Facemask analyses for the non-invasive detection of chronic and acute P. aeruginosa lung infections using nanoparticle-based immunoassays.

Pseudomonas aeruginosa (P. aeruginosa) is a pathogen that persistently colonizes the respiratory tract of patients with chronic lung diseases. The risk of acquiring a chronic P. aeruginosa infection can be minimized by rapidly detecting the pathogen in the patient's airways and promptly administrating adequate antibiotics. However, the rapid detection of P. aeruginosa in the lungs involves the analysis of sputum, which is a highly complex matrix that is not always available. Here, we propose an alternative diagnosis based on analyzing breath aerosols. In this approach, nanoparticle immunosensors identify bacteria adhered to the polypropylene layer of a surgical facemask that was previously worn by the patient. A polypropylene processing protocol was optimized to ensure the efficient capture and analysis of the target pathogen. The proposed analytical platform has a theoretical limit of detection of 105 CFU mL-1 in aerosolized mock samples, and a dynamic range between 105 and 108 CFU mL-1. When tested with facemasks worn by patients, the biosensors were able to detect chronic and acute P. aeruginosa lung infections, and to differentiate them from respiratory infections caused by other pathogens. The results shown here pave the way to diagnose Pseudomonas infections at the bedside, as well as to identify the progress from chronic to acute infection.

Association between coffee consumption and total dietary caffeine intake with cognitive functioning: cross-sectional assessment in an elderly Mediterranean population.

PURPOSE: Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS). METHODS: PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment. RESULTS: Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44-0.90 and OR 0.56; 95% CI 0.38-0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47-0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A). CONCLUSIONS: Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS. TRIAL REGISTRATION: ISRCTN89898870. Registration date: July 24, 2014.

Prevalence of distal renal tubular acidosis in patients with calcium phosphate stones.

INTRODUCTION AND PURPOSE: Distal renal tubular acidosis (DRTA) is a metabolic disorder that associates urolithiasis and urinary pH > 6. The prevalence of DRTA in patients with calcium phosphate stones is not well known. The objective is to determine the prevalence of DRTA in patients with calcium phosphate stones and urinary pH above 6 based on the furosemide test. METHODS: A total of 54 patients with calcium phosphate stones and urinary pH above 6.0 were submitted to the furosemide test. The association of DRTA with age, sex, type of stone, stone recurrence, stone bilaterality, 24-h urine biochemistry, and adverse effects of the furosemide test were examined. RESULTS: The furosemide test indicated that 19 of 54 patients (35.2%) had DRTA. The sex ratio was similar in the two groups (p < 0.776). The DRTA group was significantly younger (p < 0.001), and had a higher prevalence of bilateral stones (p < 0.001), a higher prevalence of recurrent stones (p < 0.04), a lower plasma potassium level (p < 0.001), a higher urinary Ca level (p ≤ 0.05), and a lower urinary citrate level (p < 0.001). None of the patients reported adverse effects from the furosemide test. CONCLUSIONS: There was a high prevalence of DTRA in patients with urinary pH above 6 and calcium phosphate stones. Young age, bilateral stones, stone recurrence, hypercalciuria, hypocitraturia, and plasma hypokalemia were associated with DRTA. None of the patients reported adverse effects of the furosemide test.

Structure-function relationship in COPD revisited: an in vivo microscopy view.

BACKGROUND: Fibred confocal fluorescence microscopy (FCFM) is a novel technology that allows the in vivo assessment and quantification during bronchoscopy of the bronchial wall elastic fibre pattern, alveolar and vessel diameters and thickness of the elastic fibre in the alveolar wall. AIMS: To relate these structural characteristics with lung function parameters in healthy subjects, smokers with normal spirometry and patients with chronic obstructive pulmonary disease (COPD). METHODS: We performed FCFM in 20 never smokers, 20 smokers with normal spirometry and 23 patients with COPD who required bronchoscopy for clinical reasons. The bronchial wall elastic fibre pattern was classified as lamellar, loose and mixed pattern, and later confirmed pathologically. Airspace dimensions and extra-alveolar vessel diameters were measured. Lung function measurements and pulmonary CT scans were obtained in all participants. RESULTS: Patients with COPD were characterised by a significantly higher prevalence of loose fibre bronchial deposition pattern and larger alveolar diameter which correlated inversely with several lung function parameters (forced expiratory volume in 1 s (FEV1) , FEV1/forced vital capacity ratio, maximum expiratory flow, carbon monoxide transfer factor and carbon monoxide transfer coefficient; p<0.05). Increased alveolar macrophages were demonstrated in active smokers with or without COPD. CONCLUSIONS: This is the first FCFM study to describe in vivo microscopic changes in the airways and alveoli of patients with COPD that are related to lung function impairment. These findings open the possibility of assessing the in vivo effects of therapeutic interventions for COPD in future studies.

