Cardiorenal Outcomes Among Patients With Atrial Fibrillation Treated With Oral Anticoagulants.

RATIONALE & OBJECTIVE: Direct oral anticoagulants (DOACs) have progressively replaced vitamin K antagonists (VKAs) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). DOACs cause fewer bleeding complications, but their other advantages, particularly related to kidney outcomes, remain inconclusive. We studied the risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) after DOAC and VKA administration for nonvalvular AF. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Cohort study of Swedish patients enrolled in the Stockholm Creatinine Measurements (SCREAM) project with a diagnosis of nonvalvular AF during 2011-2018. EXPOSURE: Initiation of DOAC or VKA treatment. OUTCOME: Primary outcomes were CKD progression (composite of >30% estimated glomerular filtration rate [eGFR] decline and kidney failure) and AKI (by diagnosis or KDIGO-defined transient creatinine elevations). Secondary outcomes were death, major bleeding, and the composite of stroke and systemic embolism. ANALYTICAL APPROACH: Propensity score weighted Cox regression was used to balance 50 baseline confounders. Sensitivity analyses included falsification end points, subgroups, and estimation of per-protocol effects. RESULTS: We included 32,699 patients (56% initiated DOAC) who were observed for a median of 3.8 years. Their median age was 75 years, 45% were women, and 27% had an eGFR <60mL/min/1.73m2. The adjusted HRs for DOAC versus VKA were 0.87 (95% CI, 0.78-0.98) for the risk of CKD progression and 0.88 (95% CI, 0.80-0.97) for AKI. HRs were 0.77 (95% CI, 0.67-0.89) for major bleeding, 0.93 (95% CI, 0.78-1.11) for the composite of stroke and systemic embolism, and 1.04 (95% CI, 0.95-1.14) for death. The results were similar across subgroups of age, sex, and baseline eGFR when restricting to patients at high risk for thromboembolic events and when censoring follow up at treatment discontinuation or change in type of anticoagulation. LIMITATIONS: Missing information on time in therapeutic range and treatment dosages. CONCLUSIONS: Among patients with nonvalvular AF treated in routine clinical practice compared with VKA use, DOAC use was associated with a lower risk of CKD progression, AKI, and major bleeding but a similar risk of the composite of stroke, systemic embolism, or death.

Nutritional inter-dependencies and a carbazole-dioxygenase are key elements of a bacterial consortium relying on a Sphingomonas for the degradation of the fungicide thiabendazole.

Thiabendazole (TBZ), is a persistent fungicide/anthelminthic and a serious environmental threat. We previously enriched a TBZ-degrading bacterial consortium and provided first evidence for a Sphingomonas involvement in TBZ transformation. Here, using a multi-omic approach combined with DNA-stable isotope probing (SIP) we verified the key degrading role of Sphingomonas and identify potential microbial interactions governing consortium functioning. SIP and amplicon sequencing analysis of the heavy and light DNA fraction of cultures grown on 13 C-labelled versus 12 C-TBZ showed that 66% of the 13 C-labelled TBZ was assimilated by Sphingomonas. Metagenomic analysis retrieved 18 metagenome-assembled genomes with the dominant belonging to Sphingomonas, Sinobacteriaceae, Bradyrhizobium, Filimonas and Hydrogenophaga. Meta-transcriptomics/-proteomics and non-target mass spectrometry suggested TBZ transformation by Sphingomonas via initial cleavage by a carbazole dioxygenase (car) to thiazole-4-carboxamidine (terminal compound) and catechol or a cleaved benzyl ring derivative, further transformed through an ortho-cleavage (cat) pathway. Microbial co-occurrence and gene expression networks suggested strong interactions between Sphingomonas and a Hydrogenophaga. The latter activated its cobalamin biosynthetic pathway and Sphingomonas its cobalamin salvage pathway to satisfy its B12 auxotrophy. Our findings indicate microbial interactions aligning with the 'black queen hypothesis' where Sphingomonas (detoxifier, B12 recipient) and Hydrogenophaga (B12 producer, enjoying detoxification) act as both helpers and beneficiaries.

Stopping renin-angiotensin system inhibitors after hyperkalemia and risk of adverse outcomes.

