Crohn's disease exclusion diet in children with Crohn's disease: a case series.

Exclusive enteral nutrition (EEN) represents an established, evidence-based dietary therapy used in Crohn's disease (CD); although successful, EEN is extremely restrictive with limited acceptability and prolonged use. The Crohn's disease exclusion diet (CDED) is a new, sustainable and patient-friendly dietary therapy used for the management of pediatric CD. CDED is designed to reduce exposure to dietary components hypothesized to negatively affect the microbiome, intestinal barrier and immunity. By focusing on five clinical cases, this article illustrates the benefits of using CDED as mono- or co-therapy with partial enteral nutrition in children with mild to moderate CD. CDED combined with partial enteral nutrition is a safe and effective therapeutic option for both induction and maintenance therapy in children with mild to moderate CD. It ensures sustained remission and can induce mucosal healing in children with mild to moderate Crohn's disease

Short and long term results of the laparoscopic Heller–Dor myotomy. The influence of age and previous conservative therapies

Analisi dei risultati della terapia chirurgica dell'acalasia esofagea con tecnica di Heller-Dor laparoscopica in pazienti anziani con e senza dilatazione pneumatica pregress

To Wean or Not to Wean: The Role of Autologous Reconstructive Surgery in the Natural History of Pediatric Short Bowel Syndrome on Behalf of Italian Society for Gastroenterology, Hepatology and Nutrition (SIGENP)

Pediatric Short Bowel Syndrome (SBS) can require prolonged parenteral nutrition (PN). Over the years, SBS management has been implemented by autologous gastrointestinal reconstructive surgery (AGIR). The primary objective of the present review was to assess the effect of AGIR on weaning off PN. We also evaluated how AGIR impacts survival, the need for transplantation (Tx) and the development of liver disease (LD). We conducted a systematic literature search to identify studies published from January 1999 to the present and 947 patients were identified. PN alone was weakly associated with higher probability of weaning from PN (OR = 1.1, p = 0.03) and of surviving (OR = 1.05, p = 0.01). Adjusting for age, the probability of weaning off PN but of not surviving remained significantly associated with PN alone (OR = 1.08, p = 0.03). Finally, adjusting for age and primary diagnosis (gastroschisis), any association was lost. The prevalence of TX and LD did not differ by groups. In conclusion, in view of the low benefit in terms of intestinal adaptation and of the not negligible rate of complications (20%), a careful selection of candidates for AGIR should be required. Bowel dilation associated with failure of advancing EN and poor growth, should be criteria to refer for AGIR

Late Relapse of Henoch-Schönlein Purpura in an Adolescent Presenting as Severe Gastroduodenitis

Henoch-Schönlein purpura is a systemic vasculitis, commonly affecting children. Gastrointestinal manifestations are observed in 50–75% of patients; it is well known they may occur before skin lesions in about 20% of cases during the first vasculitic episode. Relapses occur in about one third of patients, typically within 4 months from the initial presentation and with milder symptoms. We report the case of a 17-year old girl with an atypical relapse of Henoch-Schönlein purpura, presenting with acute abdominal symptoms 5 years after the first episode. Esophagogastroduodenoscopy showed duodenal multiple hyperemic and hemorrhagic lesions. To our knowledge this is the first case of hemorrhagic-erosive duodenitis representing a relapse of Henoch-Schönlein purpura occurring several years after the initial episode. Duodenojejunal inflammation should be considered as primary manifestation of Henoch-Schönlein purpura, not only during the first episode, but also in relapses. Endoscopy can be helpful for differential diagnosis, especially in patients with atypical manifestations. Further studies are needed to evaluate risk factors for Henoch-Schönlein purpura recurrence and the possible role of fecal calprotectin as an early marker for gastrointestinal involvement

Thiopurine metabolites variations during co-treatment with aminosalicylates for inflammatory bowel disease: effect of N-acetyl transferase polymorphisms

AIM: To evaluate variation of the concentration of thiopurine metabolites after 5-aminosalicylate (5-ASA) interruption and the role of genetic polymorphisms of N-acetyl transferase (NAT) 1 and 2. METHODS: Concentrations of thioguanine nucleotides (TGN) and methymercaptopurine nucleotides (MMPN), metabolites of thiopurines, were measured by high performance liquid chromatography in 12 young patients (3 females and 9 males, median age 16 years) with inflammatory bowel disease (6 Crohn's disease and 6 ulcerative colitis) treated with thiopurines (7 mercaptopurine and 5 azathioprine) and 5-ASA. Blood samples were collected one month before and one month after the interruption of 5-ASA. DNA was extracted and genotyping of NAT1, NAT2, inosine triphosphate pyrophosphatase (ITPA) and thiopurine methyl transferase (TPMT) genes was performed using PCR assays. RESULTS: Median TGN concentration before 5-ASA interruption was 270 pmol/8 x 108 erythrocytes (range: 145-750); after the interruption of the aminosalicylate, a 35% reduction in TGN mean concentrations (absolute mean reduction 109 pmol/8 7 108 erythrocytes) was observed (median 221 pmol/8 7 108 erythrocytes, range: 96-427, P value linear mixed effects model 0.0011). Demographic and clinical covariates were not related to thiopurine metabolites concentrations. All patients were wild-type for the most relevant ITPA and TPMT variants. For NAT1 genotyping, 7 subjects presented an allele combination corresponding to fast enzymatic activity and 5 to slow activity. NAT1 genotypes corresponding to fast enzymatic activity were associated with reduced TGN concentration (P value linear mixed effects model 0.033), putatively because of increased 5-ASA inactivation and consequent reduced inhibition of thiopurine metabolism. The effect of NAT1 status on TGN seems to be persistent even after one month since the interruption of the aminosalicylate. No effect of NAT1 genotypes was shown on MMPN concentrations. NAT2 genotyping revealed that 6 patients presented a genotype corresponding to fast enzymatic activity and 6 to slow activity; NAT2 genotypes were not related to thiopurine metabolites concentration in this study. CONCLUSION: NAT1 genotype affects TGN levels in patients treated with thiopurines and aminosalicylates and could therefore influence the toxicity and efficacy of these drugs; however the number of patients evaluated is limited and this has to be considered a pilot study

