| 1. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 2. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 3. |
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| 7. |
- Modvig, S, et al.
(författare)
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Value of Flow Cytometry for MRD-Based Relapse Prediction in B-Cell Precursor Acute Lymphoblastic Leukemia in a Multi-Center Setting
- 2019
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Ingår i: Blood. - 0006-4971 .- 1528-0020.
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Konferensbidrag (refereegranskat)abstract
- Background: PCR of rearranged antigen receptor genes is the method of choice for MRD quantification in ALL. Although FCM-MRD is faster and biologically more informative than PCR, the analysis requires a high level of training. The only larger published studies using FCM-MRD based stratification (Borowitz, Blood, 2008 and 2015) showed a clear association with clinical outcome in BCP-ALL. However, MRD analyses were centralized and these studies included only one MRD-based stratification (MRD levels at the end of induction). Patients and methods: We examined FCM-MRD as stratification tool in BCP-ALL at various timepoints in a large-scale multicenter (18 MRD centers) study. A total of 1487 patients with BCP-ALL (1298 children (younger than 18 years) and 189 adults (18-45 years) are included in the study and were treated according to the NOPHO ALL2008 protocol between July 2008 and February 2016. The median follow-up time for patients in first remission was 51 months (IQR 32-75). MRD was measured by FCM and/or real time quantitative PCR on days 15, 29 (end of induction) and 79 (for standard (SR) and intermediate risk (IR) patients) and prior to and after high risk blocks. A 6-colour FCM analysis including 3 standardized antibody combinations was used and performed in 18 laboratories. Patients were stratified by FCM-MRD, or by PCR-MRD if no FCM-MRD marker was available. End-of-induction MRD (cut-off 10-3) was used to stratify patients to standard risk (SR) vs intermediate risk (IR) or IR vs high risk consolidation therapy (in case of WBC > 100 x 109/L at diagnosis). Patients with MRD >=2.5x10-1 on day 15 were stratified to high risk block therapy. Patients with MRD >=5x10-2 on day 29 or day 79/post high risk-2 block MRD >=10-3 were stratified to HSCT. Primary outcomes were 5year event-free survival (5y EFS) and 5year cumulative incidence of relapse (5y CIR). Results: Only two patients (0.14% of total) had neither an informative FCM nor a PCR marker, and an informative FCM marker combination for MRD monitoring was identified in 96.2% of patients. There was a significant correlation between FCM- and PCR-MRD levels on day 15 (r=0.77, p<0.0001, n=153) and 29 (r=0.81, p<0.0001, n=140). Based on FCM-MRD only, the median MRD level on day 15, 29 and 79/post high risk-2 block was 5x10-3, 1.1x10-4, and below detection limit, respectively. Adults had significantly higher MRD levels at all time-points (p<0.0001 for day 15 and 29, p=0.0019 for day 79, Mann-Whitney). The 5y EFS was 86.1% (95% CI 84.1-88.1) with a 5y CIR of 9.5% (95% CI 7.8-11.3, n=1487). The day 29 FCM-MRD level was closely associated with clinical outcome and a higher hazard of relapse was seen independently for a FCM-MRD >=10-3 (hazard ratio (HR) 2.4, CI 1.6-3.7, p<0.0001), age>18 year (HR 3.0, CI 1.7-5.3, p<0.0001), WBC>=100 (HR 2.7, CI 1.6-4.6, p=0.0001), and B-other (HR 2.1, CI 1.2-3.5, p=0.0052) or high risk B-ALL cytogenetic aberration (rearranged KMT2A/iAMPchr21/hypodiploid) (HR 3.2, CI 1.6-6.1, p=0.0006) (multivariate cause-specific Cox regression, n=1328). Patients with a day 79 FCM-MRD >=10-4 and <10-3 had a significantly higher CIR (22.1%, CI 10.8-33.5%, n=68) compared to FCM-MRD <10-4 (7.5%, CI 2.1-12.8%, n=110) or undetectable (6.3%, CI 4.5-8.2%, n=999, p=0.0087 for FCM-MRD >=10-4 and <10-3vs <10-4 or undetectable). After adjusting for WBC, age, and the day 29 FCM-MRD level, a day 79 FCM-MRD >=10-4 and <10-3 was still significantly associated with a worse 5y CIR for non-transplanted patients (HR 2.3, CI 1.19-4.36, p=0.012 compared to undetectable FCM-MRD, n=1171). Patients with day 15 FCM-MRD <10-3 had a significantly better 5y EFS (92.0%, CI 89.2-95.0%) and CIR (3.9%, CI 1.7-6.1%, n=432) than patients with FCM-MRD >=10-3 and <2.5x10-1, who had a 5y EFS of 85.5% (CI 82.7-88.3%, p=0.0016, n=837) and a 3-fold higher 5y CIR (11.0%, CI 8.4-13.5%, p<0.0001, n=432). Among patients with day 15 FCM-MRD<10-3, the relapse incidence was comparable for patients with FCM-MRD 10-4 - <10-3 and below 10-4 (CIR 3.6, CI 0.5-6.7 vs. CIR 4.1, CI 1.0-7.2, p=0.83, n=432). Conclusion: FCM-MRD performed in a multi-center setting is a clinically useful method for disease monitoring and MRD-based treatment stratification in BCP-ALL. Moreover, FCM-MRD is a reliable indicator of outcome in BCP-ALL independently of other key risk factors. Residual disease >=10-4 and <10-3 at day 79 in SR/IR patients not allocated to HSCT further identifies patients with a high risk of relapse.
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| 8. |
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| 9. |
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| 11. |
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| 12. |
- Modvig, S, et al.
(författare)
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Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting.
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35, s. 1894-1906
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Tidskriftsartikel (refereegranskat)abstract
- PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p<0.0001), 29 (HzR 2.7, p<0.0001), and 79 (HzR 3.5, p<0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4×10-2 versus 5.2×10-3, p<0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y=3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD>10-4 associated with a CIR5y=22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.
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| 13. |
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| 14. |
- Biancari, F, et al.
(författare)
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Preoperative risk stratification of deep sternal wound infection after coronary surgery
- 2020
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Ingår i: Infection control and hospital epidemiology. - : Cambridge University Press (CUP). - 1559-6834 .- 0899-823X. ; 41:4, s. 444-451
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To develop a risk score for deep sternal wound infection (DSWI) after isolated coronary artery bypass grafting (CABG).Design:Multicenter, prospective study.Setting:Tertiary-care referral hospitals.Participants:The study included 7,352 patients from the European multicenter coronary artery bypass grafting (E-CABG) registry.Intervention:Isolated CABG.Methods:An additive risk score (the E-CABG DSWI score) was estimated from the derivation data set (66.7% of patients), and its performance was assessed in the validation data set (33.3% of patients).Results:DSWI occurred in 181 (2.5%) patients and increased 1-year mortality (adjusted hazard ratio, 4.275; 95% confidence interval [CI], 2.804–6.517). Female gender (odds ratio [OR], 1.804; 95% CI, 1.161–2.802), body mass index ≥30 kg/m2(OR, 1.729; 95% CI, 1.166–2.562), glomerular filtration rate <45 mL/min/1.73 m2(OR, 2.410; 95% CI, 1.413–4.111), diabetes (OR, 1.741; 95% CI, 1.178–2.573), pulmonary disease (OR, 1.935; 95% CI, 1.178–3.180), atrial fibrillation (OR, 1.854; 95% CI, 1.096–3.138), critical preoperative state (OR, 2.196; 95% CI, 1.209–3.891), and bilateral internal mammary artery grafting (OR, 2.088; 95% CI, 1.422–3.066) were predictors of DSWI (derivation data set). An additive risk score was calculated by assigning 1 point to each of these independent risk factors for DSWI. In the validation data set, the rate of DSWI increased along with the E-CABG DSWI scores (score of 0, 1.0%; score of 1, 1.8%; score of 2, 2.2%; score of 3, 6.9%; score ≥4: 12.1%;P< .0001). Net reclassification improvement, integrated discrimination improvement, and decision curve analysis showed that the E-CABG DSWI score performed better than other risk scores.Conclusions:DSWI is associated with poor outcome after CABG, and its risk can be stratified using the E-CABG DSWI score.Trial registration:clinicaltrials.gov identifier: NCT02319083
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| 15. |
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| 16. |
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| 17. |
- Oudin Åström, Daniel, et al.
