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IntroductionPostoperative complications are major healthcare problems and are associated with a reduced short-term and long-term survival after surgery. An excessive postoperative inflammatory response participates to the development of postoperative infection and mortality. The aim of the Perioperative Administration of Corticotherapy on Morbidity and mortality After Non-cardiac surgery (PACMAN) study is to assess the effectiveness of perioperative administration of corticosteroid to reduce postoperative morbidity and mortality in patients undergoing major non-cardiac surgery.Methods and analysisThe PACMAN is a multicentre, randomised, controlled, double-blind, superiority, two-arm trial of 1222 high-risk patients aged 50 years or older undergoing major non-cardiac surgery at 32 acute care hospital in France. Patients are randomly assigned to dexamethasone (0.2 mg/kg at the end of the surgical procedure and at day +1, n=611) or to placebo (n=611). The primary outcome is a composite of predefined 14-day major pulmonary complications and mortality. Secondary outcomes are surgical complications, infections, organ failures, critical care-free days, length of hospital stay and all-cause mortality at 28 days.Ethics and disseminationThe PACMAN trial protocol has been approved by the ethics committee of Sud Mediterranée V, and will be carried out according to the Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The PACMAN trial is a randomised controlled trial powered to investigate whether perioperative administration of corticosteroids in patients undergoing non-cardiac major surgery reduces postoperative complications. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.Trial registration numberNCT03218553; Pre-results.

Une opération d’archéologie préventive menée dans la commune d’Allonnes (Eure-et-Loir) a révélé une partie d’une vaste nécropole mérovingienne, ainsi que plusieurs petits groupes de tombes situées à sa périphérie. L’intervention a permis de caractériser l’occupation funéraire tant d’un point de vue spatial que chronologique et de cerner certains aspects des pratiques sépulcrales. Elle a notamment conduit à la mise au jour de plusieurs inhumations en sarcophages de plâtre, regroupées au sein de l’un des ensembles satellites. Si l’utilisation de ce type de contenant funéraire est bien documentée pour l’Île-de-France et la Normandie, elle n’était jusqu’alors connue pour la région Centre-Val de Loire que par quelques découvertes anciennes. Il n’en est fait mention dans aucune des synthèses chrono-typologiques régionales publiées à ce jour. La découverte réalisée à Allonnes permet en ce sens d’enrichir les connaissances archéologiques sur la diversité des pratiques funéraires adoptées dans ce secteur géographique durant le haut Moyen Âge. A rescue excavation in the village of Allonnes (Eure-et-Loir) led to the discovery of a portion of a large Merovingian necropolis, as well as several smaller groups of tombs located in its periphery. The excavation allowed to characterize the funerary occupation both spatially and chronologically, and it provided information on the burial practices. In particular, it led to the discovery of several plaster sarcophagi, grouped in one of the peripheral sepulchral sets. Whereas this type of burials is well documented in Île-de-France and Normandy, its use in Central France was until now only known from ancient discoveries. Such a type of burials was not reported in any of the regional chrono-typological studies published to date. The discovery made in Allonnes enriches the archaeological knowledge about the diversity of the early medieval funerary practices in this geographic area.

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Introduction/ Background The development of digital resources for pathologists is a long process before truly validated algorithms can be used in daily practice. Aims In addition to developing new tools for helping Whole Slide Image (WSI) analysis by pathologists, the cooperative research project FlexMIm aims at setting up a shared platform allowing further technological improvements to be tested and evaluated online by a community of pathologists. Methods The FlexMIm consortium includes 27 pathology laboratories in the Paris area (coordinated by Assistance Publique-Hôpitaux de Paris), research laboratories from University Pierre et Marie Curie (UPMC Univ Paris 06) and University Paris Diderot, as well as 3 companies: TRIBVN, PERTIMM and Orange (project coordinator). Based on a cloud architecture, the project embeds a dedicated WSI database and visualisation support. Groups of partners developed dedicated algorithms. These algorithms have been tested separately, then integrated into the online platform. A large test and validation protocol, involving operational versions of these algorithms, is on-going among the 27 pathology laboratories participating to this project. Results One algorithm was built for blur detection in WSI in order to improve the quality of the workflow. Other quantitative algorithms were built for immunohistochemical counts such as Ki67, for mitosis detection from H&E (Hematoxylin – Eosin) stained WSI and for supporting the detection of Regions of Interest (ROI) for dysplasia screening in inflammatory bowel diseases (IBD). A series of algorithms (as gland detections in IBD) are at the proof of concept stage. Dedicated semantics and research engine are included in the platform, supporting the ROI collaborative annotations in WSI. The ontology used is generated by an operational contextual graph produced and validated for IBD diagnosis, consolidated by a semantic template linked to the annotations of IBD WSI. Another collaborative tool on the platform allows the online implementation of ontologies, with creation and edition of concepts. A full IBD diagnostic ontology is already available and a prostate cancer diagnostic ontology is underway. A major point of this platform is that all participating pathologists can finally evaluate online all the resources developed during the project. Anonymised WSI uploaded by each pathologist can be annotated by all other pathologists. These WSI can then be analysed by all the algorithms and tools available in the platform. Pathologists can eventually fill evaluation forms that are analyzed by the project steering committee. Beside online resources, another goal of FlexMIm was to implement tools for faster WSI communication through networks especially in low bandwidth environments. The pathologists used a test bed in order to evaluate several compression algorithms on several visualisation devices (laptop, tablets), eventually leading to a “smart transportation” algorithm that can be activated in case of non-optimal network. Within 3 years, FlexMIm partners have thus built a platform which now integrates a whole set of algorithms to foster digital pathology adoption by a large cluster of Pathology laboratories., Diagnostic Pathology, Vol 1 No 8 (2016): 13. European Congress on Digital Pathology

Primary pulmonary hypertension (PPH) is characterized by intimal fibrosis and cell proliferation (including fibroblasts, smooth muscle and endothelial cells) in the distal pulmonary arterial tree. Considerable interest has been generated by recent reports of PPH in human immunodeficiency virus (HIV)-1-infected individuals. Although the lack of evidence for a pulmonary artery infection has suggested that in such cases HIV may act through mediator release rather than by direct endothelial infection, the mechanisms underlying HIV-associated PPH remain poorly defined. Platelet-derived growth factor (PDGF) has the ability to induce smooth muscle cell and fibroblast proliferation and migration. Given these considerations, we have attempted to document a possible role for PDGF in PPH occurring in HIV seropositive and seronegative patients. Using semiquantitative polymerase chain reaction (PCR), PDGF A-chain messenger ribonucleic acid (mRNA) expression was analysed in surgical lung biopsies from 13 HIV seronegative patients and one HIV seropositive patient, all displaying severe PPH. In parallel, lung samples from two patients with HIV-1-associated PPH were studied by immunohistochemistry and in situ hybridization. Results were compared to those obtained in three HIV-1-infected individuals with no pulmonary complication (as demonstrated by clinical, radiological, bacteriological, and necropsy findings) and five control lung biopsies. As compared to controls, PDGF A-chain mRNA expression is elevated in lung biopsies from patients displaying PPH (p=0.029). In HIV-1-associated PPH, interstitial perivascular cells expressing PDGF A-chain mRNA and protein could be detected by in situ hybridization and immunohistochemistry, respectively. Platelet-derived growth factor expression is elevated in lung biopsies of patients displaying primary pulmonary hypertension. Growth factors such as platelet-derived growth factor may play a part in the initiation and/or progression of primary pulmonary hypertension.

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Contains fulltext : 70674.pdf (Publisher’s version ) (Closed access) The purpose of the present study was to evaluate the accuracy of the diagnosis of idiopathic pulmonary fibrosis (IPF) by respiratory physicians in six European countries, and to calculate the interobserver agreement between high-resolution computed tomography reviewers and histology reviewers in IPF diagnosis. The diagnosis of usual interstitial pneumonia (UIP) was assessed by a local investigator, following the American Thoracic Society/European Respiratory Society consensus statement, and confirmed when a minimum of two out of three expert reviewers from each expert panel agreed with the diagnosis. The level of agreement between readers within each expert panel was calculated by weighted kappa. The diagnosis of UIP was confirmed by the expert panels in 87.2% of cases. A total of 179 thoracic high-resolution computed tomography scans were independently reviewed, and an interobserver agreement of 0.40 was found. Open or thoracoscopic lung biopsy was performed in 97 patients, 82 of whom could be reviewed by the expert committee. The weighted kappa between histology readers was 0.30. It is concluded that, although the level of agreement between the readers within each panel was only fair to moderate, the overall accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis in expert centres is good (87.2%).

Context.—Alcoholic liver disease in humans frequently leads to cirrhosis. Experimental models of hepatic fibrogenesis are available, but extrapolation of those findings to human ethanol-induced liver injury is difficult. Hepatic ethanol-induced fibrosis in humans has often been studied in relatively small patient populations. During the past decade, several animal models and human studies have attributed fibrogenesis in the liver to the role played by hepatocytes, Kupffer cells, endothelial cells, and especially stellate cells. Objective.—To determine the contribution of the main liver cell types to ethanol-induced fibrogenesis. For that purpose, we studied the expression of the following immunologic parameters: smooth muscle–specific α actin (SMSA), CD68, CD34, transforming growth factor β1, intercellular adhesion molecule 1, and collagen types 1 and 3. The Dako LSAB+ kit (peroxidase method) was used. Design.—We recently studied a large cohort of patients with alcoholic liver disease in France. In this cohort, we found 87 cases in which liver biopsies revealed only pericentral injury with nonpathologic portal areas. We compared cases in which the portal areas were nonpathologic with 324 patients in whom staging ranged from F0 to F3. Patients with cirrhosis (F4) were excluded from evaluation. To stage fibrosis, we used the METAVIR system. Furthermore, we selected 40 cases in which the biopsies measured at least 25 mm in length for further histochemical evaluation. Ten additional normal cases from our archives were used as controls. We divided this patient population into the following 5 groups of 10 patients each: group 1A, F0 with steatosis; group 1B, F0 without steatosis; group 2, F0 to F1, central injury; group 3, F3, fibrosis with multiple septa; and group 4, nonpathologic livers (controls). Results.—Smooth muscle–specific α actin was expressed by stellate cells, pericentrally, with increasing severity and intensity in the advanced stage of fibrosis of group 3, less intense expression was noted in group 2, and expression was practically absent in group 1 and in nonpathologic controls. CD68 was the best marker for Kupffer cells and was expressed diffusely within the lobules in all groups. Its expression correlated directly with the degree of disease severity, progressing from stage I through stage III, but was absent in nonpathologic livers. CD34 was consistently expressed by endothelial cells in the periportal areas in all groups. The expression of collagen type 1 was intense in the bands of fibrosis or bridging, while type 3 expression was poor. Transforming growth factor β1 and intercellular adhesion molecule 1 were not expressed in any group. Conclusions.—In this study, stellate cell activation (SMSA) was most intense pericentrally in the early stages and diffusely with progression to fibrosis and maximum intensity in stage III. Kupffer cell activation, as determined by CD68 expression, was intense and diffuse, while endothelial cells expressed CD34 periportally in a similar manner in all stages. Fibrogenesis in human ethanol injury is due to the activity of stellate cells, Kupffer cells, and to a lesser extent, to endothelial cells.

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