Background and Aims Dysbiosis of the gut microbiota is a well-known correlate of the pathogenesis of inflammatory bowel disease [IBD]. However, few studies have examined the microbiome in very early-onset [VEO] IBD, which is defined as onset of IBD before 6 years of age. Here we focus on the viral portion of the microbiome—the virome—to assess possible viral associations with disease processes, reasoning that any viruses potentially associated with IBD might grow more robustly in younger subjects, and so be more detectable. Methods Virus-like particles [VLPs] were purified from stool samples collected from patients with VEO-IBD [n = 54] and healthy controls [n = 23], and characterized by DNA and RNA sequencing and VLP particle counts. Results The total number of VLPs was not significantly different between VEO-IBD and healthy controls. For bacterial viruses, the VEO-IBD subjects were found to have a higher ratio of Caudovirales vs to Microviridae compared to healthy controls. An increase in Caudovirales was also associated with immunosuppressive therapy. For viruses infecting human cells, Anelloviridae showed higher prevalence in VEO-IBD compared to healthy controls. Within the VEO-IBD group, higher levels of Anelloviridae DNA were also positively associated with immunosuppressive treatment. To search for new viruses, short sequences enriched in VEO-IBD samples were identified, and some could be validated in an independent cohort, although none was clearly viral; this provides sequence tags to interrogate in future studies. Conclusions These data thus document perturbations to normal viral populations associated with VEO-IBD, and provide a biomarker—Anelloviridae DNA levels—potentially useful for reporting the effectiveness of immunosuppression.
Highlights d Multi-omics reveals markers of CDI in pediatric IBD patients d Identification of metabolites reveals distinctive features for IBD and CDI d Isocaproyltaurine is made by C. difficile and associates with active IBD d Identifies biomarkers potentially useful for distinguishing disease processes
Objective: This study aims to show how full-time telemedicine adoption has impacted patient visit volume and attendance in a comprehensive metabolic and weight loss center. Summary Background Data: Elective surgical practices have been profoundly impacted by the global COVID-19 pandemic, leading to a rapid increase in the utilization of telemedicine. The abrupt initiation of audio-video telehealth visits for all providers of a multidisciplinary clinic on March 19 th 2020 provided unique circumstances to assess the impact of telemedicine. Methods: Data from the clinical booking system (new patient and follow-up visits) for all clinical provider types of the multidisciplinary metabolic center from the pre-telehealth, post-telehealth, and a 2019 comparative period were retrospectively reviewed and compared. The primary outcome is the change in patient visit volume for all clinical providers from before to after the initiation of telemedicine for both new patient, and follow-up visits. Results: There were a total of 506 visits (162 new patient visits, and 344 follow-ups) in the pre-telehealth period, versus 413 visits (77 new patient visits, and 336 follow-ups) during the post-telehealth period. After telehealth implementation, new visits for surgeons decreased by 75%. Although follow-up visits decreased by 55.06% for surgeons, there was an increase by 27.36% for advanced practitioners. When surgeons were separated from other practitioners, their follow-up visit rate decrease by 55.06%, compared to a 16.08% increase for the group of all other practitioners ( P < 0.0001). Dietitians experienced higher rates of absenteeism with new patient visits (10.00% vs 31.42%, P = 0.0128), whereas bariatricians experienced a decrease in follow-up visit absenteeism (33.33% vs 0%, P = 0.0093). Conclusions: Although new patient visit volume fell across the board, follow-up visits increased for certain nonsurgical providers. This provides a template for adoption of a multidisciplinary telehealth clinic in a post-pandemic world.
Background and aims Recent adult evidence suggests that infliximab (IFX) trough levels (TL) in patients with severe ulcerative colitis (UC) may be decreased. The aims of our study were to compare post-induction IFX TL of children with severe versus moderate UC and to evaluate short- and long-term outcomes. Methods In this single-center retrospective study, children with a diagnosis of UC starting IFX with a Pediatric Ulcerative Colitis Activity Index (PUCAI) ≥35 and with available post-induction TL were recruited. UC characteristics, IFX dosage and interval, primary non-response, IFX failure, and surgery after 24 months were collected. Post induction TL, anti-IFX antibodies, and laboratory evaluations at the time of starting IFX were also acquired. Results A total of 90 children were enrolled, of whom 39 (43.3%) were classified as severe UC and 51 (56.6%) as moderate UC. Median post-induction IFX TL were lower in severe UC versus moderate group (5.5 vs 10.3; p = 0.03), despite a more frequently intensified IFX regimen. Children in the higher TL quartiles showed increased rates of clinical, biological, and combined remission ( p = 0.04, p < 0.001, and p = 0.01, respectively). In a multivariate analysis, a PUCAI ≥65 and time interval from last IFX infusion were the only predictors associated with IFX TL. At 24 months, children in the higher TL quartiles had a decreased risk of IFX failure ( p = 0.002). The severe UC group showed a higher risk of IFX failure at 24 months (16/23 (41%) vs. 11/40 (21.6%); p = 0.05). Kaplan–Meier methods demonstrated a trend toward statistical significance, with a two-year cumulative colectomy rate of 15.38% (95% confidence interval (CI) 8.1–15.6%) in children with severe UC and 3.92% (95% CI 2.9–10.8%) in patients with moderate UC (logrank test p = 0.06). Conclusions Children starting IFX with severe UC showed lower post-induction TL and poor disease outcomes. Achieving adequate TL was associated with better efficacy outcomes.
Background & Aims Perianal fistulizing disease can affect up to 25% of patients with Crohn’s disease (CD) and lead to significant morbidity. While the role of the gut microbiota in inflammatory bowel disease (IBD) has been increasingly recognized, its role in fistula development has scarcely been studied. Here, we aimed to define the microbial signature associated with perianal fistulizing CD in children. Methods A prospective observational study including children age 6-18 years with a diagnosis of perianal fistulizing CD was conducted. Stool samples, rectal and perianal fistula swabs were collected. Stool samples and rectal swabs from children with CD without perianal disease and healthy children were included as comparison. Whole shotgun metagenomic sequencing was performed. Results A total of 31 children (mean age 15.5 ± 3.5 years) with perianal CD were prospectively enrolled. The fistula-associated microbiome showed an increased in alpha diversity and alteration in the abundance of several taxa compared to the rectal- and fecal-associated microbiome with key taxa belonging to the Proteobacteria phylum. Genes conferring resistance to the clinically used antibiotic regimen ciprofloxacin and metronidazole were found in the three sample types. In comparison to children without the perianal phenotype (N=36) and healthy controls (N=41), the mucosally-associated microbiome of children with perianal CD harbored a reduced butyrogenic potential. Linear discriminant analysis identified key taxa distinguishing the rectal mucosally-associated microbiome of children with perianal CD from children without this phenotype. Conclusions The microbial community within CD-related anorectal fistula is compositionally and functionally unique. Taken together, these findings emphasize the need to better understand the ecosystem of the fistula milieu to guide development of novel microbiome-based strategies in this CD phenotype.
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