BACKGROUND: Stopping renin-angiotensin system inhibitors (RASi) after an episode of hyperkalemia is common but may involve therapeutic compromises, in that the cessation of RASi deprives patients of their beneficial cardiovascular effects. METHODS AND RESULTS: Observational study from the Stockholm Creatinine Measurements (SCREAM) project including patients initiating RASi in routine care and surviving a first-detected episode of hyperkalemia (potassium >5.0 mmol/L). We used target trial emulation techniques based on cloning, censoring and weighting to compare stopping vs. continuing RASi within 6 months after hyperkalemia. Outcomes were 3-year risks of mortality, major adverse cardiovascular events (MACE, composite of cardiovascular death, myocardial infarction and stroke hospitalization) and recurrent hyperkalemia. Of 5669 new users of RASi who developed hyperkalemia (median age 72 years, 44% women), 1425 (25%) stopped RASi therapy within 6 months. Compared with continuing RASi, stopping therapy was associated with a higher 3-year risk of death (absolute risk difference 10.8%; HR 1.49, 95% CI 1.34-1.64) and MACE (risk difference 4.7%; HR 1.29, 1.14-1.45), but a lower risk of recurrent hyperkalemia (risk difference -9.5%; HR 0.76, 0.69-0.84). Results were consistent for events following potassium of >5.0 or >5.5 mmol/L, after censoring when the treatment decision was changed, across prespecified subgroups, and after adjusting for albuminuria. CONCLUSION: These findings suggest that stopping RASi after hyperkalemia may be associated with a lower risk of recurrence of hyperkalemia, but higher risk of death and cardiovascular events.

Nitrogen use efficiency, rhizosphere bacterial community, and root metabolome reprogramming due to maize seed treatment with microbial biostimulants.

Seed inoculation with beneficial microorganisms has gained importance as it has been proven to show biostimulant activity in plants, especially in terms of abiotic/biotic stress tolerance and plant growth promotion, representing a sustainable way to ensure yield stability under low input sustainable agriculture. Nevertheless, limited knowledge is available concerning the molecular and physiological processes underlying the root-inoculant symbiosis or plant response at the root system level. Our work aimed to integrate the interrelationship between agronomic traits, rhizosphere microbial population and metabolic processes in roots, following seed treatment with either arbuscular mycorrhizal fungi (AMF) or Plant Growth-Promoting Rhizobacteria (PGPR). To this aim, maize was grown under open field conditions with either optimal or reduced nitrogen availability. Both seed treatments increased nitrogen uptake efficiency under reduced nitrogen supply revealed some microbial community changes among treatments at root microbiome level and limited yield increases, while significant changes could be observed at metabolome level. Amino acid, lipid, flavone, lignan, and phenylpropanoid concentrations were mostly modulated. Integrative analysis of multi-omics datasets (Multiple Co-Inertia Analysis) highlighted a strong correlation between the metagenomics and the untargeted metabolomics datasets, suggesting a coordinate modulation of root physiological traits.

Comprehensive comparison of stroke risk score performance: a systematic review and meta-analysis among 6 267 728 patients with atrial fibrillation.

AIMS: Multiple risk scores to predict ischaemic stroke (IS) in patients with atrial fibrillation (AF) have been developed. This study aims to systematically review these scores, their validations and updates, assess their methodological quality, and calculate pooled estimates of the predictive performance. METHODS AND RESULTS: We searched PubMed and Web of Science for studies developing, validating, or updating risk scores for IS in AF patients. Methodological quality was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). To assess discrimination, pooled c-statistics were calculated using random-effects meta-analysis. We identified 19 scores, which were validated and updated once or more in 70 and 40 studies, respectively, including 329 validations and 76 updates-nearly all on the CHA2DS2-VASc and CHADS2. Pooled c-statistics were calculated among 6 267 728 patients and 359 373 events of IS. For the CHA2DS2-VASc and CHADS2, pooled c-statistics were 0.644 [95% confidence interval (CI) 0.635-0.653] and 0.658 (0.644-0.672), respectively. Better discriminatory abilities were found in the newer risk scores, with the modified-CHADS2 demonstrating the best discrimination [c-statistic 0.715 (0.674-0.754)]. Updates were found for the CHA2DS2-VASc and CHADS2 only, showing improved discrimination. Calibration was reasonable but available for only 17 studies. The PROBAST indicated a risk of methodological bias in all studies. CONCLUSION: Nineteen risk scores and 76 updates are available to predict IS in patients with AF. The guideline-endorsed CHA2DS2-VASc shows inferior discriminative abilities compared with newer scores. Additional external validations and data on calibration are required before considering the newer scores in clinical practice. CLINICAL TRIAL REGISTRATION: ID CRD4202161247 (PROSPERO).

