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We introduce a novel method to derive rotation curves with light-day spatial resolution of the inner regions of lensed quasars. We aim to probe the kinematics of the inner part of the broad-line region by resolving the microlensing response—a proxy for the size of the emitting region—in the wings of the broad emission lines. Specifically, we assess the strength of the microlensing effects in the wings of the high-ionization lines Si iv and C iv across various velocity bins in five gravitationally lensed quasars: SDSS J1001+5027, SDSS J1004+4112, HE 1104−1805, SDSS J1206+4332, and SDSS J1339+1310. Using Bayesian methods to estimate the dimensions of the corresponding emission regions and adopting a Keplerian model as our baseline, we examine the consistency of the hypothesis of disklike rotation. Our results reveal a monotonic, smooth increase in microlensing magnification with velocity. The deduced velocity–size relationships inferred for the various quasars and emission lines closely conform to the Keplerian model of an inclined disk. This study provides the first direct evidence of Keplerian rotation in the innermost region of quasars across a range of radial distances spanning from ∼5 to 20 lt-days.

We propose and discuss a new experimental approach to measure the centroid shift induced by gravitational microlensing in the images of lensed quasars (astrometric microlensing). Our strategy is based on taking the photocenter of a region in the quasar large enough as to be insensitive to microlensing as reference to measure the centroid displacement of the continuum. In this way, single-epoch measurements of astrometric microlensing can be performed. Using numerical simulations, we show that, indeed, the centroid shift monotonically decreases as the size of the emitting region increases, and only for relatively large regions, like the broad line region (BLR), does the centroid shift become negligible. This opens interesting possibilities to study the stratification of the different emitters in the accretion disk and the BLR. We estimate the amplitude of the centroid shifts for 79 gravitationally lensed images and study more thoroughly the special cases Q2237+030 A, RXJ1131-1231 A, PG1115+080 A2, and SDSS J1004+4112 A. We propose to use spectro-astrometry to simultaneously obtain the photocenters of the continuum and of different emission line regions since, with the precision of forthcoming instruments, astrometric microlensing by ∼1 M _⊙ mass microlenses may be detected in many quasar lensed images. When we consider more massive micro/millilenses, M ≳ 10 M _⊙ , often proposed as the constituents of dark matter, the BLR becomes sensitive to microlensing and can no longer be used as a positional reference to measure centroid shifts. Differential microlensing between the images of a lensed quasar along several epochs should be used instead.

Background: Right bundle branch block (RBBB) is among the most common electrocardiographic abnormalities. Objectives: To establish the prevalence and incidence of RBBB in the general population without cardiovascular events (CVE) and whether RBBB increases cardiovascular morbidity and mortality compared with patients with a normal electrocardiogram (ECG). Methods: A historical study of two cohorts including 2981 patients from 29 primary health centres without baseline CVE. Cox (for CVE) and logistic (for cardiovascular factors) regression was used to assess their association with RBBB. Results: Of the patients (58% women; mean age 65.9), 92.2% had a normal ECG, 4.6% incomplete RBBB (iRBBB) and 3.2% complete RBBB (cRBBB). Mean follow-up was five years. Factors associated with appearance of cRBBB were male sex (HR = 3.8; 95%CI: 2.4–6.1) and age (HR = 1.05 per year; 95%CI: 1.03–1.08). In a univariate analysis, cRBBB was associated with an increase in all-cause mortality but only bifascicular block (BFB) was significant after adjusting for confounders. cRBBB tended to increase CVE but the results were not statistically significant. Presence of iRBBB was not associated with adverse outcomes. Patients with iRBBB who progressed to cRBBB showed a higher incidence of heart failure and chronic kidney disease. Conclusion: In this general population cohort with no CV disease, 8% had RBBB, with a higher prevalence among men and elderly patients. Although all-cause mortality and CVE tended to increase in the presence of cRBBB, only BFB showed a statistically significant association with cRBBB. Patients with iRBBB who progressed to cRBBB had a higher incidence of CVE. We detected no effect of iRBBB on morbidity and mortality.

We present new light curves for the four bright images of the five image cluster-lensed quasar gravitational lens system SDSS J1004+4112. The light curves span 14.5 yr and allow the measurement of the time delay between the trailing bright quasar image D and the leading image C. When we fit all four light curves simultaneously and combine the models using the Bayesian information criterion, we find a time delay of Δ t _DC = 2458.47 ± 1.02 days (6.73 yr), the longest ever measured for a gravitational lens. For the other two independent time delays we obtain Δ t _BC = 782.20 ± 0.43 days (2.14 yr) and Δ t _AC = 825.23 ± 0.46 days (2.26 yr), in agreement with previous results. The information criterion is needed to weight the results for light curve models with different polynomial orders for the intrinsic variability and the effects of differential microlensing. The results using the Akaike information criterion are slightly different, but, in practice, the absolute delay errors are all dominated by the ∼4% cosmic variance in the delays rather than the statistical or systematic measurement uncertainties. Despite the lens being a cluster, the quasar images show slow differential variability due to microlensing at the level of a few tenths of a magnitude.

Herein, we present the design and fabrication of a portable biochemical sensor based on the Screen Printed Electrode (SPE) concept and applied for detecting interleukin-6 (IL-6), a key player in the complex process of inflammation, in real human saliva. The sensing mechanism relies on the antigen-antibody binding between the IL-6 molecule and its antibody immobilized over a surface of a Thermally Exfoliated Graphene Oxide (TEGO) layer. TEGO, deposited by Aerosol Jet Printing (AJP), provides advantages in terms of a time/cost consumingfast, easy and efficient biofunctionalization. The biosensor shows a dynamic range comprising IL-6 concentrations falling within the normal IL-6 levels in saliva. An extensive analysis of device performance, focused on the assessment of the sensor Limit of Detection (LoD) by two modes (i.e. from the lin-log calibration curve and from blank measurements), provides a best value of about 1 × 10−2 pg/ml of IL-6 in saliva. Our work aims at providing a contribution toward applications in real environment, going beyond a proof of concept or prototyping at lab scale. Hence, the characterization of the sensor was finalized to find a reliable device-to-device reproducibility and calibration through the introduction of a measurement protocol based on comparative measurements between saliva samples without (blank) and with IL-6 spiked in it, in place of the standard addition method used in daily laboratory practice. Device-to-device reproducibility has been accordingly tested by acquiring multiple experimental points along the calibration curve using different individual devices for each point.

Abstract Food web projections are critical for evaluating potential risks to ecosystems and fisheries under global warming. The temperature dependence of biological processes and regional differences in food web structure are two important sources of uncertainty and variation in climate forced projections of fish communities, but we do not know their magnitude or relative contribution. Here we systematically evaluated a range of different assumptions about temperature‐dependence on rates, including size‐dependent effects, controlling food intake, metabolism, and non‐predation mortality in fishes using species‐resolved size spectrum food web models that link individual‐level physiological processes to population and community dynamics. We simulated the physiological effect of warming in a range of size‐structured food web models calibrated to different marine ecosystems and in simplified trait‐based models. Higher food intake in warmed conditions increased total fish biomass, catches, and mean body weight, but these effects were offset by the negative effects of warming on metabolism and mortality, which combined resulted in lower total biomasses and catches for most food webs. These effects were enhanced when warming increased metabolic rates more than food intake, and the outcomes were also sensitive to size dependency of temperature responses. Importantly, these general patterns were not uniform across all food webs—individual functional groups and fish species within food webs responded to warming in different ways depending on their position in the food web and its structure. Hence, caution is warranted when generalizing food web or species outcomes to warming because they are mediated by community interactions. Uncertainty related to temperature dependence and ecological interactions will impact food web projections and should be represented in climate change projections.

Background : Intermittent Claudication symptomatic peripheral arterial disease (ICSPAD) is associated with reduced mobility, functional capacity, and quality of life. Physical exercise is an effective non-pharmacological intervention for the management of ICSPAD. Adherence to exercise programs is challenging, due to the nature of the disease and the complex comorbidities associated with it. This study aimed to determine adherence to three supervised physical exercise programs (a walking intervention, strength intervention, and concurrent intervention) and an unsupervised exercise program (standard advice) in individuals with ICSPAD. Methods : In this clinical trial, 122 patients were divided into four groups based on the type of exercise program they followed: standard advice, walking intervention, strength intervention, and concurrent intervention. Results : The results revealed that while the demographic characteristics were similar, the strength intervention group had a younger mean age, and the walking group had a higher prevalence of hypertension and increased usage of anti-hypertensive drugs. Adherence to physical exercise and pedometer wearing was highest in the standard advice group. Logistic regression analysis showed lower odds of adherence to exercise and pedometer wearing in the intervention groups compared to the standard advice group. Adherence did not significantly vary across ankle-brachial index categories. Furthermore, there was no significant difference in adherence between the severity levels of intermittent claudication, though mild cases tended to exhibit higher adherence. Conclusions : The results show that the standard advice from healthcare professionals positively influences treatment adherence.

Peripheral artery disease (PAD) and non-compressible artery disease (NCAD) constitute predictors of subclinical atherosclerosis easily assessed through the ankle brachial index (ABI). Although both diseases show substantial genetic influences, few genetic association studies have focused on the ABI and PAD, and none have focused on NCAD. To overcome these limitations, we assessed the role of several candidate genes on the ABI, both in its continuous distribution and in the clinical manifestations associated to its extreme values: PAD and NCAD. We examined 13 candidate genomic regions in 1606 participants from the ARTPER study, a prospective population-based cohort, with the ABI assessed through ultrasonography. Association analyses were conducted independently for individuals with PAD (ABI < 0.9) or with NCAD (ABI > 1.4) vs. healthy participants. After including potential covariates and correction for multiple testing, minor alleles in the genetic markers rs10757278 and rs1333049, both in the 9p21.3 region, were significantly associated with a decreased risk of NCAD. Associations with the ABI showed limited support to these results. No significant associations were detected for PAD. The locus 9p21.3 constitutes the first genetic locus associated with NCAD, an assessment of subclinical atherosclerosis feasible for implementation in primary healthcare settings that has been systematically neglected from genetic studies.

Background: Hemovigilance (HV) is usually based on voluntary reports (passive HV). Our aim is to ascertain credible incidence, severity, and mortality of transfusion-associated adverse events (TAAEs) using an active HV program., Study Design and Methods: Prospective cohort study to estimate transfusion risk after 46,488 transfusions in 5830 patients, using an active HV program with follow-up within the first 24 h after transfusion. We compared these results to those with the previously established passive HV program during the same 30 months of the study. We explored factors associated with the occurrence of TAAEs using generalized estimating equations models., Results: With the active HV program TAAEs incidence was 57.3 (95% CI, 50.5-64.2) and mortality 1.1 (95% CI, 0.13-2.01) per 10,000 transfusions. Incidence with the new surveillance model was 14.0 times higher than with the passive. Most events occurred when transfusions had already finished (60.2%); especially pulmonary events (80.4%). Three out of five deaths and 50.3% of severe TAAEs were pulmonary. In the multivariate analysis surgical patients had half TAAEs risk when compared to medical patients (OR, 0.53; 95% CI, 0.34-0.78) and women had nearly twice the risk of a pulmonary event compared to men (OR, 1.84; 95% CI, 1.03-3.32). Patient's age, blood component type, or blood component shelf-life were unrelated to TAAEs risk., Discussion: Active hemovigilance programs provide additional data which may lead to better recognition and understanding of TAAEs and their frequency and severity., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

GABRIELL was a phase II single-arm study to evaluate the efficacy and safety of obinutuzumab plus bendamustine for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Seventy-two patients with active disease received treatment for up to six 28-day cycles. Overall response rate was 78.6% with a median progression-free survival (PFS) of 26 months, and overall survival (OS) not reached at the end of follow-up (36 months). Undetectable measurable residual disease (≤0.01%; 36.4% in bone marrow and 53.4% in peripheral blood) correlated with a significantly longer PFS and OS (vs. >0.01). Common grade ≥3 adverse events (76.4%) were neutropenia (58.3%), thrombocytopenia (26.4%) and febrile neutropenia (11.1%). TP53 disruption was the only independent predictive factor for response (Hazard ratio; HR: 0.228). Unmutated immunoglobulin heavy chain variable region (HR: 16.061) was a negative prognostic factor for PFS. In conclusion, the combination of obinutuzumab plus bendamustine is an active and generally adequately-tolerated treatment for R/R CLL.

There is evidence of an association between hypertension and retinal arteriolar narrowing. Manual measurement of retinal vessels comes with additional variability, which can be eliminated using automated software. This scoping review aims to summarize research on automated retinal vessel analysis systems. Searches were performed on Medline, Scopus, and Cochrane to find studies examining automated systems for the diagnosis of retinal vascular alterations caused by hypertension using the following keywords: diagnosis; diagnostic screening programs; image processing, computer-assisted; artificial intelligence; electronic data processing; hypertensive retinopathy; hypertension; retinal vessels; arteriovenous ratio and retinal image analysis. The searches generated 433 articles. Of these, 25 articles published from 2010 to 2022 were included in the review. The retinographies analyzed were extracted from international databases and real scenarios. Automated systems to detect alterations in the retinal vasculature are being introduced into clinical practice for diagnosis in ophthalmology and other medical specialties due to the association of such changes with various diseases. These systems make the classification of hypertensive retinopathy and cardiovascular risk more reliable. They also make it possible for diagnosis to be performed in primary care, thus optimizing ophthalmological visits.

