Josep Puig

Instituto de Salud Carlos III, Madrid, Madrid, Spain

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Publications (63)218.29 Total impact

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    ABSTRACT: Context: Different genetic and imaging iron markers are known to be increased in the liver, adipose tissue and brain of obese subjects. Objective: We aimed to investigate these markers in human skeletal muscle. Design, setting, patients and outcome measures: Markers of iron accumulation were measured in 3 different territories: Iron gene markers (TFRC1, TF, SLC11A2, FTL, FTH1 and SLC40A1) were studied in abdominal rectus abdominis (cohort 1, n=26) and quadriceps (cohort 2, n= 13) muscle using real time PCR, while paravertebral muscle R2* signal (as surrogate of iron content) (cohort 3, n=43) was evaluated by means of MRI. Intervention: In a subgroup of 14 obese participants from cohort 3, a diet induced-weight loss was performed. Results: Rectus abdominis muscle age adjusted gene expression of SLC40A1 (ferroportin) (r=0.47, p=0.04), SLC11A2 (r= 0.50, p=0.03) and CYBA (r=0.62, p=0.006) increased with body fatness. In obese participants, muscle CYBA gene expression was positively correlated with serum ferritin. Paravertebral muscle R2* was positively associated with BMI, waist circumference and fat mass (DEXA) in parallel to hepatic iron content, serum ferritin and hepcidin. In multivariate regression analyses, obesity parameters (p<0.0001) and hsCRP concentration (p< 0.05) contributed independently to the variance of sex-, serum hepcidin- and age-adjusted muscle R2*. Of note, weight loss intervention resulted in decreased muscle R2* (p=0.02) in correlation with the change of serum ferritin (r= 0.69, p=0.01). Conclusions: These findings emphasize a significant iron accumulation in human skeletal muscle in association with obesity. The mechanisms implicated in these observations should be studied further.
    No preview · Article · Jan 2016 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Background and purpose: Contrary to usual static vascular imaging techniques, contrast-enhanced dynamic magnetic resonance angiography (dMRA) enables dynamic study of cerebral vessels. We evaluated dMRA ability to assess arterial occlusion, cerebral hemodynamics, and collateral circulation in acute ischemic stroke. Methods: Twenty-five acute ischemic stroke patients with proximal anterior circulation occlusion underwent dMRA on a 3T scanner within 12 hours of symptoms onset. Diffusion weighted imaging, Tmax6 s lesion volumes and hypoperfusion intensity ratio as volume of Tmax>6 s/volume of Tmax>10 s were measured. Site and grade of occlusion (Thrombolysis in Myocardial Infarction criteria) were evaluated on time-of-flight MRA and dMRA. Leptomeningeal collaterality (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [ASITN/SIR] Scale) and asymmetries in venous clearance were assessed exclusively on dMRA. Collateral filling was dichotomized into incomplete (ASITN/SIR 0-2) or complete (ASITN/SIR 3-4). Results: On dMRA, site of occlusion was M1 in 21 patients, tandem internal carotid artery/M1 in 2 and tandem internal carotid artery/terminal internal carotid artery in 2 patients. Three tandem occlusions were not detected on time-of-flight-MRA. All patients had Thrombolysis in Myocardial Infarction 0 to 1 on time-of-flight-MRA, but three of them had Thrombolysis in Myocardial Infarction 2 on dMRA. Complete collateral filling (n=12, 48%) was associated with smaller diffusion weighted imaging lesion volume (P=0.039), smaller hypoperfused volume (P=0.018), and lower hypoperfusion intensity ratio (P=0.006). Patients with symmetrical clearance of transverse sinuses (52%) were more likely to have complete collateral filling (P=0.015). Conclusions: As a fast, direct, feasible, noninvasive, and reliable method to assess site of occlusion, collateral circulation and hemodynamic alterations, dMRA provides profound insights in acute stroke.
