Is Autologous Fecal Microbiota Transfer after Exclusive Enteral Nutrition in Pediatric Crohn's Disease Patients Rational and Feasible? Data from a Feasibility Test.

BACKGROUND: Exclusive enteral nutrition (EEN) is a highly effective therapy for remission induction in pediatric Crohn's disease (CD), but relapse rates after return to a regular diet are high. Autologous fecal microbiota transfer (FMT) using stool collected during EEN-induced clinical remission might represent a novel approach to maintaining the benefits of EEN. METHODS: Pediatric CD patients provided fecal material at home, which was shipped at 4 °C to an FMT laboratory for FMT capsule generation and extensive pathogen safety screening. The microbial community composition of samples taken before and after shipment and after encapsulation was characterized using 16S rRNA amplicon sequencing. RESULTS: Seven pediatric patients provided fecal material for nine test runs after at least three weeks of nutritional therapy. FMT capsules were successfully generated in 6/8 deliveries, but stool weight and consistency varied widely. Transport and processing of fecal material into FMT capsules did not fundamentally change microbial composition, but microbial richness was <30 genera in 3/9 samples. Stool safety screening was positive for potential pathogens or drug resistance genes in 8/9 test runs. CONCLUSIONS: A high pathogen burden, low-diversity microbiota, and practical deficiencies of EEN-conditioned fecal material might render autologous capsule-FMT an unsuitable approach as maintenance therapy for pediatric CD patients.

Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn's disease.

BACKGROUND: Crohn's disease (CD) is associated with changes in the microbiota, and murine models of CD-like ileo-colonic inflammation depend on the presence of microbial triggers. Increased abundance of unknown Clostridiales and the microscopic detection of filamentous structures close to the epithelium of Tnf ΔARE mice, a mouse model of CD-like ileitis pointed towards segmented filamentous bacteria (SFB), a commensal mucosal adherent bacterium involved in ileal inflammation. RESULTS: We show that the abundance of SFB strongly correlates with the severity of CD-like ileal inflammation in two mouse models of ileal inflammation, including Tnf ΔARE and SAMP/Yit mice. SFB mono-colonization of germ-free Tnf ΔARE mice confirmed the causal link and resulted in severe ileo-colonic inflammation, characterized by elevated tissue levels of Tnf and Il-17A, neutrophil infiltration and loss of Paneth and goblet cell function. Co-colonization of SFB in human-microbiota associated Tnf ΔARE mice confirmed that SFB presence is indispensable for disease development. Screening of 468 ileal and colonic mucosal biopsies from adult and pediatric IBD patients, using previously published and newly designed human SFB-specific primer sets, showed no presence of SFB in human tissue samples, suggesting a species-specific functionality of the pathobiont. Simulating the human relevant therapeutic effect of exclusive enteral nutrition (EEN), EEN-like purified diet antagonized SFB colonization and prevented disease development in Tnf ΔARE mice, providing functional evidence for the protective mechanism of diet in modulating microbiota-dependent inflammation in IBD. CONCLUSIONS: We identified a novel pathogenic role of SFB in driving severe CD-like ileo-colonic inflammation characterized by loss of Paneth and goblet cell functions in Tnf ΔARE mice. A purified diet antagonized SFB colonization and prevented disease development in Tnf ΔARE mice in contrast to a fiber-containing chow diet, clearly demonstrating the important role of diet in modulating a novel IBD-relevant pathobiont and supporting a direct link between diet and microbial communities in mediating protective functions. Video Abstract.

Comparing Two Proximal Measures of Unrecognized Clinical Deterioration in Children.

Critical deterioration events (CDEs) and emergency transfers (ETs) are two proximal measures to cardiopulmonary arrest, and both aim to evaluate how systems recognize and respond to clinical deterioration in children. This retrospective observational study sought to (1) characterize CDEs and ETs by timing, overlap, and intervention category, and (2) evaluate the performance of the watcher identification system and the pediatric early warning score (PEWS) to identify patients who experience these events. A total of 359 CDEs and 88 ETs occurred during the study period. Respiratory events were most common and accounted for 80.5% of CDEs and 47.7% of ETs. A narrow majority of patients were identified as watchers (55.4% of CDEs and 51.1% of ETs). In total, 85.5% of CDEs and 87.5% of ETs were identified as watchers, elevated PEWS, or both. Opportunities exist for improved escalation plans for high-risk patients to prevent the need for emergent intervention.

Measuring adverse events and levels of harm in pediatric inpatients with the Global Trigger Tool.

OBJECTIVES: To evaluate and characterize the Global Trigger Tool's (GTT's) utility in a pediatric population; to measure the rate of harm at our institution and compare it with previously established trigger tools and benchmark rates; and to describe the distribution of harm of the detected events. METHODS: Per the GTT methodology, 240 random inpatient charts were retrospectively reviewed over a 12-month pilot period for the presence of 53 predefined safety triggers. When triggers were detected, the reviewers investigated the chart more thoroughly to decide whether an adverse event occurred. Agreement with a physician reviewer was then reached, and a level of harm was assigned. RESULTS: A total of 404 triggers were detected (1.7 triggers per patient), and 88 adverse events were identified. Rates of 36.7 adverse events per 100 admissions and 76.3 adverse events per 1000 patient-days were calculated. Sixty-two patients (25.8%) had at least 1 adverse event during their hospitalization, and 18 (7.5%) had >1 event identified. Three-quarters of the events were category E (temporary harm). Two events required intervention to sustain life (category H). Two of the 6 trigger modules identified 95% of the adverse events. CONCLUSIONS: The GTT demonstrated utility in the pediatric inpatient setting. With the use of the trigger tool, we identified a rate of harm 2 to 3 times higher than previously published pediatric rates. Modifications to the trigger tool to address pediatric-specific issues could increase the test characteristics of the tool.