Population genomics reveals evolution and variation of Saccharomyces cerevisiae in the human and insects gut

The quest to discover the variety of ecological niches inhabited by Saccharomyces cerevisiae has led to research in areas as diverse as wineries, oak trees, and insect guts. The discovery of fungal communities in the human gastrointestinal tract suggested the host's gut as a potential reservoir for yeast adaptation. Here we report the existence of yeast populations associated with the human gut (HG) that differ from those isolated from other human body sites. Phylogenetic analysis on 12 microsatellite loci and 1,715 combined CDSs from whole‐genome sequencing revealed three subclusters of HG strains with further evidence of clonal colonization within the host's gut. The presence of such subclusters was supported by other genomic features, such as copy number variation, absence/introgressions of CDSs and relative polymorphism frequency. Functional analysis of CDSs specific of the different subclusters suggested possible alterations in cell wall composition and sporulation features. The phenotypic analysis combined with immunological profiling of these strains further showed that sporulation was related with strain‐specific genomic characteristics in the immune recognition pattern. We conclude that both genetic and environmental factors involved in cell wall remodeling and sporulation are the main drivers of adaptation in S. cerevisiae populations in the human gut

Age and Gender Affect the Composition of Fungal Population of the Human Gastrointestinal Tract

The fungal component of the human gut microbiota has been neglected for long time due to the low relative abundance of fungi with respect to bacteria, and only recently few reports have explored its composition and dynamics in health or disease. The application of metagenomics methods to the full understanding of fungal communities is currently limited by the under representation of fungal DNA with respect to the bacterial one, as well as by the limited ability to discriminate passengers from colonizers. Here we investigated the gut mycobiota of a cohort of healthy subjects in order to reduce the gap of knowledge concerning fungal intestinal communities in the healthy status further screening for phenotypical traits that could reflect fungi adaptation to the host. We studied the fecal fungal populations of 111 healthy subjects by means of cultivation on fungal selective media and by amplicon-based ITS1 metagenomics analysis on a subset of 57 individuals. We then characterized the isolated fungi for their tolerance to gastrointestinal tract-like challenges and their susceptibility to antifungals. A total of 34 different fungal species were isolated showing several phenotypic characteristics associated with intestinal environment such as tolerance to body temperature (37°C), to acidic and oxidative stress and to bile salts exposure. We found a high frequency of azoles resistance in fungal isolates, with potential and significant clinical impact. Analyses of fungal communities revealed that the human gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. The combination of metagenomics and fungal cultivation allowed an in-depth understanding of the fungal intestinal community structure associated to the healthy status and the commensalism-related traits of isolated fungi. We further discussed comparatively the results of sequencing and cultivation to critically evaluate the application of metagenomics-based approaches to fungal gut populations

Multisystem autoimmune disease caused by increased STAT3 phosphorylation, and dysregulated gene expression

Signal transducer and activator of transcription (STAT) 3 is a member of the STAT family, and plays a major role in various immunological mechanisms.1 Mutations in STAT3 are associated with a broad spectrum of manifestations, including immunodeficiency, autoimmunity, and malignancy.2 In particular, heterozygous germline loss-of-function (LOF) mutations cause Hyper-IgE syndrome (HIES),3–5 while heterozygous germline gain-of-function (GOF) mutations have recently been associated to multi-organ autoimmune manifestations (i.e. type 1 diabetes, enteropathy, cytopenia, interstitial lung disease, hypothyroidism), lymphoproliferation, short stature, and recurrent infections (OMIM #615952).6–8 We report a 7-year-old boy who presented with early-onset severe enteropathy, and diffuse eczematous dermatitis since birth. During the first weeks of life, Hirschsprung disease was also suspected and surgically treated. Gastrointestinal and cutaneous manifestations were first ascribed to food allergy with quite a good response to amino acid-based formula. In the following months, the patient failed to thrive, and developed respiratory tract infections. At two years, the patient presented with progressive interstitial lung disease characterized by lymphocytic interstitial infiltration leading to pulmonary hypertension, tricuspid insufficiency, and right ventricular heart failure with hepatomegaly. Because of the increased risk of infections, he received intravenous (IV) immunoglobulin infusions (400 mg/kg), prophylaxis with cotrimoxazole and fluconazole. Methylprednisolone at 0.3 mg/kg/day was also given to treat autoimmune manifestations