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| 2. |
- De Stefano, V., et al.
(författare)
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High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with Vitamin K antagonists
- 2016
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 30:10, s. 2032-2038
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Tidskriftsartikel (refereegranskat)abstract
- The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.
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| 3. |
- De Stefano, V., et al.
(författare)
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Splanchnic vein thrombosis in myeloproliferative neoplasms : Risk factors for recurrences in a cohort of 181 patients
- 2016
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Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- We retrospectively studied 181 patients with polycythaemia vera (n=67), essential thrombocythaemia (n=67) or primary myelofibrosis (n=47), who presented a first episode of splanchnic vein thrombosis (SVT). Budd-Chiari syndrome (BCS) and portal vein thrombosis were diagnosed in 31 (17.1%) and 109 (60.3%) patients, respectively; isolated thrombosis of the mesenteric or splenic veins was detected in 18 and 23 cases, respectively. After this index event, the patients were followed for 735 patient years (pt-years) and experienced 31 recurrences corresponding to an incidence rate of 4.2 per 100 pt-years. Factors associated with a significantly higher risk of recurrence were BCS (hazard ratio (HR): 3.03), history of previous thrombosis (HR: 3.62), splenomegaly (HR: 2.66) and leukocytosis (HR: 2.8). Vitamin K-antagonists (VKA) were prescribed in 85% of patients and the recurrence rate was 3.9 per 100 pt-years, whereas in the small fraction (15%) not receiving VKA more recurrences (7.2 per 100 pt-years) were reported. Intracranial and extracranial major bleeding was recorded mainly in patients on VKA and the corresponding rate was 2.0 per 100 pt-years. In conclusion, despite anticoagulation treatment, the recurrence rate after SVT in myeloproliferative neoplasms is high and suggests the exploration of new avenues of secondary prophylaxis with new antithrombotic drugs and JAK-2 inhibitors.
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| 4. |
- Barosi, G, et al.
(författare)
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Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms : consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
- 2015
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.
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| 5. |
- Barosi, G., et al.
(författare)
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A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia : results of a consensus process by an international working group
- 2007
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 21:2, s. 277-280
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Tidskriftsartikel (refereegranskat)abstract
- A widely accepted definition of resistance or intolerance to hydroxyurea (HU) in patients with essential thrombocythemia (ET) is lacking. An international working group (WG) was convened to develop a consensus formulation of clinically significant criteria for defining resistance/intolerance to HU in ET. To this aim, an analytic hierarchy process (AHP), a multiple-attribute decision-making technique, was used. The steps consisted of selecting the candidate criteria for defining resistance/intolerance; identifying the motivations that could influence the preference of the WG for any individual criterion; comparing the candidate criteria in a pair-wise manner; and grading them according their ability to fulfill the motivations. Every step in the model was derived by questionnaires or group discussion. The WG proposed that the definition of resistance/intolerance should require the fulfillment of at least one of the following criteria: platelet count greater than 600,000/micro l after 3 months of at least 2 g/day of HU (2.5 g/day in patients with a body weight over 80 kg); platelet count greater than 400,000/micro l and WBC less than 2500/micro l or Hb less than 10 g/dl at any dose of HU; presence of leg ulcers or other unacceptable muco-cutaneous manifestations at any dose of HU; HU-related fever.
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| 6. |
- Bailleul, Benjamin, et al.
(författare)
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Energetic coupling between plastids and mitochondria drives CO2 assimilation in diatoms.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7565, s. 366-9
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Tidskriftsartikel (refereegranskat)abstract
- Diatoms are one of the most ecologically successful classes of photosynthetic marine eukaryotes in the contemporary oceans. Over the past 30 million years, they have helped to moderate Earth's climate by absorbing carbon dioxide from the atmosphere, sequestering it via the biological carbon pump and ultimately burying organic carbon in the lithosphere. The proportion of planetary primary production by diatoms in the modern oceans is roughly equivalent to that of terrestrial rainforests. In photosynthesis, the efficient conversion of carbon dioxide into organic matter requires a tight control of the ATP/NADPH ratio which, in other photosynthetic organisms, relies principally on a range of plastid-localized ATP generating processes. Here we show that diatoms regulate ATP/NADPH through extensive energetic exchanges between plastids and mitochondria. This interaction comprises the re-routing of reducing power generated in the plastid towards mitochondria and the import of mitochondrial ATP into the plastid, and is mandatory for optimized carbon fixation and growth. We propose that the process may have contributed to the ecological success of diatoms in the ocean.
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| 7. |
- Finazzi, M., et al.
