Calprotectin as a new inflammatory marker of abdominal aortic aneurysm: A pilot study.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a relevant clinical problem due to the risk of rupture of progressively dilated infrarenal aorta. It is characterized by degradation of elastic fibers, extracellular matrix, and inflammation of the arterial wall. Though neutrophil infiltration is a known feature of AAA, markers of neutrophil activation are scarcely analyzed; hence, the main objective of this study. METHODS: Plasma levels of main neutrophil activation markers were quantified in patients with AAA and a double control group (CTL) formed by healthy volunteers (HV) and patients with severe atherosclerosis submitted for carotid endarterectomy (CE). Calprotectin, a cytoplasmic neutrophil protein, was quantified, by Western blot, in arterial tissue samples from patients with AAA and organ donors. Colocalization of calprotectin and neutrophil elastase was assessed by immunofluorescence. RESULTS: Plasma calprotectin and IL-6 were both elevated in patients with AAA compared with CTL (p ⩽ 0.0001) and a strong correlation was found between both molecules (p < 0.001). This difference was maintained when comparing with HV and CE for calprotectin but only with HV for IL-6. Calprotectin was also elevated in arterial tissue samples from patients with AAA compared with organ donors (p < 0.0001), and colocalized with neutrophils in the arterial wall. CONCLUSIONS: Circulating calprotectin could be a specific AAA marker and a potential therapeutical target. Calprotectin is related to inflammation and neutrophil activation in arterial wall and independent of other atherosclerotic events.

"In Vitro" Evaluation of Energy-Based Sealing of Graft Side Branches in Bypass Surgery.

INTRODUCTION: Our objective was to compare the in vitro efficacy of electrothermal bipolar [EB] vessel sealing and ultrasonic harmonic scalpel [HS] versus mechanical interruption, with conventional ties or surgical clips (SC), in sealing saphenous vein (SV) collaterals, during its eventual preparation for bypass surgery. METHODS: Experimental in vitro study on 30 segments of SV. Each fragment included two collaterals at least 2 mm in diameter. One of them was sealed by ligation with 3/0 silk ties (control) and the other one with EB (n = 10), HS (n = 10) or medium-6 mm SC (n = 10). After incorporation in a closed circuit with pulsatile flow, the pressure was progressively increased until causing rupture. Collateral diameter, burst pressure, leak point, and histological study were recorded. RESULTS: Burst pressure was higher for SC (1320.20 ± 373.847 mmHg) as compared with EB (942.2 ± 344.9 mmHg, p = 0.065), and especially with HS (637.00 ± 320.61 mmHg, p = 0.0001). No statistically significant difference between EB and HS was found, and bursting always happened at supraphysiological pressures. The leak point for HS was always detected in the sealing zone (10/10), while for EB and SC, it occurred in the sealing zone only in 6/10(60%) and 4/10(40%), respectively (p = 0.015). CONCLUSIONS: Energy delivery devices showed similar efficacy and safety in sealing of SV side branches. Although bursting pressure was lower than with tie ligature or SC, non-inferiority efficacy was shown at the range of physiological pressures in both, EB and HS. Due to their speed and easy handling, they may be useful in the preparation of the venous graft during revascularization surgery. However, remaining questions about healing process, potential spread of tissue damage and sealing durability, will require further analysis.

Update on the Use of Infrared Thermography in the Early Detection of Diabetic Foot Complications: A Bibliographic Review.

Foot lesions are among the most frequent causes of morbidity and disability in the diabetic population. Thus, the exploration of preventive control measures is vital for detecting early signs and symptoms of this disease. Infrared thermography is one of the complementary diagnostic tools available that has proven to be effective in the control of diabetic foot. The last review on this topic was published in 2015 and so, we conducted a bibliographic review of the main databases (PubMed, the Web of Science, Cochrane library, and Scopus) during the third quarter of 2023. We aimed to identify the effectiveness of infrared thermography as a diagnostic element in pre-ulcerous states in diabetic patients and to detect diabetic foot ulcer complications. We obtained a total of 1199 articles, 26 of which were finally included in the present review and published after 2013. After analyzing the use of infrared thermography in diabetic patients both with and without ulcers, as well as in healthy individuals, we concluded that is an effective tool for detecting early-stage ulcers in diabetic foot patients.

