Mucosal Eosinophil Abundance in Non-Inflamed Colonic Tissue Is Associated with Response to Vedolizumab Induction Therapy in Inflammatory Bowel Disease

Vedolizumab is used as a treatment for patients with inflammatory bowel disease (IBD), but induction therapy leads to clinical response and remission in approximately 55% and 30% of patients with IBD, respectively. In this study, we aimed to explore the predictive value of mucosal eosinophils and serum eotaxin-1 regarding response to vedolizumab induction therapy. Eighty-four (84) patients with IBD (37 Crohn’s disease [CD], 47 ulcerative colitis [UC]) were included. For 24 patients with IBD, histopathology was assessed for eosinophil counts in non-inflamed colonic tissue prior to vedolizumab treatment. For 64 patients with IBD, serum eotaxin-1 levels were quantified prior to (baseline) and during vedolizumab treatment. Serum samples of 100 patients with IBD (34 CD, 66 UC) from the GEMINI 1 and 2 trials were used for external validation. Baseline mucosal eosinophil numbers in non-inflamed colonic tissue were significantly higher in responders to vedolizumab induction therapy when compared to primary non-responders (69 [34–138] vs. 24 [18–28] eosinophils/high-power field, respectively, p < 0.01). Baseline serum eotaxin-1 levels in the discovery cohort were significantly elevated in responders, compared to primary non-responders (0.33 [0.23–0.44] vs. 0.20 [0.16–0.29] ng/mL, p < 0.01). Prediction models based on mucosal eosinophil counts and serum eotaxin-1 showed an area under the curve (AUC) of 0.90 and 0.79, respectively. However, the predictive capacity of baseline serum eotaxin-1 levels could not be validated in the GEMINI cohort. Mucosal eosinophil abundance in non-inflamed colonic tissue was associated with response to vedolizumab induction therapy in patients with IBD. Future studies are warranted to further validate the potential value of mucosal eosinophils and serum eotaxin-1 as biomarkers for response to vedolizumab therapy

Mucosal eosinophil abundance in non-inflamed colonic tissue predicts response to vedolizumab induction therapy in inflammatory bowel disease

Vedolizumab is used as a treatment for patients with inflammatory bowel disease (IBD), but induction therapy leads to clinical response and remission in approximately 55% and 30% of patients with IBD, respectively. In this study, we aimed to explore the predictive value of mucosal eosinophils and serum eotaxin-1 regarding response to vedolizumab induction therapy. Eighty-four (84) patients with IBD (37 Crohn’s disease [CD], 47 ulcerative colitis [UC]) were included. For 24 patients with IBD, histopathology was assessed for eosinophil counts in non-inflamed colonic tissue prior to vedolizumab treatment. For 64 patients with IBD, serum eotaxin-1 levels were quantified prior to (baseline) and during vedolizumab treatment. Serum samples of 100 patients with IBD (34 CD, 66 UC) from the GEMINI 1 and 2 trials were used for external validation. Baseline mucosal eosinophil numbers in non-inflamed colonic tissue were significantly higher in responders to vedolizumab induction therapy when compared to primary non-responders (69 [34–138] vs. 24 [18–28] eosinophils/high-power field, respectively, p < 0.01). Baseline serum eotaxin-1 levels in the discovery cohort were significantly elevated in responders, compared to primary non-responders (0.33 [0.23–0.44] vs. 0.20 [0.16–0.29] ng/mL, p < 0.01). Prediction models based on mucosal eosinophil counts and serum eotaxin-1 showed an area under the curve (AUC) of 0.90 and 0.79, respectively. However, the predictive capacity of baseline serum eotaxin-1 levels could not be validated in the GEMINI cohort. Mucosal eosinophil abundance in non-inflamed colonic tissue was associated with response to vedolizumab induction therapy in patients with IBD. Future studies are warranted to further validate the potential value of mucosal eosinophils and serum eotaxin-1 as biomarkers for response to vedolizumab therapy

Riboflavin Supplementation in Patients with Crohn's Disease [the RISE-UP study]

Background and Aims: Crohn's disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD. Methods: In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention. Results: In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome. Conclusions: Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD

Biomarker, kit and method for predicting clinical responsiveness to therapy with an agent that targets alpha₄beta₇ integrin

The invention relates generally to biomarkers, methods and kits to predict therapy response in patients, in particular in patients having inflammatory bowel disease (IBD). Provided is a method for predicting whether a human subject is likely to show a clinical response to therapy with an antibody or pharmacological antagonist that targets α4β7 integrin, preferably vedolizumab induction therapy, comprising (i) determining the level of eotaxin-1 in a sample obtained from the subject, and; (ii) classifying the subject as a responder based on the leve of eotaxin-1

