Peripheral artery occlusive disease in chronic phase chronic myeloid leukemia patients treated with nilotinib or imatinib.

Several retrospective studies have described the clinical manifestation of peripheral artery occlusive disease (PAOD) in patients receiving nilotinib. We thus prospectively screened for PAOD in patients with chronic phase chronic myeloid leukemia (CP CML) being treated with tyrosine kinase inhibitors (TKI), including imatinib and nilotinib. One hundred and fifty-nine consecutive patients were evaluated for clinical and biochemical risk factors for cardiovascular disease. Non-invasive assessment for PAOD included determination of the ankle-brachial index (ABI) and duplex ultrasonography. A second cohort consisted of patients with clinically manifest PAOD recruited from additional collaborating centers. Pathological ABI were significantly more frequent in patients on first-line nilotinib (7 of 27; 26%) and in patients on second-line nilotinib (10 of 28; 35.7%) as compared with patients on first-line imatinib (3 of 48; 6.3%). Clinically manifest PAOD was identified in five patients, all with current or previous nilotinib exposure only. Relative risk for PAOD determined by a pathological ABI in first-line nilotinib-treated patients as compared with first-line imatinib-treated patients was 10.3. PAOD is more frequently observed in patients receiving nilotinib as compared with imatinib. Owing to the severe nature of clinically manifest PAOD, longitudinal non-invasive monitoring and careful assessment of risk factors is warranted.

[Quantitative assessment of fungal risk in the case of construction works in healthcare establishments: Proposed indicators for the determination of the impact of management precautions on the risk of fungal infection]. / Appréciation quantitative du risque fongique en cas de travaux en établissements de santé : propositions d'indicateurs d'impact des mesures de gestion du risque infectieux fongique.

Construction works in healthcare establishments produce airborne fungal spores and considerably increase the risk of exposure of immunosuppressed patients. It is necessary to reinforce protective measures, or even to implement specific precautions, during this critical phase. The aim of these precautions is to protect both those areas, which are susceptible to dust, and patients at risk of a fungal infection particularly invasive aspergillosis. When construction works are planned in healthcare establishments, the first step consists in the characterisation of the environmental fungal risk and the second one in proposing risk management methods. It is then essential to establish impact indicators in order to evaluate the risk management precautions applied. The working group promoted by the French societies of medical mycology and hospital hygiene (SFMM & SF2H) details here both environmental and epidemiological impact indicators that can be used.

Invasive aspergillosis: an important risk factor on the short- and long-term survival of acute myeloid leukemia (AML) patients.

Invasive aspergillosis (IA) during induction chemotherapy of acute myeloid leukemia (AML) could worsen the prognosis. Our objective was to study how the development of IA during AML interferes with the therapeutic strategy and to evaluate its impact on the short- and long-term survival. Newly diagnosed AML patients between the years 2004 and 2007 were retrospectively analyzed. The outcome was death of the patient. A Cox proportional hazards model with the diagnosis of IA and post-induction response evaluation as the main exposure was fitted. Overall, 262 patients were analyzed and 58 IA were observed. The 2-year survival of patients having had remission of AML was 54% and, for patients with failure of chemotherapy, it was 5% (p < 0.001). The 2-year survival of patients having had IA was 14%, and without IA, it was 32% (p = 0.01). Multivariate analysis showed that IA was associated with a higher risk of death in case of remission compared to no IA (hazard ratio [HR] = 1.66 [1.05-2.65], p = 0.031) and also in case of failure (HR = 6.43, p < 0.001). IA was associated with an increased risk of death for patients if they were either in remission or in failure after induction chemotherapy.

[Allogeneic cord blood transplantation for adults: current results and future development]. / Allogreffe de sang placentaire chez l'adulte : actualités et perspectives.

Hematopoietic stem cell transplantation is the choice treatment of many hematopoietic disorders. However, there is still no related or HLA-matched unrelated donor for one-third of the patients. Cord blood, which contains a lot of hematopoietic progenitors immunologically naive, represents not only an interesting alternative as hematopoietic stem cell source but also allows more HLA incompatibilities than the other sources. Promising results in children lead to develop cord blood transplantation in adults first of all in hematopoietic malignancies (acute leukemias and lymphoid diseases) and in a second time, in non-malignant diseases such as aplastic anaemia. The main problems for the development of this new strategy in adults are the poor number of cells per unit, the delay for hematopoietic recovery in comparison with other hematopoietic stem cell sources and, consequently higher transplant related mortality. In order to improve the results in adults, new strategies emerged. Double cord blood transplantation, expansion methods and intra-bone injection of the graft will be reviewed here, as well as alternative transplantation strategies such as non-myeloablative conditioning.

Lipid esterification and secretion by the mouse intestine in organ culture.

Explants of adult mouse jejunum were cultured for different time periods and incubated in presence of a lipid diet emulsified by sodium taurocholate or complexed with albumin. The esterification of fatty acids and the secretion of triglycerides and phospholipids were measured and compared to the lipid absorption observed in vivo after the perfusion of the same diet. The results show that, in vitro, the enterocytes esterify the fatty acids present in the medium and secrete them with a yield improving during the culture and even better than the absorption observed in the in vivo experiments.