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Sökning: WFRF:(De Caterina Raffaele)

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  • Föregående 1234[5]67Nästa
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  • Lopes, Renato D., et al. (författare)
  • Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation : a secondary analysis of a randomised controlled trial
  • 2012
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9855, s. 1749-1758
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results differed according to patients' CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding. Methods ARISTOTLE was a double-blind, randomised trial that enrolled 18 201 patients with atrial fibrillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2.0-3.0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores of patients at randomisation. Efficacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984. Findings Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke (CHADS(2) 1, 2, or >= 3, p for interaction=0.4457; or CHA(2)DS(2)VASc 1, 2, or >= 3, p for interaction=0.1210) or bleeding (HAS-BLED 0-1, 2, or >= 3, p for interaction=0.9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no difference across all score categories (CHADS(2), p for interaction=0.4018; CHA(2)DS(2)VASc, p for interaction=0.2059; HAS-BLED, p for interaction=0.7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0.22, 95% CI 0.10-0.48) than in those with HAS-BLED scores of 0-1 (HR 0.66, 0.39-1.12; p for interaction=0.0604). Interpretation Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratification for both stroke and bleeding is needed, particularly for patients with atrial fibrillation at low risk for these events.
  • Norante, Rosa Pia, et al. (författare)
  • Generation and validation of novel adeno-associated viral vectors for the analysis of Ca2+ homeostasis in motor neurons
  • 2017
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • A finely tuned Ca2+ homeostasis in restricted cell domains is of fundamental importance for neurons, where transient Ca2+ oscillations direct the proper coordination of electro-chemical signals and overall neuronal metabolism. Once such a precise regulation is unbalanced, however, neuronal functions and viability are severely compromised. Accordingly, disturbed Ca2+ metabolism has often been claimed as a major contributor to different neurodegenerative disorders, such as amyotrophic lateral sclerosis that is characterised by selective motor neuron (MN) damage. This notion highlights the need for probes for the specific and precise analysis of local Ca2+ dynamics in MNs. Here, we generated and functionally validated adeno-associated viral vectors for the expression of gene-encoded fluorescent Ca2+ indicators targeted to different cell domains, under the transcriptional control of a MN-specific promoter. We demonstrated that the probes are specifically expressed, and allow reliable local Ca2+ measurements, in MNs from murine primary spinal cord cultures, and can also be expressed in spinal cord MNs in vivo, upon systemic administration to newborn mice. Preliminary analyses using these novel vectors have shown larger cytosolic Ca2+ responses following stimulation of AMPA receptors in the cytosol of primary cultured MNs from a murine genetic model of ALS compared to the healthy counterpart.
  • Patti, Giuseppe, et al. (författare)
  • Clustering of blood cell count abnormalities and future risk of death
  • 2022
  • Ingår i: European Journal of Clinical Investigation. - : Wiley-Blackwell. - 0014-2972.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The identification of novel predictors of poor outcome may help stratify cardiovascular risk. Aim was to evaluate the individual contribution of blood cell count parameters, as well as their clustering, on the risk of death and cardiovascular events over the long term in the population-based Malmö Diet and Cancer Study cohort.METHODS: In 30,447 individuals (age 57 ± 8 years), we assessed the incidence of all-cause death (primary endpoint) and major adverse cardiovascular events (MACE, secondary outcome measure) according to absence or presence of one, two and three factors at baseline out of the following: anaemia, leukocytosis and thrombocytosis. Median follow-up was 16 years.RESULTS: The percentages of all-cause death were 19.5% in individuals without factors, 21.3% in those with one factor, 27.4% with two and 46.4% with three (log-rank test P < .001). The crude incidence of MACE was 28.0%, 29.2%, 35.5% and 57.1%, respectively (log-rank test P < .001). At multivariate analysis, we found a stepwise increase in overall mortality with increasing number of prevalent factors (one factor: HR 1.23, 95% CI 1.14-1.31, P < .001; two factors: 1.61, 1.37-1.89, P < .001; three factors: 2.69, 1.44-5.01, P = .002, vs no factor). Similar findings were observed for the incidence of MACE (one factor: adjusted HR 1.18, 95% CI 1.11-1.24, P < .001; two factors: 1.52, 1.33-1.76, P < .001; three factors: 2.03, 1.21-3.67, P < .001, vs no factor).CONCLUSIONS: The easily assessable clustering of anaemia, leukocytosis and thrombocytosis heralds higher incidence of death and adverse cardiovascular events.
