| 1. |
- Aad, G., et al.
(author)
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- 2014
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In: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :11
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Journal article (peer-reviewed)
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| 2. |
- Gualandro, Danielle M. M., et al.
(author)
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Acute heart failure after non-cardiac surgery: incidence, phenotypes, determinants and outcomes
- 2023
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 25:3, s. 347-357
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Journal article (peer-reviewed)abstract
- Aims Primary acute heart failure (AHF) is a common cause of hospitalization. AHF may also develop postoperatively (pAHF). The aim of this study was to assess the incidence, phenotypes, determinants and outcomes of pAHF following non-cardiac surgery.Methods and results A total of 9164 consecutive high-risk patients undergoing 11 262 non-cardiac inpatient surgeries were prospectively included. The incidence, phenotypes, determinants and outcome of pAHF, centrally adjudicated by independent cardiologists, were determined. The incidence of pAHF was 2.5% (95% confidence interval [CI] 2.2-2.8%); 51% of pAHF occurred in patients without known heart failure (de novo pAHF), and 49% in patients with chronic heart failure. Among patients with chronic heart failure, 10% developed pAHF, and among patients without a history of heart failure, 1.5% developed pAHF. Chronic heart failure, diabetes, urgent/emergent surgery, atrial fibrillation, cardiac troponin elevations above the 99th percentile, chronic obstructive pulmonary disease, anaemia, peripheral artery disease, coronary artery disease, and age, were independent predictors of pAHF in the logistic regression model. Patients with pAHF had significantly higher all-cause mortality (44% vs. 11%, p < 0.001) and AHF readmission (15% vs. 2%, p < 0.001) within 1 year than patients without pAHF. After Cox regression analysis, pAHF was an independent predictor of all-cause mortality (adjusted hazard ratio [aHR] 1.7 [95% CI 1.3-2.2]; p < 0.001) and AHF readmission (aHR 2.3 [95% CI 1.5-3.7]; p < 0.001). Findings were confirmed in an external validation cohort using a prospective multicentre cohort of 1250 patients (incidence of pAHF 2.4% [95% CI 1.6-3.3%]).Conclusions Postoperative AHF frequently developed following non-cardiac surgery, being de novo in half of cases, and associated with a very high mortality.
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| 3. |
- Willem, Michael, et al.
(author)
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eta-Secretase processing of APP inhibits neuronal activity in the hippocampus
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7573, s. 443-447
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Journal article (peer-reviewed)abstract
- Alzheimer disease (AD) is characterized by the accumulation of amyloid plaques, which are predominantly composed of amyloid-beta peptide(1). Two principal physiological pathways either prevent or promote amyloid-beta generation from its precursor, beta-amyloid precursor protein (APP), in a competitive manne(r)1. Although APP processing has been studied in great detail, unknown proteolytic events seem to hinder stoichiometric analyses of APP metabolism in vivo(2). Here we describe a new physiological APP processing pathway, which generates proteolytic fragments capable of inhibiting neuronal activity within the hippocampus. We identify higher molecular mass carboxy-terminal fragments (CTFs) of APP, termed CTF-eta, in addition to the long-known CTF-alpha and CTF-beta fragments generated by the alpha- and beta-secretases ADAM10 (a disintegrin and metalloproteinase 10) and BACE1 (beta-site APP cleaving enzyme 1), respectively. CTF-eta generation is mediated in part by membrane-bound matrix metalloproteinases such as MT5-MMP, referred to as g-secretase activity. g-Secretase cleavage occurs primarily at amino acids 504-505 of APP(695), releasing a truncated ectodomain. After shedding of this ectodomain, CTF-eta is further processed by ADAM10 and BACE1 to release long and short A eta peptides (termed A eta-alpha and A eta-beta). CTFs produced by g-secretase are enriched in dystrophic neurites in an AD mouse model and in human AD brains. Genetic and pharmacological inhibition of BACE1 activity results in robust accumulation of CTF-eta and A eta-alpha. In mice treated with a potent BACE1 inhibitor, hippocampal long-term potentiation was reduced. Notably, when recombinant or synthetic A eta-alpha was applied on hippocampal slices ex vivo, long-term potentiation was lowered. Furthermore, in vivo single-cell two-photon calcium imaging showed that hippocampal neuronal activity was attenuated by A eta-alpha. These findings not only demonstrate a major functionally relevant APP processing pathway, but may also indicate potential translational relevance for therapeutic strategies targeting APP processing.
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| 4. |
- Bima, Paolo, et al.
(author)
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Chest Pain in Cancer Patients Prevalence of Myocardial Infarction and Performance of High-Sensitivity Cardiac Troponins
- 2023
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In: JACC: CARDIOONCOLOGY. - : Elsevier. - 2666-0873. ; 5:5, s. 591-609
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Journal article (peer-reviewed)abstract
- BACKGROUND Little is known about patients with cancer presenting with acute chest discomfort to the emergency department (ED).OBJECTIVES The aim of this study was to assess the prevalence of acute myocardial infarction (AMI), outcomes, and the diagnostic utility of recommended diagnostic tools in this population.METHODS Patients presenting with chest pain to the ED were prospectively enrolled in an international multicenter diagnostic study with central adjudication. Cancer status was assessed prospectively and additional cancer details retrospectively. Findings were externally validated in an independent multicenter cohort.RESULTS Among 8,267 patients, 711 (8.6%) had cancer. Patients with cancer had a higher burden of cardiovascular risk factors and pre-existing cardiac disease. Total length of stay in the ED (5.2 hours vs 4.3 hours) and hospitalization rate (49.8% vs 34.3%) were both increased in patients with cancer (P < 0.001 for both). Among 8,093 patients eligible for the AMI analyses, those with cancer more often had final diagnoses of AMI (184 of 686 with cancer [26.8%] vs 1,561 of 7,407 without cancer [21.1%]; P < 0.001). In patients with cancer, high-sensitivity cardiac troponin T (hs-cTnT) but not high sensitivity cardiac troponin I (hs-cTnI) concentration had lower diagnostic accuracy for non-ST-segment elevation myocardial infarction (for hs-cTnT, area under the curve: 0.89 [95% CI: 0.86-0.92] vs 0.94 [95% CI: 0.93-0.94] [P < 0.001]; for hs-cTnI, area under the curve: 0.93 [95% CI: 0.91-0.95] vs 0.95 [95% CI: 0.94-0.95] [P 1/4 0.10]). In patients with cancer, the European Society of Cardiology 0/1-hour hs-cTnT and hs-cTnI algorithms maintained very high safety but had lower efficacy, with twice the number of patients remaining in the observe zone. Similar findings were obtained in the external validation cohort.CONCLUSIONS Patients with cancer have a substantially higher prevalence of AMI as the cause of chest pain. Length of ED stay and hospitalization rates are increased. The diagnostic performance of hs-cTnT and the efficacy of both the European Society of Cardiology 0/1-hour hs-cTnT and hs-cTnI algorithms is reduced. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587) (J Am Coll Cardiol CardioOnc 2023;5:591-609) (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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