Incidence and Risk Factors of Neutropenic Enterocolitis after Myelosuppressive Chemotherapy

Background Neutropenic enterocolitis (NE) is a serious complication in patients receiving intensive chemotherapy for the treatment of onco-haematological diseases. Yet, the relative incidence of the disease and its risk factors among patients treated with different regimen is not well defined. Methods The development of NE was analysed in 1223 neutropenic episodes from 692 onco-hematological patients receiving chemotherapy at the isolation Unit of CHUV who signed an informed consent (Swissethics 2017-01975). NE was defined by the presence abdominal signs and symptoms during neutropenic fever together with bowel wall thickening >4mm in any bowel segment by computed tomography or ultrasound. The incidence of NE and risk factors known at hospitalization baseline were analysed by using uni- and multivariate regression models according to the chemotherapy regimen, including those used for the induction of acute myeloblastic (AML) or lymphoblastic (ALL) leukemia and autologous hematopoietic cell transplantation (HCT). Results. A total of 72 episodes of radiologically-proven NE (5.9%) occurred; the percentage of NE was 16.3% for AML induction (e.g. HOVON based protocol), 5.6% for autologous HCT using the BEAM protocol, 4.8% for ALL induction, 2.9% for AML salvage (e.g. CLAG or FLAG +/- idarubicin), 1.9% for autologous HCT using a non-BEAM protocol (e.g. melphalan) and 1.9% for the other types of chemotherapy (Figure 1). In the HCT population, the single independent risk factor for NE was the BEAM versus non-BEAM protocol (Odd ratio [OR]=3.40, 95% confidence interval [CI] 1.14-10.1, P=0.03). In AML patients, independent risk factors for NE included induction versus salvage chemotherapy (OR=3.87, CI 1.31-11.4, P=0.01), chemotherapy with amsacrine (OR=2.94, CI 1.40-6.21, P=0.005) and triple intrathecal chemotherapy (OR=2.03, CI 1.01-4.08, P=0.048). Conclusions. Susceptibility to NE is strongly influenced by the type of chemotherapy. Patients receiving salvage therapy for AML have a surprisingly low rate of NE, possibly due to the concomitant use of G-CSF or an immunomodulaor effect of fludarabine or cladribine. Intrathecal chemotherapy has probably not a direct effect on NE but reflect the patients with high-risk AML quickly neutropenic or presenting a leukemic digestive infiltration

Bacterial Brain Abscesses: Factors Influencing Mortality and Sequelae

Thirty-nine cases of brain abscess diagnosed since the advent of the computed tomographic (CT) scan were analyzed for factors influencing the outcome. The mortality rate was 13%, and severe sequelae were present in 22% of the survivors. The mean delay between occurrence of the first symptoms and hospitalization was significantly shorter for the 12 patients with poor outcome (death or severe sequelae) than for the 25 who recovered (fully or with moderate sequelae). Moreover, severely impaired mental status and neurological impairment at admission were associated with a poor outcome in terms of both mortality and sequelae. In all cases with fatal outcome or severe sequelae, the diagnosis was made and treatment was initiated within 24 hours of admission. There was no apparent correlation between the outcome and the presence or type of predisposing factors, the radiological, biological, or microbiological findings, or the treatment modalities. Thus, with the advent of the CT scan and the possibility of early diagnosis and treatment, the prognosis of brain abscess appears to be mainly determined by the rapidity of progression of the disease before hospitalization and the patient's mental status on admissio

Isocitratase studies in Neurospora

Isocitratase studies in Neurospor

Pathway to Totipotency: Lessons from Germ Cells

Oocytes and sperm are some of the most differentiated cells in our bodies, yet they generate all cell types after fertilization. Accumulating evidence suggests that this extraordinary potential is conferred to germ cells from the time of their formation during embryogenesis. In this Review, we describe common themes emerging from the study of germ cells in vertebrates and invertebrates. Transcriptional repression, chromatin remodeling, and an emphasis on posttranscriptional gene regulation preserve the totipotent genome of germ cells through generations