Validation of risk scores for ischaemic stroke in atrial fibrillation across the spectrum of kidney function.

AIMS: The increasing prevalence of ischaemic stroke (IS) can partly be explained by the likewise growing number of patients with chronic kidney disease (CKD). Risk scores have been developed to identify high-risk patients, allowing for personalized anticoagulation therapy. However, predictive performance in CKD is unclear. The aim of this study is to validate six commonly used risk scores for IS in atrial fibrillation (AF) patients across the spectrum of kidney function. METHODS AND RESULTS: Overall, 36 004 subjects with newly diagnosed AF from SCREAM (Stockholm CREAtinine Measurements), a healthcare utilization cohort of Stockholm residents, were included. Predictive performance of the AFI, CHADS2, Modified CHADS2, CHA2DS2-VASc, ATRIA, and GARFIELD-AF risk scores was evaluated across three strata of kidney function: normal kidney function [estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2], mild CKD (eGFR 30-60 mL/min/1.73 m2), and advanced CKD (eGFR <30 mL/min/1.73 m2). Predictive performance was assessed by discrimination and calibration. During 1.9 years, 3069 (8.5%) patients suffered an IS. Discrimination was dependent on eGFR: the median c-statistic in normal eGFR was 0.75 (range 0.68-0.78), but decreased to 0.68 (0.58-0.73) and 0.68 (0.55-0.74) for mild and advanced CKD, respectively. Calibration was reasonable and largely independent of eGFR. The Modified CHADS2 score showed good performance across kidney function strata, both for discrimination [c-statistic: 0.78 (95% confidence interval 0.77-0.79), 0.73 (0.71-0.74) and 0.74 (0.69-0.79), respectively] and calibration. CONCLUSION: In the most clinically relevant stages of CKD, predictive performance of the majority of risk scores was poor, increasing the risk of misclassification and thus of over- or undertreatment. The Modified CHADS2 score performed good and consistently across all kidney function strata, and should therefore be preferred for risk estimation in AF patients.

Gas exchange, vine performance and modulation of secondary metabolism in Vitis vinifera L. cv Barbera following long-term nitrogen deficit.

MAIN CONCLUSION: A reprogramming of secondary metabolism to acclimate to nitrogen deficiency was seen in grapevine eliciting an accumulation of strigolactones and jasmonate. This response links with photosynthetic compensation and enhanced ripening. In addition to the metabolism directly related to nitrogen assimilation, long-term nitrogen depletion may affect plant secondary metabolism, in turn affecting grapevine performance. In this work, the effect of nitrogen deficit was investigated in V. vinifera cv. Barbera potted vines following three years of deprivation, using a combination of morpho-physiological assessments and mass spectrometry-based untargeted metabolomics. Plants grown under nitrogen limitation showed reduced growth and even more curtailed yields, lowered SPAD values, and a quite preserved leaf gas exchange, compared to plants grown under non-limiting nitrogen availability. Ripening was decidedly accelerated, and berry composition improved in terms of higher sugar and phenolic contents under nitrogen-limiting conditions. Metabolomics showed the broad involvement of secondary metabolism in acclimation to nitrogen deficiency, including a distinctive modulation of the phytohormone profile. Several nitrogen-containing metabolites were down accumulated under nitrogen-limiting conditions, including alkaloids, glucosinolates, hypoxanthine, and inosine. On the other hand, phenylpropanoids showed an accumulation trend. Concerning the recruitment of hormones, nitrogen deprivation elicited an accumulation of strigolactones and jasmonate. Noteworthy, both strigolactones and jasmonates have been previously related to increased photosynthetic efficiency under abiotic stress. Furthermore, the severe reduction of lateral shoot development we recorded in N-deprived vines is consistent with the accumulation of strigolactones. Overall, our results suggest that nitrogen deprivation induced a rather broad metabolic reprogramming, mainly including secondary metabolism and hormones profile, reflected in the modulation of photosynthetic performance, canopy growth, and possibly fruit quality.

Impact of Climatic Conditions on the Resveratrol Concentration in Blend of Vitis vinifera L. cvs. Barbera and Croatina Grape Wines.

The aim of this work was to investigate the effect of meteorological conditions on resveratrol concentration of red wines produced in Piacenza viticultural region (Italy). In this regard, six representative estates producing Colli Piacentini Gutturnio DOC (a blend of V. vinifera L. cvs. Barbera and Croatina) vintage wines were analysed for trans- and cis-resveratrol over an 8-year period (1998-2005). Grapes were taken from the same vineyard in each estate by using the same enological practices over the entire investigated period. The meteorological conditions corresponding to the production areas were recorded, and bioclimatic indices were calculated as well. Overall, cis-resveratrol concentration was negatively correlated to Huglin index and August mean temperature, whilst positive correlation coefficients were found when considering the Selianinov index and the rainfall of September.

Identification of markers of sensory quality in ground coffee: an untargeted metabolomics approach.

INTRODUCTION: In the last years, consumers increased the demand for high-quality and healthy beverages, including coffee. To date, among the techniques potentially available to determine the overall quality of coffee beverages, metabolomics is emerging as a valuable tool. OBJECTIVE: In this study, 47 ground coffee samples were selected during the 2018 Edition of the "International coffee tasting" (ICT) in order to provide discrimination based on both chemical and sensory profiles. In particular, 20 samples received a gold medal ("high quality" group), while lower sensory scores characterized 27 samples (without medal). METHODS: Untargeted metabolomics based on ultra-high pressure liquid chromatography coupled with quadrupole-time-of-flight (UHPLC-QTOF) and head space-gas chromatography coupled with mass spectrometry platforms followed by multivariate statistical approaches (i.e., both supervised and unsupervised) were used to provide new insight into the searching of potential markers of sensory quality. RESULTS: Several compounds were identified, including polyphenols, alkaloids, diazines, and Maillard reaction products. Also, the headspace/GC-MS highlighted the most important volatile compounds. Polyphenols were scarcely correlated to the sensory parameters, whilst the OPLS-DA models built using typical coffee metabolites and volatile/Maillard compounds possessed prediction values > 0.7. The "high quality" group showed specific metabolomic signatures, thus corroborating the results from the sensory analysis. Overall, methyl pentanoate (ROC value = 0.78), 2-furfurylthiol (ROC value = 0.75), and L-Homoserine (ROC value = 0.74) established the higher number of significant (p < 0.05) correlations with the sensory parameters. CONCLUSION: Although ad-hoc studies are advisable to further confirm the proposed markers, this study demonstrates the suitability of untargeted metabolomics for evaluating coffee quality and the potential correlations with the sensory attributes.

Short- and long-term outcomes after incident pneumonia in adults with chronic kidney disease: a time-dependent analysis from the Stockholm CREAtinine Measurement project.

BACKGROUND: Little is known about the health sequelae of pneumonia in persons with chronic kidney disease (CKD). METHODS: We studied adults with CKD in Stockholm during 2006-11, who not previously been diagnosed with lower respiratory tract infections. We used multivariable-adjusted Cox regression with pneumonia as a time-varying exposure to estimate hazard ratios (HRs) [95% confidence intervals (CIs)] for the events of death, major adverse cardiovascular events (MACEs), acute kidney injury (AKI), CKD progression or hospitalization for urinary tract infections (UTIs)/sepsis. Cataract and knee/joint replacement served as negative control outcomes. RESULTS: We identified 71 931 adults (mean age 79 years, 59% women), of whom 8379 (12%) were diagnosed with pneumonia during follow-up; incident pneumonia was associated with 10 times higher adjusted mortality risk during the first 90 days [HR = 10.0, 95% confidence interval (CI) 9.5-10.5] and double the mortality beyond 90 days from pneumonia diagnosis (HR = 2.0; 95% CI 1.9-2.1). Incident pneumonia was similarly associated with higher adjusted risk of MACE (<90 days: HR = 12.6; 95% CI 12.0-13.3; ≥90 days: HR = 1.5; 95% CI 1.4-1.6). The adjusted risk of CKD progression and UTI/sepsis hospitalization was highest within 90 days from pneumonia but remained elevated thereafter. For AKI, the association with incident pneumonia was only seen within 90 days. Neither cataract nor knee/joint replacement was related to pneumonia. CONCLUSIONS: Incident pneumonia was associated with increased risks of MACE, CKD progression, severe UTI/sepsis and death, with risks highest soon after pneumonia diagnosis but extending beyond 90 days. Our findings highlight the susceptibility for adverse outcomes of CKD patients following pneumonia diagnosis, and may inform clinical decisions regarding vaccination strategies.