Objective: To evaluate, with real world data (SIDIAP and CMBD), the evolution of the prevalence of peripheral arterial disease (PAD) in the Catalan population and the cardiovascular risk factors present in people with this pathology., Design: Longitudinal descriptive population study. SITE: Primary health care., Participants: Patients listed in SIDIAP and CMBD with a diagnosis of peripheral artery disease between 2008 and 2018 ≥ 35 years, as well as those without a diagnosis, but with an ABI < 0.9 in SIDIAP., Interventions and Main Measurements: Main variable AP (ICD-9, ICD-10). Sociodemographic data, risk factors and cardiovascular disease, drug use and prevalent cardiovascular events at the time of diagnosis., Results: 141,520 patients were studied. 75% had hypertension, 58% were smokers or former smokers, and 23% had a myocardial infarction. The global prevalence increased from 1.15% in 2008 to 3.10% in 2018. The prevalence of PAD increased with age, with a moderate increase at younger ages, and more pronounced in > 55 years, exceeding 10% in > 85 years., Conclusion: This is a population study where it is observed that the evolution of the prevalence of peripheral artery disease has presented a constant increase during the years 2008-2018, being higher in men, especially from 55 years of age. Studies with large databases can facilitate the design and implementation of new policies in national health systems., (Copyright © 2022 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To study the relationship between physical activity during leisure time and progression of ankle-brachial index (ABI) in the Spanish general population., Method: Prospective, multicentre cohort study with 1941 subjects over 49 years of age, free of peripheral arterial disease at the time of recruitment of the cohort, were studied. Physical activity during leisure time variable was obtained using the VREM questionnaire. Peripheral arterial disease was considered to be an ankle-brachial index (ABI) <0.9. A multivariate logistic regression analysis was performed to evaluate the independent association between physical activity during leisure time and ABI., Results: The mean age was 63.4 years and 54.6% were women. In the multivariate analysis, there was a positive relationship between physical activity during leisure time and ABI in patients with an energy consumption of more than 5000 MET in 14 days (odds ratio: 0.37; 95% confidence interval: 0.18-0.80). These specific activities doing sports or dancing, going shopping on foot, and cleaning the house for more than an hour a day showed a protective effect. In the group of subjects who maintained the physical activity during leisure time during the time of the research, a protective effect was observed with overall physical activity (MET) and going shopping on foot., Conclusions: In our research, PALT was favorably associated with ABI, in a sample of the Spanish general population that is very active and has a low-cardiovascular risk., (Copyright © 2021 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Peripheral arterial disease (PAD) is a marker of cardiovascular morbidity, causing disability, loss of mobility and poor quality of life, manifesting clinically in the form of intermittent claudication (IC). Physical exercise increases the distance walked and improves quality of life. The aim of our study will be increased walking distance prolonging the time of onset of pain in patients with symptomatic PAD (IC)., Methods and Analysis: This study will be performed in Mataró Hospital's vascular surgery service and School of Health Sciences, TecnoCampus. This population comes from 15 primary healthcare centres ofNorth Barcelona, Spain (450 000 inhabitants).This study will be a four-group parallel, longitudinal, randomised controlled trial, blind to analysis.The main primary outcome of this study will be the improvement in pain-free walking distance. Others primary objectives are and improvement in functional status, quality of life and Ankle-Brachial Index (ABI). Secondary outcomes will be the analysis of cardiorespiratory fitness, evaluation of muscle fitness, determine the maintenance of primary objectives at 6 and 12 months.We will be included 124 patients (31 per group). The changes of the outcome (Barthel, SF-12, VascQOL-6, ABI) of the three intervention groups vs the control group at 3, 6 and 12 months will be compared, both continuously (linear regression) and categorically (logistic regression). A person who has not performed at least 75% of the training will be considered to have not completed the intervention., Ethics and Dissemination: The study will be conducted according to the Declaration of Helsinki . It was approved by the Ethics Committee of the Research Institute Primary Health IDIAP Jordi Gol (20/035 P),Barcelona 6 October 2020. Informed consent will be obtained from all patients before the start of the study. We will disseminate results through academic papers and conference presentations., Trial Registration Number: NCT04578990., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aims of this study are to analyze the role of artery-vein ratio AVR assessment using VesselMap 2 software (Imedos Systems) and cardiovascular risk evaluation by means of REGICOR in the prediction of silent brain infarction (SBI) in middle-age hypertensive patients from the ISSYS study., Material and Methods: A cross-sectional study with 695 patients with hypertension aged 50 to 70 years who participated in the project Investigating Silent Strokes in HYpertensives: a Magnetic Resonance Imaging Study (ISSYS), was conducted in two Primary Care Centres of Barcelona. Participants agreed to a retinography and an MRI to detect silent brain infarction (SBI). The IMEDOS software was used for the semiautomatic caliber measurement of retinal arteries and veins, and the AVR was considered abnormal when <0.66. The REGICOR score was calculated for all patients., Results: Multivariate logistic regression analysis was used to evaluate the impact of AVR and REGICOR scores on SBI. The OR (odds ratio) for a high REGICOR score and an abnormal AVR were 3.16 and 4.45, respectively. When analysing the interaction of both factors, the OR of an abnormal AVR and moderate REGICOR score was 3.27, whereas with a high REGICOR score it reached 13.07., Conclusions: The measurement of AVR in patients with hypertension and with a high REGICOR score can contribute to the detection of silent brain infarction.

Objective: High blood pressure is one of the most prevalent diseases in general adult population. Its importance lies in the complications it causes in target organs such as kidney, heart, brain and eye. The aim of this work is to evaluate the agreement in the evaluation and interpretation of retinographies of hypertensive patients by family doctors and ophthalmologists., Material and Methods: This is a multicentric cross-sectional study in which 976 hypertensive patients from 50 to 70 years old were involved. They were participants of the «Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study» (ISSYS project) carried out in primary care centers of Barcelona and who agreed to undergo retinography. Six family physicians and 2 ophthalmologists evaluated the presence of retinal lesions through the Keith-Wagener-Barker criteria., Results: The inter/intra-observer Kappa concordance of the evaluations was analyzed. The evaluation of the retinographies under the usual conditions of clinical practice obtained a high subjective component with slight and fair intra-observer concordance values in the Keith-Wagener-Barker criteria. Only the assessment of the microaneurysms showed a moderate concordance and the ratio artery/vein was the worst concordant., Conclusions: The evaluation of the retinographies in habitual conditions of clinical practice has a high subjective component that is reflected in slight and fair inter-intraobserver concordance values. The use of objective reading systems in the assessment of retinography in hypertensive patients would be useful., (Copyright © 2019 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses., Methods: One hundred and forty healthy physically inactive older adults will be randomly assigned to computerized cognitive training (CCT), aerobic exercise (AE), combined training (COMB), or a control group. The intervention consists of a 3 month home-based program 5 days per week in sessions of 45 min. Data from cognitive, physical, and psychological tests, cardiovascular risk factors, structural and functional brain scans, and blood samples will be obtained before and after the intervention., Results: Effects of the interventions on cognitive outcomes will be described in intention-to-treat and per protocol analyses. We will also analyze potential genetic, demographic, brain, and physiological molecular correlates that may predict the effects of intervention, as well as the association between cognitive effects and changes in these variables using the per protocol sample., Discussion: Projecte Moviment is a multi-domain intervention trial based on prior evidence that aims to understand the effects of CCT, AE, and COMB on cognitive and psychological outcomes compared to a passive control group, and to determine related biological correlates and predictors of the intervention effects. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03123900.