  • Patti, Giuseppe, et al. (författare)
  • Net Clinical Benefit of Non-Vitamin K Antagonist vs Vitamin K Antagonist Anticoagulants in Elderly Patients with Atrial Fibrillation
  • 2019
  • Ingår i: American Journal of Medicine. - : Elsevier. - 0002-9343. ; 132:6, s. 5-757
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The risks of thromboembolic and hemorrhagic events in patients with atrial fibrillation both increase with age; therefore, net clinical benefit analyses of anticoagulant treatments in the elderly population are crucial to guide treatment. We evaluated the 1-year clinical outcomes with non-vitamin-K antagonist and vitamin K antagonist oral anticoagulants (NOACs vs VKAs) in elderly (≥75 years) patients with atrial fibrillation in a prospective registry setting. Methods: Data on 3825 elderly patients were pooled from the PREFER in AF and PREFER in AF PROLONGATION registries. The primary outcome was the incidence of the net composite endpoint, including major bleeding and ischemic cardiovascular events on NOACs (n = 1556) compared with VKAs (n = 2269). Results: The rates of the net composite endpoint were 6.6%/year with NOACs vs 9.1%/year with VKAs (odds ratio [OR] 0.71; 95% confidence interval [CI], 0.51-0.99; P =.042). NOAC therapy was associated with a lower rate of major bleeding compared with VKA use (OR 0.58; 95% CI, 0.38-0.90; P =.013). Ischemic events were nominally reduced too (OR 0.71; 95% CI, 0.51-1.00; P =.050). Major bleeding with NOACs was numerically lower in higher-risk patients with low body mass index (BMI; OR 0.50; 95% CI, 0.22-1.12; P =.07) or with age ≥85 years (OR 0.44; 95% CI, 0.13-1.49; P =.17). Conclusions: Our real-world data indicate that, compared with VKAs, NOAC use is associated with a better net clinical benefit in elderly patients with atrial fibrillation, primarily due to lower rates of major bleeding. Major bleeding with NOACs was numerically lower also in higher-risk patients with low BMI or age ≥85 years.
  • Patti, Giuseppe, et al. (författare)
  • Platelet Indices and Risk of Death and Cardiovascular Events : Results from a Large Population-Based Cohort Study
  • 2019
  • Ingår i: Thrombosis and Haemostasis. - : Schattauer GmbH. - 0340-6245. ; 119:11, s. 1773-1784
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies evaluating the relationship between platelet indices and cardiovascular (CV) outcomes yielded conflicting results. We assessed the incidence of adverse events according to baseline quintiles of platelet indices in the prospective cohort of the Malmö Diet and Cancer Study. A total of 30,314 individuals (age 57 ± 8 years) were followed for a median of 16 years (468,490 person-years). Outcome measures included all-cause death, CV death, myocardial infarction (MI), and ischemic stroke. The fifth quintile of platelet count (> 274.6 × 109/L) was associated with higher incidence of all-cause death (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.32, p < 0.001), CV death (HR 1.19, 95% CI 1.00-1.42; p = 0.044), MI (HR 1.32, 95% CI 1.12-1.54; p = 0.001), and ischemic stroke (HR 1.27, 95% CI 1.08-1.50, p = 0.004) compared with the first quintile (≤ 185 × 109/L), and also associated with a lower survival, regardless of previous history of MI (p for interaction = 0.58) or stroke (p for interaction = 0.42). In the highest quintile, history of stroke had a higher risk of CV death (HR 3.18, 95% CI 1.54-6.54) compared with no previous stroke (HR 1.12, 95% CI 0.96-1.31). The risk of MI and stroke was greatest in the fifth quintile, regardless of previous MI or previous stroke, respectively. The risk of all adverse events was similar across different quintiles of mean platelet volume. In conclusion, elevated platelet count is associated with higher mortality and risk of CV events, regardless of previous MI and stroke. Platelet count may thus be a useful marker for further stratification of CV risk, and especially of death.