Fractures and their sequelae in non-dialysis-dependent chronic kidney disease: the Stockholm CREAtinine Measurement project.

INTRODUCTION: People undergoing maintenance dialysis are at high risk for fractures, but less is known about fracture incidence and associated outcomes in earlier stages of chronic kidney disease (CKD). METHODS: We conducted an observational analysis from the Stockholm Creatinine Measurement project, a Swedish health care utilization cohort during 2006-11. We identified all adults with confirmed CKD Stages 3-5 and no documented history of fractures and extracted information on comorbid history, ongoing medication, cardiovascular events and death. We studied incidence rates of fractures (overall and by location), with the estimated glomerular filtration rate (eGFR) as time-dependent exposure. We then studied hazard ratios [HRs and 95% confidence intervals (CIs)] for the events of death and major adverse cardiac events (MACE) using Cox regression with fracture as time-varying exposure. RESULTS: We identified 68 764 individuals with confirmed CKD (mean age 79 years, 56% women). During a median follow-up of 2.7 years, 9219 fractures occurred, of which 3105 were hip fractures. A more severe CKD stage was associated with a higher risk of fractures, particularly hip fractures: compared with CKD Stage 3a, the adjusted HR was 1.10 (95% CI 1.02-1.19), 1.32 (1.17-1.49) and 2.47 (1.94-3.15) for CKD Stage 3b, 4 and 5, respectively. Spline curves suggested a linear association with fracture risk with an eGFR <30 mL/min/1.73 m2. Compared with non-fracture periods, incident fracture was associated with a 4-fold increased mortality within 90 days [HR 4.21 (95% CI 3.95-4.49)]. The risk remained elevated beyond 90 days [HR 1.47 (95% CI 1.40-1.54)] and was stronger after hip fractures. Post-fracture MACE risk was also highest in the first 90 days [HR 4.02 (95% CI 3.73-4.33)], particularly after hip fractures, and persisted beyond 90 days [HR 1.20 (95% CI 1.10-1.30)]. CONCLUSION: Our findings highlight the commonness of fractures and the increased risk for subsequent adverse outcomes in CKD patients. These results may inform clinical decisions regarding post-fracture clinical surveillance and fracture prevention strategies.

Initiation of sodium polystyrene sulphonate and the risk of gastrointestinal adverse events in advanced chronic kidney disease: a nationwide study.

BACKGROUND: Despite long-standing clinical use of sodium polystyrene sulphonate (SPS) for hyperkalaemia management in chronic kidney disease (CKD), its safety profile remains poorly investigated. METHODS: We undertook an observational analysis of nephrology-referred adults with incident CKD Stage 4+ in Sweden during 2006-16 and with no previous SPS use. We studied patterns of use and adverse events associated to SPS initiation during follow-up. Patterns of SPS use were defined by chronicity of treatment and by prescribed dose. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with SPS initiation (time-varying exposure) for the risk of severe (intestinal ischaemia, thrombosis or ulceration/perforation) and minor (de novo dispensation of laxatives or anti-diarrheal drugs) gastrointestinal (GI) events. RESULTS: Of 19 530 SPS-naïve patients with CKD, 3690 initiated SPS during follow-up. A total of 59% took SPS chronically, with an average of three dispensations/year. The majority (85%) were prescribed lower dosages than specified on the product label. During follow-up, 202 severe and 1149 minor GI events were recorded. SPS initiation was associated with a higher incidence of severe adverse events [adjusted HR 1.25 95% CI 1.05-1.49)], particularly in those receiving per label doses [1.54 (1.09-2.17)] and mainly attributed to ulcers and perforations. SPS initiation was also associated with higher incidence of minor GI events [adjusted HR 1.11 (95% CI 1.03-1.19)], regardless of dose, and mainly accounted for by de novo dispensation of laxatives. CONCLUSIONS: Initiation of SPS in patients with advanced CKD is associated with a higher risk of severe GI complications as well as the initiation of GI-related medications, particularly when prescribed at per label doses.

