PhysioPathologie des Adaptations Nutritionnelles

Abstract Background Evaluation of cleanliness in capsule endoscopy is essential to validate the exam. However, yet reliable evaluation of bowel cleanliness remains challenging. The validated KODA score provides robust assessment but is time-consuming and impractical in routine practice. We aimed to evaluate the performance of an AI-based tool (AXAROlite®, Augmented Endoscopy) compared with the KODA score for assessing small bowel cleanliness in Crohn’s disease (CD) patients. Methods This was a post-hoc analysis of a multicenter randomized controlled trial (NCT05117996) including 142 CD patients undergoing small bowel capsule endoscopy (SBCE) after either a standard PEG-based or simplified clear liquid preparation. All videos were evaluated for cleanliness using the KODA score by trained readers. The same videos were analyzed using the AI-based AXAROlite® tool. Correlation, agreement, and diagnostic performance of AXAROlite® were compared with the KODA score. Clinical factors influencing AI-assessed cleanliness were also investigated. Results Correlation between the KODA score and the AI-AXAROlite® score was found strong for the whole SB (ρ = 0.61; r2=0.35; p < 0.001) and moderate to strong for each of the four quartiles analyzed: ρ = 0.52; r2=0.24; p < 0.001, ρ = 0.56; r2=0.24; p < 0.001, ρ = 0.50; r2=0.21; p < 0.001, ρ = 0.62; r2=0.41; p < 0.001 for the first, the second, the third and the fourth quartiles, respectively. When compared to the qualitative evaluation of the SB cleanliness i.e. good, fair or poor, both the KODA and the AXAROlite® scores decreased similarly. The median [IQR] values of AXAROlite® scores were respectively 75.0 [59.0-84.0], 56.0 [42.0-67.0] and 41.00 [25.75-59.75]. The differences were statistically significant between a good and a fair or poor cleanliness (p < 0.001). AXAROlite® demonstrated excellent diagnostic accuracy for detecting adequate cleanliness defined as KODA > 2.25 (AUROC=0.85, 95% CI 0.79–0.92), with an optimal threshold of 72% clean frames (sensitivity 86%, specificity 72%). In multivariate analysis, the activity of the disease and the SB transit time influenced negatively the AXAROlite® score: β=-7.87 [-15.29; -0.44], p = 0.0382 and β=-0.04 [-0.06; -0.01], p = 0.0031 respectively. The behavior, the location of the disease, the endoscopic severity and the presence of an anastomosis, did not modify independently the AXAROlite® SBscore. Conclusion AXAROlite® provides a rapid, fully automated, and accurate evaluation of small bowel cleanliness in CD, comparable to the validated KODA score. Its integration into routine workflows may streamline reporting and reduce inter-observer variability. Conflict of interest: Rouveyre, Raphaelle: No conflict of interest Le Berre, Catherine: Abbvie, Amgen, Celltrion, Ferring, Fresenius Kabi, Galapagos, Gielad, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda. Leenhardt, Romain: co-founder and shareolder of Augmented Endoscopy Collins, Michael: consulting fees from Abbvie, Celltrion, Janssen, Amgen, Sanofi, Sandoz and Takeda De Maissin, Astrid: fees from Abbvie, Galapagos and Takeda Flamant, Mathurin: lecture or consulting fees from Abbvie, Amgen, Celltrion, Ferring, Fresenius Kabi, Lilly Janssen, MSD, OSE Immunotherapeutics, Pfizer, Sandoz, Takeda, and Tillotts Trang Poisson, Caroline: personal fees from Ferring, Janssen, Mayoly Spindler, Norgine, Abbvie, MSD, and Takeda Bouguen, Guillaume: Grant: Abbvie, Ferisinus Personal Fees: Abbvie, Takeda, Fresinus, Amgen, Biogène, Arena, Ferring, Gilead, Janssen, MSD, Pfizer, Sandoz, Takeda, Tillots, Vifor pharma Dib, Nina: No conflict of interest Histace, Aymeric: co-founder and shareolder of Augmented Endoscopy Soude, Theo: No conflict of interest Dray, Xavier: co-founder and shareolder of Augmented Endoscopy Prof. Bourreille, Arnaud: Grant: Takeda, MaunaKea technologies Personal Fees: AbbVie, Celltrion, Ferring, Galapagos, Gilead, MSD, Medtronic, OSE Immunotherapeutics, Janssen, Pfizer, Roche, Takeda, Tillotts, Vifor pharma

