Comparative Assessment of the Structural Features of Originator Recombinant Human Follitropin Alfa Versus Recombinant Human Follitropin Alfa Biosimilar Preparations Approved in Non-European Regions.

Although the full primary structures of the alfa and beta subunits of reference r-hFSH-alfa and its biosimilars are identical, cell context-dependent differences in the expressing cell lines and manufacturing process can lead to variations in glycosylation profiles. In the present study, we compared the structural features of reference r-hFSH-alfa with those of five biosimilar preparations approved in different global regions outside Europe (Primapur®, Jin Sai Heng®, Follitrope®, Folisurge®, and Corneumon®) with respect to glycosylation, macro- and microheterogeneity, and other post-translational modifications and higher order structure. The mean proportion of N-glycosylation-site occupancy was highest in reference r-hFSH-alfa, decreasing sequentially in Primapur, Jin Sai Heng, Corneumon, Follisurge and Follitrope, respectively. The level of antennarity showed slightly higher complexity in Corneumon, Primapur and Follitrope versus reference r-hFSH-alfa, whereas Jin Sai Heng and Folisurge were aligned with reference r-hFSH-alfa across all N-glycosylation sites. Sialylation level was higher in Corneumon and Follitrope, but small differences were detected in other biosimilar preparations compared with reference r-hFSH-alfa. Jin Sai Heng showed higher levels of N-glyconeuramic acid than the other preparations. Minor differences in oxidation levels were seen among the different products. Therefore, in summary, we identified var ious differences in N-glycosylation occupancy, antennarity, sialylation and oxidation between reference r-hFSH-alfa and the biosimilar preparations analyzed.

[Management of foreign bodies ingestion]. / Prise en charge des corps étrangers digestifs.

Foreign bodies ingestion is a common event, with a potential morbidity and mortality. In the majority of cases, the foreign bodies pass through the digestive tract without any complication. An endoscopy for removal of the foreign body is necessary in 10 to 20 % of cases and a surgical intervention is required in < 1 % of cases. In this article, we describe the clinical presentation, the potential complications, as well as the timing and endoscopic technics of foreign bodies retrieval, essentially based on the European Society of Gastrointestinal Endoscopy recommendations.

L'ingestion de corps étrangers est un événement fréquent, potentiellement grevée d'une morbi-mortalité et engendrant des coûts importants. Dans la majorité des cas, les corps étrangers suivent le tube digestif sans complication. Une endoscopie est nécessaire dans 10 à 20 % des cas et une intervention chirurgicale pour extraction du corps étranger/complications dans moins de 1 % des cas. Dans cet article, nous traitons de la prise en charge des corps étrangers chez l'adulte et passons en revue leur présentation clinique, leurs complications potentielles, ainsi que les délais et modalités de la prise en charge endoscopique basée essentiellement sur les recommandations de la Société européenne d'endoscopie digestive.

[Gastroenterology and hepatology update 2018]. / Gastroentérologie et hépatologie.

The purpose of this article is to detail the major gastroenterology novelties for 2018. In the field of hepatology we address the monitoring of hepatocellular carcinoma, the Baveno VI extended criteria for the detection of oesophageal varices and the management of cramps in cirrhotic patients. Concerning intestinal inflammatory diseases, two novel treatments have recently been approved by the European Commission, including injection of stem cells for the treatment of complex perianal fistulas and the JAK inhibitor tofacitinib for the RCH (ulcerative colitis). Finally, we provide an update on the diagnostic criteria for eosinophilic esophagitis and a new therapy that's was recently validated for the treatment of primitive biliary cirrhosis.

Cet article a pour but de détailler les nouveautés majeures survenues en gastroentérologie en 2018. Nous présentons les nouveautés hépatologiques sur la surveillance du carcinome hépatocellulaire, les critères Baveno VI étendus pour le dépistage des varices œsophagiennes et la prise en charge des crampes chez les patients cirrhotiques. Concernant les maladies inflammatoires intestinales, deux nouveaux traitements ont reçu récemment l'autorisation de mise sur le marché de la Commission européenne, notamment l'injection des cellules souches dans le traitement de fistules périanales complexes et l'inhibiteur de JAK tofacitinib pour la rectocolite hémorragique (RCH). Enfin, nous rapportons une mise à jour des critères diagnostiques de l'œsophagite à éosinophiles et un traitement récemment validé pour la cirrhose biliaire primitive.

[Gastric intestinal metaplasia and cancer risk: how to follow ?] / Métaplasie intestinale gastrique et risque de cancer: quelle surveillance ?

In 2019, gastric cancer still has high mortality. Gastric intestinal metaplasia (IGM) is an intermediate step in the process of carcinogenesis of intestinal adenocarcinoma. Gastroscopy with biopsies can detect the presence of MIG. Characterization in terms of intensity and distribution allows to stratify the risks and to target the population in which surveillance endoscopies are indicated for the purpose of detecting endoscopic resectable neoplasia in endoscopy.

Le cancer gastrique a encore en 2019 une mortalité élevée. La métaplasie intestinale gastrique (MIG) est une étape intermédiaire dans le processus de cancérogenèse de l'adénocarcinome de type intestinal. La gastroscopie avec biopsies permet de détecter la présence de MIG. Sa caractérisation en termes d'intensité et de distribution permet de stratifier les risques et de cibler la population chez qui des endoscopies de surveillance sont indiquées dans le but de détecter les néoplasies superficielles résécables en endoscopie.

[How to deal with drug-induced diarrhoea]. / Diarrhée médicamenteuse : comment s'orienter ?

Diarrhoea is a frequent drug adverse event, implicating a number of different treatments. It occurs in an acute setting or even several months after the beginning of the treatment and different pathophysiological mechanisms are involved. It must be proactively suspected and promptly treated, however this diagnosis is often mentioned only after multiple diagnostic tests. In this review we aim to offer a practical approach to promptly identify drug-induced diarrhoea, recognise most common implicated drugs and establish the best clinical management.

La diarrhée est un effet secondaire fréquent de nombreux médicaments à travers des mécanismes physiopathologiques divers. Elle peut survenir dans un délai d'apparition variable et devrait être suspectée et prise en charge rapidement. Ce diagnostic est cependant souvent évoqué tardivement après de multiples investigations. Dans cet article, nous revoyons les différentes classes de médicaments incriminés, les examens complémentaires à réaliser en cas de suspicion de diarrhée médicamenteuse, et nous proposons une approche pratique de prise en charge.

Calprotectin in Daily Practice: Where Do We Stand in 2017?

BACKGROUND: To make a distinction between organic and functional disease is essential for gastroenterologists in their daily practice, but it may be challenging, given the variety and aspecificity of gastrointestinal symptoms among the general population. The clinician aim is to avoid diagnostic delay and to restrict unnecessary invasive and expensive exams. SUMMARY: Faecal markers, in particular faecal calprotectin (FC), have given proof of being reliable markers of intestinal inflammation with good clinical sensitivity. Calprotectin is useful in the differential diagnosis between inflammatory bowel disease and irritable bowel syndrome, as well as in the follow-up of inflammatory bowel disease patients and in predicting treatment response, with an excellent correlation with endoscopic activity. Its role in collagenous colitis and infectious colitis is less clear and still under investigation. Key Message: Despite the growing evidence supporting its use, many clinicians are uncomfortable in dosing FC, due to its low specificity and the variability of cut-off values. Indeed there are no clear guidelines about how to manage patients with intermediate levels of FC. The aim of this article is to review recent literature on calprotectin and its use. The strong points and the limits of FC measurement will be analysed, and a practical approach in the daily clinical routine will be proposed.

[Gastroenterology and hepatology in 2016]. / Gastroentérologie et hépatologie.

This article aims to detail the major innovations occurred in Gastro-enterology in 2016, including the introduction of a new molecule, the vonoprazan, for the treatment of refractory gastroesophagal reflux disease (GERD) and a new way of eradication of H. pylori. The possibility to use an intermittent dose of PPI rather than continuously in severe gastric and duodenal ulcers after successful endoscopic hemostasis is also discussed as well as the withdrawal of corticosteroids in the treatment of autoimmune pancreatitis. The formulation of corticosteroids in the treatment of eosinophilic esophagitis, the interest of the chromo-endoscopy during colonoscopy highlighting small polyps (from 1 to 5 mm = « diminutive polyps ¼) and the introduction on the Swiss market for biosimilars in the treatment of inflammatory bowel disease (IBD) are also discussed.

Cet article a pour but de détailler les nouveautés majeures survenues en gastroentérologie pour 2016, notamment avec l'introduction d'une nouvelle molécule, le vonoprazan, destiné à la prise en charge du reflux gastro-œsophagien (RGO) réfractaire et des nouvelles modalités d'éradication d' H. pylori. La possibilité d'utilisation de doses intermittentes d'IPP plutôt qu'en mode continu dans les ulcères gastriques et duodénaux sévères après hémostase réussie, le sevrage des corticoïdes dans la prise en charge des pancréatites auto-immunes, leur formulation dans la prise en charge de l'œsophagite à éosinophiles, l'intérêt de la chromo-endoscopie lors de coloscopie mettant en évidence des petits polypes (de 1 à 5 mm = diminutive polyps) et l'introduction sur le marché suisse des biosimilaires pour le traitement des maladies inflammantoires chroniques de l'intestin sont également discutés.

[Faecal calprotectin : a useful tool for the primary care physician ?] / Calprotectine fécale : une utilité pour le généraliste ?

Faecal calprotectin (FC) is a marker of intestinal inflammation. FC dosing has a sensitivity between 80­100% for differentiating functional and organic intestinal disease. It is therefore a very useful diagnostic tool in general practice, where the prevalence of functional disease is particularly high. Nevertheless, FC is not specific for inflammatory bowel diseases and cannot distinguish between various inflammatory conditions. FC cut-off values are not clearly defined. Nevertheless, levels < 150 µg/g are considered ruling out organic disease and levels > 150 µg/g warrant an endoscopy. In the intermediate range 50­150 µg/g, the result is indeterminate and the decision to perform further tests should be made on an individual basis.

La calprotectine fécale (CF) est un marqueur d'inflammation intestinale dosé dans les selles. Elle a démontré une sensibilité entre 80­100 % dans la distinction entre atteintes digestives organiques et non organiques, ce qui en fait un outil diagnostique très intéressant en médecine de premier recours où la prévalence des atteintes digestives fonctionnelles est élevée. Toutefois, le dosage de la CF n'est pas spécifique pour les maladies inflammatoires de l'intestin et ne permet pas de différencier entre les différents types d'atteinte inflammatoire, et les valeurs seuils ne sont pas bien définies. En principe, une valeur < 150 µg / g exclut une pathologie organique, et une valeur > 150 µg/g est considérée comme posant l'indication à une endoscopie. Entre 50­150 µg/g, la décision de poursuivre les investigations est prise de cas en cas.

Critical role of the GM-CSF signaling pathway in macrophage pro-repair activities.

OBJECTIVE: Macrophages play a critical role in intestinal wound repair. However, the molecular pathways that regulate macrophage wound repair activities remain poorly understood. The aim of this study was to evaluate the role of GM-CSF receptor signaling in the wound repair activities of macrophages. METHODS: Murine macrophages were differentiated from bone marrow cells and human macrophages from monocytes isolated from peripheral blood mononuclear cells of Crohn's disease (CD) patients. In vitro models were used to study the repair activities of macrophages. RESULTS: We provide evidence that GM-CSF receptor signaling is required for murine macrophages to promote epithelial repair. In addition, we demonstrate that the deficient repair properties of macrophages from CD patients with active disease can be recovered via GM-CSF therapy. CONCLUSION: Our data support a critical role of the GM-CSF signaling pathway in the pro-repair activities of mouse and human macrophages.