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Background and Aims Faecal microbiota transplant [FMT] is effective in treating recurrent Clostridioides difficile infection [CDI] and restores gut microbiota composition. This is unlikely to account for its entire mechanism of efficacy, as studies have shown that factors such as bile acids influence the risk of infection by affecting Clostridioides difficile germination. We therefore aimed to investigate longitudinal changes in the gut bile acid composition after FMT performed for recurrent CDI, in children with and without inflammatory bowel disease [IBD]. Methods Eight children received FMT; five had underlying IBD. Primary and secondary faecal bile acids were measured by liquid chromatography–mass spectrometry in recipients [pre-FMT and longitudinally post-FMT for up to 6 months] and donors. Results Pre-FMT, recipients had higher primary and lower secondary bile acid proportions compared with donors. Post-FMT, there was a gradual increase of secondary and decrease of primary bile acids. Whereas gut bacterial diversity had been shown to be restored in all children shortly after FMT, normalisation of bile acids to donor levels occurred only by 6 months. In children with IBD, although microbiota diversity returned to pre-FMT levels within 6 months, secondary bile acids remained at donor levels. Conclusions The differences in bile acid profiles compared with gut bacterial diversity post-FMT suggests that interactions between the two may be more complex than previously appreciated and may contribute to FMT efficacy in different ways. This initial finding demonstrates the need to further investigate gut metabolites in larger cohorts, with longitudinal sampling to understand the mechanisms of FMT effectiveness.

BACKGROUND The clinical course of IBD varies considerably among patients1. One barrier to personalized medicine in IBD is the lack of a reliable prognostic assay that can be used at diagnosis to guide effective therapy for each patient, to optimize clinical outcomes and minimize complications. To address this need, a whole-blood qPCR-based prognostic assay was developed to divide IBD patients into two subgroups2. This transcriptional signature yields CD8 T-cell exhaustion level data that correlated with disease outcomes among IBD patients in UK2. Here, we aimed to determine if this prognostic assay could stratify an ethnically diverse North American cohort of IBD patients at diagnosis into low and high-risk subgroups. METHODS PRECIOUS (Predicting Crohn’s & Colitis Outcomes in the United States) is a multi-centre, observational, double-blinded study of patients with active IBD, who are not receiving systemic steroids, immunomodulator, advanced small molecules or biologics. The study is recruiting up to 200 patients between 16-80 years of age, from 14 centres across the US and Canada. Patients are prospectively followed for >12 months after enrolment to monitor disease course, including the requirement for IBD-related surgery or treatment escalations. Patients and clinicians are blinded to the biomarker results and patients are treated according to local practice. RESULTS Of 120 patients recruited to date, 86 have reached the 12-month follow-up timepoint (Table 1). Of the 102 patients with complete race and ethnicity data (Table 1), 63.5% are non-Hispanic Whites, 13.7% identified as Hispanic/Latino, 11.8% Asian and 9.8% Black/African American. Biomarker results were obtained for 80 (88.8%) of the 90 samples tested to date – 10 (11.1%) of samples failed quality control. Of these 80 results, 38 patients (47.5%) were identified as high risk for disease progression and 42 (52.5%) as low risk – a similar breakdown to that seen in the UK cohort2. DISCUSSION This is the first trial of a prognostic biomarker for patients with CD and UC in North America. This patient population was significantly more diverse than the UK cohort which had ~98% White. This diversity is not generally reflected in clinical trials performed in the United States in which approximately 90% of participants for all conditions are White whereas non-Hispanic Whites represent approximately 60% of the U.S. population. 4,5. Our enrolment of only 63.5% non-Hispanic White subjects speaks to our targeted efforts to recruit a representative level of diversity into our study population to that represents the diversity of patients with IBD that are being diagnosed globally6.