Optimal perfusion pressure targets during cardiopulmonary bypass in children are debated. Monitoring of CAR allow determination of optimal perfusion pressures, but its feasibility within a large cohort of children warrants further investigations. Prospective, single center, observational study. Cerebral Oxygenation Index (COx) was calculated as a moving linear correlation coefficient between slow waves of mean arterial pressure (MAP) and cerebral oxygenation saturation. Postoperative outcomes were recorded and associations with CAR derived metrics were explored. Mean COx values demonstrated CAR disruption during CPB (0.17 ± 0.17 before vs. 0.36 ± 0.13 during, p < 0.001). Post-CPB, CAR restored partially (mean Cox 0.32 ± 0.16, p < 0.05). Factors associated with CAR Disruption were age at surgery and average hematocrit during CPB. MAPopt determination was feasible in 83.3%, 75.4%, and 67.5% of patients before, during, and after surgery, respectively. LLA was determined in 78.1%, 53.5%, and 56.1%, and ULA in 71%, 50%, and 57% during the same time frames. Dose of MAP below LLA during CPB was independently associated with pre-postoperative serum creatinine ratio and 24 h postoperative serum lactate levels. The findings highlight the clinical significance of CAR monitoring, with implications for optimizing cerebral and systemic perfusion in this vulnerable population. In most cases, cardiopulmonary bypass is associated with CAR disruption, highlighting the need for rigorous perfusion pressure management. Individualized determination of optimal MAP target is feasible in neonates and infants undergoing cardiopulmonary bypass using CAR-derived metrics. The time spent within a range of optimal pressure is associated with better body perfusion. Live determination of optimal MAP may be used to develop individualized PAM management interventions, and ultimately improve body perfusion including the brain.

Summary In autoimmune hepatitis (AIH), hepatocellular damage is linked to an accumulation of autoreactive T cells in the liver of patients, but how these cells emerge in the tissue remains unclear. Here we used a mouse model based on recombination-dependent inducible expression of influenza A hemagglutinin (HA) by hepatocytes to investigate initiation of liver antigen-specific response. Our study revealed that peripheral immunization, unlike inflammatory triggers, is essential to initiate an immune response against a liver antigen. We showed that liver T cell reactivity after peripheral immunization is marked by PD-1 and TIGIT co-expression and that the frequency of PD-1 + TIGIT + HLA-DR + CD38 + CD8 T cells in the blood of AIH patients is associated with liver injury. Our findings suggest a potential influence of the peripheral immunization for the liver-antigen-specific responses during AIH. Liver tissue-activated T cells probably recirculate during active phase of the disease, unveiling potential immunomarkers to monitor disease activity. Highlights Peripheral immunization rather than local inflammation induces an immune response against a hepatic antigen PD-1 and TIGIT co-expression by T cells is found after tissue antigen-specific T cell reactivity Frequency of circulating PD-1 + TIGIT + HLA-DR + CD38 + CD8 T cells is associated with AIH disease activity In brief Guinebretière et al. demonstrate that after peripheral immunization, liver-antigen-specific T cell accumulation in the tissue is marked by local PD-1/TIGIT co-expression, a phenotype shared with liver and circulating T cell subsets enriched in active autoimmune hepatitis (AIH) patients. These findings suggest the influence of peripheral immunization on the initiation of AIH and provide potential immunomarker of AIH activity.