Cell Therapy of Vascular and Neuropathic Complications of Diabetes: Can We Avoid Limb Amputation?

Globally, a leg is amputated approximately every 30 seconds, with an estimated 85 percent of these amputations being attributed to complications arising from diabetic foot ulcers (DFU), as stated by the American Diabetes Association. Peripheral arterial disease (PAD) is a risk factor resulting in DFU and can, either independently or in conjunction with diabetes, lead to recurring, slow-healing ulcers and amputations. According to guidelines amputation is the recommended treatment for patients with no-option critical ischemia of the limb (CTLI). In this article we propose cell therapy as an alternative strategy for those patients. We also suggest the optimal time-frame for an effective therapy, such as implanting autologous mononuclear cells (MNCs), autologous and allogeneic mesenchymal stromal cells (MSC) as these treatments induce neuropathy relief, regeneration of the blood vessels and tissues, with accelerated ulcer healing, with no serious side effects, proving that advanced therapy medicinal product (ATMPs) application is safe and effective and, hence, can significantly prevent limb amputation.

Thrombospondins in human aortic aneurysms.

Thrombospondins are a family of matricellular proteins with a multimeric structure that is known to be involved in several biological and pathological processes. Their relationship with vascular disorders has raised special interest recently. Aortic aneurysms are related to the impairment of vascular remodeling, in which extracellular matrix proteins seem to play an important role. Thus, research in thrombospondins, and their potential role in aneurysm development is progressively gaining importance. Nevertheless, studies showing thrombospondin dysregulation in human samples are still scarce. Although studies performed in vitro and in vivo models are essential to understand the molecular mechanisms and pathways underlying the disorder, descriptive studies in human samples are also necessary to ascertain their real value as biomarkers and/or novel therapeutic targets. The present article reviews the latest findings regarding the role of thrombospondins in aortic aneurysm development, paying particular attention to the studies performed in human samples.

Comparison of Three Workstations For Abdominal Aortic Aneurysm Sizing: Impact in Decision Making and Graft Selection.

PURPOSE: The aim of this study was to assess the agreement of multiplanar reconstruction (MPR) and semiautomated central lumen line (CLL) analysis of abdominal aortic aneurysms (AAA), with 3 different software workstations (WS1, WS2, WS3) and 2 experienced practitioners as well as to analyze its eventual impact in graft selection. MATERIALS AND METHODS: Twenty computed tomography (CT) angiography data sets were randomly chosen from a series of 100 consecutive studies. Measurements were performed twice by each reader, in random order, and included 8 parameters (5 diameters and 3 lengths). Each observer performed a complete set of 60 studies. Intra-observer and interobserver variability for every WS was assessed. Measurements were evaluated using Bland-Altman analysis, correlation coefficients (r), and concordance correlation coefficients (CCC [95% confidence interval (CI)]). RESULTS: A high overall agreement between repeated measurements for both observers was obtained (r=0.989; CCC=0.988 [0.982-0.992] and r=0.998; CCC=0.996 [0.994-0.997], for observers 1 and 2, respectively). However, reproducibility for individual parameters was excellent for observer 2 and only moderate for observer 1. A high overall agreement was obtained for interobserver concordance (r=0.987; CCC=0.986 [0.982-0.989]). When analyzing for individual parameters, greatest interobserver differences were found at CLL measurement of the diameter of aortic neck (WS2) and bifurcation (WS1 and WS2) as well as iliac diameter in all 3 WS for both CLL and MPR. Similar differences were observed in paired comparison between WS when involving these parameters. Careful inspection of Bland-Altman charts revealed some cases of disagreement between WS and observers that would affect decision making on graft selection, changing the neck diameter to a different size, in 2 cases when measuring with WS1, and iliac diameter in 4 cases (2 of them with WS1 and 2 with WS2). Greatest discordance was observed regarding ipsilateral iliac length affecting 7 measurements that would lead to change the length of the selected limb graft (2 with WS1, 3 with WS2, and 2 with WS3). CONCLUSIONS: Although a high agreement between different observers using different WS for AAA measurements is to be expected, small differences may lead to the selection of a different graft size. The use of a single software by experienced users, and double check by a different one, may be advisable. CLINICAL IMPACT: Influence of inter and intraobserver variability in CT measurements during planning of endovascular aneurysm repair (EVAR) has been extensively reviewed. However, its impact in graft selection (final choose of diameter and lengths) has been scarcely analyzed. The results of this study suggest that, although a high agreement between different observers using different workstations for AAA measurements is to be expected, small differences may lead to the selection of a different graft size. The use of a single software by experienced users, and double check by a different one, may be advisable.