    No preview · Article · Dec 2015 · Stroke
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    ABSTRACT: Objective: Circulating and adipose tissue markers of iron overload are increased in subjects with obesity. The aim is to study iron signals in adipose tissue. Methods: Adipose tissue R2* values and hepatic iron concentration (HIC) were evaluated using magnetic resonance imaging (MRI) in 23 middle-aged subjects with obesity and 20 subjects without obesity. Results: Subcutaneous (SAT) and visceral adipose tissue (VAT) R2* were increased in subjects with obesity (P = 0.004 and P = 0.008) and correlated significantly and positively with HIC in all subjects. Strikingly, most of the associations of liver iron with metabolic parameters were replicated with SAT and VAT R2*. BMI, waist circumference, fat mass, HOMA value, and C-reactive protein positively correlated with HIC and SAT and VAT R2*. BMI or percent fat mass (but not insulin resistance) contributed independently to 26.8-34.8% of the variance in sex- and age-adjusted SAT or VAT R2* (β > 0.40, P < 0.005). Within subjects with obesity, total cholesterol independently contributed to 14.8% of sex- and age-adjusted VAT iron variance (β = 0.50, P = 0.025). Conclusions: Increased R2* in adipose tissue, which might indicate iron content, runs in parallel to liver iron stores of subjects with obesity. VAT iron seems also associated with serum cholesterol within subjects with obesity.
    No preview · Article · Dec 2015 · Obesity
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    ABSTRACT: Context: Evidence from animals suggests that gut microbiota affects brain structure and function but evidence in humans is scarce. Objective: To evaluate potential interactions among gut microbiota composition, brain microstructure and cognitive tests in obese and non obese subjects. Design: Cross-sectional study. Setting: A tertiary hospital. Participants: Twenty consecutive obese and 19 non-obese subjects similar in age and sex. Main outcome measures: Gut microbiota (16S bacterial gene pyrosequencing), brain microstructure (diffusion tensor imaging (DTI) of brain white and grey matter and R2* sequences in MRI) and cognitive tests. Results: Hierarchical clustering revealed a specific gut microbiota-brain map profile for obese individuals who could be discriminated from non-obese subjects (accuracy of 0.81). Strikingly, Shannon index was linked to R2* and fractional anisotropy of the hypothalamus, caudate nucleus and hippocampus, suggesting sparing of these brain structures with increased bacterial biodiversity. Microbiota profile also clustered with cognitive function. The relative abundance of Actinobacteria phylum was linked not only to MRI DTI variables in the thalamus, hypothalamus and amygdala but also to cognitive test scores related to speed, attention, and cognitive flexibility. Conclusions: In sum, obesity status affects microbiota-brain microstructure and function crosstalk.
    No preview · Article · Oct 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Introduction: The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Methods: Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Results: Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Conclusions: Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival.
    No preview · Article · Oct 2015 · Neuroradiology
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    ABSTRACT: Rodent models have found that osteocalcin crosses the blood-brain barrier and regulates behavior. No data are available on osteocalcin's effects on brain microstructure and cognitive performance in humans. We evaluated the association between serum osteocalcin concentrations and a) brain microstructural changes on magnetic resonance imaging (MRI) and b) neuropsychological performance. We studied 24 consecutive obese subjects (13 women; age,49.8±8.1 years; body mass index [BMI],43.9±4.54 kg/m2) and 20 healthy volunteers (10 women; age, 48.8±9.5 years; BMI, 24.3±3.54 kg/m2) in a cross-sectional study within the multicenter FLORINASH Project. FLAIR signal intensity and DTI-metrics (primary (λ1), secondary (λ2), and tertiary (λ3) eigenvalues; fractional anisotropy (FA); and mean diffusivity) in the caudate, hypothalamus, thalamus, and putamen, and in subcortical white matter were assessed. Cognitive performance evaluated by neuropsychological test-battery. Lower osteocalcin concentrations were associated with BMI, higher λ1, λ2, and λ3 values at the caudate and lower FLAIR signal intensity at the caudate and putamen. Obese patients with lower osteocalcin concentrations had higher FA at putamen and thalamus. Lower osteocalcin concentrations were associated with higher Iowa Gambling Task (IGT) scores. FLAIR signal intensity at the caudate<601.832 yielded 85.7% sensitivity, 64.3% specificity, 70.6% negative predictive value, and 81.8% positive predictive value for IGT score. Lower osteocalcin was an independent predictor of worse cognitive performance on multivariate analysis (F=3.551, p=0.01343; R2=0.103). Bayesian information criterion demonstrated that osteocalcin had the predominant role in predicting IGT score. Lower serum osteocalcin concentrations are associated with brain microstructural changes and worse cognitive performance. This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Clinical Endocrinology