There is a paucity of data on arrhythmia burden in patients with congenitally corrected transposition of the great arteries (ccTGAs). The present study sought to quantify the incidence of atrial arrhythmia (AA), ventricular arrhythmia (VA), and complete atrioventricular block (CAVB) in patients with ccTGA and identify associated factors. An international, multi-centre, retrospective cohort study was conducted in 29 tertiary hospitals (six countries) between 1990 and 2018. Primary analyses consisted of determining the incidence of a combined outcome consisting of AA, VA, or CAVB, along with its individual components. Factors associated with the different types of arrhythmias were assessed by uni-variable and multi-variable Cox regression analyses. A total of 1131 patients with ccTGA were followed for 9.0 (interquartile range 4.0-17.2) years. Cumulative rates of the primary endpoint at 10, 15, and 20 years were 44.5%, 51.0%, and 58.8%, respectively. AA, VA, and CAVB occurred in 2.1, 1.4, and 2.0 cases per 100 person-years, respectively. In multi-variable analyses, surgery/intervention conferred a greater than three-fold higher risk of AA [hazard ratio (HR) 3.01, 95% confidence interval (CI) 1.90-4.78, P < .001]. Furthermore, surgery/intervention was significantly associated with a greater risk of VA (HR 1.73, 95% CI 0.98-3.05, P = .003) and CAVB (HR 3.65, 95% CI 2.20-6.05, P < .001). The left bundle branch block was associated with a higher risk of VA (HR 4.03, 95% CI 1.59-10.23, P = .003) and the right bundle branch block with a higher risk of CAVB (HR 3.71, 95% CI 1.81-7.63, P < .001). The arrhythmia burden in patients with ccTGA is substantial, with a high incidence of AA, VA, and CAVB.

Summary Parkinson disease (PD) is a major cause of disability with significant personal and system financial implications 1,2 . GBA1 variants are the commonest genetic risk factor for PD and increase the risk up to 30-fold 3,4 . Why only ∼20% of GBA1 variant carriers develop PD remains unknown. Here, by combining clinical and faecal metagenomics data from PD individuals carrying or not GBA1 variants, carriers of GBA1 variants not manifesting PD symptoms (GBA-NMC) and healthy controls, and using an innovative microbiome analysis, we show that a large component of the gut microbiome evolves from healthy across GBA-NMC towards PD and is strongly correlated with disease progression in patients, and prodromal symptoms suggestive of future development of PD in GBA-NMC. By using species altered in PD and GBA-NMC, we detect healthy individuals with the strongest prodromal PD clinical profile. These findings indicate that gut microbiome alterations can identify individuals with GBA1 variants most prone to develop PD and individuals in the general population that may be progressing towards PD. Healthy nutrition mitigates microbiome alterations associated with disease severity, suggesting that it could modify disease progression in PD patients and decrease the risk of disease development in healthy individuals including those with GBA1 variants.

BackgroundOver the past 2 decades, the gut microbiota has emerged as a key player in human health, being involved in many different clinical contexts. Yet, many aspects of the relationship with its host are poorly documented. One obstacle is the substantial variability in wet-laboratory procedures and data processing implemented during gut microbiota studies, which poses a challenge of comparability and potential meta-analysis.ObjectiveThe study protocol described here aimed to better understand the relationship between health, dietary habits, and the observed heterogeneity of gut microbiota composition in the general population. “Le French Gut – Le microbiote français” aimed to collect, sequence, and analyze 100,000 fecal samples from French residents using a high-quality shotgun metagenomic pipeline, complemented with comprehensive health, lifestyle, and dietary metadata.Methods“Le French Gut – Le microbiote français” is a prospective, noninterventional French national study involving individuals, the creation of a biological collection (feces), and the exploitation of data from questionnaires and the National Health Data System (Système National des Données de Santé). This national study is open to all metropolitan French adult residents, excluding those who have undergone a colectomy or digestive stoma, or who have had a colonoscopy or taken antibiotics in the last 3 months. This is a home-based trial in which volunteers complete a questionnaire with insights about their health and habits, and in which stool samples are self-collected. Data analysis is structured into 6 work packages, each focusing on a specific aspect of the gut microbiome, including its composition and associations with lifestyle, quality of life, and health.ResultsThis paper outlines the study protocol, with recruitment having started in September 2022 and expected to continue until the end of December 2025. As of January 2025, a total of 20,000 participants have been enrolled. The first scientific publications based on the data analysis are expected by mid-2025.Conclusions“Le French Gut” aims to provide a reference database and new ecosystem tools for understanding the relationship between the gut microbiota, its host, and diet. We expect to be able to find new signatures or targets and promote the design of innovative preventive strategies, personalized nutrition, and precision medicine.Trial RegistrationClinicalTrials.gov NCT05758961; https://clinicaltrials.gov/study/NCT05758961International Registered Report Identifier (IRRID)DERR1-10.2196/64894