Extended methane mitigation capacity of a mid-season drainage beyond the rice growing season: a case in Spain.

Rice cultivation is a major source of methane (CH4) emissions. Intermittent irrigation systems in rice cultivation, such as the mid-season drainage (MSD), are effective strategies to mitigate CH4 emissions during the growing season, though the reduction rates are variable and dependent on the crop context. Aeration periods induce alteration of soil CH4 dynamics that can be prolonged after flooding recovery. However, whether these changes persist beyond the growing season remains underexplored. A field experiment was conducted in Spain to study the effect of MSD implemented during the rice growing season on greenhouse gas (GHG) emissions in relation to the standard permanently flooded water management (PFL). Specifically, the study aimed at (1) assessing the CH4 mitigation capacity of MSD in the studied area and (2) testing the hypothesis that the mitigating effect of MSD can be extended into the following winter flooded fallow season. Year-round GHG sampling was conducted, seasonal and annual cumulative emissions of CH4 and N2O as well as the global warming potential were calculated, and grain yield was measured. MSD reduced growing season CH4 emissions by ca. 80% without yield penalties. During the flooded fallow season, MSD reduced CH4 emissions by ca. 60%, despite both fields being permanently flooded. The novelty of our observations lies in the amplified mitigation capacity of MSD by extending the CH4 mitigation effect to the following flooded winter fallow season. This finding becomes especially relevant in rice systems with flooded winter fallow season given the large contribution of this season to the annual CH4 emissions.

Genotype FBN1/phenotype relationship in a cohort of patients with Marfan syndrome.

Marfan syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene, and cardiovascular involvement is the leading cause of mortality. We sought to examine the genotype/phenotype realtionship in 61 consecutive patients with a phenotype and genotype compatible with MFS. The FBN1 gene was analyzed by massive sequencing using a hybridization capture-based target enrichment custom panel. Forty-three different variants of FBN1 were identified, of which 17 have not been previously reported. The causal variants of MFS were grouped into mutations resulting in haploinsufficiency (HI group; 23 patients) and mutations producing a dominant-negative effect (DN group; 38 patients). Patient information was collected from electronic medical records and clinical evaluation. While no significant differences were found between the two groups, the HI group included more cases with aortic dissection and occurring at a younger age that the DN group (34.7% vs. 15.8%; p = 0.160). Irrespective of the mutation group, males presented with a higher probability of aortic involvement (4-fold higher risk than females) and aortic dissections events occurred at younger ages. Patients with DN variants carrying a cysteine substitution had a higher incidence of ectopia lentis.

Trans-popliteal hybrid retrograde technique for revascularization of chronic total occlusions of the superficial femoral artery.