(författare)
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Multiatomic resonant photoemission spectroscopy on CuO and NiO : Observation of antiresonant behavior
- 2000
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 62:24, s. R16215-R16218
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Tidskriftsartikel (refereegranskat)abstract
- The intensity of the O 1s core photoemission peak has been measured for CuO and NiO as the photon energy is scanned across the L-3 absorption edge of the metal ion. In CuO, the O 1s peak shows a typical antiresonant behavior, with a sizable decrease of its cross section at photon energies below the Cu L-3 threshold. No detectable effect is observed for NiO. The CuO data are well reproduced by a multiatom resonant photoemission model based on resonant light scattering.
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| 8. |
- Finazzi, M., et al.
(författare)
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Photon energy dependence of the perpendicular geometry magnetic circular dichroism in the 2p3p3p resonant photoemission from Ni
- 2000
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 12:9, s. 2123-2133
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Tidskriftsartikel (refereegranskat)abstract
- The magnetic circular dichroism in the perpendicular geometry of the resonant 2p3p3p photoemission (PE) spectroscopy has been investigated in metallic Ni as a function of the photon energy across the Ni Lj absorption edge. Within the experimental error bars, the photon energy dependence of the PE dichroism signal is the same as the one shown by the magnetic circular dichroism of the corresponding x-ray absorption (XMCD), obtained in the collinear geometry. This is attributed to the fact that, in metal Ni, the orbital [L-z] and dipolar [T-z] moments are smaller than the spin angular moment [S-z]. The latter is the dominating term in both the expressions that give the integrated values of the PE dichroism or XMCD intensities, Although the respective photon energy dependence is very similar, the normalized PE dichroism intensity is a factor similar to 5.6 smaller than the normalized XMCD signal, while only a factor similar to 1.6 is expected from theoretical considerations. This factor is observed even below the L-3 threshold, thus we exclude that the small intensity of the perpendicular geometry dichroism in the Ni 2p3p3p resonant photoemission is due to fast relaxation processes in the intermediate state.
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| 9. |
- Finazzi, M., et al.
(författare)
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Radiationless Raman versus Anger behavior at the Cu L-3 resonance of CuO and Cu2O
- 2000
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 61:7, s. 4629-4635
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the behavior of the 2p3p3p and 2p3s3p Anger lines of CuO and Cu2O scanning the photon energy across the Cu L-3 resonance. For both samples, when the excitation energy is below the L-3 resonance, we observe the 2p3p3p and 2p3s3p peaks at constant binding energy. This behavior is typical of nonradiative resonant Raman scattering. If the photon energy is raised above the L-3 maximum, the two samples behave in different ways. In CuO, the Auger peaks are always observed at constant binding energy, while in Cu2O their kinetic energy first reaches a maximum at correspondence with the absorption threshold, and then stabilizes at a value slightly higher than the off-resonance Auger peaks. These differences are interpreted in terms of the different electronic structure of the Auger intermediate state at resonance. In CuO, the intermediate state corresponds to a single 2p(3/2) core hole, with the Cu 3d band completely filled. On the contrary, in Cu2O the intermediate state is represented by the combination of a 2p(3/2) hole with a 4sp electron in strong interaction with the O-2sp valence band. In CuO, for photon energies higher than 1.5 eV above the L-3-edge maximum, the constant binding energy radiationless Raman peaks are accompanied by constant kinetic energy replicas. These are attributed to the relaxation of the Auger intermediate state through electron-hole pair generation across the band gap of the material. Satellites that could be associated to relaxation precesses involving energies smaller than the band gap are not resolved. No variation of the lineshape of the Anger peaks is observed as a function of the sample temperature, indicating that different densities of thermally accessible excitations do not have a strong influence on the recombination process of the core hole.
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| 10. |
- Flori, Serena, et al.
(författare)
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Plastid thylakoid architecture optimizes photosynthesis in diatoms
- 2017
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Photosynthesis is a unique process that allows independent colonization of the land by plants and of the oceans by phytoplankton. Although the photosynthesis process is well understood in plants, we are still unlocking the mechanisms evolved by phytoplankton to achieve extremely efficient photosynthesis. Here, we combine biochemical, structural and in vivo physiological studies to unravel the structure of the plastid in diatoms, prominent marine eukaryotes. Biochemical and immunolocalization analyses reveal segregation of photosynthetic complexes in the loosely stacked thylakoid membranes typical of diatoms. Separation of photosystems within subdomains minimizes their physical contacts, as required for improved light utilization. Chloroplast 3D reconstruction and in vivo spectroscopy show that these subdomains are interconnected, ensuring fast equilibration of electron carriers for efficient optimum photosynthesis. Thus, diatoms and plants have converged towards a similar functional distribution of the photosystems although via different thylakoid architectures, which likely evolved independently in the land and the ocean.
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