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    ABSTRACT: Background: We have theorized that clots with stasis are longer. We therefore explored the relationship between thrombus imaging characteristics on noncontrast computed tomography (NCCT) and magnetic resonance imaging (MRI) with clot length and pial collaterals on baseline computed tomography angiography (CTA). Methods: Prospective study of acute ischemic stroke patients (2005-2009) from Keimyung University. Patients with known stroke symptom onset time, baseline CTA, MRI, and with M1-Middle Cerebral Artery (MCA)±intracranial internal carotid artery (ICA) occlusions were included. Clot length and pial collaterals were measured on baseline CTA. Results: A total of 104 patients (mean age 65.1±12.28 years, 56.7% male, median baseline National Institutes of Health Stroke Scale 13) with intracranial ICA + MCA (n=50) or isolated M1-MCA (n=54) occlusions were included. Hyperdense sign on NCCT had a median clot length of 42.3 mm versus 29.5 mm when hyperdense negative (p=0.02). Clots showing blooming artifact on gradient recall echo MRI had a median length of 39.1 mm versus 24.5 mm without blooming (p=0.005). Patients with poor baseline collaterals on CTA had longer clots than those with intermediate/good collaterals (median clot length 49.4 mm vs 34.9 mm vs 20.5 mm respectively, p<0.001). In censored logistic regression modeling, clot length was an independent predictor of hyperdense sign (p=0.05) and of the presence of blooming artifact (p=0.006). Conclusions: Clot length and baseline collateral status are independent predictors of clot hyperdensity on NCCT and blooming artifact on gradient recall echo. Longer clots are more likely to be hyperdense and to bloom more, probably because portions of these clots are freshly formed locally due to of stasis of blood around the original clot. This stasis could be because of poor collaterals and inefficient angio-architecture within the cerebral arterial tree.
    Full-text · Article · Sep 2015 · The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
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    ABSTRACT: Background and aims: Obesity is an important determinant of increased cardiovascular risk. Increased fat mass has been assumed to constitute the main prominent contributor to changes in carotid intima-media thickness (c-IMT). Methods: In 421 consecutive subjects (301 women), c-IMT was evaluated ultrasonographically in 6 independent territories and body composition was assessed by dual-energy X-ray absorptiometry. Results: c-IMT was positively associated with lean body mass in both men (r = 0.328, p = <0.0001) and women (r = 0.268 p = <0.0001) and increased across lean mass quartiles (p = <0.0001 for linear-trend ANOVA). Stepwise linear regression analysis showed that age and lean mass (but not fat mass or traditional cardiovascular risk factors) contributed to 46.2% of c-IMT variance in men (p = <0.0001). Even within obese men, lean mass was an independent contributor to c-IMT variance. Among women, age, lean mass and ultrasensitive CRP levels contributed independently to 47.7% of c-IMT variance (p < 0.0001). Conclusions: Lean mass, and not fat mass, might contribute to increase c-IMT in obese patients independently of classical atherosclerotic risk factors. These data reinforce the concept that the increase in metabolically fat-free mass that accompanies the body weight enlargement is closely related to the raise in blood pressure.
    No preview · Article · Sep 2015 · Atherosclerosis
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    ABSTRACT: Lesion detection in acute stroke by computed-tomography perfusion (CTP) can be affected by incomplete bolus coverage in veins and hypoperfused tissue, so-called bolus truncation (BT), and low contrast-to-noise ratio (CNR). We examined the BT-frequency and hypothesized that image down-sampling and a vascular model (VM) for perfusion calculation would improve normo- and hypoperfused tissue classification. CTP datasets from 40 acute stroke patients were retrospectively analysed for BT. In 16 patients with hypoperfused tissue but no BT, repeated 2-by-2 image down-sampling and uniform filtering was performed, comparing CNR to perfusion-MRI levels and tissue classification to that of unprocessed data. By simulating reduced scan duration, the minimum scan-duration at which estimated lesion volumes came within 10 % of their true volume was compared for VM and state-of-the-art algorithms. BT in veins and hypoperfused tissue was observed in 9/40 (22.5 %) and 17/40 patients (42.5 %), respectively. Down-sampling to 128 × 128 resolution yielded CNR comparable to MR data and improved tissue classification (p = 0.0069). VM reduced minimum scan duration, providing reliable maps of cerebral blood flow and mean transit time: 5 s (p = 0.03) and 7 s (p < 0.0001), respectively). BT is not uncommon in stroke CTP with 40-s scan duration. Applying image down-sampling and VM improve tissue classification. • Too-short imaging duration is common in clinical acute stroke CTP imaging. • The consequence is impaired identification of hypoperfused tissue in acute stroke patients. • The vascular model is less sensitive than current algorithms to imaging duration. • Noise reduction by image down-sampling improves identification of hypoperfused tissue by CTP.