OBJECTIVES: We present the technical description and preliminary results of a hybrid approach for the treatment of chronic total occlusions of superficial femoral artery in the setting of critical limb-threatening ischemia (CLTI). METHODS: A retrospective analysis of selected case series was performed. A trans-popliteal hybrid technique was carried out in seven limbs (six patients). Open exposure of above-the-knee popliteal artery was performed over its maximum calcification zone. After retrograde recanalization and graft-stenting of the entire superficial femoral artery, endarterectomy of the popliteal artery was performed for debulking and widening of the distal landing zone of the endoprosthesis. The latter is included in the bovine patch suture to avoid leaving a segment untreated. RESULTS: Technical success, haemodynamic and clinical improvement were achieved in all procedures. Median length of treated occlusion was 19.8 cm. After a mean follow-up of 12 months (range 6-26 months), the primary patency was 85.7% (only one asymptomatic occlusion occurred). There were no major cardiovascular or limb adverse events. No re-interventions were required. CONCLUSION: This less-invasive, one-incision technique is safe and effective for the restoration of in-line flow from groin to ankle, currently recommended in CLTI revascularization. It could be especially useful in highly calcified popliteal artery lesions, hostile groins or those at high risk of infection and in cases of vein absence for bypass surgery.

Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients.

microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma study (30 AAA patients, 16 healthy volunteers and 11 patients with atherosclerosis). The expression level of 179 miRNAs was screened in plasma from a subset of samples, and dysregulated miRNAs were validated in the entire study population. Dysregulated miRNAs were also quantified in aortic tissue of 21 AAA patients and 8 organ donors. Applying a gene set enrichment analysis, an interaction map of dysregulated miRNAs and their targets was built, and selected targets were quantified in tissue samples. miR-27b-3p and miR-221-3p were overexpressed in plasma of AAA patients compared with healthy controls, 1.6 times and 1.9 times, respectively. In AAA tissue, six miRNAs (miR-1, miR-27b-3p, miR-29b-3p, miR-133a-3p, miR-133b, and miR-195-5p) were underexpressed from 1.6 to 4.8 times and four miRNAs (miR-146a-5p, miR-21-5p, miR-144-3p, and miR-103a-3p) were overexpressed from 1.3 to 7.2 times. Thrombospondin-2, a target of miR-195-5p, was increased in AAA tissue and negatively correlated with the expression of miR-195-5p, suggesting their involvement in a common regulatory mechanism.

Volumetric assessment of the carotid bifurcation: an alternative concept to stenosis grading.

BACKGROUND: To design a volumetric method for the assessment of carotid atheromatosis (CA) based on computed tomography (CT) angiography and three-dimensional (3D) reconstructions; to analyze the accuracy and optimal threshold values to differentiate between equivalent degrees of severity by duplex scanning and CT angiography (two-dimensional maximum intensity projection [2D MIP]; internal carotid artery stenosis [ICS] <50%; ICS >50%); and to assess the method's suitability to detect progression of CA. DESIGN: suitability and accuracy of a new diagnostic method. POPULATION: 90 carotid bifurcations (45 patients) were assessed with duplex scanning and CT angiography, and reevaluated after 12 ± 2 months follow-up. Determinations: Assessment of internal carotid artery (ICA) stenosis degree with duplex scanning and 2D MIP CT angiography projections. Volumetric assessment of carotid bifurcation by CT angiography (contrast volume [mm(3)] and density [Hounsfield units, H.U.] between 2-cm below and 1-cm above the anatomic bifurcation of the carotid artery [BifV], and its ratio with 1-cm segment of the common carotid artery [CCV]). STATISTICAL ANALYSIS: descriptive statistics; intraobserver and interobserver agreement (Bland-Altman plot and intraclass correlation coefficient [ICC], accuracy of 3D volumetry and duplex scanning as referred to MIP 2D CT angiography as gold standard: sensitivity (Sens), specificity (Sp), kappa index, and receiver operating characteristic curves (ROCs). RESULTS: Estimation of MIP 2D images (CT angiography) confirmed the findings of duplex scanning in 23 of 30 ICS <50% and 48 of 53 ICS >50% (Sens, 0.91; Sp, 0.77% kappa = 0.68). Three-dimensional volumetric assessment of carotid bifurcation showed an intraobserver and interobserver agreement with an ICC of 0.96 (95% confidence interval [CI], 0.904-0.985) and 0.94 (95% CI, 0.822-0.977), respectively. The BifV-to-CCV ratio was 5.2 ± 1.8 in the ICS <50% group versus 3.8 ± 1.3 in the ICS >50% group (P = 0.001). The optimal cutoff point of the BifV-to-CCV relationship was identified from the ROC curve in 4.1 (Sens, 0.75; Sp, 0.75; kappa, 0.46). At 12 months, a decrease of the average BifV with regard to the baseline value (475.45 [155.6] mm(3) × H.U. vs. 501.3 [171.9] mm(3) × H.U.; P = 0.04) was observed. CA progression was detected in 32 bifurcations (14 ICS <50%; 18 ICS> 50%), with a reduced bifurcation volume of 137.8 (71.4) mm(3) × H.U.; P < 0.001. CONCLUSIONS: Volumetric assessment of carotid bifurcation is a new concept based on assessing plaque burden rather than its hemodynamic effect or maximum stenosis; thus, justifying its moderate accuracy with regard to ICS conventional ICA grading based on biplanar images. This method can be especially useful in plaque progression studies given its accuracy to detect minor changes in the arterial lumen.