(författare)
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Temperature effects on incidence of surgery for acute type A aortic dissection in the Nordics
- 2022
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Ingår i: Global health action. - : Informa UK Limited. - 1654-9880 .- 1654-9880 .- 1654-9716. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (<=-5 degrees C) and hot temperatures (>= 21 degrees C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- E Johnsen, H, et al.
(författare)
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Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment
- 2011
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Ingår i: BONE MARROW TRANSPLANTATION. - : Nature Publishing Group. - 0268-3369 .- 1476-5365. ; 46:1, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant methionyl human G-CSF (filgrastim, r-metHuG-CSF) (experimental arm A) or routine chemotherapy plus filgrastim (conventional arm B). The primary objective was to evaluate the side effects and toxicity during priming and mobilization. The secondary objectives were efficacy by the level of blood-circulating PBPCs, the number of harvest days and the time to three-lineage engraftment after autografting. First, during priming 5 patients had 8 serious events, 4 in each arm. A summary of all adverse events revealed 30 (94%) patients suffering from 132 events of all grading. Second, neutropenia and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34(+) cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial very unlikely may challenge chemotherapy plus r-metHuG-CSF priming in candidates for high-dose therapy.
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| 24. |
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| 25. |
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| 26. |
- Modvig, S, et al.
(författare)
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Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia
- 2019
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Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 33:6, s. 1324-1336
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Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
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| 27. |
- Nyman, H., et al.
(författare)
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Impact of germinal center and non-germinal center phenotypes on overall and failure-free survival after high-dose chemotherapy and auto-SCT in primary diffuse large B-cell lymphoma
- 2008
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 42:2, s. 93-8
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Tidskriftsartikel (refereegranskat)abstract
- Non-germinal center (non-GC) phenotype is an adverse prognostic factor in chemotherapy (CT)-treated diffuse large B-cell lymphoma (DLBCL) patients. To determine how high-dose therapy (HDT) supported with auto-SCT as first line therapy influences GC-associated outcome in young high-risk DLBCL patients GC and non-GC phenotypes were determined immunohistochemically from 63 patients. Of these, 29 primary high-risk DLBCL patients were treated with auto-SCT, whereas 34 CT-treated patients served as a control group. Consistent with previous studies, non-GC phenotype was associated with adverse outcome in CT-treated high-risk patients. In contrast, immunohistochemical classification by cell of origin did not associate with survival after auto-SCT. When the impact of treatment on the predictive value of cell of origin was analyzed, the non-GC patients, who received HDT, had a better failure-free survival (FFS) and overall survival (OS) than the patients treated with CT alone. In multivariate analyses, both age-adjusted International Prognostic Index (aaIPI) and treatment were independent prognostic factors for FFS and OS. For the patients with GC phenotype, the influence of auto-SCT on survival was not significant. The data imply that auto-SCT can overcome the adverse prognostic impact of the non-GC phenotype in patients with high-risk DLBCL and warrant additional prospective studies.
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| 28. |
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| 29. |
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| 30. |
- Abu-Bakar, A'edah, et al.
(författare)
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Metabolism of bilirubin by human cytochrome P450 2A6
- 2012
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 261:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- The mouse cytochrome P450 (CYP) 2A5 has recently been shown to function as hepatic "Bilirubin Oxidase" (Abu-Bakar, A., et al., 2011. Toxicol. Appl. Pharmacol. 257, 14-22). To date, no information is available on human CYP isoforms involvement in bilirubin metabolism. In this paper we provide novel evidence for human CYP2A6 metabolising the tetrapyrrole bilirubin. Incubation of bilirubin with recombinant yeast microsomes expressing the CYP2A6 showed that bilirubin inhibited CYP2A6-dependent coumarin 7-hydroxylase activity to almost 100% with an estimated K-i of 2.231 mu M. Metabolite screening by a high-performance liquid chromatography/electrospray ionisation mass spectrometry indicated that CYP2A6 oxidised bilirubin to biliverdin and to three other smaller products with m/z values of 301,315 and 333. Molecular docking analyses indicated that bilirubin and its positively charged intermediate interacted with key amino acid residues at the enzyme's active site. They were stabilised at the site in a conformation favouring biliverdin formation. By contrast, the end product, biliverdin was less fitting to the active site with the critical central methylene bridge distanced from the CYP2A6 haem iron facilitating its release. Furthermore, bilirubin treatment of HepG2 cells increased the CYP2A6 protein and activity levels with no effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half-life of the CYP2A6 compared to cells treated only with CHX. Collectively, the observations indicate that the CYP2A6 may function as human "Bilirubin Oxidase" where bilirubin is potentially a substrate and a regulator of the enzyme.