    Full-text · Article · Apr 2015 · European Radiology

  • No preview · Article · Apr 2015 · International Journal of Stroke
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    ABSTRACT: Objective Whether nonalcoholic fatty liver disease (NAFLD) can predict atherosclerosis in obese patients remains unclear. The aim of our study was to investigate the usefulness of NAFLD and other cardiometabolic parameters in predicting subclinical atherosclerosis in obese patients.Design, Patients and MeasurementsWe studied 314 consecutive obese subjects (223 women; mean age, 45.04±9.34 years; body mass index 44.3±5 Kg/m2) and 47 healthy lean individuals. Hepatic steatosis and atherosclerosis (carotid intima-media thickness [cIMT]>0.8 mm and/or presence of plaques) were evaluated ultrasonographically. Liver biopsies were obtained in 51 patients.ResultsIn obese patients, mean c-IMT was greater in those with NAFLD (P<0.001). Hepatic steatosis and age were independent predictors of atherosclerosis: the NAFLD-associated OR for atherosclerosis was 5.96 (95%CI, 1.60-22.25;p=0.008) in men and 8.26 (95%CI, 4.02-16.99;p<0.001) in women, and the age-associated OR for atherosclerosis was 1.14 (95%CI, 1.07-1.22; p<0.001) in men and 1.12 (95%CI, 1.08-1.17; p<0.001) in women. The sensitivity, specificity, and positive and negative predictive values of steatosis for atherosclerosis were 78.70%, 70.50%, 74.00%, and 75.60% (AUC=0.840) in men ≥43.5 years and 86.90%, 52.50%, 68.80%, and 76.80% (AUC=0.761) in women ≥47.5 years, respectively. Agreement between ultrasound-diagnosed steatosis and histology was good (ICC=0.79). Combined NAFLD and age was the strongest predictor of atherosclerosis in obesity.ConclusionsNAFLD and age may be independent risk factors for carotid atherosclerosis in obese individuals. Obese men and women with steatosis aged over 43.5 and 47.5 years, respectively, should be screened for carotid atherosclerosis. However, further evidence is necessary before suggesting an intervention based on current findings.This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Clinical Endocrinology
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    ABSTRACT: Arterial pulse wave velocity (PWV), an independent predictor of cardiovascular disease, physiologically increases with age; however, growing evidence suggests metabolic syndrome (MetS) accelerates this increase. Magnetic resonance imaging (MRI) enables reliable noninvasive assessment of arterial stiffness by measuring arterial PWV in specific vascular segments. We investigated the association between the presence of MetS and its components with carotid PWV (cPWV) in asymptomatic subjects without diabetes. We assessed cPWV by MRI in 61 individuals (mean age, 55.3 ± 14.1 years; median age, 55 years): 30 with MetS and 31 controls with similar age, sex, body mass index, and LDL-cholesterol levels. The study population was dichotomized by the median age. To remove the physiological association between PWV and age, unpaired t tests and multiple regression analyses were performed using the residuals of the regression between PWV and age. cPWV was higher in middle-aged subjects with MetS than in those without (p = 0.001), but no differences were found in elder subjects (p = 0.313). cPWV was associated with diastolic blood pressure (r = 0.276, p = 0.033) and waist circumference (r = 0.268, p = 0.038). The presence of MetS was associated with increased cPWV regardless of age, sex, blood pressure, and waist (p = 0.007). The MetS components contributing independently to an increased cPWV were hypertension (p = 0.018) and hypertriglyceridemia (p = 0.002). The presence of MetS is associated with an increased cPWV in middle-aged subjects. In particular, hypertension and hypertriglyceridemia may contribute to early progression of carotid stiffness.
    Full-text · Article · Nov 2014 · The International Journal of Cardiovascular Imaging
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    ABSTRACT: Context: Growing evidence implicates hypothalamic inflammation in the pathogenesis of diet-induced obesity and cognitive dysfunction in rodent models. Few studies have addressed the association between obesity and hypothalamic damage in humans and its relevance. Objective: To determine markers of obesity-associated hypothalamic damage on diffusion tensor imaging (DTI) and to determine whether DTI-metrics are associated with performance on cognitive testing. Design and Participants: This cross-sectional study analyzed DTI-metrics (primary (λ1), secondary (λ2), and tertiary (λ3) eigenvalues; fractional anisotropy (FA); and mean diffusivity (MD)) in the hypothalamus of 24 consecutive middle-aged obese subjects (13 women; 49.8 ± 8.1 years; body mass index [BMI] 43.9 ± 0.92 Kg/m(2)) and 20 healthy volunteers (10 women; 48.8 ± 9.5 years; BMI 24.3 ± 0.79 Kg/m(2)). Outcome: measures: Hypothalamic damage assessed by DTI-metrics and cognitive performance evaluated by neuropsychological test-battery. Results: λ1 values in the hypothalamus were significantly lower in obese subjects (P<0.0001). The sensitivity, specificity, and positive and negative predictive values for obesity-associated hypothalamic damage by λ1<1.072 were 75%, 87.5%, 83.3%, and 80.7%, respectively. Patients with hypothalamic λ1<1.072 had higher values of BMI, fat mass, inflammatory markers, carotid-intima media thickness, and hepatic steatosis and lower scores on cognitive tests. Combined BMI and alanine aminotransferase had the strongest association with hypothalamic damage reflected by λ1<1.072 (AUC=0.89). Conclusions: DTI detects obesity-associated hypothalamic damage associated with inflammatory markers and worse cognitive performance. This study highlights the potential utility of λ1 as a surrogate marker of obesity-associated hypothalamic damage.
    No preview · Article · Nov 2014 · Journal of Clinical Endocrinology & Metabolism

  • No preview · Article · Oct 2014 · International Journal of Stroke
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    ABSTRACT: Objective: The linkage among the tissue iron stores, insulin resistance (IR), and cognition remains unclear in the obese population. We aimed to identify the factors that contribute to increased hepatic iron concentration (HIC) and brain iron overload (BIO), as evaluated by MRI, and to evaluate their impact on cognitive performance in obese and nonobese subjects. Research design and methods: We prospectively recruited 23 middle-aged obese subjects without diabetes (13 women; age 50.4 ± 7.7 years; BMI 43.7 ± 4.48 kg/m2) and 20 healthy nonobese volunteers (10 women; age 48.8 ± 9.5 years; BMI 24.3 ± 3.54 kg/m2) in whom iron load was assessed in white and gray matter and the liver by MRI. IR was measured from HOMA-IR and an oral glucose tolerance test. A battery of neuropsychological tests was used to evaluate the cognitive performance. Multivariate regression analysis was used to identify the independent associations of BIO and cognitive performance. Results: A significant increase in iron load was detected at the caudate nucleus (P < 0.001), lenticular nucleus (P = 0.004), hypothalamus (P = 0.002), hippocampus (P < 0.001), and liver (P < 0.001) in obese subjects. There was a positive correlation between HIC and BIO at caudate (r = 0.517, P < 0.001), hypothalamus (r = 0.396, P = 0.009), and hippocampus (r = 0.347, P < 0.023). The area under the curve of insulin was independently associated with BIO at the caudate (P = 0.001), hippocampus (P = 0.028), and HIC (P = 0.025). BIOs at the caudate (P = 0.028), hypothalamus (P = 0.006), and lenticular nucleus (P = 0.012) were independently associated with worse cognitive performance. Conclusions: Obesity and IR may contribute to increased HIC and BIO being associated with worse cognitive performance. BIO could be a potentially useful MRI biomarker for IR and obesity-associated cognitive dysfunction.