  • Patti, Giuseppe, et al. (författare)
  • The co-predictive value of a cardiovascular score for CV outcomes in diabetic patients with no atrial fibrillation
  • 2019
  • Ingår i: Diabetes/Metabolism Research and Reviews. - : John Wiley & Sons Inc.. - 1520-7560. ; 35:5, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Risk factors included in the cardiovascular (CHA2DS2‐VASc) score, currently used for atrial fibrillation (AF), may predispose to cardiovascular events whether or not AF is present. The aim was to explore the predictive role of CHA2DS2‐VASc score on cardiovascular outcomes in diabetic patients without AF. Methods We accessed individual data from 610 diabetic patients without AF at baseline included in the prospective cohort of the Malmö Diet and Cancer study. Main outcome measure was the occurrence of cardiovascular events (stroke, coronary events) and death. Mean follow‐up was 14.5 ± 5 years (8845 person/years). Results The CHA2DS2‐VASc score significantly predicted the risk of all outcome measures. There was a significant increase in stroke, coronary events, and death risk by each point of CHA2DS2‐VASc score elevation [stroke: adjusted hazard ratio (aHR) 1.43, 95% CI 1.14‐1.79, P = 0.001; coronary events: aHR 1.55, 95% CI 1.34‐1.80, P < 0.0001; death: aHR 1.94, 95% CI 1.71‐2.21, P < 0.0001]. A CHA2DS2‐VASc score ≥4 was associated with higher incidence of ischemic stroke (aHR 1.47, 95% CI 1.18‐1.82; P = 0.001), coronary events (aHR 1.32; 95% CI 1.11‐1.58; P = 0.002), and death (aHR 1.36; 95% CI 1.20‐1.54; P < 0.001). Conclusions In this population‐based study on diabetic patients without AF, the CHA2DS2‐VASc score was an independent predictor of ischemic stroke, coronary events, and overall mortality. Regardless of the AF status, the CHA2DS2‐VASc score might represent a rapid and user‐friendly tool for clinical assessment of diabetic patients at higher cardiovascular risk.
  • Patti, Giuseppe, et al. (författare)
  • Thromboembolic and bleeding risk in obese patients with atrial fibrillation according to different anticoagulation strategies
  • 2020
  • Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273. ; 318, s. 67-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Data on the relationship between body mass index (BMI), thromboembolic events (TEE) and bleeding in patients with atrial fibrillation (AF) are controversial, and further evidence on the risk of such events in obese patients with AF receiving different anticoagulant therapies (OAC) is needed. Methods and results: We divided a total of 9330 participants from the prospective PREFER in AF and PREFER in AF PROLONGATION registries into BMI quartiles at baseline. Outcome measures were TEE and major bleeding complications at the 1-year follow-up. Without OAC, there was a ≥6-fold increase of TEE in the 4th vs other BMI quartiles (P =.019). OAC equalized the rates of TEE across different BMI strata. The occurrence of major bleeding was highest in patients with BMI in the 1st as well as in the 4th BMI quartile [OR 1.69, 95% CI 1.03–2.78, P =.039 and OR 1.86, 95% CI 1.13–3.04, P =.014 vs those in the 3rd quartile, respectively]. At propensity score-adjusted analysis, the incidence of TEE and major bleeding in obese patients receiving non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K-antagonist anticoagulants (VKAs) was similar (P ≥.34). Conclusions: Our real-world data suggest no obesity paradox for TEE in patients with AF. Obese patients are at higher risk of TEE, and here OAC dramatically reduces the risk of events. We here found a comparable clinical outcome with NOACs and VKAs in obese patients. Low body weight and obesity were also associated with bleeding, and therefore OAC with the best safety profile should be considered in this setting.
  • Pol, Tymon, et al. (författare)
  • Evaluation of the prognostic value of GDF-15, ABC-AF-bleeding score and ABC-AF-death score in patients with atrial fibrillation across different geographical areas
  • 2021
  • Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Growth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk. Our aim was to assess the consistency of the association between GDF-15, ABC-AF-bleeding score and ABC-AF-death score, with major bleeding and death, across world geographic regions. Methods Data were available from 14 767 patients with AF from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and 8651 patients with AF from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial in this cohort study. GDF-15 was analysed from plasma samples obtained at randomisation. The geographical consistency of the associations between outcomes and GDF-15, ABC-AF-bleeding score and ABC-AF-death scores were assessed by Cox-regression models including interactions with predefined geographical region. Results GDF-15 and the ABC-AF-bleeding score were associated with major bleeding in both trials across regions (p<0.0001). Similarly, GDF-15 and the ABC-AFdeath score were associated with all-cause mortality in both trials across regions (p<0.0001). Overall, the association between GDF-15, the ABC-AF-bleeding score and ABC-AF-death risk score with major bleeding and death was consistent across regions in both ARISTOTLE and the RE-LY trial cohorts. The ABC-AF-bleeding and ABC-AF-death risk scores were consistent regarding discriminative ability when comparing geographic regions in both trial cohorts. The C-indices ranged from 0.649 to 0.760 for the ABC-AF-bleeding and from 0.677 to 0.806 for the ABC-AF-death score by different geographic regions. Conclusions In patients with AF on anticoagulation, GDF-15 and the biomarker-based ABC-AF-bleeding and ABC-AF-death risk scores are consistently associated with respectively increased risk of major bleeding and death and have similar prognostic value across world geographic regions.
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