A Fructo-Oligosaccharide Prebiotic Is Well Tolerated in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I Dose-Escalation Trial.

Alterations of the gut microbiota after allogeneic hematopoietic cell transplantation (allo-HCT) are a key factor in the development of transplant-related complications such as graft-versus-host disease (GVHD). Interventions that preserve the gut microbiome hold promise to improve HCT-associated morbidity and mortality. Murine models demonstrate that prebiotics such as fructo-oligosaccharides (FOSs) may increase gut levels of short-chain fatty acids (SCFAs) such as butyrate and consequently induce proliferation of immunomodulatory FOXP3+CD4+ regulatory T cells (Tregs), which impact GVHD risk. We conducted a pilot phase I trial to investigate the maximum tolerated dose of FOS in patients undergoing reduced-intensity allo-HCT (n = 15) compared with concurrent controls (n = 16). We administered the FOS starting at pretransplant conditioning and continuing for a total of 21 days. We characterized the gut microbiome using shotgun metagenomic sequencing, measured stool short-chain fatty acids (SCFAs) using liquid chromatography-mass spectrometry, and determined peripheral T cell concentrations using cytometry by time-of-flight. We found that FOS was safe and well-tolerated at 10 g/d without significant adverse effects in patients undergoing allo-HCT. Community-level gut microbiota composition differed significantly on the day of transplant (day 0) between patients receiving FOS and concurrent controls; however, FOS-associated alterations of the gut microbiota were not sustained after transplant. Although the impact of FOS was fleeting, transplantation itself impacted a substantial number of taxa over time. In our small pilot trial, no significant differences were observed in gut microbial metabolic pathways, stool SCFAs, or peripheral Tregs, although Tregs trended higher in those patients who received FOS. A marker of CD4+ T cell activation (namely, CTLA4+) was significantly higher in patients receiving FOS, whereas a non-significant trend existed for FOP3+CD4+ Treg cells, which were higher in those receiving FOS compared with controls. FOS is well tolerated at 10 g/d in patients undergoing reduced-intensity allo-HCT. Although the alterations in gut microbiota and peripheral immune cell composition in those receiving FOS are intriguing, additional studies are required to investigate the use of prebiotics in HCT recipients.

Gastric heterotopia with extensive involvement of the small intestine associated with congenital short bowel syndrome and intestinal malrotation.

We present a case of extensive gastric heterotopia involving the small intestine associated with congenital short bowel syndrome and malrotation. The infant showed a normal mesenteric artery, without signs of "apple peel" deformity. Gastric heterotopia extended from the duodenum to the mid-ileum involving the short bowel. Gastric mucosa heterotopia may involve any segment of the gastrointestinal tract. It can be associated with pancreatic heterotopia and Meckel diverticulum. However, our case showed involvement of two-thirds of the small intestine without pancreatic heterotopia. To our knowledge, this is the first report of gastric heterotopia with congenital short gut syndrome and malrotation.

The association between alcohol consumption and risk of COPD exacerbation in a veteran population.

BACKGROUND: Alcohol has been associated with COPD-related mortality but has not yet been demonstrated to be an independent risk factor for COPD exacerbation. Our objective was to evaluate the association between alcohol consumption and the subsequent risk of COPD exacerbation. METHODS: A prospective cohort study of general medicine outpatients seen at one of seven Veterans Affairs (VA) medical centers who returned health screening questionnaires. Three screening questionnaires, AUDIT-C (0 to 12 points), CAGE (0 to 4 points), and a single item about the frequency of drinking six or more drinks on an occasion (binge drinking), were used to classify alcohol consumption. The main outcome, COPD exacerbation, was based on primary VA discharge diagnosis (International Classification of Diseases, Ninth Revision) or outpatient diagnosis of COPD accompanied by prescriptions for either antibiotics or prednisone within 2 days. RESULTS: Among the 30,503 patients followed up for a median of 3.35 years, those patients with AUDIT-C scores > or = 6, CAGE scores > or = 2, or who reported binge drinking at least weekly were at an increased risk of COPD exacerbation in age-adjusted analysis. Adjusted hazard ratios were 1.4 (95% confidence interval [CI], 1.1 to 1.7) for AUDIT-C score > or = 6, 1.4 (95% CI, 1.3 to 1.5) for CAGE score > or = 2, and 1.6 (95% CI, 1.2 to 2.2) for those who reported binge drinking daily or almost daily. However, with adjustment for measures of tobacco use, the association between alcohol consumption and increased risk of COPD exacerbation was no longer evident. CONCLUSIONS: Alcohol consumption, whether quantified by AUDIT-C, CAGE score, or binge drinking, was not associated with an increased risk of COPD exacerbation independent of tobacco use.