Full kinetic modeling analysis of [18F]fluorocholine Positron Emission Tomography (PET) at initial diagnosis of high-grade glioma.

PURPOSE: The main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. MATERIALS AND METHODS: Twenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. RESULTS: Tumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808-0.861), SUVmean (r = 0.794-0.851) and TBR (r = 0.643-0.784), p < 0.002. HGG was confirmed in 21 patients, of which those with methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter showed higher mean Ki (p = 0.020), K1 (p = 0.025) and TBR (p = 0.001) than the unmethylated ones. CONCLUSION: [18F]F-CHO uptake kinetics in HGG is best explained by a 2-tissue-compartment model. The conventional static [18F]F-CHO-PET measures have been validated against the perfusion-transport constant (K1) and the net influx rate (Ki) derived from kinetic modeling. A relationship between [18F]F-CHO uptake rate and MGMT methylation is suggested but needs further confirmation.

Redefining the Role of Bronchoscopy in the Workup of Severe Uncontrolled Asthma in the Era of Biologics: A Prospective Study.

BACKGROUND: Severe uncontrolled asthma (SUA) is frequently treated with biologic therapy if a T2 phenotype is found. Bronchoscopy is not routinely recommended in these patients unless a specific indication to rule out comorbidities is present. RESEARCH QUESTION: Is routine bronchoscopy safe and useful in phenotyping and endotyping patients with SUA before the indication of a biologic therapy? STUDY DESIGN AND METHODS: Prospective study of consecutive patients with SUA who were referred to a specialized asthma clinic to assess the indication of a biologic therapy. Patients were clinically phenotyped as T2-allergic, T2-eosinophilic, and non-T2. All patients underwent bronchoscopy, and systematic data collection of endoscopic findings, microbiology of bronchial aspirate, and presence of eosinophils in bronchial biopsy were recorded and compared between asthma phenotypes. Cluster analysis was performed accordingly. RESULTS: One hundred patients were recruited and classified as T2-allergic (28%), T2-eosinophilic (64%), and non-T2 (8%). On bronchoscopy, signs of gastroesophageal reflux disease were detected in 21%, vocal cord dysfunction in 5%, and tracheal abnormalities in 3%. Bronchial aspirate culture isolated bacteria in 27% of patients and fungi in 14%. Three clusters were identified: nonspecific, upper airway, and infection, the latter being less frequently associated with submucosal eosinophilia. Eosinophils were detected in 91% of bronchial biopsies. Despite a correlation to blood eosinophils, five patients with T2-phenotypes showed no eosinophils in bronchial biopsy, and three patients with non-T2 showed eosinophils in bronchial biopsy. Only one patient had moderate bleeding. INTERPRETATION: Routine bronchoscopy in SUA eligible for biologic therapy is a safe procedure that can help to better phenotype and personalize asthma management.

Association between ankle-brachial index and cognitive function in participants in the PREDIMED-Plus study: cross-sectional assessment.