    No preview · Article · Aug 2014 · Diabetes Care
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    ABSTRACT: Mast cells participate in atherogenesis by releasing cytokines to induce vascular cell protease expression. Tryptase is expressed highly in human atherosclerotic lesions and the inhibition of tryptase activity hampers its capacity to maintain cholesterol inside macrophague foam cells. We aimed to investigate the association between circulating tryptase levels and subclinical atherosclerosis through estimation of carotid intima-media thickness (c-IMT) as surrogate marker for increased cardiovascular risk in obese and non-obese subjects. Circulating tryptase levels (ELISA) and metabolic parameters were analyzed in 228 subjects. Atherosclerosis (c-IMT>0.9 mm) was evaluated ultrasonographically. Significant positive associations were evident between circulating tryptase levels and BMI, fat mass, glycated haemoglobin, fasting insulin, HOMAIR, fasting triglycerides and ultrasensitive PCR (p<0.05 from linear-trend ANOVA). The positive association between tryptase levels and insulin resistance parameters, suggested a glucose homeostasis impairment in individuals with higher tryptase levels. The negative asociation between tryptase levels and HDL-cholesterol supports the proatherogenic role of this protease (p<0.0001). Circulating tryptase levels were strongly associated with c-IMT measurements (p<0.0001 from linear-trend ANOVA), and were higher in subjects with presence of carotid plaque (p<0.0001). Tryptase levels (beta = 0.015, p = 0.001) contributed independently to subclinical atherosclerosis variance after controlling for cardiovascular risk factors (BMI, blood pressure, LDL-cholesterol). Circulating tryptase level is associated to obesity related parameters and has a close relation with various metabolic risk factors. Moreover, serum tryptase level was independently associated with c-IMT, suggesting its potential use as a surrogate marker for subclinical atherosclerosis in obese subjects.
    Full-text · Article · May 2014 · PLoS ONE
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    ABSTRACT: In the early days after ischemic stroke, information on structural brain damage from MRI supports prognosis of functional outcome. It is rated widely by the modified Rankin Scale that correlates only moderately with lesion volume. We therefore aimed to elucidate the influence of lesion location from early MRI (days 2-3) on functional outcome after 1 month using voxel-based lesion symptom mapping. We analyzed clinical and MRI data of patients from a prospective European multicenter stroke imaging study (I-KNOW). Lesions were delineated on fluid-attenuated inversion recovery images on days 2 to 3 after stroke onset. We generated statistic maps of lesion contribution related to clinical outcome (modified Rankin Scale) after 1 month using voxel-based lesion symptom mapping. Lesion maps of 101 patients with middle cerebral artery infarctions were included for analysis (right-sided stroke, 47%). Mean age was 67 years, median admission National Institutes of Health Stroke Scale was 11. Mean infarct volumes were comparable between both sides (left, 37.5 mL; right, 43.7 mL). Voxel-based lesion symptom mapping revealed areas with high influence on higher modified Rankin Scale in regions involving the corona radiata, internal capsule, and insula. In addition, asymmetrically distributed impact patterns were found involving the right inferior temporal gyrus and left superior temporal gyrus. In this group of patients with stroke, characteristic lesion patterns in areas of motor control and areas involved in lateralized brain functions on early MRI were found to influence functional outcome. Our data provide a novel map of the impact of lesion localization on functional stroke outcome as measured by the modified Rankin Scale.
    Full-text · Article · Apr 2014 · Stroke
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    ABSTRACT: WAKE-UP is a randomized, placebo-controlled MRI-based trial of thrombolysis in wake-up stroke using the mismatch between a lesion's visibility in diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) sequences as its main imaging inclusion criterion. Visual judgment of lesion conspicuity on FLAIR is however methodically limited by moderate inter-rater agreement. We therefore sought to improve rating homogeneity by incorporating quantitative signal intensity measurements. One hundred forty-three data sets of patients with acute ischemic stroke were visually rated by 8 raters with respect to WAKE-UP study inclusion and exclusion criteria, and inter-rater agreement was calculated. A subanalysis was performed on 45 cases to determine a threshold value of relative signal intensity (rSI) between the ischemic lesion and contralateral healthy tissue which best corresponded to a visually established verdict of FLAIR positivity. The usefulness of this threshold in improving inter-rater agreement was evaluated in an additional sample of 50 patients. Inter-rater agreement for inclusion into the WAKE-UP trial was 73% with a free-marginal κ of 0.46. A threshold of rSI which best correlated with the visual rating of lesions as FLAIR positive was 1.20. The addition of rSI measurements to visual evaluation did not change the inter-rater agreement. Introducing a semiquantitative measure for FLAIR rSI did not improve the agreement between individual raters. However, enhancing visual assessment with rSI measurements can provide reassurance to local investigators in cases of uncertainty.
