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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.

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.

Background: To know the epidemiology (prevalence, incidence, progression and morbidity and mortality associated) of peripheral artery disease in general population and the factors associated with this progression is essential to know the evolution of atherosclerosis and develop preventive strategies. The aim of the study was to determine the incidence of PAD after 5 years of follow-up population-based cohort ARTPER, and the evolution of Ankle brachial Index (ABI) in this period., Methods: Peripheral artery disease incidence analysis after 5 years of follow-up of 3786 subjects > 50 years old. Peripheral artery disease incident when the second cross section Ankle brachial Index was <0.9 in any of the lower limbs, with normal baseline (0.9 to 1.4)., Results: Between 2012 and 2013 2762 individuals (77% participation) were re-examined . Finally analyzed 2256 subjects (after excluding pathological Ankle brachial Index) followed for 4.9 years (range 3.8 to 5.8 years), totalling 11,106 person-years. Peripheral artery disease 95 new cases were detected, representing an incidence of 4.3% at 5 years and 8.6 per 1000 person-years (95% CI 6.9 to 10.5) being higher in men (10.2, 95% CI 7.4 to 13.5) than in women (7.5, 95% CI 5.5 to 9.9). Linear correlation between the baseline Ankle brachial Index and the second cross section was low (r = 0.23)., Conclusions: The incidence of peripheral artery disease in ARTPER cohort was 8.6 cases per 1000 person-years, being higher in men, especially <65 years. The correlation between two measures Ankle brachial Index after 5 years of follow-up was low. One might consider whether Ankle brachial Index repeated measures could improve the correlation.

Resting-state studies conducted with stroke patients are scarce. The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of brain rewiring after stroke and plasticity changes. This study sought to identify dynamic changes in the functional organization of the default mode network (DMN) of stroke patients at three months after stroke. Eleven patients (eight male and three female; age range: 48-72) with right cortical and subcortical ischemic infarctions and 17 controls (eleven males and six females; age range: 57-69) were assessed by neurological and neuropsychological examinations and scanned with resting-state functional magnetic ressonance imaging. First, we explored group differences in functional activity within the DMN by means of probabilistic independent component analysis followed by a dual regression approach. Second, we estimated functional connectivity between 11 DMN nodes both locally by means of seed-based connectivity analysis, as well as globally by means of graph-computation analysis. We found that patients had greater DMN activity in the left precuneus and the left anterior cingulate gyrus when compared with healthy controls (P < 0.05 family-wise error corrected). Seed-based connectivity analysis showed that stroke patients had significant impairment (P = 0.014; threshold = 2.00) in the connectivity between the following five DMN nodes: left superior frontal gyrus (lSFG) and posterior cingulate cortex (t = 2.01); left parahippocampal gyrus and right superior frontal gyrus (t = 2.11); left parahippocampal gyrus and lSFG (t = 2.39); right parietal and lSFG (t = 2.29). Finally, mean path length obtained from graph-computation analysis showed positive correlations with semantic fluency test (r(s)  = 0.454; P = 0.023), phonetic fluency test (r(s)  = 0.523; P = 0.007) and the mini mental state examination (r(s)  = 0.528; P = 0.007). In conclusion, the ability to regulate activity of the DMN appears to be a central part of normal brain function in stroke patients. Our study expands the understanding of the changes occurring in the brain after stroke providing a new avenue for investigating lesion-induced network plasticity., (© 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.)

Background: Peripheral arterial disease (PAD) of the lower limbs is a cardiovascular disease highly prevalent particularly in the asymptomatic form. Its prevalence starts to be a concern in low coronary risk countries like Spain. Few studies have analyzed the relationship between ankle-brachial index (ABI) and cardiovascular morbi-mortality in low cardiovascular risk countries like Spain where we observe significant low incidence of ischemic heart diseases together with high prevalence of cardiovascular risk factors. The objective of this study is to determine the relationship between pathological ABI and incidence of cardiovascular events (coronary disease, cerebrovascular disease, symptomatic aneurism of abdominal aorta, vascular surgery) and death in the >49 year population-based cohort in Spain (ARTPER)., Methods: Baseline ABI was measured in 3,786 randomly selected patients from 28 Primary Health Centers in Barcelona, distributed as: ABI<0.9 peripheral arterial disease (PAD), ABI ≥1.4 arterial calcification (AC), ABI 0.9-1.4 healthy; and followed during 4 years., Results: 3,307 subjects were included after excluding those with previous vascular events. Subjects with abnormal ABI were older with higher proportion of men, smokers and diabetics. 260 people presented cardiovascular events (incidence 2,117/100,000 person-years) and 124 died from any cause (incidence 978/100,000 person-years). PAD had two-fold greater risk of coronary disease (adjusted hazard ratio (HR) = 2.0, 95% confidence interval (CI) 1.3-3.2) and increased risk of vascular surgery (HR = 5.6, 95%CI 2.8-11.5) and mortality (HR = 1.8, 95%CI 1.4-2.5). AC increased twice risk of cerebrovascular events (HR = 1.9, 95%CI 1.0-3.5) with no relationship with ischemic heart disease., Conclusions: PAD increases coronary disease risk and AC cerebrovascular disease risk in low cardiovascular risk Mediterranean population. ABI could be a useful tool to detect patients at risk in Primary Health Care.