Untargeted metabolomics with multivariate analysis to discriminate hazelnut (Corylus avellana L.) cultivars and their geographical origin.

BACKGROUND: In the present study a metabolomics-based approach was used to discriminate among different hazelnut cultivars and to trace their geographical origins. Ultra-high-pressure liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-ESI/QTOF-MS) was used to profile phenolic and sterolic compounds. RESULTS: Compounds were identified against an in-house database using accurate monoisotopic mass and isotopic patterns. The screening approach was designed to discern 15 hazelnut cultivars and to discriminate among the geographical origins of six cultivars from the four main growing regions (Chile, Georgia, Italy, and Turkey). This approach allowed more than 1000 polyphenols and sterols to be annotated. The metabolomics data were elaborated with both unsupervised (hierarchical clustering) and supervised (orthogonal projections to latent structures discriminant analysis, OPLS-DA) statistics. These multivariate statistical tools allowed hazelnut samples to be discriminated, considering both 'cultivar type' and 'geographical origin'. Flavonoids (anthocyanins, flavanols and flavonols - VIP scores 1.34-1.49), phenolic acids (mainly hydroxycinnamics - VIP scores 1.35-1.55) together with cholesterol, ergosterol, and stigmasterol derivatives (VIP scores 1.34-1.49) were the best markers to discriminate samples according to geographical origin. CONCLUSIONS: This work illustrates the potential of untargeted profiling of phenolics and sterols based on UHPLC-ESI/QTOF mass spectrometry to discriminate hazelnut and support authenticity and origin. © 2019 Society of Chemical Industry.

Enrichment of ATP Binding Proteins Unveils Proteomic Alterations in Human Macrophage Cell Death, Inflammatory Response, and Protein Synthesis after Interaction with Candida albicans.

Macrophages are involved in the primary human response to Candida albicans. After pathogen recognition, signaling pathways are activated, leading to the production of cytokines, chemokines, and antimicrobial peptides. ATP binding proteins are crucial for this regulation. Here, a quantitative proteomic and phosphoproteomic approach was carried out for the study of human macrophage ATP-binding proteins after interaction with C. albicans. From a total of 547 nonredundant quantified proteins, 137 were ATP binding proteins and 59 were detected as differentially abundant. From the differentially abundant ATP-binding proteins, 6 were kinases (MAP2K2, SYK, STK3, MAP3K2, NDKA, and SRPK1), most of them involved in signaling pathways. Furthermore, 85 phosphopeptides were quantified. Macrophage proteomic alterations including an increase of protein synthesis with a consistent decrease in proteolysis were observed. Besides, macrophages showed changes in proteins of endosomal trafficking together with mitochondrial proteins, including some involved in the response to oxidative stress. Regarding cell death mechanisms, an increase of antiapoptotic over pro-apoptotic signals is suggested. Furthermore, a high pro-inflammatory response was detected, together with no upregulation of key mi-RNAs involved in the negative feedback of this response. These findings illustrate a strategy to deepen the knowledge of the complex interactions between the host and the clinically important pathogen C. albicans.

Estimated GFR and Hospital-Acquired Infections Following Major Surgery.

RATIONALE & OBJECTIVE: Low estimated glomerular filtration rate (eGFR) increases infection risk, but its contribution to hospital-acquired infection following major surgery is unknown. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Residents of Stockholm, Sweden, 18 years or older with at least 1 recorded serum creatinine measurement, no recent diagnoses of infection, and hospitalized for orthopedic, abdominal, cardiothoracic and vascular, or neurologic surgery between January 2007 and December 2011. EXPOSURES: eGFR<60mL/min/1.73m2 (termed low eGFR) and other clinical comorbid conditions at admission: cancer, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), coronary heart disease, diabetes, heart failure (HF), and liver disease. OUTCOMES: Incidence and population-attributable fractions of 4 major types of hospital-acquired infections: pneumonia, urinary tract infection, surgical-site infection, and bloodstream infection. ANALYTICAL APPROACH: Logistic regression analysis. RESULTS: 66,126 patients with a history of orthopedic (n=31,630), abdominal (n=26,317), cardiothoracic and vascular (n=6,266), or neurologic (n=1,913) surgery were studied. Cancer (21%) and low eGFR (18%) were the most prevalent comorbid conditions at admission, followed by diabetes, HF, and COPD (12%). Overall, 3,617 patients (5.5%) had at least 1 type of hospital-acquired infection (1,650 cases of urinary tract infection, 1,196 cases of pneumonia, 635 cases of surgical site infection, and 411 cases of bloodstream infection). The OR of hospital-acquired infection was highest for low eGFR (1.64; 95% CI, 1.51-1.77), followed by HF (1.60; 95% CI, 1.46-1.76), cerebrovascular disease (1.47; 95% CI, 1.34-1.61), cancer (1.43; 95% CI, 1.33-1.55), and COPD (1.37; 95% CI, 1.25-1.50). Low eGFR demonstrated the highest population-attributable fraction for hospital-acquired infections (0.13), followed by cancer (0.10), HF (0.09), and cerebrovascular disease (0.06). When assessed by type of infection, low eGFR particularly contributed to pneumonia (0.15) and urinary tract infection (0.10). LIMITATIONS: Outcome ascertainment based on diagnostic codes. CONCLUSIONS: These findings highlight the association between low eGFR and hospital-acquired infection and may inform evidence-based hospital-acquired infection prevention policies following major surgery.