Revisiting the role of microtubules in C. elegans polarity

Cells must break symmetry to acquire polarity. Microtubules have been implicated in the induction of asymmetry in several cell types, but their role in the Caenorhabditis elegans zygote, a classic polarity model, has remained uncertain. One study (see Tsai and Ahringer on p. 397 of this issue) brings new light to this problem by demonstrating that severe loss of microtubules impairs polarity onset in C. elegans

Warthin-Tumor mit Karzinom: Maligne Transformation oder Metastase?

Zusammenfassung: Wir berichten über einen ungewöhnlichen Fall eines langjährig klinisch diagnostizierten Warthin-Tumors (WT) mit plötzlicher Größenzunahme und nachfolgender Resektion. Histologisch konnte der WT bestätigt werden, zeigte jedoch zusätzlich diffuse Infiltrate eines dissolut wachsenden Adenokarzinoms. Unter der Annahme eines maligne transformierten WT wurden radiologische Staging-Untersuchungen angeschlossen, mit deren Hilfe ein metastasierendes Mammakarzinom mit identischer Morphologie zu den WT-Infiltraten entdeckt wurde. Die seltene Diagnose eines maligne transformierten WT erfordert daher immer den Ausschluss eines metastasierten Tumorleiden

Rôle d'une base de connaissance dans SemIoTics, un système autonome contrôlant un appartement connecté

National audienceL'Internet des Objets représente une réalité de plus en plus concrète au fur et à mesure que se déploient de larges réseaux d'objets connectés. Ceux-ci ouvrent de larges perspectives d'applications, mais rencontrent des difficultés en terme d'interopérabilité, de configuration ou de passage à l'échelle. Ces probléma-tiques peuvent être traitées par le recours aux principes du web de données liées, d'où l'émergence d'ontologies dédiées aux applications de l'IoT, comme IoT-O, une ontologie pour l'IoT.Par ailleurs, une description en-richie des systèmes permet d'envisager leur configuration autonome : on parle alors d'autonomic computing. Ce papier présente SemIoTics, un système autonome reposant sur des bases de connaissance pour la gestion d'un appartement connecté. Nous présentons tout d'abord une vision générique d'une architecture de réseaux d'objets connectés qui permet de guider une analyse des travaux à l'interface du web sémantique et de l'IoT. Nous décrivons ensuite les deux bases de connaissances spécialisant IoT-O sur lesquelles s'appuie SemIoTics, et leur relation avec le dispositif expérimental. Enfin, la structure de ce système autonome de domotique est présenté en détails, et mis en relation avec l'architecture identifiée dans l'état de l'art

Regulation of the MEX-5 Gradient by a Spatially Segregated Kinase/Phosphatase Cycle

SummaryProtein concentration gradients encode spatial information across cells and tissues and often depend on spatially localized protein synthesis. Here, we report that a different mechanism underlies the MEX-5 gradient. MEX-5 is an RNA-binding protein that becomes distributed in a cytoplasmic gradient along the anterior-to-posterior axis of the one-cell C. elegans embryo. We demonstrate that the MEX-5 gradient is a direct consequence of an underlying gradient in MEX-5 diffusivity. The MEX-5 diffusion gradient arises when the PAR-1 kinase stimulates the release of MEX-5 from slow-diffusive, RNA-containing complexes in the posterior cytoplasm. PAR-1 directly phosphorylates MEX-5 and is antagonized by the spatially uniform phosphatase PP2A. Mathematical modeling and in vivo observations demonstrate that spatially segregated phosphorylation and dephosphorylation reactions are sufficient to generate stable protein concentration gradients in the cytoplasm. The principles demonstrated here apply to any spatially segregated modification cycle that affects protein diffusion and do not require protein synthesis or degradation