Background: The removal of mercury sphygmomanometers from health centers requires the validation of other instruments to measure blood pressure in the limbs to calculate the ankle-brachial index (ABI)., Methods: Descriptive cross-sectional study of agreement between two measurement methods in type 2 diabetes patients from three urban primary healthcare centres in the Barcelonès Nord i Maresme area (Catalonia, Spain)., Results: 211 patients were included, from these, 421 limbs were available for study. The mean age of the participants was 67 years (SD = 10), 51.7% were women., Conclusion: The combination of a Doppler device with the hybrid sphygmomanometer is a simple and reliable method to measure ABI showing that hybrid sphygmomanometer is a good alternative to the use of mercury sphygmomanometers.

Background: The aim of this study is to develop and validate a shorter version (VREM) of the Spanish version of the Minnesota leisure time Physical Activity Questionnaire (CAFM), in order to have a shorter physical activity questionnaire to be used in Primary Care., Methods: Descriptive study of validation of a new physical activity measurement questionnaire. 200 patients older than 50, who visited one of 5 primary care centers in Barcelona for any reason were selected, with age-sex Catalonia's distribution. Two phases: first, VREM construction through items reduction. Second, validity of VREM against CAFM (gold standard) and test-retest reliability of VREM were analyzed, using kappa index and the intraclass correlation coefficient (ICC)., Results: 6 items were included in the VREM: Walking, Gardening, Sport/dancing, Climbing stairs, Shopping walking and Cleaning house. The interview using VREM lasted 5 minutes (standard deviation 2). Agreement between both questionnaires, using 4 levels of physical activity, was 95.5% (kappa=0.93). Test-retest reliability of the questionnaire was 92.5% (kappa=0.88). Using a continuous outcome in metabolic energy turnover (MET), VREM also proved to be valid and reliable (ICC=0.95 and ICC=0.96 respectively)., Conclusion: This short version of CAFM has shown good validity and reliability in people ≥50 years.

Objective: To determine the prevalence of arterial calcification (ankle-brachial index ≥1.4) and its related factors among the general population aged >49 years., Methods: We performed a cross-sectional study of 3,786 people randomly selected from 28 centers. To assess the factors associated with arterial calcification using a multivariate logistic model, the whole sample was used to compute prevalence, excluding persons with peripheral arterial disease (ankle-brachial index <0.9)., Results: Arterial calcification was found in 235 persons (prevalence: 6.2%; 95% CI: 5.6-7.0), and was twice as frequent in men as in women. Patients with arterial calcification were older, had more previous cardiovascular events, diabetes and obesity, and were less able to perform physical activity than persons with a healthy ankle-brachial index., Conclusions: We recommend measurement of the ankle-brachial index in primary care centers to detect arterial calcification among men, persons with diabetes, overweight, obesity or difficulty in performing physical activity, and in those with left ventricular hypertrophy., (Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.)

Introduction and Objectives: The sensitivity of cardiovascular risk functions is low because many cardiovascular events occur in low- or intermediate-risk patients. The aim of the present study was to evaluate how the ankle-brachial index (ABI) reclassifies these patients., Methods: We conducted a descriptive, transversal, multicenter study (28 centers) of 3171 randomly selected patients aged >49 years. We studied demographic variables, clinical history and cardiovascular risk factors, ABI (defined as pathologic if <0.9) and 10-year cardiovascular risk with the Framingham-Wilson, REGICOR and SCORE equations, dividing risk into three categories: low (Framingham<10%, REGICOR<5% and SCORE<2.5%, intermediate (10-19.9%, 5-9.9% and 2.5-4.9%, respectively) and high (≥20%, ≥10% and ≥5%, respectively). Low- or intermediate-risk patients were reclassified as high-risk if they presented ABI <0.9., Results: We compared patients with ABI <0.9 and patients with ABI ≥0.9 and found the former were significantly older, more frequently men, had a worse history and more cardiovascular risk factors, and included more high-risk patients than when the classification used Framingham-Wilson (42.7% vs. 18.5%), REGICOR (25.8% vs. 9.3%) and SCORE (42.2% vs. 15.9%) equations. In men, using ABI led to a 5.8% increase in the high-risk category versus Framingham-Wilson, a 19.1% increase versus REGICOR and a 4.4% increase versus SCORE. In women, the increases were 78.6% versus Framingham-Wilson, 151.6% versus REGICOR and 50.0% versus SCORE., Conclusions: The ABI reclassifies a substantial proportion of patients towards the high-risk category. This is particularly marked in women and by comparison with REGICOR scores., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Background: The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the study is to know the prevalence and associated risk factors of peripheral arterial disease in the general population., Methods: We performed a cross-sectional, multicentre, population-based study in 3786 individuals >49 years, randomly selected in 28 primary care centres in Barcelona (Spain). Peripheral arterial disease was evaluated using the ankle-arm index. Values < 0.9 were considered as peripheral arterial disease., Results: The prevalence (95% confidence interval) of peripheral arterial disease was 7.6% (6.7-8.4), (males 10.2% (9.2-11.2), females 5.3% (4.6-6.0); p < 0.001).Multivariate analysis showed the following risk factors: male sex [odds ratio (OR) 1.62; 95% confidence interval 1.01-2.59]; age OR 2.00 per 10 years (1.64-2.44); inability to perform physical activity [OR 1.77 (1.17-2.68) for mild limitation to OR 7.08 (2.61-19.16) for breathless performing any activity]; smoking [OR 2.19 (1.34-3.58) for former smokers and OR 3.83 (2.23-6.58) for current smokers]; hypertension OR 1.85 (1.29-2.65); diabetes OR 2.01 (1.42-2.83); previous cardiovascular disease OR 2.19 (1.52-3.15); hypercholesterolemia OR 1.55 (1.11-2.18); hypertriglyceridemia OR 1.55 (1.10-2.19). Body mass index > or =25 Kg/m2 OR 0.57 (0.38-0.87) and walking >7 hours/week OR 0.67 (0.49-0.94) were found as protector factors., Conclusions: The prevalence of peripheral arterial disease is low, higher in males and increases with age in both sexes. In addition to previously described risk factors we found a protector effect in physical exercise and overweight.

Background Aims: Cord blood (CB) transplants with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC) have been shown to result in 'bridge' engraftment with prompt neutrophil recovery and high final rates of CB engraftment and full chimerism. This strategy overcomes the limitation posed by low cellularity of CB units for unrelated transplants in adults. Enhancement of adaptive immunity reconstitution without increasing risks of graft-versus-host disease (GvHD) is required to optimize results further. Our objectives were to evaluate co-infusion of mesenchymal stromal cells (MSC) from the same TPD regarding tolerance, CB engraftment and effects on acute (a)GvHD, both preventive and therapeutic., Methods: Ex vivo-expanded bone marrow MSC were infused at the time of the transplant or the in case of refractory aGvHD., Results: Nine patients received 1.04 - 2.15 x 10(6)/kg (median 1.20) MSC immediately after CB and TPD MHSC. Neither immediate adverse side-effects nor significant differences regarding CB engraftment or aGvHD development were observed. Four patients developed grade II aGvHD, refractory to steroids in two. These reached complete remission after therapeutic infusions of MSC., Conclusions: In recipients of 'dual CB/TPD MHSC transplants', MSC infusions were therapeutically effective for severe aGvHD but no significant differences in CB engraftment and incidence of severe aGvHD were observed following their prophylactic use. Although results of this study alone cannot conclusively determine the application of MSC in CB transplantation, we believe that, in this setting, the best use of MSC could be as pre-emptive treatment for aGvHD.

Background: In Spain, stroke is one of the major causes of death and the main cause of severe disability in people over 65 years. We analyzed the incidence of ischemic stroke, stroke subtypes, case fatality and disability at 90 days after the event in a Spanish population., Methods: A prospective community-based register of ischemic strokes was established in Santa Coloma de Gramenet (Barcelona) [116,220 inhabitants of all ages, according to the municipal census of December 31,2001], from January 1 to December 31, 2003. Standard definitions and case finding methods were used to identify all cases in all age groups. Every patient underwent a complete clinical evaluation and systematic tests including neuroimaging (CT/MRI) and vascular studies (carotid duplex ultrasound intra and extracranial and MR angiography)., Results: Over a one year period, 196 ischemic strokes were registered [107 men; median age = 76 years (range 39-98)], being the first event in 159 patients (81.1%) and a recurrent stroke in 37 (18.9%). After age-adjustment to the European population, the incidence of ischemic stroke per 100,000 inhabitants was 172 (95% CI, 148-196); 219 (176-261) in men and 133 (105-160) in women, with an annual incidence for first ischemic stroke of 139 (118-161); 165 (128-201) in men and 115 (89-140) in women. The incidence of stroke increased with age. Stroke subtypes (TOAST classification criteria) were lacunar in 28.8%, atherothrombotic in 18.6%, cardioembolic in 26.6% and undetermined in 26.0% of patients. At 90 days, the case-fatality was 12%, and among survivors, moderate-to-severe disability was present in 45 % at 3 months., Conclusion: This prospective community-based study shows one of the lowest incidences of stroke in Europe, as well as one of the lowest case fatality and disability rates at 90 days after stroke.

Background: The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index (AAI) is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the PERART study (PERipheral ARTerial disease) is to determine the prevalence of peripheral arterial disease (both silent and symptomatic) in a general population of both sexes and determine its predictive value related to morbimortality (cohort study)., Methods/design: This cross-over, cohort study consists of 2 phases: firstly a descriptive, transversal cross-over study to determine the prevalence of peripheral arterial disease, and secondly, a cohort study to evaluate the predictive value of AAI in relation to cardiovascular morbimortality. From September 2006 to June 2007, a total of 3,010 patients over the age of 50 years will be randomly selected from a population adscribed to 24 healthcare centres in the province of Barcelona (Spain). The diagnostic criteria of peripheral arterial disease will be considered as an AAI < 0.90, determined by portable Doppler (8 Mhz probe) measured twice by trained personnel. Cardiovascular risk will be calculated with the Framingham-Wilson tables, with Framingham calibrated by the REGICOR and SCORE groups. The subjects included will be evaluted every 6 months by telephone interview and the clnical history and death registries will be reviewed. The appearance of the following cardiovascular events will be considered as variables of response: transitory ischaemic accident, ictus, angina, myocardial infartction, symptomatic abdominal aneurysm and vascular mortality., Discussion: In this study we hope to determine the prevalence of peripheral arterial disease, especially the silent forms, in the general population and establish its relationship with cardiovascular morbimortality. A low AAI may be a better marker of arterial disease than the classical cardiovascular risk factors and may, therefore, contribute to improving the predictive value of the equations of cardiovascular risk and thereby allowing optimisation of multifactorial treatment of atherosclerotic disease.

Unlabelled: OBJECTIVE, METHODS, AND RESULTS: To reduce the period of posttransplant neutropenia and related early morbidity and mortality of cord blood (CB) transplants, we assessed the feasibility of co-infusion of a low number of highly purified peripheral blood CD34+ cells from a related haploidentical donor with a CB graft. Between March 1999 and May 2002, 11 patients with high-risk hematologic malignancies were transplanted using this strategy. The seven patients who received a haploidentical peripheral blood graft and a CB graft from a sibling (6) or the father (1) had prompt recovery (9-17 days, median 10) of the absolute neutrophil count (ANC) to greater than 0.5 x 10(9)/L. Analysis of DNA polymorphisms showed initial predominance of the haploidentical genotype both in granulocytes and in mononuclear cells, and subsequent progressive replacement by cells of CB genotype until final complete CB chimerism was achieved by patients who survived for sufficient periods of time. The four patients who received maternal haploidentical cells had no significant contribution of these to blood leukocytes, although complete CB chimerism was achieved by three of them and two reached engraftment of the CB on days +20 and +36. Morbidity due to early bacterial or fungal infections was remarkably low in patients with prompt ANC recovery., Conclusion: Our data show that co-infusion of a CB unit and a low number of haploidentical CD34+ cells may result in a shortened period of posttransplant neutropenia. This is likely the result of prompt and transient engraftment of the haploidentical hematopoietic stem cells that may provide the patient antimicrobial protection until the later engraftment of the CB hematopoietic stem cells.