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| 31. |
- Biancari, Fausto, et al.
(författare)
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Gender and the Outcome of Postcardiotomy Veno-arterial Extracorporeal Membrane Oxygenation
- 2022
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 36:6, s. 1678-1685
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There is a paucity of sex-specific data on patients’ postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO). The present study sought to assess this issue in a multicenter study. Design: Retrospective, propensity score–matched analysis of an international registry. Setting: Multicenter study, tertiary university hospitals. Participants: Data on adult patients undergoing postcardiotomy VA-ECMO. Measurements and Main Results: Between January 2010 and March 2018, patients treated with postcardiotomy VA-ECMO at 17 cardiac surgery centers were analyzed. Index procedures considered were coronary artery bypass graft surgery, isolated valve surgery, their combination, and proximal aortic root surgery. Hospital and five-year mortality constituted the endpoints of interest. Propensity score matching was adopted with logistic regression. A total of 358 patients (mean age: 63.3 ± 12.3 years; 29.6% female) were identified. Among 94 propensity score–matched pairs, women had a higher hospital mortality (70.5% v 56.4%, p = 0.049) compared with men. Logistic regression analysis showed that women (odds ratio [OR], 1.87; 95% confidence interval [CI] 1.10-3.16), age (OR, 1.06; 95%CI 1.04-1.08) and pre-ECMO arterial lactate (OR, 1.09; 95%CI 1.04-1.16) were independent predictors of hospital mortality. No differences between female and male patients were observed for other outcomes. Among propensity score–matched pairs, one-, three-, and five-year mortality were 60.6%, 65.0%, and 65.0% among men, and 71.3%, 71.3%, and 74.0% among women, respectively (p = 0.110, adjusted hazard ratio, 1.27; 95%CI 0.96-1.66). Conclusions: In postcardiotomy VA-ECMO, female patients demonstrated higher hospital mortality than men. Morbidity and late mortality were similar between the two groups.
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| 32. |
- Biancari, Fausto, et al.
(författare)
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Inter-institutional analysis of the outcome after postcardiotomy veno-arterial extracorporeal membrane oxygenation
- 2024
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Ingår i: International Journal of Artificial Organs. - 0391-3988. ; 47:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Patients requiring postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) have a high risk of early mortality. In this analysis, we evaluated whether any interinstitutional difference exists in the results of postcardiotomy V-A-ECMO. Methods: Studies on postcardiotomy V-A-ECMO were identified through a systematic review for individual patient data (IPD) meta-analysis. Analysis of interinstitutional results was performed using direct standardization, estimation of observed/expected in-hospital mortality ratio and propensity score matching. Results: Systematic review of the literature yielded 31 studies. Data from 10 studies on 1269 patients treated at 25 hospitals were available for the present analysis. In-hospital mortality was 66.7%. The relative risk of in-hospital mortality was significantly higher in six hospitals. Observed versus expected in-hospital mortality ratio showed that four hospitals were outliers with significantly increased mortality rates, and one hospital had significantly lower in-hospital mortality rate. Participating hospitals were classified as underperforming and overperforming hospitals if their observed/expected in-hospital mortality was higher or lower than 1.0, respectively. Among 395 propensity score matched pairs, the overperforming hospitals had significantly lower in-hospital mortality (60.3% vs 71.4%, p = 0.001) than underperforming hospitals. Low annual volume of postcardiotomy V-A-ECMO tended to be predictive of poor outcome only when adjusted for patients’ risk profile. Conclusions: In-hospital mortality after postcardiotomy V-A-ECMO differed significantly between participating hospitals. These findings suggest that in many centers there is room for improvement of the results of postcardiotomy V-A-ECMO.
