Cosmological time versus CMC time I: Flat spacetimes

This paper gives a new proof that maximal, globally hyperbolic, flat spacetimes of dimension $n\geq 3$ with compact Cauchy hypersurfaces are globally foliated by Cauchy hypersurfaces of constant mean curvature, and that such spacetimes admit a globally defined constant mean curvature time function precisely when they are causally incomplete. The proof, which is based on using the level sets of the cosmological time function as barriers, is conceptually simple and will provide the basis for future work on constant mean curvature time functions in general constant curvature spacetimes, as well for an analysis of the asymptotics of constant mean foliations

Transient colonization of the airways by unusual Aspergillus species in two cystic fibrosis patients

Date du colloque&nbsp;: 06/2009</p

Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis.

peer reviewedSystemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released

Azacytidine Enhances Regulatory T-Cells In Vivo and Prevents Experimental Xenogeneic Graft-Versus-Host Disease

Background The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Tregs). Objective We investigated the impact of AZA on xenogeneic graft-versus-host disease (xGVHD) in a humanized murine model of transplantation, and described the impact of the drug on human T cells in vivo. Methods In order to induce xGVHD, human peripheral blood mononuclear cells (huPBMC) were administered intravenously in NOD-scid IL-2Rγnull (NSG) mice. Results AZA successfully improved both survival (p&lt;0.0001) and xGVHD scores (p&lt;0.0001). Further, AZA significantly decreased human T-cell proliferation as well as INF-γ and TNF-α serum levels, and reduced the expression of GRANZYME B and PERFORIN 1 by cytotoxic T cells. In addition, AZA administration significantly increased the function, proliferation and frequency of Tregs through demethylation of FOXP3i1 and higher secretion of IL-2 by conventional T cells due to IL2 gene promoter site 1 demethylation. Interestingly, among AZA-treated mice surviving the acute phase of xGVHD, there was an inverse correlation between the presence of Tregs and signs of chronic GVHD. Finally, Tregs harvested from the spleen of AZA-treated mice were suppressive and stable over time since they persisted at high frequency in secondary transplant experiments. Conclusion These findings emphasize a potential role for AZA as prevention or treatment of GVHD

Feed-back on the development of a small scale Contact Erosion Test in the laboratory (characteristic size ~ 30 cm)

To determine the hydraulic load requested to initiate contact erosion process, tests are performed with an apparatus called the “Contact Erosion Test”. This device originally results from research carried out by Grenoble University, Électricité de France and Compagnie Nationale du Rhône, at the scale of ~60 cm. It has been adapted to a smaller scale in geophyConsult laboratory to conduct tests on samples extracted from core drilling. The instrumentation was improved to enable a better control of the hydraulic loading and avoid biases. The test protocol was modified, especially to better constrain the soil density at the interface. From the first series of test, we drew conclusions on the test repeatability and on the influence of parameters of the soil state. Discrepancies with previous results obtained at the scale of ~60 cm were identified. Therefore, a new erosion test campaign was planned to confirm and determine the reasons for these differences

Palliatieve inpatients in general hospitals : a one day observational study in Belgium

Background: Hospital care plays a major role at the end-of-life. But little is known about the overall size and characteristics of the palliative inpatient population. The aim of our study was to analyse these aspects. Methods: We conducted a one-day observational study in 14 randomly selected Belgian hospitals. Patients who met the definition of palliative patients were identified as palliative. Then, information about their sociodemographic characteristics, diagnoses, prognosis, and care plan were recorded and analysed. Results: There were 2639 in-patients on the day of the study; 9.4% of them were identified as “palliative”. The mean age of the group was 72 years. The primary diagnosis was cancer in 51% of patients and the estimated life expectancy was shorter than 3 months in 33% of patients and longer than 1 year in 28% of patients. The professional caregivers expected for most of the patients (73%), that the treatment would improve patient comfort rather than prolong life. Antibiotics, transfusions, treatments specific to the pathology, and artificial nutrition were administered in 90%, 78%, 57% and 50% of the patients, respectively, but were generally given with a view to controlling the symptoms. Conclusions: This analysis presents a first national estimate of the palliative inpatient population. Our results confirm that hospitals play a major role at the end-of-life, with one out of ten inpatients identified as a “palliative” patient. These data also demonstrate the complexity of the palliative population and the substantial diversity of care that they can require

Management of Myelodysplastic Syndrome Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the French Society of Bone Marrow Transplantation and Cell Therapies

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P < .001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P ¼ .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P ¼.007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT

Practical management of Chronic Myeloid Leukemia in Belgium

peer reviewedImatinib has drastically changed the outcome of patients with chronic myeloid leukemia (CML), with the majority of them showing a normal life span. Recently, the development of second and third generation tyrosine kinase inhibitors (TKIs) and the possibility of treatment discontinuation made the management of these patients more challenging. In this review, practical management guidelines of CML are presented, adapted to the Belgian situation in 2014. In first line chronic phase patients, imatinib, nilotinib and dasatinib can be prescribed. While second generation TKIs give faster and deeper responses, their impact on long-term survival remain to be determined. The choice of the TKI depends on CML risk score, priority for a deep response to allow a treatment-free remission protocol, age, presence of comorbid conditions, side effect profile, drug interactions, compliance concerns and price. Monitoring the response has to be made according the 2013 ELN criteria, and is based on the bone-marrow cytogenetic response during the first months and on the blood molecular response. Molecular follow-up is sufficient in patients with a complete cytogenetic response. For patients who fail frontline therapy, nilotinib, dasatinib, bosutinib and ponatinib are an option depending of the type of intolerance or resistance. T315I patients are only sensitive to ponatinib, which has to be carefully handled due to cardiovascular toxicity. Advanced phase diseases are more difficult to handle, with treatments including allogeneic stem cell transplantation, which is also an option for patients failing at least two TKIs. The possibility of treatment-free remission and pregnancy are also discussed