Untargeted screening of the bound / free phenolic composition in tomato cultivars for industrial transformation.

BACKGROUND: Tomato is one of the most important agricultural crops and it is characterized by a wide bioactive compound profile. However, little information is reported on its comprehensive polyphenol profile. In this work, 13 commercial tomato cultivars for industrial transformation were screened by ultra-high-pressure liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS) for both free and bound phenolic profiles. Thereafter, the in vitro antioxidant activity of each cultivar was assessed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance activity (ORAC) assays. Multivariate statistics, i.e. orthogonal projection to latent structures discriminant analysis (OPLS-DA), were then used to model samples according to their distinct phenolic signatures, thus providing compounds that better discriminated between the distributions of the cultivars that were considered. RESULTS: More than 350 phenolic compounds could be identified across the samples that were considered: flavonoids (such as flavones and flavanols), hydroxycinnamic acids, lignans, and lower-molecular-weight phenolics were the most frequently observed classes of phenolics in tomato berries. Anthocyanins were the most abundant class among bound phenolics (being highest in the Leader F1 and Defender F1 cultivars), followed by tyrosols (mainly in Heinz cultivars). However, flavones and hydroxybenzoic acids were the most represented discriminant phenolics in the bound fraction. CONCLUSIONS: Untargeted metabolomics allowed significant differences in phenolic composition to be outlined across the tomato cultivars that were analyzed. Such differences were particularly evident regarding the free-to-bound phenolic ratio, hence allowing differences in the bioaccessibility of phenolics to be postulated. © 2019 Society of Chemical Industry.

Association Between Proton Pump Inhibitor Use and Risk of Progression of Chronic Kidney Disease.

BACKGROUND & AIMS: Proton pump inhibitors (PPI) have been associated with acute kidney injury and recent studies suggest that they may be associated with the risk of chronic kidney disease (CKD). METHODS: We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n = 105,305) and new users of H2 blockers (H2B; n = 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury. Complete collection of repeated PPI and H2B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated with cumulative PPI exposure. RESULTS: Users of PPIs, compared with users of H2Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio [HR], 1.26; 95% CI, 1.05-1.51) and decrease in estimated glomerular filtration rate of 30% or more (11,045 events; 1.26; 95% CI, 1.16-1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 95% CI, 0.76-7.58) and acute kidney injury (HR, 1.30; 95% CI, 1.00-1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H2B use. CONCLUSIONS: Initiation of PPI therapy and cumulative PPI exposure is associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.

Dyskalemias and adverse events associated with discharge potassium in acute myocardial infarction.