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| 33. |
- Biancari, Fausto, et al.
(författare)
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Prognostic Significance of Arterial Lactate Levels at Weaning from Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The outcome after weaning from postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) is poor. In this study, we investigated the prognostic impact of arterial lactate levels at the time of weaning from postcardiotomy VA.METHODS: This analysis included 338 patients from the multicenter PC-ECMO registry with available data on arterial lactate levels at weaning from VA-ECMO.RESULTS: Arterial lactate levels at weaning from VA-ECMO (adjusted OR 1.426, 95%CI 1.157-1.758) was an independent predictor of hospital mortality, and its best cutoff values was 1.6 mmol/L (<1.6 mmol/L, 26.2% vs. ≥ 1.6 mmol/L, 45.0%; adjusted OR 2.489, 95%CI 1.374-4.505). When 261 patients with arterial lactate at VA-ECMO weaning ≤2.0 mmol/L were analyzed, a cutoff of arterial lactate of 1.4 mmol/L for prediction of hospital mortality was identified (<1.4 mmol/L, 24.2% vs. ≥1.4 mmol/L, 38.5%, p = 0.014). Among 87 propensity score-matched pairs, hospital mortality was significantly higher in patients with arterial lactate ≥1.4 mmol/L (39.1% vs. 23.0%, p = 0.029) compared to those with lower arterial lactate.CONCLUSIONS: Increased arterial lactate levels at the time of weaning from postcardiotomy VA-ECMO increases significantly the risk of hospital mortality. Arterial lactate may be useful in guiding optimal timing of VA-ECMO weaning.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Itälä, M, et al.
(författare)
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Standard-dose anti-CD20 antibody rituximab has efficacy in chronic lymphocytic leukaemia : Results from a nordic multicentre study
- 2002
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 69:3, s. 129-134
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This prospective multicentre study was conducted to assess the efficacy of the monoclonal anti-CD20 antibody rituximab in patients with chronic lymphocytic leukaemia (CLL). Secondary objectives were defined as the tolerability and feasibility of rituximab in patients with CLL. Methods: Twenty-four heavily pretreated patients with CLL were treated with a standard dose of 375 mg m-2 of rituximab given once weekly for four doses. Results: The overall response rate was 35% and all the responses were partial as defined by the revised NCI criteria. In 17 (85%) of 20 patients with initially measurable peripheral lymph nodes the size of lymph nodes decreased by at least 50%, while an improvement of the bone marrow infiltration was observed only in two (11%) of 18 evaluable patients. The median duration of the overall response was 12.5 wk. Rituximab was relatively well tolerated. Although side-effects were common (75%) they were usually mild or moderate. There was only one grade 3 adverse event and no grade 4 events. Conclusions: Standard-dose rituximab has activity in heavily pretreated patients with CLL, although the response is mainly limited to the lymph nodes and of short duration. Since rituximab has in vitro synergism with chemotherapeutic agents and is well tolerated by CLL patients, it is reasonable to investigate rituximab in combination with other treatments.
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| 41. |
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| 42. |
- Juvonen, V, et al.
(författare)
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Quantification of point mutations associated with Leber hereditary optic neuroretinopathy by solid-phase minisequencing
- 1994
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Ingår i: Human Genetics. - 0340-6717 .- 1432-1203. ; 93:1, s. 16-20
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Tidskriftsartikel (refereegranskat)abstract
- About two-thirds of patients with Leber hereditary optic neuroretinopathy (LHON) harbor mutations in mitochondrial DNA at positions 11778 (ND4) or 3460 (ND1). Thus, the clinical diagnosis of LHON can often be confirmed with mutation analysis. Detection of pathogenic mutations and quantification of heteroplasmy has mainly relied on PCR and restriction site analysis and densitometric scanning. We applied the recently developed solid-phase minisequencing method, based on primer-guided nucleotide incorporation, to the simultaneous detection and quantitation of the ND4/11778 and ND1/3460 mutations. The method was highly sensitive, heteroplasmy as low as 1.5% being easily detected. Rapid, reproducible, and accurate results prove solid-phase minisequencing to be the method of choice for quantitative analysis of LHON mutations.