Background: Right bundle branch block (RBBB) is among the most common electrocardiographic abnormalities. Objectives: To establish the prevalence and incidence of RBBB in the general population without cardiovascular events (CVE) and whether RBBB increases cardiovascular morbidity and mortality compared with patients with a normal electrocardiogram (ECG). Methods: A historical study of two cohorts including 2981 patients from 29 primary health centres without baseline CVE. Cox (for CVE) and logistic (for cardiovascular factors) regression was used to assess their association with RBBB. Results: Of the patients (58% women; mean age 65.9), 92.2% had a normal ECG, 4.6% incomplete RBBB (iRBBB) and 3.2% complete RBBB (cRBBB). Mean follow-up was five years. Factors associated with appearance of cRBBB were male sex (HR = 3.8; 95%CI: 2.4-6.1) and age (HR = 1.05 per year; 95%CI: 1.03-1.08). In a univariate analysis, cRBBB was associated with an increase in all-cause mortality but only bifascicular block (BFB) was significant after adjusting for confounders. cRBBB tended to increase CVE but the results were not statistically significant. Presence of iRBBB was not associated with adverse outcomes. Patients with iRBBB who progressed to cRBBB showed a higher incidence of heart failure and chronic kidney disease. Conclusion: In this general population cohort with no CV disease, 8% had RBBB, with a higher prevalence among men and elderly patients. Although all-cause mortality and CVE tended to increase in the presence of cRBBB, only BFB showed a statistically significant association with cRBBB. Patients with iRBBB who progressed to cRBBB had a higher incidence of CVE. We detected no effect of iRBBB on morbidity and mortality.

Background: Guidelines recommended adopting the same cardiovascular risk modification strategies used for coronary disease in case of low Ankle-brachial index (ABI), but here exist few studies on long-term cardiovascular outcomes in patients with borderline ABI and even fewer on the general population., Aim: The aim of the present study was to analyze the relationship between long-term cardiovascular events and low, borderline and normal ABI after a 9-year follow up of a Mediterranean population with low cardiovascular risk., Design and Setting: A population-based prospective cohort study was performed in the province of Barcelona, Spain., Method: A total of 3,786 subjects >49 years were recruited from 2006-2008. Baseline ABI was 1.08 ± 0.16. Subjects were followed from the time of enrollment to the end of follow-up in 2016 via phone calls every 6 months, systematic reviews of primary-care and hospital medical records and analysis of the SIDIAP (Information System for Primary Care Research) database to confirm the possible appearance of cardiovascular events., Results: 3146 individuals participated in the study. 2,420 (77%) subjects had normal ABI, 524 (17%) had borderline ABI, and 202 (6.4%) had low ABI. In comparison with normal and borderline subjects, patients with lower ABI had more comorbidities, such as hypertension, hypercholesterolemia and diabetes. Cumulative MACE incidence at 9 years was 20% in patients with low ABI, 6% in borderline ABI and 5% in normal ABI. The annual MACE incidence after 9 years follow-up was significantly higher in people with low ABI (26.9/1000py) (p<0.001) than in borderline (6.6/1000py) and in normal ABI (5.6/1000py). Subjects with borderline ABI are at significantly higher risk for coronary disease (HR: 1.58; 95% CI: 1.02-2, 43; p = 0,040) compared to subjects with normal ABI, after adjustment., Conclusion: The results of the present study support that low ABI was independently associated with higher incidence of MACE, ICE, cardiovascular and no cardiovascular mortality; while borderline ABI had significantly moderate risk for coronary disease than normal ABI., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the utility of the granulocyte CD64 index as a marker of infection in patients with postoperative fever., Methods: Prospective observational study of a cohort of patients with postoperative fever (2nd-21st day after the intervention) collected during 14 months. Obtaining blood samples during the first 24 hours after the febrile peak to determine the CD64 index (ratio of fluorescence intensity, measured, in the granulocytes of the patient with respect to healthy controls), procalcitonin and C-reactive protein (CRP)., Results: During the study period, 50 patients were included, 28 patients (56%) with infection and 22 patients (44%) without evidence of infection. The PCR, procalcitonin and the CD64 index showed significantly higher values in the group of patients who suffered infection. The CD64 index showed a sensitivity of 88.9%, with a specificity of 65.2%. The positive predictive value (PPV) was 75% and the negative predictive value (NPV) was 83.3%, with an area under the curve (AUC) of 0.805 (95% CI 0.68-0.93). Procalcitonin presented a sensitivity of 53.9% and specificity of 86.4%, with NPV and PPV of 82.4% and 61.3% respectively, with AUC of 0.752 (95% CI 0.61-0.89). Regarding the PCR, it showed a sensitivity of 100%, with specificity of 4.4% with an area under the curve of 0.676 (95% CI 0.52-0.83)., Conclusions: The quantification of the CD64 index in patients who develop fever in the early postoperative period is useful to distinguish post-surgical inflammatory phenomena from episodes of established infection., (©The Author 2018. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Cilostazol has been associated with spontaneous reports of cardiovascular adverse events and serious bleeding. The objective of this study is to determine the relative risk of cardiovascular adverse events or haemorrhages in patients with peripheral artery disease treated with cilostazol in comparison to pentoxifylline users., Methods: Population-based cohort study including all individuals older than 40 who initiated cilostazol or pentoxifylline during 2009-2011 in SIDIAP database. The two treatment groups were matched through propensity score (PS)., Results: Nine thousand one hundred twenty-nine patients met inclusion criteria and after PS matching, there were 2905 patients in each group. 76% of patients were men, with similar mean ages in both groups (68.8 for cilostazol and 69.4 for pentoxifylline). There were no differences in bleeding, cerebrovascular and cardiovascular events between both groups., Conclusions: Patients treated with cilostazol were different from those treated with pentoxifylline at baseline, so they were matched through PS. We did not find differences between treatment groups in the incidence of bleeding or cardiovascular and cerebrovascular events. Cilostazol should be used with precaution in elderly polymedicated patients.

