BackgroundStudies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only).MethodV3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group.ResultsSignificant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the...

We investigated the hypothesis that salivary gland inoculation stimulates formation of ectopic germinal centers (GCs), transforming the gland into a mucosal inductive site. Intraglandular infection of mice with murine cytomegalovirus (MCMV; control: UV-inactivated MCMV) induces salivary gland ectopic follicles comprising cognate interactions between CD4(+) and B220(+) lymphocytes, IgM(+) and isotype-switched IgG(+) and IgA(+) B cells, antigen presenting cells, and follicular dendritic cells. B cells coexpressed the GC markers GCT (57%) and GL7 (52%), and bound the lectin peanut agglutinin. Lymphoid follicles were characterized by a 2- to 3-fold increase in mRNA for CXCL13 (lymphoid neogenesis), syndecan-1 (plasma cells), Blimp-1 (plasma cell development/differentiation), and a 2- to 6-fold increase for activation-induced cytidine deaminase, PAX5, and the nonexcised rearranged DNA of an IgA class-switch event, supporting somatic hypermutation and class-switch recombination within the salivary follicles. Intraglandular inoculation also provided protection against a systemic MCMV challenge, as evidenced by decreased viral titers (10(5) plaque-forming units to undetectable), and restoration of normal salivary flow rates from a 6-fold decrease. Therefore, these features suggest that the salivary gland participates in oral mucosal immunity via generation of ectopic GCs, which function as ectopic mucosal inductive sites.

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BackgroundSuccessful breastfeeding is a goal set forth by the World Health Organization to improve neonatal care. Increasingly, patients express the desire to breastfeed, and clinicians should facilitate successful breastfeeding. The primary aim of this study is to determine if postoperative nausea and vomiting (PONV) or postoperative pain are associated with decreased breastfeeding success after cesarean delivery.MethodsThis is a historical cohort study using the Stony Brook Elective Cesarean Delivery Database. Self-reported breastfeeding success at 4 weeks postoperative was analyzed for associations with postoperative antiemetic use and postoperative pain scores. Breastfeeding success was also analyzed for associations with patient factors and anesthetic medications.ResultsOverall, 86% of patients (n = 81) who intended on breastfeeding reported breastfeeding success. Breastfeeding success was not associated with postoperative nausea or vomiting as measured by post anesthesia care unit antiemetic use (15% use in successful vs. 18% use in unsuccessful, p = 0.67) or 48-h antiemetic use (28% use in successful group vs 36% use in unsuccessful group, p = 0.732). Pain visual analog scale scores at 6, 12 and 24 h postoperatively were not significantly different between patients with or without breastfeeding success. Breastfeeding success was associated with having had at least 1 previous child (86% vs 36%, p < 0.001). Patients with asthma were less likely to have breastfeeding success (45% vs 4%, p = 0.002).ConclusionsEfforts to improve PONV and pain after cesarean delivery may not be effective in improving breastfeeding success. To possibly improve breastfeeding rates, resources should be directed toward patients with no previous children and patients with asthma.

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of an opportunistic infection following treatment of high dose steroids. Patient 4 had multi-organ failure prior to start of treatment with vedolizumab and died. Patients 5 and 6 have no symptoms of serious GvHD after 2 and 3 doses of vedolizumab. Four out of 6 patients could be discharged from hospital. Immunophenotyping of peripheral blood revealed initial high levels of CD25 + Treg cells in 4 out of 6 evaluable patients and the values showed a decline into normal range after start of therapy and with signs of clinical effect. Conclusions: This case series suggests that targeting integrin a4b7 is feasible, safe and gives clinical responses in steroid refractory intestinal GvHD. The mechanism of action is not known, but may be due to the inhibition of alloreactive T-cells homing to the intestinal mucosa. The mechanism behind the Treg patterns is unclear. One might speculate that the initially high levels of Tregs are part of the physiologic reaction to the alloreactive inflammation in the intestinal mucosa.