BACKGROUND: The incidence of dyskalemias and associated outcomes in acute myocardial infarction (AMI) are unknown in real-world settings and likely differ from the controlled environment of randomized controlled trials. METHODS: We examined consecutive survivors of an AMI during 2006-2011 in SWEDEHEART registry and with plasma potassium at discharge (exposure). Study outcomes were 1-year risk of hyperkalemia (potassium >5.0 mmol/L), hypokalemia (potassium <3.5 mmol/L), and others (1-year risk of death, new myocardial infarction, heart failure, and de novo atrial fibrillation). Covariates included demographics, comorbidities, hospital procedures, and medications. RESULTS: We included 4,861 patients (65% male, age 71.4 ±â€¯12.6 years) with mean discharge potassium of 4.0 ±â€¯0.4 mmol/L. Within 1 year, 784 (16.1%) new hyperkalemic and 991 (20.4%) new hypokalemic events occurred. Discharge potassium and kidney dysfunction were independent predictors of their occurrence. Compared with discharge potassium of 4.0 to <4.5 mmol/L, the adjusted risk of incident hyperkalemia was 1.71 (95% confidence interval 1.41-2.06) for potassium of 4.5-5.0 mmol/L and 2.38 (1.69-3.35) for potassium of >5.0 mmol/L; the adjusted risk of incident hypokalemia was 1.43 for potassium of 3.5 to <4.0 mmol/L (1.23-1.66) and 3.12 (2.58-3.77) for potassium of <3.5 mmol/L. A U-shaped association was observed between discharge potassium and the risk of death (n = 718), with increased hazards for potassium <3.5 and >4.5 mmol/L. No association was found between discharge potassium and the risk of new myocardial infarction, heart failure, or de novo atrial fibrillation. CONCLUSIONS: Among real-world AMI survivors, both hyperkalemia and hypokalemia are frequent. Discharge potassium and kidney function strongly predicted their occurrence, as well as the 1-year risk of death.

A novel risk prediction score in atrial fibrillation for a net clinical outcome from the ENGAGE AF-TIMI 48 randomized clinical trial.

AIMS: The choice between initiating a non-vitamin K antagonist oral anticoagulant (NOAC) and a vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) may be challenging. To assist in this decision, we developed a risk score to identify patients for whom a therapeutic benefit of NOACs over VKA is predicted. METHODS AND RESULTS: ENGAGE AF-TIMI 48 was a randomized clinical trial of edoxaban vs. warfarin in 21 105 patients with AF. Cox proportional hazard models identified factors associated with a serious net clinical outcome (NCO) of disabling stroke, life-threatening bleeding, and all-cause mortality in VKA naïve patients from the warfarin arm. These were used to develop an integer risk score. Performance was assessed by C-indices and validation by bootstrapping. Kaplan-Meier analyses were stratified by three score categories and treatment arm. Over a median of 2.7 years, 457 NCO events occurred in 2898 patients with a total person-time of 7549.5 years (6.05%/year). The risk prediction model (C = 0.693) for the NCO was translated into a 17-point integer score, with annualized event rates for the low, intermediate, and high-risk categories in the warfarin arm of 3.5%, 9.9%, and 20.8%, respectively. Therapeutic benefit of higher- and lower-dose edoxaban over warfarin was demonstrated in the high- and intermediate-risk, with equal benefit in the low-risk categories (P-interaction 0.008 and 0.014, respectively). CONCLUSION: In VKA naive patients with AF, the TIMI-AF score can assist in the prediction of a poor composite outcome and guide selection of anticoagulant therapy by identifying a differential clinical benefit with a NOAC or VKA.

Climate Change and Photochemical Ozone Creation Potential Impact Indicators of Cow Milk: A Comparison of Different Scenarios for a Diet Assessment.

An estimate of the environmental impact of dairy farms in Northern Italy producing milk for hard cheese (protected designation of origin) has been obtained through a comprehensive life cycle assessment. The estimate focused on climate change (CC) and photochemical ozone creation potential (POCP) indicators, which were evaluated according to the Intergovernmental Panel on Climate Change (IPCC) guidelines and interpreted with the aid of the feeds' composition evaluated using near-infrared reflectance spectroscopy (Foss NIR-System 5000) as well as with a diet evaluation according to the NRC (National Research Council) or the CNCPS (Cornell Net Carbohydrate and Protein System) nutrient requirement modeling. Herds were classified into high-, mid-, and low-performing based on the daily milk yield per cow. A lower impact on indicators was observed as herd performance increased. The high-performing herds had a lower contribution from enteric fermentation (6.30 × 10-1 kgCO2-eq), and the more milk that they produced allowed for a differentiation of CC from land use and transformation (2.39 × 10-1 kgCO2-eq), compared to low-performing herds (3.66 × 10-1 kgCO2-eq). Compared to the IPCC approach, the CC and POCP indicator estimates were reduced when addressing the feed's quality, particularly in mid- and high-performing herds. The results could be helpful in the dairy sector as they provide an insight into how diet quality affects the environmental impact of milk.