Sentinel node biopsy for melanoma. Analysis of our experience (125 patients).

INTRODUCTION: The objective of this study is to analyze our experience in the use of sentinel node biopsy (SNB) in melanoma and identify the predictive factors of positive SNB and multiple drainage. MATERIAL AND METHODS: Retrospective study of patients who underwent SNB for melanoma between August of 2000 and February of 2013. RESULTS: SNB was performed in 125 patients with a median of age of 55,6 (±15) years. The anatomic distribution was: 44 (35,2%) in legs, 24 (19,2%) in arms, 53 (42,4%) trunk and 3 (2,4%) in head and neck. The median Breslow index was 1,81 (0,45-5). Between 1 and 6 nodes were isolated. The drainage was unique in 98 (78,4%) and multiple in 27 (21,6%). The trunk was the localization of 25 (92,6%) nodes with multiple drainage. The definitive result of sentinel node (SN) was positive in 18 cases (7,1%). Breslow thickness (p=0,01) was statistically significant predictor of a positive SNB. CONCLUSIONS: The SNB allows patients to be selected for lymphadenectomy. Melanoma of the trunk was the principle location of multiple drainage. The only predictive factor of positive SNB was Breslow thickness.

Reducing preanalytical laboratory sample errors through educational and technological interventions.

BACKGROUND: A correct preanalytical phase procedure is critical to get an adequate sample and consequently to achieve the most reliable laboratory results, promoting patient safety. Continuous laboratory staff changes create the need to establish improvement strategies to reduce the error risk. The objective was to show how the numbers of preanalytical errors related to unsuitable samples in a hospital setting decrease following two improvement strategies related to new technology and educational actions and how their effects were measured by monitoring indicators. METHODS: Samples were drawn by the laboratory and other hospital departments' nurses without previous patient appointment, therefore, prior tube preparation was not available before the phlebotomy. Corrective measures for these activities were established: educational program for nurses and a system of custom labels, which correlate each laboratory test in the Laboratory Information System (LIS) with the corresponding tube. Three phases were defined based on the implementation dates of the improvement actions to be assessed. The set of indicators designed to monitor the improvement related to clotted, hemolyzed, insufficient, and uncollected samples. Data were collected and indicators calculated from the LIS using a data warehouse application. Patient satisfaction with respect to phlebotomy was also measured annually using a scoring survey. RESULTS: There was a reduction in all types of preanalytical sample errors related to the improvement strategies adopted. The indicators demonstrated that the unavailable, insufficient, and clotted samples decreased between two- and three-fold, whereas hemolysis errors benefited more from these improvement strategies. Patient satisfaction with the laboratory and phlebotomy procedures improved over the past several years as based on the annual satisfaction surveys. CONCLUSIONS: The educational program for nursing personnel is relevant and important as can be seen in the decrease of sample errors and the resulting quality improvement. The custom label system minimizes the potential oversight of forgetting to draw a tube, which happens frequently when operating without appointments, by printing the labels according to requested tests. Detection, identification, and monitoring of the error and implementing strategies to improve preanalytical quality reduces error numbers and thereby improves patient safety and health system outcomes.

