Cumulative Exposure to Infliximab, But Not Trough Concentrations, Correlates With Rate of Infection.

BACKGROUND & AIMS: Infliximab increases the risk of infection in patients with inflammatory bowel diseases (IBD), but there is controversy over the relationship between drug concentration and infections. We aimed to assess factors associated with infection in infliximab-treated patients, including pharmacokinetic features. METHODS: We collected data from 209 patients with IBD (102 men; mean age, 39 y; 159 with Crohn's disease; 54 received combination therapy) who received an infliximab maintenance regimen from November 2016 through April 2017 in France. Data were collected from each infusion visit (total of 640 infusions). Infliximab exposure was estimated based on the area under the curve (AUC) of drug concentration in pharmacokinetic models; individual exposures over the 6-month period were estimated based on the sum of the AUC (ΣAUC). RESULTS: The mean infliximab trough level was 5.46 mg/L, and the mean ΣAUC was 3938 ± 1427 mg.d/L. A total of 215 infections were collected from the 640 infusion visits; 123 patients (59%) had at least 1 infection. Factors independently associated with infection after multivariate analysis were smoking (odds ratio [OR], 2.05; P = .046), IBD flare (OR, 2.71; P = .006), and a high ΣAUC of infliximab (above 3234 mg x d/L) (OR, 2.02; P = .02). The ΣAUC was higher in patients with an occurrence of infection (P = .04) and correlated with the number of infections (P = .04). Trough concentration of infliximab alone was not associated with infection. CONCLUSIONS: Almost two-thirds of patients treated with infliximab developed an infection; risk was individually correlated with cumulative increase in drug exposure, but not infliximab trough level.

Incidental anal 18fluorodeoxyglucose uptake: Should we further examine the patient?

BACKGROUND: There are no studies on incidental anal 18F-fluorodeoxyglucose (18FDG) uptake. AIM: To assess the rate and aetiologies of incidental anal 18FDG uptake and to evaluate the correlation between 18FDG positron-emission tomography/computed tomography (PET/CT) parameters and the diagnosis of an anorectal disease. METHODS: The data from patients with incidental anal 18FDG uptake were retrospectively analysed. Patients who underwent anorectal examinations were identified and compared to those who did not undergo examinations. Patients who were offered treatment were then identified and compared to those who did not receive treatment. RESULTS: Among the 43020 18FDG PET/CT scans performed, 197 18FDG PET/CT scans of 146 patients (0.45%) reported incidental anal uptake. Among the 134 patients included, 48 (35.8%) patients underwent anorectal examinations, and anorectal diseases were diagnosed in 33 (69.0%) of these patients and treated in 18/48 (37.5%) patients. Among the examined patients, those with a pathology requiring treatment had significantly smaller metabolic volumes (MV) 30 and MV41 values and higher maximal and mean standardized uptake value measurements than those who did not require treatment. CONCLUSION: Incidental anal 18FDG uptake is rare, but a reliable anorectal diagnosis is commonly obtained when an anorectal examination is performed. The diagnosis of an anorectal disease induces treatment in more than one-third of the patients. These data should encourage practitioners to explore incidental anal 18FDG uptake systematically.

Inter-kingdom effect on epithelial cells of the N-Acyl homoserine lactone 3-oxo-C12:2, a major quorum-sensing molecule from gut microbiota.

BACKGROUND AND AIMS: N-acyl homoserine lactones (AHLs), which are autoinducer quorum-sensing molecules involved in the bacterial communication network, also interact with eukaryotic cells. Searching for these molecules in the context of inflammatory bowel disease (IBD) is appealing. The aims of our study were to look for AHL molecules in faecal samples from healthy subjects (HS) and IBD patients to correlate AHL profiles with the microbiome and investigate the effect of AHLs of interest on epithelial cells. METHODS: Using mass spectrometry, we characterised AHL profiles in faecal samples from HS (n = 26) and IBD patients in remission (n = 24) and in flare (n = 25) and correlated the presence of AHLs of interest with gut microbiota composition obtained by real-time qPCR and 16S sequencing. We synthesised AHLs of interest to test the inflammatory response after IL1ß stimulation and paracellular permeability on Caco-2 cells. RESULTS: We observed 14 different AHLs, among which one was prominent. This AHL corresponded to 3-oxo-C12:2 and was found significantly less frequently in IBD patients in flare (16%) and in remission (37.5%) versus HS (65.4%) (p = 0.001). The presence of 3-oxo-C12:2 was associated with significantly higher counts of Firmicutes, especially Faecalbacterium prausnitzii, and lower counts of Escherichia coli. In vitro, 3-oxo-C12:2 exerted an anti-inflammatory effect on Caco-2 cells. Interestingly, although 3-oxo-C12, the well-known AHL from Pseudomonas aeruginosa, increased paracellular permeability, 3-oxo-C12:2 did not. CONCLUSIONS: We identified AHLs in the human gut microbiota and discovered a new and prominent AHL, 3-oxo-C12:2, which correlates with normobiosis and exerts a protective effect on gut epithelial cells.