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| 44. |
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| 45. |
- Mariscalco, Giovanni, et al.
(författare)
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Duration of Venoarterial Extracorporeal Membrane Oxygenation and Mortality in Postcardiotomy Cardiogenic Shock
- 2021
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 35:9, s. 2662-2668
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The optimal duration of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in patients affected by postcardiotomy cardiogenic shock (PCS) remains controversial. The present study was conducted to investigate the effect of VA-ECMO duration on hospital outcomes. Design: Retrospective analysis of an international registry. Setting: Multicenter study including 19 tertiary university hospitals. Participants: Between January 2010 and March 2018, data on PCS patients receiving VA-ECMO were retrieved from the multicenter PC-ECMO registry. Interventions: Patients were stratified according to the following different durations of VA-ECMO therapy: ≤three days, four-to-seven days, eight-to-ten days, and >ten days. Measurements and Main Results: A total of 725 patients, with a mean age of 62.9 ± 12.9 years, were included. The mean duration of VA-ECMO was 7.1 ± 6.3 days (range 0-39 d), and 39.4% of patients were supported for ≤three days, 29.1% for four-seven days, 15.3% for eight-ten days, and finally 20.7% for >ten days. A total of 391 (53.9%) patients were weaned from VA-ECMO successfully; however, 134 (34.3%) of those patients died before discharge. Multivariate logistic regression showed that prolonged duration of VA-ECMO therapy (four-seven days: adjusted rate 53.6%, odds ratio [OR] 0.28, 95% confidence interval [CI] 0.18-0.44; eight-ten days: adjusted rate 61.3%, OR 0.51, 95% CI 0.29-0.87; and >ten days: adjusted rate 59.3%, OR 0.49, 95% CI 0.31-0.81) was associated with lower risk of mortality compared with VA-ECMO lasting ≤three days (adjusted rate 78.3%). Patients requiring VA-ECMO therapy for eight-ten days (OR 1.96, 95% CI 1.15-3.33) and >10 days (OR 1.85, 95% CI 1.14-3.02) had significantly greater mortality compared with those on VA-ECMO for 4 to 7 days. Conclusions: PCS patients weaned from VA-ECMO after four-seven days of support had significantly less mortality compared with those with shorter or longer mechanical support.
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| 46. |
- Mariscalco, Giovanni, et al.
(författare)
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Venoarterial Extracorporeal Membrane Oxygenation After Surgical Repair of Type A Aortic Dissection
- 2020
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 125:12, s. 1901-1905
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Tidskriftsartikel (refereegranskat)abstract
- Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support for postcardiotomy cardiogenic shock (PCS) in patients undergoing surgery for acute type A aortic dissection (TAAD) is controversial and the available evidence is confined to limited case series. We aimed to evaluate the impact of this salvage therapy in this patient population. Between January 2010 and March 2018, all TAAD patients receiving VA-ECMO for PCS were retrieved from the PC-ECMO registry. Hospital mortality and other secondary outcomes were compared with PCS patients undergoing surgery for other cardiac pathologies and treated with VA-ECMO. Among the 781 patients in the PC-ECMO registry, 62 (7.9%) underwent TAAD repair and required VA-ECMO support for PCS. In-hospital mortality accounted for 46 (74.2%) patients, while 23 (37.1%) were successfully weaned from VA-ECMO. No significant differences were observed between the TAAD and non-TAAD cohorts with reference to in-hospital mortality (74.2% vs 63.4%, p = 0.089). However, patients in the TAAD group had a higher rate of neurological events (33.9% vs 17.6%, p = 0.002), but similar rates of reoperation for bleeding/tamponade (48.4% vs 41.5%, p = 0.29), transfusion of ≥10 red blood cell units (77.4% vs 69.5%, p = 0.19), new-onset dialysis (56.7% vs 53.1%, p = 0.56), and other secondary outcomes. VA-ECMO provides a valid support for patients affected by PCS after surgery for TAAD.
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