| 1. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 2. |
- Alexandrov, Ludmil B., et al.
(författare)
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Signatures of mutational processes in human cancer
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
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Tidskriftsartikel (refereegranskat)abstract
- All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
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| 3. |
- Archilletti, Federico, et al.
(författare)
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Coronary angiography- or fractional flow reserve-guided complete revascularization in multivessel disease STEMI : A Bayesian hierarchical network meta-analysis
- 2023
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 370, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To identify the best strategy to achieve complete revascularization (CR) in patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). Methods and results: We systematically reviewed the literature for randomized controlled trials (RCTs) comparing IRA-only PCI and CR guided by angiography or fractional flow reserve (FFR) in MVD-STEMI. Both frequentist (classical) and Bayesian network meta-analysis were performed, including a comparative hierarchy estimation of the probability to reduce the primary composite endpoint of all-cause death and new myocardial infarction (MI). We identified 11 RCTs, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the primary endpoint (OR: 0.73; 95%CI0.55–0.97). We observed non-significant difference between angiography and FFR guidance in reducing the primary endpoint (OR: 0.73, 95% CI 0.35–1.57). The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of all-cause death or new MI (SUCRA92%). Conclusions: In patients with MVD-STEMI, CR is associated with a reduction in all-cause mortality and new MI compared with IRA-only PCI. Angio-guided CR is associated with the lowest risk of all-cause death or new MI, therefore the role of FFR-guidance in this setting is questionable. Condensed abstract: Both frequentist and Bayesian network meta-analysis were performed to compare infarct-related artery (IRA)-only percutaneous coronary intervention (PCI) and complete revascularization (CR) guided by angiography or fractional flow reserve (FFR) in multivessel disease (MVD) and acute ST-elevation myocardial infarction (STEMI). Eleven randomized controlled trials were identified, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the incidence of the composite endpoint of all-cause death and new myocardial infarction without significant difference in angio-guided and FFR-guided CR. The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of the composite endpoint and, therefore the role of FFR-guidance in this setting is questionable.
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| 4. |
- Archilletti, Federico, et al.
(författare)
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Timing of mechanical circulatory support during primary angioplasty in acute myocardial infarction and cardiogenic shock : Systematic review and meta-analysis
- 2022
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Ingår i: Catheterization and Cardiovascular Interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 99:4, s. 998-1005
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We aim to define whether the timing of microaxial left ventricular assist device (IMLVAD) implantation might impact on mortality in acute myocardial infarction (AMI) cardiogenic shock (CS) patients who underwent primary percutaneous coronary intervention (PPCI). Background: Despite the widespread use of PPCI, mortality in patients with AMI and CS remains high. Mechanical circulatory support is a promising bridge to recovery strategy, but evidence on its benefit is still inconclusive and the optimal timing of its utilization remains poorly explored. Methods: We compared clinical outcomes of upstream IMLVAD use before PPCI versus bailout use after PPCI in patients with AMI CS. A systematic review and meta-analysis of studies comparing the two strategies were performed. Effect size was reported as odds ratio (OR) using bailout as reference group and a random effect model was used. Study-level risk estimates were pooled through the generic inverse variance method (random effect model). Results: A total of 11 observational studies were identified, including a pooled population of 6759 AMI-CS patients. Compared with a bailout approach, upstream IMLVAD was associated with significant reduction of 30-day (OR = 0.65; 95% confidence interval [CI] = 0.51–0.82; I2 = 43%, adjusted OR = 0.54; 95% CI = 0.37–0.59; I2 = 3%, test for subgroup difference p = 0.30), 6-month (OR = 0.51; 95% CI = 0.27–0.96; I2 = 66%), and 1-year (OR = 0.56; 95% CI = 0.39–0.79; I2 = 0%) all-cause mortality. Incidence of access-related bleeding, acute limb ischemia and transfusion outcomes were similar between the two strategies. Conclusion: In patients with AMI-CS undergoing PPCI, upstream IMLVAD was associated with reduced early and midterm all-cause mortality when compared with a bailout strategy.
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| 5. |
- Bisogno, Marco, et al.
(författare)
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Standardizing local governments’ audit reports : for better or for worse?
- 2022
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Ingår i: Public Money and Management. - : Taylor and Francis Ltd.. - 0954-0962 .- 1467-9302. ; 42:7, s. 482-490
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Tidskriftsartikel (refereegranskat)abstract
- IMPACT: This article contributes to the policy debate on whether to standardize audit reports in public sector organizations. It offers useful insights that national regulators and standard-setters can consider when introducing new rules and standards in the audit regulatory space. Regulators and standard-setters interested in teasing out the professional support that auditors can offer should be aware of the need for a balance between standardization and freedom in preparing annual audit reports. ABSTRACT: The article investigates audit reports in Italian local governments using the theoretical lens of standardization theory. By means of a content analysis on 90 audit reports for the financial year 2018, the effectiveness of a standardized audit model for the audit report is discussed. The findings reveal that standardization seems to lead to a rigid approach in producing the audit reports of local governments. The study offers insights into rethinking the audit regulatory space in public sector organizations.
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| 6. |
- Flex, Elisabetta, et al.