Background and Objectives: Patients with B-cell lymphoma can be induced to mount a specific immune response against the individual idiotypic determinants expressed in their tumor cells. This form of active immunotherapy is now under evaluation in the clinical setting. We evaluated the feasibility and effectiveness of this kind of immunotherapy in a group of patients with low-grade lymphoma, which included two cases of bi/triclonal lymphoma., Design and Methods: Nine patients with a histopathologic diagnosis of follicular non-Hodgkin's (NHL) low-grade B-cell lymphoma were initially selected for this disease-free survival study. Idiotypic proteins were recovered by somatic fusion of the tumor cells and their identity with the tumor idiotype determined by molecular methods. The patients received the vaccine consisting of their tumor Ig protein coupled to keyhole limpet hemocyanine and were observed for toxicity, anti-idiotypic immune response, clinical outcome and circulating t(14;18)+ tumor cells., Results: The median duration of follow-up was 40 (10-64) months from the initiation of immunotherapy. Tumor regression was detected in two patients. No tumor progression was observed in the other patients. Eight patients generated specific anti-idiotypic antibodies and 3 out of five were cleared of circulating t(14;18)+ cells., Interpretation and Conclusions: Induction of tumor-specific anti-idiotypic immune responses may be of benefit to patients affected by low-grade B-cell NHL. Our results are in line with those previously reported and call attention to the issue of tumor clonality in this kind of treatment.

The case of a 62-year-old diabetic and smoker male who was under study in another hospital due to anemia, thrombopenia and hematuria of several months of evolution is presented. The patient was admitted to the coronary unit for an acute extensive transmural myocardial infarction and treated with t-PA. A few hours later the patient presented hematuric urine, a decrease in hemoglobin and platelets and acute renal insufficiency. Hematologic study confirmed the diagnosis of paroxystic nocturnal hemoglobinuria. The evolution of the patient was poor despite intensive medical treatment requiring hemodialysis. The patient presented cardiac tamponade and died. The role of hematologic disease in acute myocardial infarction and the treatment and evolution of the coronary syndrome in the context of the disease are discussed.

Cost-efficient umbilical cord blood (UCB) banking requires well-standardized methods of volume reduction and storage. To compare UCB fractionation using a technique of hydroxyethyl starch (HES) sedimentation with the Ficoll (double) and Percoll methods, 50 whole units was allocated randomly to each procedure. HES resulted in a significantly better recovery of mononuclear cells (87.5%), granulocyte/macrophage colony-forming units (CFU-GM) (88.4%), and CD34- cells (87.4%) and lesser volume reduction (85.5%). HES was the least laborious, time consuming, and expensive of the three procedures, costing 3.4- and 4.4-fold less than the Ficoll and Percoll methods, respectively. Five units processed by each method was frozen in 4.5-mL cryotubes under optimal conditions. After thawing, the greatest degree of recovery of viable nucleated cells and number of CFU-GM per unit were obtained using the HES procedure. Using 4.5-mL cryotubes, the calculated number of units that could be stored in 600-L containers was 3.8- and 2.2-fold higher for Ficoll- and Percoll-separated than for HES-separated units, respectively. Nevertheless, the higher direct costs of the density gradient separation procedures outweighed their lower storage cost. For long-term cryopreservation, we assessed the freezing of HES-processed units in 50-mL cryobags and their specifically designed canisters. We found cell recoveries similar to those obtained with cryotubes, but storage capacity was decreased. Special racks designed for these canisters resulted in a 5-fold increase over the number of units stored in standard cryobags. This system also is feasible for Percoll- and Ficoll-separated units, resulting in comparable storage costs for the three separation methods. We conclude that this HES procedure and the 50-mL cryobags constitute a cost-efficient system for large-scale UCB banking.

An asymptomatic 26-year-old woman with mild macrocytic anemia (11.6 g Hb/dl) was studied. All biochemical parameters, bone marrow histology and cytogenetics were normal. The Ham's and sucrose tests were negative. A flow cytometric analysis revealed that CD55 and CD59 staining was absent in 20% and 21% of the granulocytes, but erythrocytes and CD34-positive bone marrow cells were CD55 and CD59 positive. Seven months after the initial study, the patient suffered an episode of hemoglobinuria, with mild anemia, moderate thrombocytopenia and a weak positive sucrose lysis test. A new flow cytometric analysis disclosed an increased percentage of CD55 and CD59 negative granulocytes and a 25% of erythrocytes with an intermediate pattern of fluorescence after CD59 labelling. At fourteen months, a population of CD55-deficient erythrocytes was detected and the Ham's test became positive. The present report is, to our knowledge, the first case of smoldering paroxysmal nocturnal hemoglobinuria in a patient with no previous aplastic anemia, or evident pancytopenia. The diagnosis was established by flow cytometry of peripheral blood granulocytes, with apparently phenotipically normal progenitor cells in an early stage of the disease. Flow cytometry appears to be a useful tool in our knowledge of paroxysmal nocturnal hemoglobinuria evolution.