    Preview · Article · Feb 2014 · Stroke
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    ABSTRACT: Recently, serum lipopolysaccharide-binding protein (LBP) has been closely associated with coronary artery disease. Here, we aimed to investigate the possible relationship between serum LBP and markers of atherosclerosis. Serum LBP and carotid intima media thickness (C-IMT) were measured in 332 subjects (101 men and 231 women) who were recruited from an ongoing multicenter project. Serum LBP was significantly associated with obesity [BMI, fat mass and waist circumference (r > 0.38, p < 0.0001)], HOMA (r = 0.36, p < 0.0001) and high sensitivity CRP (hsCRP) (r = 0.50, p < 0.0001). Circulating LBP was also positively associated with C-IMT (r = 0.27, p < 0.0001). Circulating LBP (β = 0.16; p = 0.001) contributed independently to C-IMT variance, after controlling for the effects of age, gender, BMI and hsCRP. Of note, circulating LBP was found to be increased in the population with carotid plaque (n = 50; 32.7 ± 12.5 vs 28.7 ± 10.7; p = 0.021). The consistent association between serum LBP and the carotid intima media thickness, a widely used atherosclerosis marker, reveals serum LBP as a putative factor related to atherosclerosis.
    No preview · Article · Oct 2013 · Atherosclerosis
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    ABSTRACT: Cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAo) in rodents has been proposed as an experimental model of white matter damage and vascular dementia. However, the histopathological and behavioral alterations reported in this model are variable and a full characterization of the dynamic alterations is not available. Here we implemented a longitudinal multimodal magnetic resonance imaging (MRI) design, including time-of-flight angiography, high resolution T1-weighted images, T2 relaxometry mapping, diffusion tensor imaging, and cerebral blood flow measurements up to 12 weeks after BCCAo or sham-operation in Wistar rats. Changes in MRI were related to behavioral performance in executive function tasks and histopathological alterations in the same animals. MRI frequently (70%) showed various degrees of acute ischemic lesions, ranging from very small to large subcortical infarctions. Independently, delayed MRI changes were also apparent. The patterns of MRI alterations were related to either ischemic necrosis or gliosis. Progressive microstructural changes revealed by diffusion tensor imaging in white matter were confirmed by observation of myelinated fiber degeneration, including severe optic tract degeneration. The latter interfered with the visually cued learning paradigms used to test executive functions. Independently of brain damage, BCCAo induced progressive arteriogenesis in the vertebrobasilar tree, a process that was associated with blood flow recovery after 12 weeks. The structural alterations found in the basilar artery were compatible with compensatory adaptive changes driven by shear stress. In summary, BCCAo in rats induces specific signatures in multimodal MRI that are compatible with various types of histological lesion and with marked adaptive arteriogenesis.
    Full-text · Article · Sep 2013 · PLoS ONE

Publication Stats

548 Citations
218.29 Total Impact Points

Institutions

  • 2014-2015
    • Instituto de Salud Carlos III
      • CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM)
      Madrid, Madrid, Spain
  • 2013-2015
    • IDIBGI Girona Biomedical Research Institute
      Girona, Catalonia, Spain
    • Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y la Nutrición (CIBERobn)
      Santiago, Galicia, Spain
  • 2006-2015
    • Hospital Universitari de Girona Dr. Josep Trueta
      Girona, Catalonia, Spain
  • 2011-2013
    • Universitat de Girona
      Girona, Catalonia, Spain
  • 2010
    • Autonomous University of Barcelona
      • Department of Medicine
      Cerdanyola del Vallès, Catalonia, Spain
  • 2007
    • Clinica Girona
      Girona, Catalonia, Spain