[This corrects the article DOI: 10.1371/journal.pone.0191283.].

Background: The different cardiovascular risk prediction scales currently available are not sufficiently sensitive., Aim: The aim of the present study was to analyze the contribution of the ankle-brachial index (ABI) added to the Framingham and REGICOR risk scales for the reclassification of cardiovascular risk after a 9-year follow up of a Mediterranean population with low cardiovascular risk., Design and Setting: A population-based prospective cohort study was performed in the province of Barcelona, Spain., Method: A total of 3,786 subjects >49 years were recruited from 2006-2008. Baseline ABI was performed and cardiovascular risk was calculated with the Framingham and REGICOR scales. The participants were followed until November 2016 by telephone and review of the clinical history every 6 months to confirm the possible appearance of cardiovascular events., Results: 2,716 individuals participated in the study. There were 126 incidental cases of first coronary events (5%) during follow up. The incidence of coronary events in patients with ABI <0.9 was 4-fold greater than that of subjects with a normal ABI (17.2/1,000 persons-year versus 4.8/1,000 persons-year). Improvement in the predictive capacity of REGICOR scale was observed on including ABI in the model, obtaining a net reclassification improvement of 7% (95% confidence interval 0%-13%) for REGICOR+ ABI. Framingham + ABI obtained a NRI of 4% (-2%-11%)., Conclusion: The results of the present study support the addition of the ABI as a tool to help in the reclassification of cardiovascular risk and to confirm the greater incidence of coronary events in patients with ABI < 0.9.

Importance: The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients., Objective: To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant., Design, Setting, and Participants: This multicenter clinical study included 185 patients with de novo AML at 12 centers in China, the United States, and Spain in the Microtransplantation Interest Group. Patients were divided into the following 4 age groups: 60 to 64 years, 65 to 69 years, 70 to 74 years, and 75 to 85 years. The study period was May 1, 2006, to July 31, 2015., Exposures: Induction chemotherapy and postremission therapy with cytarabine hydrochloride with or without anthracycline, followed by highly HLA-mismatched related or fully mismatched unrelated donor cell infusion. No graft-vs-host disease prophylaxis was used., Main Outcomes and Measures: The primary end point of the study was to evaluate the complete remission rates, leukemia-free survival, and overall survival in different age groups. Additional end points of the study included hematopoietic recovery, graft-vs-host disease, relapse rate, nonrelapse mortality, and other treatment-related toxicities., Results: Among 185 patients, the median age was 67 years (range, 60-85 years), and 75 (40.5%) were female. The denominators in adjusted percentages in overall survival, leukemia-free survival, relapse, and nonrelapse mortality are not the sample proportions of observations. The overall complete remission rate was not significantly different among the 4 age groups (75.4% [52 of 69], 70.2% [33 of 47], 79.1% [34 of 43], and 73.1% [19 of 26). The 1-year overall survival rates were 87.7%, 85.8%, and 77.8% in the first 3 age groups, which were much higher than the rate in the fourth age group (51.7%) (P = .004, P = .008, and P = .04, respectively). The 2-year overall survival rates were 63.7% and 66.8% in the first 2 age groups, which were higher than the rates in the last 2 age groups (34.2% and 14.8%) (P = .02, P = .03, P < .001, and P < .001, respectively). The 1-year cumulative incidences of nonrelapse mortality were 10.2%, 0%, 3.4%, and 26.0% in the 4 age groups and 8.1% in all patients. The median times to neutrophil and platelet recovery were 12 days and 14 days after induction chemotherapy, respectively. Five patients had full or mixed donor engraftment, and 30.8% (8 of 26) of patients demonstrated donor microchimerism. Two patients (1.1%) developed severe acute graft-vs-host disease., Conclusions and Relevance: Microtransplant achieved a high complete remission rate in AML patients aged 60 to 85 years and higher 1-year overall survival in those aged 60 to 74 years.

Background and Objective: Although cardiovascular risk factors (CVRF) are well known, their degree of control is not optimal. The aim of this study is to assess the evolution and control of CVRFs after 5 years of monitoring a population-based cohort and their association with the incidence of peripheral arterial disease (PAD)., Material and Method: Prospective cohort study recruited between 2006-2008. Second phase between 2011-2012. An ankle brachial index was determined for all participants in both phases. Demographic variables, CVRF and previous cardiovascular events, blood pressure, total cholesterol and its fractions (HDL, LDL), triglycerides, glucose and glycosylated hemoglobin levels in diabetic patients and the cardiovascular risk score according to the REGICOR table were recorded., Results: A total of 2,125 individuals were analyzed. We observed an increase in the prevalence of hypertension (HT) (15.4%), diabetes (DM) (8.2%) and hypercholesterolemia (20.4%), with no changes in obesity and smoking. The cardiovascular risk determined on the basis of the REGICOR table remained at around 5.5%. We observed an increased control of CVRF throughout the follow-up period, except in the case of DM and obesity. In the multivariate analysis, uncontrolled HT 2-folded the risk of onset of PAD (odds ratio [OR] 2.3; 95% confidence interval [95% CI] 1.3-4.1), whereas smoking 5-folded this risk (OR 5.0; 95% CI 2.5-10.2)., Conclusions: Smoking and uncontrolled HT increase the risk of onset of PAD in this population. Despite the increase in drug treatments, the control of CVRFs continues to be suboptimal., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by complement-mediated intravascular hemolysis that is effectively treated with eculizumab. However, treatment responses are reported heterogeneous with some patients presenting residual hemolysis and requiring RBC transfusions. Recent reports have shown that both extravascular hemolysis and incomplete C5 blockade can explain these suboptimal hematological responses. Here we have tested our eculizumab-treated PNH patients (n=12) for signs of hemolysis and assessed complement biomarkers. Patients were also genotyped for complement receptor 1 (CR1, CD35) and C5 polymorphisms and evaluated for free eculizumab in plasma. We report that 10 patients (83%) present parameters suggesting persistent hemolysis, although they did not require additional transfusions. Seven of them (58%) become direct Coombs-test positive as a consequence of treatment, including all patients carrying the low-expression CR1-L allele. CH50 and sC5b-9 assays demonstrate that the persistent low-level hemolysis identified in our treated patients is not a consequence of incomplete C5 blockade, supporting that this hemolysis, as has been suggested previously, results from the extravascular removal of C3 opsonized PNH erythrocytes. We also show that continuous alternative pathway activation in eculizumab-treated individuals carrying the CR1-L allele results in abnormally decreased levels of C3 in plasma that could, potentially, increase their susceptibility to bacterial infections. Finally, we encourage a routine evaluation of free eculizumab levels and terminal pathway activity to personalize eculizumab administration., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objective: To evaluate the usefulness of a semiautomatic measuring system of arteriovenous relation (RAV) from retinographic images of hypertensive patients in assessing their cardiovascular risk and silent brain ischemia (ICS) detection., Methods: Semi-automatic measurement of arterial and venous width were performed with the aid of Imedos software and conventional fundus examination from the analysis of retinal images belonging to the 976 patients integrated in the cohort Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study (ISSYS), group of hypertensive patients. All patients have been subjected to a cranial magnetic resonance imaging (RMN) to assess the presence or absence of brain silent infarct., Results: Retinal images of 768 patients were studied. Among the clinical findings observed, association with ICS was only detected in patients with microaneurysms (OR 2.50; 95% CI: 1.05-5.98) or altered RAV (<0.666) (OR: 4.22; 95% CI: 2.56-6.96). In multivariate logistic regression analysis adjusted by age and sex, only altered RAV continued demonstrating as a risk factor (OR: 3.70; 95% CI: 2.21-6.18)., Conclusions: The results show that the semiautomatic analysis of the retinal vasculature from retinal images has the potential to be considered as an important vascular risk factor in hypertensive population., (Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)