INTRODUCTION AND OBJECTIVES: The ankle-brachial index (ABI) is an indicator of peripheral artery disease (PAD). The aim of this study was to assess the association between PAD, measured with the ABI, and cognitive function in persons with overweight or obesity and metabolic syndrome. METHODS: Cross-sectional study conducted with baseline data from the PREDIMED-Plus study, which included 4898 participants (after exclusion of those without ABI measurements) aged between 55 and 75 years, and with overweight or obesity and metabolic syndrome. At the baseline assessment, we measured the ABI with a standardized protocol and assessed the presence of other cardiovascular risk factors (eg, diabetes, dyslipidemia, hypertension). Cognitive function was evaluated using several tests validated for the Spanish population (mini-mental state examination [MMSE], phonological and semantic verbal fluency test, WAIS-III working memory index [WMI], parts A and B of the trail making test (TMT), and clock drawing test). Generalized linear models were used to assess the association between the ABI and cognitive function. RESULTS: Among the participants, 3.4% had PAD defined as ABI ≤ 0.9, and 3.3% had arterial calcification defined as ABI ≥ 1.4. PAD was associated with age, systolic blood pressure and obesity indicators, while arterial calcification was also associated with obesity and diabetes. No significant associations were observed between cognitive function and ABI or PAD. CONCLUSIONS: In our sample, the presence of PAD increased with age, blood pressure, and obesity. No significant association was observed between ABI, PAD, or cognitive function.

Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk.

BACKGROUND AND AIMS: The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome. METHODS: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≤1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure. RESULTS: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≤1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48]). CONCLUSIONS: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed.

Increased rate of FEV1 decline in HIV patients despite effective treatment with HAART.

INTRODUCTION: Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immune-viral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. METHODS: We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. RESULTS: We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. DISCUSSION: Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population.

Tromboc@t Working Group recommendations for management in patients receiving direct oral anticoagulants. / Recomendaciones del Grupo Catalán de Trombosis (Tromboc@t Working Group) para el tratamiento de los pacientes que reciben anticoagulantes orales directos.

BACKGROUND AND OBJECTIVES: In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation. MATERIAL AND METHODS: A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence. RESULTS: As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs. CONCLUSIONS: Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs.

Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis. METHODS: The expression of TLR-2, TLR-4 and CD14 in monocytes was analyzed by flow cytometry. To study the functional responses of these receptors, monocytes were stimulated with peptidoglycan or lipopolysaccharide and the amounts of TNFalpha and IL-6 secreted were determined by ELISA. RESULTS: We found that the expression of TLR-2 was up-regulated in peripheral blood monocytes from COPD patients, either clinically stable or during AECOPD, as compared to never smokers or smokers with normal lung function. Upon stimulation with TLR-2 ligand monocytes from COPD patients secreted increased amounts of cytokines than similarly stimulated monocytes from never smokers and smokers. In contrast, the expressions of TLR-4 and CD14 were not significantly different between groups, and the response to lipopolysaccharide (a TLR-4 ligand) stimulation was not significantly different either. At discharge from hospital TLR-2 expression was down-regulated in peripheral blood monocytes from AECOPD patients. This could be due to the treatment with systemic steroids because, in vitro, steroids down-regulated TLR-2 expression in a dose-dependent manner. Finally, we demonstrated that IL-6, whose plasma levels are elevated in patients, up-regulated in vitro TLR-2 expression in monocytes from never smokers. CONCLUSION: Our results reveal abnormalities in TLRs expression in COPD patients and highlight its potential relationship with systemic inflammation in these patients.

Pulmonary and systemic hepatocyte and keratinocyte growth factors in patients with chronic obstructive pulmonary disease.

BACKGROUND: The potential role of growth factors in chronic obstructive pulmonary disease (COPD) has begun to be addressed only recently and is still poorly understood. For this study, we investigated potential abnormalities of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in patients with COPD. METHODS: To this end, we compared the levels of HGF and KGF, measured by enzyme-linked immunosorbent assay (ELISA), in bronchoalveolar lavage (BAL) fluid and in serum in 18 patients with COPD (62 +/- 9 yrs, forced expiratory volume in one second [FEV1] 57 +/- 12% ref, X +/- standard deviation of mean), 18 smokers with normal lung function (58 +/- 8 yrs, FEV1 90 +/- 6% ref) and 8 never smokers (67 +/- 9 yrs, 94 +/- 14% ref). RESULTS: We found that in BAL, HGF levels were higher in patients with COPD than in the other two groups whereas, in serum, HGF concentration was highest in smokers with normal lung function (p < 0.01). KGF levels were not significantly different between groups, neither in blood nor in BAL (most values were below the detection limit). CONCLUSIONS: These results highlight a different response of HGF in BAL and serum in smokers with and without COPD that may be relevant for tissue repair in COPD.