Intraplaque calcium and its relation with the progression of carotid atheromatous disease.

BACKGROUND: Calcification and progression of atheromatous disease (AD) both have been independently related with the risk of stroke. However, the link between the two phenomena is still unclear. The main objective of this study was to analyze the temporal evolution of Ca content of carotid atheromatous plaques and its relation with the progression of carotid AD using quantitative CT Angiography (CTA). METHODS: Forty-three asymptomatic patients with stenosis of the internal carotid artery (ICA)>50% completed the study. Contrast mold volume and calcium (Ca) content by quantitative CTA and Modified Agatston Score (Ca volume × radiological density) were assessed at baseline and after 12±2 months. Biochemical parameters, including main markers of Ca/Phosphorus (P) metabolism, were determined. RESULTS: CTA measurement showed an increase of volumetric stenosis (volume decrease of the contrast mold), compared to baseline (475.45 [155.6] mm3 × U.H vs. 501.3 [171.9] mm3 × U.H; P=0.04) as well as an increase of intraplaque Ca (64.58 [57.8] mm3 × U.H. vs. 56.8 [52.3] P=0.002). An inverse correlation between baseline Ca content and volumetric stenosis progression (r=-0.481; P<0.001), as well as between the increase of carotid Ca and plasma levels of vitamin D (r=0.4; P=0.025) were also found. Multiple regression analysis found a model with baseline intraplaque Ca, adjusted by Body Mass Index (BMI) as most predictive of carotid AD progression. CONCLUSIONS: These results suggest that a higher content of Ca confers greater stability against the progression of carotid AD and, eventually, its ability to generate symptomatology.

[Clinical characteristics and in-hospital outcomes of patients with critical leg ischemia: ICEBERG Study]. / Características clínicas y evolución intrahospitalaria de los pacientes con isquemia crítica de miembros inferiores: estudio ICEBERG.

BACKGROUND AND OBJECTIVES: Critical leg ischemia (CLI) is a medical emergency with a high morbidity and mortality. Although its prognosis has improved during the last years, there are no data on its clinical characteristics, treatment and in-hospital prognosis in our country. PATIENTS AND METHOD: 671 patients (81% males, mean age 71.2 years) with atherosclerotic CLI, attended in 46 departments of vascular surgery were included in the study. RESULTS: Participants had a high prevalence of cardiovascular risk factors (72% hypertensive, 27% current smokers, 59% diabetics) and comorbidity (25% coronary heart disease, 18% cerebrovascular disease). 71% had a previous diagnosis of peripheral arterial disease. Upon admission, 71% were referred for revascularization, 5% for direct amputation and 24% for conservative treatment. During hospitalization 22 patients died and 49 were discharged with a major amputation. On multivariate analysis, the only factor associated with the risk of amputation was gangrenous lesions (OR 2.45; IC95% 1.22-4.92). Factors associated with mortality were the presence of chronic renal failure (OR 3.38; IC95% 1.36-8.39) and previous CLI (OR 0.20; IC95% 0.05-0.89). At discharge, 59% received lipid lowering drugs, 70% blood-pressure lowering medications and 85% antiplatelet drugs. CONCLUSION: CLI patients attended in Spanish vascular surgery departments have a low amputation rate and a low hospital mortality. However, and due to their high cardiovascular risk, it is necessary to improve the prescription rate of evidence-based cardiovascular prevention therapies at discharge.

Usefulness of red cell distribution width to predict mortality in patients undergoing endovascular repair of abdominal aortic aneurysms.

