OBJECTIVE: To determine the accuracy of pre-contrast abdominal MR imaging for lesion detection and characterization in pediatric oncology patients.
MATERIALS AND METHODS: We included 120 children (37 boys and 83 girls; mean age 8.94 years) referred by oncology services. Twenty-five had MRI for the first time and 95 were follow-up scans. Two authors independently reviewed pre-contrast MR images to note the following information about the lesions: location, number, solid vs. cystic and likely nature. Pre- and post-contrast imaging reviewed together served as the reference standard.
RESULTS: The overall sensitivity was 88% for the first reader and 90% for the second; specificity was 94% and 91%; positive predictive value was 96% and 94%; negative predictive value was 82% and 84%; accuracy of pre-contrast imaging for lesion detection as compared to the reference standard was 90% for both readers. The difference between mean number of lesions detected on pre-contrast imaging and reference standard was not significant for either reader (reader 1, P = 0.072; reader 2, P = 0.071). There was substantial agreement (kappa values of 0.76 and 0.72 for readers 1 and 2) between pre-contrast imaging and reference standard for determining solid vs. cystic lesion and likely nature of the lesion. The addition of post-contrast imaging increased confidence of both readers significantly (P
METHODS AND RESULTS: We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and β-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and β-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%).
CONCLUSION: Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable.