Blood group is a long-term cardiovascular risk factor after carotid endarterectomy.

BACKGROUND: ABO blood group system has been clinically related to an increased incidence of cardiovascular diseases. Preliminary data relating Rhesus (Rh) factor and these outcomes also have been published. Our aim was to analyse the impact of blood group on the short and long-term outcomes after carotid endarterectomy (CEA). MATERIALS AND METHODS: From 2012 to 2019, patients from a referral centre who underwent CEA for atherosclerotic carotid stenosis were prospectively followed. Our primary outcomes were long-term major adverse cardiovascular events (MACEs) and all-cause mortality. Secondary outcomes were perioperative complications and myocardial injury after non-cardiac surgery (MINS). Median follow-up was 50 months (interquartile range 21-69). Time-to-event analysis was used to determine the effect of ABO and Rh groups in long-term outcomes. RESULTS: One hundred and eighty-four patients were included, with a mean age of 70.1 ± 9.1 years. Eighteen (25.7%) patients with O type and 48 (42.1%) patients with non-O type presented coronary artery disease (odds ratio [OR]: 2.313, 5-95% confidence interval (CI) 1.245-4.297, p = .008). Patients Rh+ presented significantly more congestive heart failure, 23 (14.7%), p = .03. The incidence of MACE in the long-term was higher in non-O patients (adjusted hazard ratio: 2.034; CI: 1.032-4.010, p = .040). Rh- patients, presented a higher incidence of perioperative MINS. However, there was no statistically significant association with long-term risk of MACE. CONCLUSION: The incidence of MACE in long-term analysis was higher in non-O blood type and 30-day MINS was significantly more common amongst Rh- patients. The benefit from a more complete preoperative cardiac study in these patients should be performed.

A Delphi Consensus Study on Undergoing Carotid Endarterectomy: Patient Reported Outcome Measures.

OBJECTIVE: Currently, evidence is lacking for disease specific patient reported outcome measures (PROMs) for use in atherosclerotic carotid artery stenosis (either symptomatic or asymptomatic) submitted to carotid endarterectomy (CEA). This study aimed to obtain expert consensus on the most important items to include in a PROM designed to capture the impact of atherosclerotic carotid artery stenosis and its treatment on health related quality of life. METHODS: A three round modified Delphi consensus study was performed. A mixed expert Delphi panel of doctors (international panel of dedicated vascular surgeons and neurologists) and patients (either symptomatic or asymptomatic patients meeting criteria for carotid artery revascularisation) was implemented. The aim was to obtain pre-defined consensus on items in four pre-defined domains: generic, quality of life, symptom related, and treatment related. Consensus was reached in rounds two and three with > 70% overall expert agreement. RESULTS: The experts agreed on 23 items (out of 49) which were distributed as follows: five in the generic, six in the quality of life, six in the symptom, and six in the treatment related domain. Interestingly, comparing the items that reached consensus in this study, with the generic and disease specific PROMs previously used in carotid artery disease investigation, the only constant items were "difficulty with walking" and "ability to perform daily activities" included in the symptom domain. Considering the items that reached expert consensus in the additional domains, emphasis was given to the impact of the diagnosis, treatment and follow up, and to fear or concern "about the future" and "about severe stroke". In the treatment domain emphasis was also attained on the side effects, long term patient satisfaction, and on the information provided regarding treatment options. DISCUSSION: As hard clinical outcomes become increasingly rare, assessment of the impact of CEA becomes increasingly difficult. The consensus reached provides a newly defined disease specific PROM that warrants independent validation in specific populations in the future.

VCAM1, HMOX1 and NOS3 differential endothelial expression may impact sickle cell anemia vasculopathy.

Endothelial dysfunction plays a major role in sickle cell anemia (SCA) systemic vasculopathy, with upregulation of adhesion molecules (e.g., VCAM-1), decreased nitric oxide bioavailability, and oxidative stress. We aimed to assess the modulation role of pro-inflammatory and pro-oxidative stimuli on endothelial VCAM1, NOS3, and HMOX1 expression. We also evaluated the effect of the main SCA therapeutic agent, hydroxyurea, on that modulation. Our results showed that two VCAM1 promoter haplotypes, we previously associated with pediatric cerebral vasculopathy and severe hemolysis in SCA, increased promoter activity in TNF-α-stimulated transfected EA.hy926 and HBEC cell lines, consistent with a higher VCAM1 expression in macro and microvascular settings. In non-transfected cells, we also observed TNF-α-induced VCAM1 overexpression as well as heme-induced overexpression of HMOX1 in both cell models. Heme did not affect VCAM1 nor NOS3 expression and the latter was also not affected by TNF-α stimulus. Hydroxyurea treatment lowered TNF-induced VCAM1 and NOS3 expression but did not affect heme-induced HMOX1 expression. These data further indicate that VCAM1 haplotypes we studied lead to higher VCAM1 expression affecting not only cerebral but also systemic vasculopathy risk. The differential endothelial expression of VCAM1, NOS3, and HMOX1 also confirms their genetic modulation role in SCA systemic vasculopathy.

Critical analysis of the literature and standards of reporting on stroke after carotid revascularization.

OBJECTIVE: Mechanisms of procedural stroke after carotid endarterectomy (CEA) or carotid artery stenting are surprisingly underresearched. However, understanding the underlying mechanism could (1) assist in balancing the choice for revascularization vs conservative therapy, (2) assist in choosing either open or endovascular techniques, and (3) assist in taking appropriate periprocedural measures to further decrease procedural stroke rate. The purpose of this study was to overview mechanisms of procedural stroke after carotid revascularization and establish reporting standards to facilitate more granular investigation and individual patient data meta-analysis in the future. METHODS: A systematic review was conducted according to the PRISMA statement. RESULTS: The limited evidence in the literature was heterogeneous and of low quality. Thus, no formal data meta-analysis could be performed. Procedural stroke was classified as hemorrhagic or ischemic; the latter was subclassified as hemodynamic, embolic (carotid embolic or cardioembolic) or carotid occlusion derived, using a combination of clinical inference and imaging data. Most events occurred in the first 24 hours after the procedure and were related to hypoperfusion (pooled incidence 10.2% [95% confidence interval (CI), 3.0-17.5] vs 13.9% [95% CI, 0.0-60.9] after CEA vs carotid artery stenting events, respectively) or atheroembolism (28.9% [95% CI, 10.9-47.0]) vs 34.3 [95% CI, 0.0-91.5]). After the first 24 hours, hemorrhagic stroke (11.6 [95% CI, 5.7-17.4] vs 9.0 [95% CI, 1.3-16.7]) or thrombotic occlusion (18.4 [95% CI, 0.9-35.8] vs 14.8 [95% CI, 0.0-30.5]) became more likely. CONCLUSIONS: Although procedural stroke incidence and etiology may have changed over the last decades owing to technical improvements and improvements in perioperative monitoring and quality control, the lack of literature data limits further statements. To simplify and enhance future reporting, procedural stroke analysis and classification should be documented preemptively in research settings. We propose a standardized form enclosing reporting standards for procedural stroke with a systematic approach to inference of the most likely etiology, for prospective use in registries and randomized controlled trials on carotid revascularization.

Association of Weight Change, Inflammation Markers and Disease Staging with Survival of Patients Undergoing Chemotherapy for Pancreatic Adenocarcinoma.

INTRODUCTION: Cancer-associated-cachexia represents a systemic syndrome of unintended weight-loss (WL) and systemic inflammation, affecting >80% patients with pancreatic adenocarcinoma (PA). We aimed to evaluate the association of weight change (WC) with survival of patients treated with chemotherapy (ChT) for PA and the influence of disease staging. We also studied the prognostic and predictive value of inflammation-based scores. METHODS: Observational, retrospective cohort study. Individuals were divided into two cohorts, according to WC (WL ≥5% vs. non-WL <5%) after ChT. Main endpoints were weight change and survival time. Statistical analysis was performed using Stata software. RESULTS: Sixty-five patients were included (median age 69; 48% female), 60% with advanced disease. At 3 months after ChT start, 54% experienced WL. Advanced disease independently predicted WL (OR 2.10; 95% CI, 1.11-19.6; p = 0.041). With median follow-up of 14.8 mo, median survival time of patients with WL was 18.5 mo, vs. 33.2 vs. for non-WL (HR 2.28; 95% CI, 1.15-4.52; p = 0.019). In patients with early-stage disease, WL was associated with decreased survival time (21.9 vs. 67.6 mo; HR 23.68; 95% CI 2.39-234.75; p = 0.007), while the association of WL on survival time in advanced disease was not significant (HR 0.74; 95% CI, 0.34-1.60; p = 0.449). The multivariate survival model showed that WL (HR 1.11, 95% CI 1.03-1.20, p = 0.005) and cachexia (HR 3.76, 95% CI 1.07-13-18), p = 0.041) were associated with survival time, as well as location in body or tail (HR 3.05; 95% CI, 1.75-5.31; p < 0.001) and high Neutrophil-to-lymphocyte ratio (NLR) at 3 months (HR 6.20; 95% CI, 2.59-14.87; p < 0.001). CONCLUSION: WL was an independent prognostic factor for survival. Particularly in early stage disease, interventions targeting this modifiable factor may translate into better outcomes for PA patients. NLR may be a surrogate marker of systemic inflammatory status in this setting.

Endovascular Treatment of Renal Artery Thrombosis in Living-Donor Kidney Transplant Recipient With Severe COVID-19 Disease.

PURPOSE: Coronavirus disease 2019 (COVID-19) patients have a higher prevalence of micro-and macrovascular thrombotic events. However, the underlying mechanism for the increased thrombotic risk is not completely understood. Solid organ transplant recipients infected with SARS-CoV-2 may have an exponential increase in thrombotic risk and the best management strategy is unknown. CASE REPORT: A female kidney transplant recipient presented with allograft's renal artery thrombosis after a recent COVID-19 infection. Due to the risk of kidney failure or exclusion, catheter directed thrombolysis was performed. Residual thrombus was excluded using an endoprosthesis with an excellent result. There were no adverse events and kidney function improved. CONCLUSION: This paper reports the endovascular treatment of renal artery thrombosis in a living-donor kidney transplant recipient with severe COVID-19 disease.

Editor's Choice - Timing of Carotid Intervention in Symptomatic Carotid Artery Stenosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: This review aimed to analyse the timing of carotid endarterectomy (CEA) and carotid artery stenting (CAS) after the index event as well as 30 day outcomes at varying time periods within 14 days of symptom onset. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-analysis statement, comprising an online search of the Medline and Cochrane databases. Methodical quality assessment of the included studies was performed. Endpoints included procedural stroke and/or death stratified by delay from the index event and surgical technique (CEA/CAS). RESULTS: Seventy-one studies with 232 952 symptomatic patients were included. Overall, 34 retrospective analyses of prospective databases, nine prospective, three RCT, three case control, and 22 retrospective studies were included. Compared with CEA, CAS was associated with higher 30 day stroke (OR 0.70; 95% CI 0.58 - 0.85) and mortality rates (OR 0.41; 95% CI 0.31 - 0.53) when performed ≤ 2 days of symptom onset. Patients undergoing CEA/CAS were analysed in different time frames (≤ 2 vs. 3 - 14 and ≤ 7 vs. 8 - 14 days). Expedited CEA (vs. 3 - 14 days) presented a sampled 30 day stroke rate of 1.4%; 95% CI 0.9 - 1.8 vs. 1.8%; 95% CI 1.8 - 2.0, with no statistically significant difference. Expedited CAS (vs. 3 - 14 days) was associated with no difference in stroke rate but statistically significantly higher mortality rate (OR 2.76; 95% CI 1.39 - 5.50). CONCLUSION: At present, CEA is safer than transfemoral CAS within 2/7 days of symptom onset. Also, considering absolute rates, expedited CEA complies with the accepted thresholds in international guidelines. The ideal timing for performing CAS (when indicated against CEA) is not yet defined. Additional granular data and standard reporting of timing of intervention will facilitate future monitoring.

Pre-operative Neutrophil to Lymphocyte Ratio is Associated With 30 Day Death or Amputation After Revascularisation for Acute Limb Ischaemia.

OBJECTIVE: Inflammation is an early feature of acute limb ischaemia (ALI), hence the potential prognostic significance of inflammatory biomarkers. This study aimed to assess the value of pre-operative inflammatory biomarkers, specifically the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), for predicting an adverse outcome after revascularisation for ALI. METHODS: All patients submitted to lower limb revascularisation for Rutherford IIa or IIb ALI at the authors' institution between 2009 and 2019 were screened retrospectively. Pre-operative NLR and PLR were analysed, along with other known prognostic factors. Primary outcome was the composite endpoint of 30 day death or amputation. RESULTS: A total of 345 patients were included, 84 of whom suffered the primary outcome (24.3%). The median follow up was 23.1 months (3.1 - 52.2). Higher age (OR 1.05 per year increase, 95% CI 1.01 - 1.09), diabetes (OR 2.63, 95% CI 1.14 - 6.06), Rutherford grade IIb vs. IIa (OR 5.51, 95% CI 2.11 - 14.42), higher NLR (OR 1.28 per unit increase, 95% CI 1.12 - 1.47), and fasciotomy need (OR 3.44, 95% CI 1.14 - 10.34) were independently associated with 30 day death or amputation, whereas pre-operative statin or anticoagulant medication were associated with a risk reduction (OR 0.23, 95% CI 0.53 - 0.96 and OR 0.20, 95% CI 0.05 - 0.84, respectively). PLR did not show an independent effect on this population. Pre-operative NLR presented a good discriminative ability (AUC 0.86, 95% CI 0.82 - 0.90). A cut off NLR level ≥ 5.4 demonstrated a 90.5% sensitivity and 73.6% specificity for 30 day death or amputation. Kaplan-Meier analysis showed that patients with pre-operative NLR ≥ 5.4 had significantly lower 30 day, six month and one year amputation free survival when compared with those with NLR < 5.4 (64.8 ± 4.0%, 44.1 ± 4.1%, and 37.5 ± 4.1% vs. 98.5 ± 0.9%, 91.9 ± 2.0%, and 85.9 ± 2.5%, log rank p < .001). CONCLUSION: In this study, higher pre-operative NLR was associated with 30 day death or amputation following intervention for Rutherford grade IIa or IIb ALI. NLR potentially stands as a simple, widely available and inexpensive biomarker that can refine decision making and possibly contribute to ALI morbidity and mortality reduction.

Critical Appraisal on the Quality of Reporting on Safety and Efficacy of Transcarotid Artery Stenting With Flow Reversal.

Transcarotid revascularization is an alternative to transfemoral carotid artery stenting, designed to avoid aortic arch manipulation and concomitant periprocedural stroke. This article aims to perform a detailed analysis on the quality of the currently available evidence on safety and efficacy of transcarotid artery revascularization. Although current evidence is promising, independent randomized controlled studies comparing transcarotid artery revascularization with carotid endarterectomy in recently symptomatic patients are lacking and will be necessary to establish the true value of transcarotid artery revascularization in carotid artery revascularization.

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia.

We investigated biomarkers and genetic modulators of the cerebral vasculopathy (CV) subphenotype in pediatric sickle cell anemia (SCA) patients of sub-Saharan African ancestry. We found that one VCAM1 promoter haplotype (haplotype 7) and VCAM1 single nucleotide variant rs1409419_T were associated with stroke events, stroke risk, as measured by time-averaged mean of maximum velocity in the middle cerebral artery, and with high serum levels of the hemolysis biomarker lactate dehydrogenase. Furthermore, VCAM-1 ligand coding gene ITGA4 variants rs113276800_A and rs3770138_T showed a positive association with stroke events. An additional positive relationship between a genetic variant and stroke risk was observed for ENPP1 rs1044498_A. Conversely, NOS3 variants were negatively associated with silent cerebral infarct events (VNTR 4b_allele and haplotype V) and CV globally (haplotype VII). The -alpha3.7kb-thal deletion did not show association with CV. However, it was associated with higher red blood cell and neutrophil counts, and lower mean corpuscular volume, mean corpuscular hemoglobin and red cell distribution width. Our results underline the importance of genetic modulators of the CV sub-phenotype and their potential as SCA therapeutic targets. We also propose that a biomarker panel comprising biochemical, hematological, imaging and genetic data would be instrumental for CV prediction, and prevention.

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.

Genetic modulators of fetal hemoglobin expression and ischemic stroke occurrence in African descendant children with sickle cell anemia.

Sickle cell anemia (SCA) is an autosomal recessive monogenic disease with significant clinical variability. Cerebrovascular disease, particularly ischemic stroke, is one of the most severe complications of SCA in children. This study aimed to investigate the influence of genetic variants on the levels of fetal hemoglobin (Hb F) and biochemical parameters related with chronic hemolysis, as well as on ischemic stroke risk, in ninety-one unrelated SCA patients, children of sub-Saharan progenitors. Our results show that a higher Hb F level has an inverse relationship with the occurrence of stroke, since the group of patients who suffered stroke presents a significantly lower mean Hb F level (5.34 ± 4.57% versus 9.36 ± 6.48%; p = 0.024). Furthermore, the co-inheritance of alpha-thalassemia improves the chronic hemolytic pattern, evidenced by a decreased reticulocyte count (8.61 ± 3.58% versus 12.85 ± 4.71%; p < 0.001). In addition, our findings have confirmed the importance of HBG2 and BCL11A loci in the regulation of Hb F expression in sub-Saharan African SCA patients, as rs7482144_A, rs11886868_C, and rs4671393_A alleles are significantly associated with a considerable increase in Hb F levels (p = 0.019, p = 0.026, and p = 0.028, respectively). Concerning KLF1, twelve different variants were identified, two of them novel. Seventy-three patients (80.2%) presented at least one variant in this gene. However, no correlation was observed between the presence of these variants and Hb F level, severity of hemolysis, or stroke occurrence, which is consistent with their in silico-predicted minor functional consequences. Thus, we conclude that the prevalence of functional KLF1 variants in a sub-Saharan African background does not seem to be relevant to SCA clinical modulation.

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.

Arterial Vascular Complications in Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) has evolved as a life-saving measure for patients requiring emergent support of respiratory and cardiac function. The femoral artery is the standard site for vascular access when initiating adult venoarterial (VA) ECMO. Cannulation-related complications are a known source of morbidity and it has been speculated that patients undergoing ECMO via femoral arterial cannulation are more likely to develop peripheral vascular complications (up to 70%). METHODS: Retrospective institutional review of patients requiring ECMO (January 2011-August 2017). The primary outcome of this study was to investigate the prevalence of cannulation-related complications on VA ECMO and to determine its effect on patient morbimortality. RESULTS: Eighty-two patients underwent ECMO during the period of study, 56,1% were male with a mean age of 55,8 years. The VA mode was used in 61 patients, 56 with peripheral cannulation. Femoral arterial access was established in 52 patients (73% percutaneously). Vascular complications were observed in 28,6% of the VA femoral ECMOs: 12 acute limb ischemias and 3 major hemorrhages. At the time of femoral cannulation, distal peripheral catheter (DPC) was placed in 5 patients and none developed limb ischemia. For those who developed limb ischemia, several interventions were performed: DPC placement in 9 cases, fasciotomy in 4 and 2 major amputations. Thirty patients underwent arterial cannulas open surgical removal: 8 underwent balloon catheter trombectomy and 5 needed femoral reconstruction. There was an association between PAD (p=0,03) and ischemic cardiopathy (p=0,02;OR 4,5) with the present of vascular complications after ECMO implantation. CONCLUSIONS: Cannulation of femoral vessels remains associated with considerable rates of vascular events (28.6%). PAD and ischemic cardiopathy are associated with vascular complications in this form of cannulation.

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.

Cry1A(b)16 toxin from Bacillus thuringiensis: Theoretical refinement of three-dimensional structure and prediction of peptides as molecular markers for detection of genetically modified organisms.

Transgenic maize produced by the insertion of the Cry transgene into its genome became the second most cultivated crop worldwide. Cry gene from Bacillus thuringiensis kurstaki expresses protein derivatives of crystalline endotoxins which confer insect resistance onto the maize crop. Mandatory labeling of processed food containing or made by genetically modified organisms is in force in many countries, so, it is very urgent to develop fast and practical methods for GMO identification, for example, biosensors. In the absence of an available empirical structure of Cry1A(b)16 protein, a theoretical model was effectively generated, in this work, by homology modeling and molecular dynamics simulations based on two available homologous protein structures. Molecular dynamics simulations were carried out to refine the selected model, and an analysis of its global structure was performed. The refined models of Cry1A(b)16 showed a standard fold and structural characteristics similar to those seen in Bacillus thuringiensis Cry1A(a) insecticidal toxin and Bacillus thuringiensis serovar kurstaki Cry1A(c) toxin. After in silico analysis of Cry1A(b)16, two immunoreactive candidate peptides were selected and specific polyclonal antibodies were produced resulting in antibody-peptide interaction. Biosensing devices are expected to be developed for detection of the Cry1A(b) protein as a marker of transgenic maize in food. Proteins 2017; 85:1248-1257. © 2017 Wiley Periodicals, Inc.

Widening the spectrum of deletions and molecular mechanisms underlying alpha-thalassemia.

Inherited deletions of α-globin genes and/or their upstream regulatory elements (MCSs) give rise to α-thalassemia, an autosomal recessive microcytic hypochromic anemia. In this study, multiplex ligation-dependent probe amplification performed with commercial and synthetic engineered probes, Gap-PCR, and DNA sequencing were used to characterize lesions in the sub-telomeric region of the short arm of chromosome 16, possibly explaining the α-thalassemia/HbH disease phenotype in ten patients. We have found six different deletions, in heterozygosity, ranging from approximately 3.3 to 323 kb, two of them not previously described. The deletions fall into two categories: one includes deletions which totally remove the α-globin gene cluster, whereas the other includes deletions removing only the distal regulatory elements and keeping the α-globin genes structurally intact. An indel was observed in one patient involving the loss of the MCS-R2 and the insertion of 39 bp originated from a complex rearrangement spanning the deletion breakpoints. Finally, in another case, no α-globin gene cluster deletion was found and the patient revealed to be a very unusual case of acquired α-thalassemia-myelodysplastic syndrome. This study further illustrates the diversity of genomic lesions and underlying molecular mechanisms leading to α-thalassemia.

Evaluation of in vitro cytotoxicity, biocompatibility, and changes in the expression of apoptosis regulatory proteins induced by cerium oxide nanocrystals.

Cerium oxide nanocrystals (CeO2-NCs) exhibit superoxide dismutase and catalase mimetic activities. Based on these catalytic activities, CeO2-NCs have been suggested to have the potential to treat various diseases. The crystalline size of these materials is an important factor that influences the performance of CeO2-NCs. Previous reports have shown that several metal-based nanocrystals, including CeO2-NCs, can induce cytotoxicity in cancer cells. However, the underlying mechanisms have remained unclear. To characterize the anticancer activities of CeO2-NCs, several assays related to the mechanism of cytotoxicity and induction of apoptosis has been performed. Here, we have carried out a systematic study to characterize CeO2-NCs phase purity (X-ray diffraction), morphology (electron microscopy), and optical features (optical absorption, Raman scattering, and photoluminescence) to better establish their potential as anticancer drugs. Our study revealed anticancer effects of CeO2-NCs in HT29 and SW620 colorectal cancer cell lines with half-maximal inhibitory concentration (IC50) values of 2.26 and 121.18 µg ml-1, respectively. Reductions in cell viability indicated the cytotoxic potential of CeO2-NCs in HT29 cells based on inverted and florescence microscopy assessments. The mechanism of cytotoxicity confirmed by estimating possible changes in the expression levels of Bcl2, BclxL, Bax, PARP, cytochrome c, and ß-actin (control) proteins in HT29 cells. Down-regulation of Bcl2 and BclxL and up-regulation of Bax, PARP, and cytochrome c proteins suggested the significant involvement of CeO2-NCs exposure in the induction of apoptosis. Furthermore, biocompatibility assay showed minimum effect of CeO2-NCs on human red blood cells.