BACKGROUND: Red cell distribution width (RDW) reflecting impaired erythropoyesis, has been associated with poor prognosis and mortality in several conditions. The aim of this study was to determine the relationship between RDW and the 5-year survival after the endovascular repair of abdominal aortic aneurysms (EVAR) and its ability to improve the discriminative power of a survival predictive score. METHODS: Retrospective analysis of 284 patients undergoing EVAR at a single centre. The pattern of relationship between RDW and survival was assessed with penalized smoothing splines. Categorized RDW values were added to a predictive score based in standard preoperative variables, whose improvement in discriminative power was calculated on the basis of changes in the C-statistics and the continuous Net Reclassification Index (c-NRI). RESULTS: The survival rate at 5 years was 66.2% and was independently associated with hemoglobin (HR=0.85, P<0.004), statin intake (HR=0.54, P<0.004), heart failure (HR=2.53, P<0.018), atrial fibrillation (HR=2.53, P<0.000) and the non-revascularized coronary artery disease (HR=2.15, P<0.005). The relationship between RDW values and 5-year survival was linear. RDW-CV and RDW-SD were categorized to cut-off values of ≥15% (N.=83, 29.2%) and ≥50 fL (N.=82, 28.9%) that were independently associated with poorer 5-year survival rates (HR=2.03, CI 95%=1.29-3.19, P=0.002 and HR=1.89, CI 95%=1.21-2.95, P=0.005, respectively). The addition of the RDW CV or the RDW-SD to the baseline predictive score significantly improved the c-NRI (0.437, P<0.001 and 0.442, P<0.001, respectively). CONCLUSIONS: High preoperative RDW levels were linear and adversely related to 5-year survival after EVAR, improved the discriminative power of a predictive score based in standard preoperative variables and may help in decision-making at the time of surgical planning.

Applications of liquid biopsy in the Pharmacological Audit Trail for anticancer drug development.

Anticancer drug development is a costly and protracted activity, and failure at late phases of clinical testing is common. We have previously proposed the Pharmacological Audit Trail (PhAT) intended to improve the efficiency of drug development, with a focus on the use of tumour tissue-based biomarkers. Blood-based 'liquid biopsy' approaches, such as targeted or whole-genome sequencing studies of plasma circulating cell-free tumour DNA (ctDNA) and circulating tumour cells (CTCs), are of increasing relevance to this drug development paradigm. Liquid biopsy assays can provide quantitative and qualitative data on prognostic, predictive, pharmacodynamic and clinical response biomarkers, and can also enable the characterization of disease evolution and resistance mechanisms. In this Perspective, we examine the promise of integrating liquid biopsy analyses into the PhAT, focusing on the current evidence, advances, limitations and challenges. We emphasize the continued importance of analytical validation and clinical qualification of circulating tumour biomarkers through prospective clinical trials.

Preimplantation genetic testing for carriers of BRCA1/2 pathogenic variants.

The detection of germline BRCA1/2 pathogenic variant has relevant implications for the patients and their family members. Family planning, prophylactic surgery and the possibility of preimplantation genetic testing for monogenic disorders (PGT-M) to avoid transmittance of pathogenic variants to the offspring are relevant topics in this setting. PGT-M is valuable option for BRCA carriers, but it remains a controversial and underdiscussed topic. Although the advances in PGT technologies have improved pregnancy rate, there are still several important challenges associated with its use. The purpose of this review is to report the current evidence on PGT-M for BRCA1/2 carriers, ethical concerns and controversy associated with its use, reproductive implications of BRCA pathogenic variants, underlying areas in which an educational effort would be beneficial as well as possibilities for future research efforts in the field.

In Silico Hemodynamics and Filtering Evaluation of a Commercial Embolic Protection Device.

During the last years, several kinds of Embolic Protection Devices (EPD) have been developed, with the aim of minimizing complication caused by thrombi generated during Carotid Artery Stenting (CAS). These devices are capable of capturing small particles generated during the intervention, avoiding cerebral stroke and improving the outcomes of the surgery. However, they have associated complications, like the increase on flow resistance associated by their use or the lack of knowledge on their actual filtration efficiency for thrombi of low size. Current work proposes a validated computational methodology in order to predict the hemodynamic features and filtering efficiency of a commercial EPD. It will be observed how Computational Fluid Dynamics predicts pressure drop with fair agreement with the experimental measurements. Finally, this work analyzes the filtration efficiency and the influence of the distribution of injected particles on this parameter. The capabilities of the filter for retaining particles of diameter below the pore size is, additionally, discussed.