Antibiotic use is increasing worldwide. However, the use of antibiotics is clearly associated with changes in gut microbiome composition and function, and perturbations have been identified as potential environmental risk factors for chronic inflammatory disorders of the gastrointestinal tract. In this Review, we examine the association between the use of antibiotics and the onset and development of both type 1 and type 2 diabetes, inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, as well as coeliac disease and eosinophilic oesophagitis. We discuss the key findings of epidemiological studies, provide mechanistic insights into the pathways by which the gut microbiota might contribute to these diseases, and assess clinical trials investigating the effects of antibiotics. Such studies indicate that antibiotic exposures, varying in type, timing and dosage, could explain differences in disease risk. There seems to be a critical window in early life in which perturbation of the microbiome has a substantial effect on disease development. Identifying the antibiotic-perturbed gut microbiota as a factor that contributes to the pathophysiology of these inflammatory disorders might stimulate new approaches to prevention, diagnosis and treatment.

INTRODUCTION: Recently significant interest from families and healthcare providers has arisen to use blenderized tube feedings (BTF). Although many institutions are providing this nutritional option, literature documenting outcomes and safety is lacking. METHODS: A retrospective chart review was performed on pediatric patients receiving BTF at Rutgers-Robert Wood Johnson University Hospital between January 2013 and April 2017.Demographic data and dietary information prior to and after BTF were collected. Reasons for diet initiation, symptoms and anthropometrics were recorded. Adverse events and outcomes were assessed through physician documentation and relevant medication changes. RESULTS: Thirty-five patients (24 male) received BTF. Age at initiation of BTF ranged from 1-19 years (mean 8.3 +/- 5.8 [SD] years). Length of follow-up ranged from 1- 45 months (mean 15 +/- 12.2 months). The most common reason for starting BTF was gastroesophageal reflux disease (GERD) (N = 32). Almost all patients were on medications for GERD, constipation or gastrointestinal dysmotility prior to starting BTF (N = 33). Majority of patients had improvement in relevant symptoms (N = 20); 13 of 33 patients on gastrointestinal medications were able to wean or stop medication(s). BMI z scores did not before and after BTF initiation (p = 0.558). No serious life-threatening adverse events were found. CONCLUSION: Our data suggest that BTF is a safe dietary intervention that may improve gastrointestinal symptoms in pediatric patients. Further prospective studies are needed to compare safety and efficacy of BTF and commercial formulas in pediatric patients.

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) in adults and children, but donor stool samples are currently screened for only a limited number of potential pathogens. We sought to determine whether putative procarcinogenic bacteria (enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli harboring the colibactin toxin) could be durably transmitted from donors to patients during FMT. METHODS: Stool samples were collected from 11 pediatric rCDI patients and their respective FMT donors prior to FMT as well as from the patients at 2–10 weeks, 10–20 weeks, and 6 months after FMT. Bacterial virulence factors in stool DNA extracts and stool cultures were measured by quantitative PCR: Bacteroides fragilis toxin (bft), Fusobacterium adhesin A (fadA), and Escherichia coli colibactin (clbB). RESULTS: Four of 11 patients demonstrated sustained acquisition of a procarcinogenic bacteria. Whole genome sequencing was performed on colony isolates from one of these donor/recipient pairs and demonstrated that clbB(+) E. coli strains present in the recipient after FMT were identical to a strain present in the donor, confirming strain transmission. Conversely, 2 patients exhibited clearance of procarcinogenic bacteria following FMT from a negative donor. CONCLUSION: Both durable transmission and clearance of procarcinogenic bacteria occurred following FMT, suggesting that additional studies on appropriate screening measures for FMT donors and the long-term consequences and/or benefits of FMT are warranted. FUNDING: Crohn’s & Colitis Foundation, the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, the National Cancer Institute, and the Canadian Institutes of Health Research.

