 65.9% (N = 112) of which had to undergo surgical or endovascular revision. The most frequent complication was vein stenosis (39.7% of late complications, N = 92). Albeit its greater technical complexity, the transposed basilic vein represents a hemodialysis access with good patency rates. Complication rates, although high, are less than those of CVC or prosthetic grafts. These results support the use of the transposed basilic vein as hemodialysis access after the brachiocephalic fistula.

Iatrogenic arteriovenous fistula following endovenous laser therapy of the short saphenous vein.

Short saphenous vein incompetence is present in up to 20% of patients with varicose veins. Studies looking at the success and complication rates associated with endovenous laser ablation of the short saphenous vein included only a small number of patients. The authors report the case of a 51-year-old woman presenting with a painful right leg edema. She had a history of previous endovenous laser ablation of the right and left great saphenous veins and right short saphenous vein. Duplex scan was performed and showed an arteriovenous fistula between branches of the popliteal artery and vein. Surgical ligation of the fistula was performed. At 8-month follow-up, the patient remains asymptomatic.