(författare)
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Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:16, s. 4315-4327
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Tidskriftsartikel (refereegranskat)abstract
- RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused by constitutional dysregulation of RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup and p.Val55Met) in RRAS, a gene encoding a small monomeric GTPase controlling cell adhesion, spreading and migration, underlying a rare (2 subjects among 504 individuals analysed) and variable phenotype with features partially overlapping Noonan syndrome, the most common RASopathy. We also identified somatic RRAS mutations (p.Gly39dup and p.Gln87Leu) in 2 of 110 cases of non-syndromic juvenile myelomonocytic leukaemia, a childhood myeloproliferative/myelodysplastic disease caused by upregulated RAS signalling, defining an atypical form of this haematological disorder rapidly progressing to acute myeloid leukaemia. Two of the three identified mutations affected known oncogenic hotspots of RAS genes and conferred variably enhanced RRAS function and stimulus-dependent MAPK activation. Expression of an RRAS mutant homolog in Caenorhabditis elegans enhanced RAS signalling and engendered protruding vulva, a phenotype previously linked to the RASopathy-causing SHOC2(S2G) mutant. Overall, these findings provide evidence of a functional link between RRAS and MAPK signalling and reveal an unpredicted role of enhanced RRAS function in human disease.
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| 7. |
- Pingitore, Piero, 1986, et al.
(författare)
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PNPLA3 overexpression results in reduction of proteins predisposing to fibrosis.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:23, s. 5212-5222
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Tidskriftsartikel (refereegranskat)abstract
- Liver fibrosis is a pathological scarring response to chronic hepatocellular injury and hepatic stellate cells (HSCs) are key players in this process. PNPLA3 I148M is a common variant robustly associated with liver fibrosis but the mechanisms underlying this association are unknown.We aimed to examine a) the effect of fibrogenic and proliferative stimuli on PNPLA3 levels in HSCs and b) the role of wild type and mutant PNPLA3 overexpression on markers of HSC activation and fibrosis.Here we show that PNPLA3 is upregulated by the fibrogenic cytokine transforming growth factor-beta (TGF-β), but not by platelet-derived growth factor (PDGF), and is involved in the TGF-β-induced reduction in lipid droplets in primary human HSCs. Furthermore, we show that retinol release from human HSCs ex vivo is lower in cells with the loss-of-function PNPLA3 148M compared with 148I wild type protein. Stable overexpression of PNPLA3 148I wild type, but not 148M mutant, in human HSCs (LX-2 cells) induces a reduction in the secretion of matrix metallopeptidase 2 (MMP2), tissue inhibitor of metalloproteinase 1 and 2 (TIMP1 and TIMP2), which is mediated by retinoid metabolism.In conclusion, we show a role for PNPLA3 in HSC activation in response to fibrogenic stimuli. Moreover, we provide evidence to indicate that PNPLA3-mediated retinol release may protect against liver fibrosis by inducing a specific signature of proteins involved in extracellular matrix remodeling.
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| 8. |
- Ricci, Fabrizio, et al.
(författare)
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Exercise-induced myocardial edema in master triathletes : Insights from cardiovascular magnetic resonance imaging
- 2022
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media SA. - 2297-055X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Strenuous exercise has been associated with functional and structural cardiac changes due to local and systemic inflammatory responses, reflecting oxidative, metabolic, hormonal, and thermal stress, even in healthy individuals. We aimed to assess changes in myocardial structure and function using cardiovascular magnetic resonance (CMR) imaging in master triathletes early after a full-distance Ironman Triathlon race. Materials and methods: Ten master triathletes (age 45 ± 8 years) underwent CMR within 3 h after a full-distance Ironman Triathlon race (3.8 km swimming, 180 km cycling, and 42.2 km running) completed with a mean time of 12 ± 1 h. All the triathletes had a 30-day follow-up CMR. Cine balanced steady-state free precession, T2-short tau inversion recovery (STIR), tagging, and late gadolinium enhancement (LGE) imaging sequences were performed on a 1.5-T MR scanner. Myocardial edema was defined as a region with increased T2 signal intensity (SI) of at least two SDs above the mean of the normal myocardium. The extent of myocardial edema was expressed as the percentage of left ventricular (LV) mass. Analysis of LV strain and torsion by tissue tagging included the assessment of radial, longitudinal, and circumferential peak systolic strain, rotation, and twist. Results: Compared with postrace, biventricular volumes, ejection fraction, and LV mass index remained unchanged at 30-day follow-up. Global T2 SI was significantly higher in the postrace CMR (postrace 10.5 ± 6% vs. follow-up 3.9 ± 3.8%, P = 0.004) and presented with a relative apical sparing distribution (P < 0.001) matched by reduction of radial peak systolic strain of basal segments (P = 0.003). Apical rotation and twist were significantly higher immediately after the competition compared with follow-up (P < 0.05). Conclusion: Strenuous exercise in master triathletes is associated with a reversible regional increase in myocardial edema and reduction of radial peak systolic strain, both presenting with a relative apical sparing pattern.
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| 9. |
- Stylidis, Konstantinos, 1978, et al.
(författare)
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Perceived quality estimation by the design of discrete-choice experiment and best–worst scaling data: An automotive industry case
- 2019
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Ingår i: Smart Innovation, Systems and Technologies. - Singapore : Springer Singapore. - 2190-3026 .- 2190-3018. ; 134, s. 859-870
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Konferensbidrag (refereegranskat)abstract
- “Which product attributes do engineers have to focus on to receive the highest level of a customer’s appreciation?” In other words, can we design for high perceived quality? In this paper, discrete-choice experiment design is presented with the combination of best–worst scaling method to evaluate the perceived quality of the complete vehicle in application to the premium automotive industry. The application of Perceived Quality Framework (PQF) and Perceived Quality Attributes Importance Ranking (PQAIR) method to measure the importance of perceived quality attributes for the automotive engineers and customers depicted commonalities and differences in perception. This information and approach can significantly improve engineering practices regarding the perceived quality of cars.
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