BackgroundFecal microbiota transplantation (FMT) treats Clostridioides difficile infection (CDI). Little is known regarding the changes in antimicrobial resistance (AMR) genes and potential pathogen burden that occur in pediatric recipients of FMT. The aim of this study was to investigate changes in AMR genes, potential pathogens, species, and functional pathways with FMT in children.MethodsNine children with recurrent CDI underwent FMT. Stool was collected from donor and recipient pre-FMT and longitudinally post-FMT for up to 24 weeks. Shotgun metagenomic sequencing was performed. Reads were analyzed using PathoScope 2.0.ResultsAll children had resolution of CDI. AMR genes decreased post-FMT (P < .001), with a sustained decrease in multidrug resistance genes (P < .001). Tetracycline resistance genes increased post-FMT (P < .001). Very low levels of potential pathogens were identified in donors and recipients, with an overall decrease post-FMT (P < .001). Prevotella sp. 109 expanded in all recipients post-FMT, and no recipients had any clinical infection. Alpha diversity was lower in recipients vs donors pre-FMT (P < .001), with an increase post-FMT (P ≤ .002) that was sustained. Beta diversity differed significantly in pre- vs post-FMT recipient samples (P < .001). Bacterial species Faecalibacterium prausnitzii and Bacteroides ovatus showed higher abundance in donors than recipients (P = .008 and P = .040, respectively), with expansion post-FMT. Biosynthetic pathways predominated in the donor and increased in the recipient post-FMT.ConclusionsFMT for CDI in children decreases AMR genes and potential pathogens and changes microbiota composition and function. However, acquisition of certain AMR genes post-FMT combined with low levels of potential pathogens found in donors suggests that further study is warranted regarding screening donors using metagenomics sequencing before FMT.

In children with biliary atresia, hepatoportoenterostomy (HP) is recommended to improve bile flow. Biliary strictures are known potential complications after HP, which can again impair bile flow often leading to biliary cirrhosis and liver transplantation. In patients who are status post HP and have biliary strictures, nonsurgical therapeutic options such as endoscopic dilation can pose technical difficulties due to altered anatomy. Percutaneous transhepatic cholangiography with cholangioplasty is a valuable tool for obstructive cholangiopathies, but to our knowledge this has not been previously demonstrated to be successful in patients with multiple intrahepatic biliary strictures status post HP. Herein, we present 3 patients status post HP who presented with multiple intrahepatic biliary strictures and underwent successful percutaneous transhepatic cholangiography with cholangioplasty.

SummaryBackground Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis. Aim To investigate C. difficile eradication and microbiome changes with FMT in children with and without IBD. Methods Children with a history of recurrent CDI (≥3 recurrences) underwent FMT via colonoscopy. Stool samples were collected pre-FMT and post-FMT at 2–10 weeks, 10–20 weeks and 6 months. The v4 hypervariable region of the 16S rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was performed. Results Eight children underwent FMT for CDI; five had IBD. All had resolution of CDI symptoms. All tested had eradication of C. difficile at 10–20 weeks and 6 months post-FMT. Pre-FMT patient samples had significantly decreased bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02) and without IBD (P = 0.01). Post-FMT, bacterial diversity in patients increased. Six months post-FMT, there was no significant difference between bacterial diversity of donors and patients without IBD; however, bacterial diversity in those with IBD returned to pre-FMT baseline. Microbiome composition at 6 months in IBD-negative patients more closely approximated donor composition compared to IBD-positive patients. Conclusions FMT gives sustained C. difficile eradication in children with and without IBD. FMT-restored diversity is sustained in children without IBD. In those with IBD, bacterial diversity returns to pre-FMT baseline by 6 months, suggesting IBD host-related mechanisms modify faecal microbiome diversity.

