| 1. |
- Ferri, F., et al.
(author)
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Donor small-droplet macrovesicular steatosis affects liver transplant outcome in HCV-negative recipients
- 2019
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In: Canadian Journal of Gastroenterology. - : Hindawi Limited. - 0835-7900 .- 2291-2789 .- 2291-2797. ; 2019
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Journal article (peer-reviewed)abstract
- - Background. No data are available on liver transplantation (LT) outcome and donor liver steatosis, classified as large droplet macrovesicular (Ld-MaS), small-droplet macrovesicular (Sd-MaS), and true microvesicular (MiS), taking into account the recipient Hepatitis C virus (HCV) status. Aim. We investigate the impact of allograft steatosis reclassified according to the Brunt classification on early graft function and survival after LT. Methods. We retrospectively reviewed 204 consecutive preischemia biopsies of grafts transplanted in our center during the period 2001-2011 according to recipient HCV status. Results. The median follow-up after LT was 7.5 years (range: 0.0-16.7). In negative recipients (n=122), graft loss was independently associated with graft Sd-MaS, in multivariable Cox regression models comprehending only pre-/intraoperative variables (HR=1.03, 95%CI=1.01-1.05; P=0.003) and when including indexes of early postoperative graft function (HR=1.04, 95%CI=1.02-1.06; P=0.001). Graft Sd-MaS>15% showed a risk for graft loss > 2.5-folds in both the models. Graft Sd-MaS>15% was associated with reduced graft ATP content and, only in HCV-recipients, with higher early post-LT serum AST peaks. Conclusions. In HCV-negative recipients, allografts with >15% Sd-MaS have significantly reduced graft survival and show low ATP and higher AST peaks in the immediate posttransplant period. Donors with >15% Sd-MaS have significantly higher BMI, longer ICU stays, and lower PaO2. © 2019 Flaminia Ferri et al.
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| 2. |
- Lam, MT, et al.
(author)
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A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function
- 2019
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:12, s. 2778-2799
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Journal article (peer-reviewed)abstract
- Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival.
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| 3. |
- Stolk, Lisette, et al.
(author)
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
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Journal article (peer-reviewed)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
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| 4. |
- Beumer, B. R., et al.
(author)
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Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria
- 2022
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In: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 13:5, s. 2373-2382
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Journal article (peer-reviewed)abstract
- Background: Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. Method: Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. Results: Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8months (IQR: 0.77–2.67). The median follow-up period was 5.1 95% CI [4.7–5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51–10.59], P<0.001) and body mass index (0.74 95% CI [0.59–0.89], P<0.001) were significant. Univariable survival analysis of patients with sarcopenia versus patients without sarcopenia showed a significant difference in OS (HR 1.44 95% CI [1.07−1.94], P=0.018). Also the SMI was significant (HR 0.98 95% CI [0.96–0.99], P=0.014). The survival difference between the lowest SMI quartile versus the highest SMI quartile was significant (log-rank: P=0.005) with 5year OS of 57% and 71%, respectively. Data from 423 patients, describing 139 deaths, was used for multivariate analysis. Both sarcopenia (HR 1.45 95% CI [1.02−2.05], P=0.036) and SMI were (HR 0.98 95% CI [0.95–0.99], P=0.035) significant. On the survival scale this translates to a 5year OS difference of 11% between sarcopenia and no sarcopenia. Whereas for SMI, this translates to a survival difference of 8% between first and third quartiles for both genders. Conclusions: Overall, we can conclude that higher muscle mass contributes to a better long-term survival. However, for individual patients, low muscle mass should not be considered an absolute contra-indication for LT as its discriminatory performance was limited.
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| 5. |
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| 6. |
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| 7. |
- Belli, LS, et al.
(author)
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COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study
- 2021
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:10, s. 1914-
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Journal article (peer-reviewed)abstract
- Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course.DesignData from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed.ResultsFrom 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10–30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15–19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44–102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31–170).ConclusionsIncreased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).
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| 8. |
- Marini, L., et al.
(author)
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Reliability assessment of the 2018 classification case definitions of peri-implant health, peri-implant mucositis, and peri-implantitis
- 2023
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In: Journal of Periodontology. - 0022-3492. ; 94:12, s. 1461-1474
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Journal article (peer-reviewed)abstract
- BackgroundThe purpose of this study was to evaluate the reliability and accuracy in the assignment of the case definitions of peri-implant health and diseases according to the 2018 Classification of Periodontal and Peri-implant Diseases and Conditions. MethodsTen undergraduate students, 10 general dentists, and 10 experts in implant dentistry participated in this study. All examiners were provided with clinical and radiographic documentation of 25 dental implants. Eleven out the 25 cases were also accompanied by baseline readings. Examiners were asked to define all cases using the 2018 classification case definitions. Reliability among examiners was evaluated using the Fleiss kappa statistic. Accuracy was estimated using percentage of complete agreement and quadratic weighted kappa for pairwise comparisons between each rater and a gold standard diagnosis. ResultsThe Fleiss kappa was 0.50 (95% CI: 0.48 to 0.51) and the mean quadratic weighted kappa value was 0.544. Complete agreement with the gold standard diagnosis was achieved in 59.8% of the cases. Expertise in implantology affected accuracy positively (p < 0.001) while the absence of baseline readings affected it negatively (p < 0.001). ConclusionBoth reliability and accuracy in assigning case definitions to dental implants according to the 2018 classification were mostly moderate. Some difficulties arose in the presence of specific challenging scenarios.
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| 9. |
- Moreau, V., et al.
(author)
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Pool CFD modelling : lessons from the SESAME project
- 2019
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In: Nuclear Engineering and Design. - : ELSEVIER SCIENCE SA. - 0029-5493 .- 1872-759X. ; 355
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Journal article (peer-reviewed)abstract
- The current paper describes the Computational Fluid-Dynamics (CFD) modelling of Heavy Liquid Metal (HLM) flows in a pool configuration and in particular how this is approached within the Horizon 2020 SESAME project. SESAME's work package structure, based on a systematic approach of redundancy and diversification, is explained along with its motivation. The main achievements obtained and the main lessons learned during the project are illustrated. The paper focuses on the strong coupling between the experimental activities and CFD simulations performed within the SESAME project. Two different HLM fluids are investigated: pure lead and Lead-Bismuth Eutectic. The objective is to make CFD a valid instrument used during the design of safe and innovative Gen-IV nuclear plants. Some effort has also been devoted to Proper Orthogonal Decomposition with Galerkin projection modelling (POD-Galerkin), a reduced order model suited for Uncertainty Quantification that operates by post-processing CFD results. Assessment of Uncertainty highly improves the reliability of CFD simulations. Dedicated experimental campaigns on heavily instrumented facilities have been conceived with the specific objective to build a series of datasets suited for the calibration and validation of the CFD modelling. In pool configuration, the attention is focused on the balance between conductive and convective heat transfer phenomena, on transient test-cases representative of incidental scenarios and on the possible occurrence of solidification phenomena. Four test sections have been selected to generate the datasets: (i) the CIRCE facility from ENEA, (ii) the TALL-3D pool test section from KTH, (iii) the TALL-3D Solidification Test Section (STS) from KTH and (iv) the SESAME Stand facility from CVR. While CIRCE and TALL-3D were existing facilities, the STS and SESAME Stand facility have been conceived, built and operated within the project, heavily relying on the use of CFD support. Care has been taken to ensure that almost all tasks were performed by at least two partners. Specific examples are given on how this strategy has allowed to uncover flaws and overcome pitfalls. Furthermore, an overview of the performed work and the achieved results is presented, as well as remaining or new uncovered issues. Finally, the paper is concluded with a description of one of the main goals of the SESAME project: the construction of the Gen-IV ALFRED CFD model and an investigation of its general circulation.
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| 10. |
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| 11. |
- Benetton, M., et al.
(author)
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Molecular Measurable Residual Disease Assessment before Hematopoietic Stem Cell Transplantation in Pediatric Acute Myeloid Leukemia Patients: A Retrospective Study by the I-BFM Study Group
- 2022
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In: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:7
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Journal article (peer-reviewed)abstract
- Hematopoietic stem cell transplantation (HSCT) is a curative post-remission treatment in patients with acute myeloid leukemia (AML), but relapse after transplant is still a challenging event. In recent year, several studies have investigated the molecular minimal residual disease (qPCR-MRD) as a predictor of relapse, but the lack of standardized protocols, cut-offs, and timepoints, especially in the pediatric setting, has prevented its use in several settings, including before HSCT. Here, we propose the first collaborative retrospective I-BFM-AML study assessing qPCR-MRD values in pretransplant bone marrow samples of 112 patients with a diagnosis of AML harboring t(8;21)(q22; q22)RUNX1::RUNX1T1, or inv(16)(p13q22)CBFB::MYH11, or t(9;11)(p21;q23)KMT2A::MLLT3, or FLT3-ITD genetic markers. We calculated an ROC cut-off of 2.1 x 10(-4) that revealed significantly increased OS (83.7% versus 57.1%) and EFS (80.2% versus 52.9%) for those patients with lower qPCR-MRD values. Then, we partitioned patients into three qPCR-MRD groups by combining two different thresholds, 2.1 x 10(-4) and one lower cut-off of 1 x 10(-2), and stratified patients into low-, intermediate-, and high-risk groups. We found that the 5-year OS (83.7%, 68.6%, and 39.2%, respectively) and relapse-free survival (89.2%, 73.9%, and 67.9%, respectively) were significantly different independent of the genetic lesion, conditioning regimen, donor, and stem cell source. These data support the PCR-based approach playing a clinical relevance in AML transplant management.
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| 12. |
- Ortolani, L., et al.
(author)
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Electrical and holographic characterization of gold catalyzed titania-based layers
- 2007
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In: Journal of the European Ceramic Society. - : Elsevier BV. - 0955-2219 .- 1873-619X. ; 27:13-15, s. 4131-4134
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Journal article (peer-reviewed)abstract
- The sensing properties of titanium oxide have been tailored through doping with niobium and dispersion of nanosized Au particles. The microstructural features of the gold-titania composite system were investigated by transmission electron microscopy and the electronic properties of Au nanoparticles were specifically investigated by electron holography. Holography provides quantitative determination of the mean inner potential with the high spatial resolution attained by transmission electron microscopy. Large increase of the mean inner potential has been measured for ultra small Au particles arising from the nano-scale assembling. Electrical tests were performed at low operating temperatures and demonstrated the considerable enhancement of CO sensitivity owing to the extremely high catalytic activity of gold particles. © 2007 Elsevier Ltd. All rights reserved.
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| 13. |
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