Contribution to Waste Thermal Energy Recovery on Hot Gases by Heat Pipe Heat Exchanger - Expeirmental Approach and Modeling

L’objectif de la thèse porte sur l’analyse de la récupération de l’énergie thermique sur gaz chauds à température élevée(250°C - 450°C). Pour cela, la technologie de récupérateur à caloduc de type thermosiphon a été retenue. L’un des points cruciaux porte sur le choix d’un fluide de travail adapté à ces niveaux de température. Une analyse bibliographique a permis d’identifier le naphtalène comme élément de fluide potentiel pour cette gamme de température. Cependant le manque d’informations sur son comportement et ses capacités de transport a nécessité le développement d’un montage fondamental spécifique.Un caloduc thermosiphon chargé en naphtalène et de la forme d’un tube inox lisse de diamètre 23,9 mm, de longueur 1m (zone évaporateur : 20 cm ; zone condenseur : 20 cm) a été réalisé et testé. Les résultats expérimentaux obtenus démontrent tout d’abord la faisabilité d’un tel système dans cette gamme de température et pour les puissances thermiques envisagées. Ils révèlent un comportement inhabituel du thermosiphon lors des phases de démarrage (régime transitoire). En régime permanent, l’analyse a porté sur l’influence de la température de saturation, la puissance transférée ainsi que l’inclinaison. En termes de performances, les conductances thermiques (évaporateur, condenseur, système) augmentent avec la température vapeur et diminuent avec la puissance apportée à l’évaporateur. La puissance transférée peut s’échelonner de 0,2 kW à 1,5 kW, soit 1 à 8 W/cm² à l’évaporateur. Une faible sensibilité à l’inclinaison a été constatée lors des tests (0°-78°), un peu plus marqué pour 84°. Enfin pour une orientation à l’horizontale (90°), le caloduc fonctionne malgré tout et sa capacité de transfert reste élevée bien qu’éloignée du mode thermosiphon. En parallèle, un modèle de thermosiphon a été développé dans lequel les coefficients d’échanges locaux (évaporateur et condenseur) sont calculés par différentes corrélations issues de la littérature. La comparaison avec les résultats expérimentaux a permis de valider les modèles physiques retenus avec un bon accord, et de prédire le fonctionnement du caloduc pour d’autres sollicitations.Ainsi et enfin, un premier prototype récupérateur à thermosiphon au naphtalène a été conçu, fabriqué et couplé sur la veine « gaz chauds » conçue et développée aussi au sein du laboratoire. Les premiers résultats obtenus du système complet permettent de développer des stratégies de récupération et de valorisation de l’énergie thermique sur la ligne d’échappement, dans un contexte d’application automobile.The aim of the thesis is to analyze the heat recovery on hot gases at intermediate temperature range (250°C - 450°C). For this purpose, the thermosyphon heat exchanger recuperation technology has been chosen. The choice of a working fluid adapted to these temperature levels is one of the crucial points. A literature review identified naphthalene as a potentialfluid for this temperature range. However, because of the lack of information about naphthalene heat pipes, the development of a fundamental test-rig was necessary to fully characterize the thermal behavior and transport capacities of this fluid.A thermosyphon heat-pipe charged with naphthalene in the shape of a smooth stainless steel tube with a diameter of 23.9mm, a length of 1 m (evaporator zone: 20 cm, condenser zone: 20 cm) has been manufactured and tested. The experimental results obtained demonstrate the feasibility of such system in this temperature range and for the thermal powers required.They reveal an unusual behavior of the thermosyphon during the start-up process. In steady state, the analysis deals with the influence of the saturation temperatures, the transferred heat power and the thermosyphon inclination. In terms of performances, the thermal conductance (evaporator, condenser, system) increases with the vapor temperature and decreases with the heat power supplied to the evaporator. The heat flow rate can be applied from 0.2 to 1.5 kW, or 1 to 8W/cm² at the evaporator. During the tests, the system is found to be less sensitive to inclination (0° to 78°), but more important for 84°. In the horizontal position, the thermosyphon operates, but its heat transfer remains high even far away from the thermosyphon mode. A theoretical model has been developed in which the local heat transfer coefficients(evaporator and condenser) are evaluated by different correlations from literature. The comparison with the experimental results allowed to validate the models retained with good agreement, and to make it possible to predict the heat pipe operation for other solicitations.Thus, and finally, a first thermosyphon charged naphthalene recuperator prototype was designed, manufactured and coupled to the "hot gas" line designed and performed in the laboratory. The first results obtained from the complete system allowed us to develop a strategy for heat recovery system on the exhaust line of an automotive application