Background: Flurandrenolide tape has recently been listed as a group I topical cortico-steroid. There are no studies that compare this product to group I ointments in the treatment of steroid-responsive dermatoses. Objective: Our purpose was to determine the relative efficacy of flurandrenolide (4 mg/cm 2 ) tape versus 0.05% diflorasone diacetate ointment in plaque psoriasis. Methods: Thirty patients participated in an investigator-blinded, randomized, bilateral paired-comparison study of flurandrenolide tape applied to lesions of one side of the body once daily for up to 16 hours versus diflorasone diacetate ointment applied contralaterally twice daily. Lesions were assessed at baseline, then reevaluated at 2 and 4 weeks. Results: Flurandrenolide tape–treated plaques showed consistently greater clearing in terms of erythema, scaling, induration, and treatment success for all plaques, as well as the subset of knee and elbow plaques, when compared with the lesions receiving diflorasone diacetate ointment. Conclusion: The efficacy of flurandrenolide tape in the treatment of psoriatic plaques surpasses that of diflorasone diacetate ointment. (J Am Acad Dermatol 1998;38:186-90.)

Rosacea is a chronic skin disease that requires long-term therapy. Oral antibiotics and topical metronidazole successfully treat rosacea. Because long-term use of systemic antibiotics carries risks for systemic complications and adverse reactions, topical treatments are preferred.To determine if the use of topical metronidazole gel (Metrogel) could prevent relapse of moderate to severe rosacea.A combination of oral tetracycline and topical metronidazole gel was used to treat 113 subjects with rosacea (open portion of the study). Successfully treated subjects (n = 88) entered a randomized, double-blind, placebo-controlled study applying either 0.75% topical metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo) twice daily (blinded portion of the study).Subjects were enrolled at 6 separate sites in large cities at sites associated with major medical centers.One hundred thirteen subjects with at least 6 inflammatory papules and pustules, moderate to severe facial erythema and telangiectasia entered the open phase of the study. Eighty-eight subjects responded to treatment with systemic tetracycline and topical metronidazole gel as measured by at least a 70% reduction in the number of inflammatory lesions. These subjects were randomized to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel.Subjects were evaluated monthly for up to 6 months to determine relapse rates.Inflammatory papules and pustules were counted at each visit. Relapse was determined by the appearance of a clinically significant increase in the number of papules and pustules. Prominence of telangiectases and dryness (roughness and scaling) were also observed.In the open phase, treatment with tetracycline and metronidazole gel eliminated all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%) displayed fewer papules and pustules after treatment, and 82 subjects (73%) exhibited less erythema. In the randomized double-blind phase, the use of topical metronidazole significantly prolonged the disease-free interval and minimized recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43 subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39 subjects applying metronidazole gel (P.05). The metronidazole group had fewer papules and/or pustules after 6 months of treatment (P.01). Relapse of erythema also occurred less often in subjects treated with metronidazole (74% vs 55%).In a majority of subjects studied, continued treatment with metronidazole gel alone maintains remission of moderate to severe rosacea induced by treatment with oral tetracycline and topical metronidazole gel.

Sixty-four healthy men with early male pattern baldness completed a 6-month, double-blind, placebo-controlled study in which the efficacy of 2% minoxidil gel and solution formulations was compared. Treatment with topical 2% minoxidil in both formulations resulted in a statistically significant increase in terminal hair growth referenced against baseline counts. The patients' subjective assessments of hair growth did not correlate well with actual increase in terminal hair counts.

† The effect of intralesional α2-interferon (IFN) on actinic keratoses was examined in this two-part study. In phase I, 11 of 12 lesions cleared following nine injections of IFN (5 × 10 5 IU per dose) compared with none of 12 keratoses injected with placebo. Smaller doses of IFN (1 × 10 5 IU and 1 × 10 4 IU per injection) produced clearing of 42% and 58% of lesions, respectively. The second phase, which was designed to investigate the optimum schedule for treatment with IFN, showed that a minimum of six injections of IFN (5 × 10 5 IU per injection) was necessary to clear 14 of 15 actinic keratoses. Although this mode of delivery is not practical for clinical use, intralesional α2-IFN demonstrates biologic activity against actinic keratoses. ( Arch Dermatol 1986;122:779-782)