Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Septic Shock Sera Containing Circulating Histones Induce Dendritic Cell–Regulated Necrosis in Fatal Septic Shock Patients

Objectives: Innate immune system alterations, including dendritic cell loss, have been reproducibly observed in patients with septic shock and correlated to adverse outcomes or nosocomial infections. The goal of this study is to better understand the mechanisms behind this observation in order to better assess septic shock pathogenesis.Design: Prospective, controlled experimental study. Setting: Research laboratory at an academic medical center. Subjects: The study enrolled 71 patients, 49 with septic shock and 22 with cardiogenic shock. Seventeen healthy controls served as reference. In vitro monocyte-derived dendritic cells were generated from healthy volunteers. Interventions: Sera were assessed for their ability to promote in vitro dendritic cell death through flow cytometry detection in each group of patients. The percentage of apoptotic or necrotic dendritic cells was evaluated by annexin-V and propidium iodide staining. Measurements and Main Results: We observed that only patients with septic shock and not patients with pure cardiogenic shock were characterized by a rapid and profound loss of circulating dendritic cells. In vitro analysis revealed that sera from patients with septic shock induced higher dendritic cell death compared to normal sera or cardiogenic shock (p < 0.005). Sera from surviving patients induced dendritic cell death through a caspase-dependent apoptotic pathway, whereas sera from nonsurviving patients induced dendritic cell-regulated necrosis. Dendritic cell necrosis was not due to necroptosis but was dependent of the presence of circulating histone. The toxicity of histones toward dendritic cell could be prevented by recombinant human activated protein C. Finally, we observed a direct correlation between the levels of circulating histones in patients and the ability of the sera to promote dendritic cell-regulated necrosis. Conclusions: The study demonstrates a differential mechanism of dendritic cell death in patients with septic shock that is dependent on the severity of the disease

Depletion of Dendritic Cells Enhances Innate Anti-Bacterial Host Defense through Modulation of Phagocyte Homeostasis

Dendritic cells (DCs) as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye). We used CD11c-diphtheria toxin (DT) mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS) by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection

Unusual expression of villous adenoma

Les tumeurs villeuses recto-coliques, plus rares que les polyadénomes sont de localisation préférentiellement distale. Une symptomatologie volontiers plus riche les caractérise, dominée par une sécrétion importante responsable d'une déperdition hydro-électrique pouvant engager le pronostic vital comme en témoigne l'observation rapportée. Le risque de dégénérescence est de 24 à 43 %, l'exérèse complète est fondamentale. L'écho-endoscopie doit maintenant faire partie du bilan pré-thérapeutique, elle précise l'intégrité ou l'atteinte de la musculeuse et l'éventuelle présence d'adénopathie périrectale

A case of duodenal metastasis of an esophageal squamous cell carcinoma

La localisation de métastases au tube digestif est rare. Leur siège est plus souvent jéjuno-iléal. Les auteurs rapportent un cas de métastase d'un carcinome épidermoïde de l'œsophage chez un homme de 47 ans qui avait été traité par radiochimiothérapie puis chirurgie deux mois auparavant. Une revue de la littérature retrouve le caractère exceptionnel de ces métastases duodénale

A performance assessment framework for hospitals: the WHO regional office for Europe PATH project

Objective. The World Health Organization (WHO) Regional Office for Europe launched in 2003 a project aiming to develop and disseminate a flexible and comprehensive tool for the assessment of hospital performance and referred to as the performance assessment tool for quality improvement in hospitals (PATH). This project aims at supporting hospitals in assessing their performance, questioning their own results, and translating them into actions for improvement, by providing hospitals with tools for performance assessment and by enabling collegial support and networking among participating hospitals. Methods. PATH was developed through a series of four workshops gathering experts representing most valuable experiences on hospital performance assessment worldwide. An extensive review of the literature on hospital performance projects was carried out, more than 100 performance indicators were scrutinized, and a survey was carried out in 20 European countries. Results. Six dimensions were identified for assessing hospital performance: clinical effectiveness, safety, patient centredness, production efficiency, staff orientation and responsive governance. The following outcomes were achieved: (i) definition of the concepts and identification of key dimensions of hospital performance; (ii) design of the architecture of PATH to enhance evidence-based management and quality improvement through performance assessment; (iii) selection of a core and a tailored set of performance indicators with detailed operational definitions; (iv) identification of trade-offs between indicators; (v) elaboration of descriptive sheets for each indicator to support hospitals in interpreting their results; (vi) design of a balanced dashboard; and (vii) strategies for implementation of the PATH framework. Conclusion. PATH is currently being pilot implemented in eight countries to refine its framework before further expansio

The central vein sign in multiple sclerosis patients with vascular comorbidities.

The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS <sup>+</sup> ) lesions in MS has never been evaluated. To investigate the association between different VRFs and the percentage of CVS <sup>+</sup> lesions in MS. In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. The median frequency of CVS <sup>+</sup> lesions was 71% (range: 35%-100%). In univariate analysis, age (p < 0.0001), hypertension (p < 0.001), diabetes (p < 0.01), obesity (p < 0.01), smoking (p < 0.05), and the presence of enlarged-perivascular-spaces on MRI (p < 0.005) were all associated with a lower percentage of CVS <sup>+</sup> lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS <sup>+</sup> lesions in MS (adjusted R <sup>2</sup> = 0.46; p < 0.0001 and p = 0.01, respectively). The proportion of CVS <sup>+</sup> lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment