| 1. |
|
|
| 2. |
- De Stefano, V., et al.
(author)
-
High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with Vitamin K antagonists
- 2016
-
In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 30:10, s. 2032-2038
-
Journal article (peer-reviewed)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.
|
|
| 3. |
- De Stefano, V., et al.
(author)
-
Splanchnic vein thrombosis in myeloproliferative neoplasms : Risk factors for recurrences in a cohort of 181 patients
- 2016
-
In: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 6:11
-
Journal article (peer-reviewed)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.
|
|
| 4. |
- Wernly, B, et al.
(author)
-
Sex-specific outcome disparities in very old patients admitted to intensive care medicine: a propensity matched analysis
- 2020
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 18671-
-
Journal article (peer-reviewed)abstract
- Female and male very elderly intensive patients (VIPs) might differ in characteristics and outcomes. We aimed to compare female versus male VIPs in a large, multinational collective of VIPs with regards to outcome and predictors of mortality. In total, 7555 patients were included in this analysis, 3973 (53%) male and 3582 (47%) female patients. The primary endpoint was 30-day-mortality. Baseline characteristics, data on management and geriatric scores including frailty assessed by Clinical Frailty Scale (CFS) were documented. Two propensity scores (for being male) were obtained for consecutive matching, score 1 for baseline characteristics and score 2 for baseline characteristics and ICU management. Male VIPs were younger (83 ± 5 vs. 84 ± 5; p < 0.001), less often frail (CFS > 4; 38% versus 49%; p < 0.001) but evidenced higher SOFA (7 ± 6 versus 6 ± 6 points; p < 0.001) scores. After propensity score matching, no differences in baseline characteristics could be observed. In the paired analysis, the mortality in male VIPs was higher (mean difference 3.34% 95%CI 0.92–5.76%; p = 0.007) compared to females. In both multivariable logistic regression models correcting for propensity score 1 (aOR 1.15 95%CI 1.03–1.27; p = 0.007) and propensity score 2 (aOR 1.15 95%CI 1.04–1.27; p = 0.007) male sex was independently associated with higher odds for 30-day-mortality. Of note, male gender was not associated with ICU mortality (OR 1.08 95%CI 0.98–1.19; p = 0.14). Outcomes of elderly intensive care patients evidenced independent sex differences. Male sex was associated with adverse 30-day-mortality but not ICU-mortality. Further research to identify potential sex-specific risk factors after ICU discharge is warranted.Trial registration: NCT03134807 and NCT03370692; Registered on May 1, 2017 https://clinicaltrials.gov/ct2/show/NCT03370692.
|
|
| 5. |
- Barosi, G, et al.
(author)
-
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
-
In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:1, s. 20-26
-
Journal article (peer-reviewed)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.
|
|
| 6. |
- Saussele, S., et al.
(author)
-
Klinische Forschung im „European LeukemiaNet”
- 2006
-
In: Deutsche Medizinische Wochenschrift. - : Georg Thieme Verlag KG. - 0012-0472 .- 1439-4413. ; 131:43, s. 2423-2426
-
Journal article (peer-reviewed)abstract
- Because of their mortality, morbidity and incidence in all age groups, leukemias represent a challenge and a cost factor for society. In research, they serve as models for a variety of diseases and have a pivotal function in basic research and for patient care. The European LeukemiaNet (ELN) is a EU funded Network of excellence. Its major goal is the construction of an exemplary cooperative leukemia network for the improvement of medical care and of health related research in acute and chronic leukemias. This is achieved by improved mechanisms of cooperation among 78 national leukemia study groups and their 83 interdisciplinary partner groups that deal with the leukemias in research and in patient care in 22 countries. The network integrates about 1000 researchers in 125 participating institutions. In practice, cooperation between clinical and research groups is mediated by various instruments that improve communication, flow of information and interdisciplinary cooperation, and also increase information transfer from top research institutions to clinical translation. The improved cooperation and the accelerated information transfer from the „bench to the bedside” results in a better patient care that ultimately results in improved survival of patients and in superior competitiveness of involved research workers and clinicians. The major goals are: Establishing common information and communication structures, Creation of European networks for each leukemia Establishing European platforms for each inter-disciplinary speciality Performing clinical trials on an European level Establishing European leukemia registries Developing common definitions and standards Developing guidelines and meta-analyses Spread of excellence To reach these goals the network is organized in 17 Workpackages (WPs) each of which is subdivided into several components and deliverables. The WPs represent central services, set up European networks for each major leukemia or related syndrome and interdisciplinary European platforms for diagnostic specialities, and support treatment research, registries, meta-analyses and guidelines. After the second year of networking, the main structures concerning management, communication and information of the ELN have been established and consolidated. Web-based information is available on the central website (www.leukemia-net.org). Communication is accomplished through annual symposia, regular network and WP-meetings (nearly 60 in 2005), website, and the biannual newsletters. A central randomization service and registries are available for distinct leukemia entities, and a prototype of the electronic data capture facility service has been implemented. Several studies were initiated and are ongoing on a European level. Nearly all WPs have prepared or are preparing guidelines or consensus papers, e. g. guidelines on CML therapy, definitions for transplantation associated microangiopathy (TAM), therapy of infections in leukemias, harmonization of molecular monitoring in CML and a consensus on microarray-technology based diagnostics in leukemias. The main goals of the second funding period have been achieved, and thus the ELN is well prepared for further progress in its goals to improve diagnosis and treatment of the leukemias.
|
|
| 7. |
- Barosi, G., et al.
(author)
-
A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia : results of a consensus process by an international working group
- 2007
-
In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 21:2, s. 277-280
-
Journal article (peer-reviewed)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.
|
|
| 8. |
|
|
| 9. |
- Mansson, M., et al.
(author)
-
Using High Energy Angle Resolved Photoelectron Spectroscopy to Reveal the Charge Density in Solids
- 2008
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 101:22
-
Journal article (peer-reviewed)abstract
- The charge density in solids is a fundamental parameter. Here we demonstrate that the charge density can be determined by the use of angle resolved photoelectron spectroscopy. The method, which involves a Fourier-like transform from momentum space to real space, is demonstrated by utilizing soft x-ray angle resolved photoelectron spectroscopy to sample the complete three-dimensional Brillouin zone of copper. It is also shown that this can be done in an energy resolved way as to extract the charge density contribution from states of a particular energy.
|
|
| 10. |
|
|
