Short-term Psychodynamic Psychotherapy in Addition to Standard Medical Therapy Increases Clinical Remission in Adolescents and Young Adults with Inflammatory Bowel Disease: a Randomised Controlled Trial.

BACKGROUND: Inflammatory bowel diseases [IBD] are chronic and pervasive conditions of the gastrointestinal tract with a rising incidence in paediatric and young adult populations. Evidence suggests that psychological disorders might be associated with relapse of disease activity. This study aims to evaluate the efficacy of short-term psychodynamic psychotherapy [STPP] in addition to standard medical therapy [SMT] in maintaining clinical remission in adolescents and young adults [AYA] with quiescent IBD, compared with SMT alone. METHODS: A two-arm, single-centre, randomised, controlled trial was conducted in 60 IBD AYA in clinical remission. Patients were randomised to receive an 8-week STPP + SMT [n = 30] or SMT alone [n = 30]. The primary outcome was the steroid-free remission rate at 52 weeks after treatment. Secondary outcomes included the overall hospitalisation rate within 52 weeks after treatment, and medication adherence obtained from patient's electronic medical records. RESULTS: Intention-to-treat analysis showed significant improvement in maintaining disease remission rates in the 8-week STPP + SMT group compared with the control one. The proportion of patients maintaining steroid-free remission at 52 weeks was higher in patients in STTP group [93.1%] compared with patients randomised to control group [64.3%; p = 0.01]. There were no significant differences in secondary outcomes, except for depression reduction in STPP + SMT group. CONCLUSIONS: An 8-week STPP intervention in addition to SMT effectively increases the steroid-free remission rates in AYA with quiescent IBD. Results do not support effects for other secondary outcomes, except for depression reduction.

Characterization of the Gut Microbiota and Mycobiota in Italian Pediatric Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis. METHODS: By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs). RESULTS: Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients. CONCLUSIONS: We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.

In this study, we report the gut microbiota and mycobiota dysbiosis in pediatric patients affected by primary sclerosing cholangitis (PSC) associated with ulcerative colitis (UC), with an increase in pro-inflammatory pathobionts and a reduction in anti-inflammatory commensals.

Epidemiological trends of pediatric IBD in Italy: A 10-year analysis of the Italian society of pediatric gastroenterology, hepatology and nutrition registry.

INTRODUCTION: The present study aimed at evaluating Italian epidemiological trends of pediatric inflammatory bowel diseases (IBD) over the period 2009-2018. MATERIALS AND METHODS: Data from 1969 patients enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition Registry, by 49 pediatric IBD centers throughout the country, were analyzed, comparing three different time intervals (2009-2012, 2013-2015, 2016-2018). RESULTS: The number of new IBD diagnoses ranged from 175 to 219 per year, evenly distributed over the examined period of time. From 2009 to 2018, the minimal incidence ranged from 1.59 to 2.04 /105 inhabitants aged < 18 years, with an overall slight predominance of ulcerative colitis (UC) over Crohn's disease (CD) (ratio: 1.1). Mean diagnostic delay was 6.8 months for CD and 4.1 months for UC, with a significant reduction for CD when comparing the three-time intervals (p =0.008). The most frequent disease locations according to the Paris classification were ileocolonic for CD (41.3%) and pancolitis for UC (54.6%). CONCLUSIONS: The minimal incidence rate in Italy seems to have stabilized over the last two decades, even if it has increased when compared to previous reports. UC is still slightly more prevalent than CD in our country. Diagnostic delay significantly decreased for CD, reflecting an improved diagnostic capacity.

Transition of inflammatory bowel disease patients from pediatric to adult care: an observational study on a joint-visits approach.

BACKGROUND: Transition from pediatric to adult care of patients affected by Inflammatory Bowel Disease (IBD) is a critical step that needs specific care and multidisciplinary involvement. The aim of our study was to evaluate the outcome of the transition process of a cohort of IBD patients, exploring their readiness and the possible impact on quality of life. METHODS: This observational study followed transitioned IBD patients from pediatric to adult care. Transition was carried-out through combined visits, jointly performed by the pediatrician and the adult gastroenterologist. Clinical data were collected before and after transition. A subgroup of patients was submitted to an anonymous online questionnaire of 38 items based on the validated questionnaires TRAQ and SIBDQ within the first 6 months from the beginning of the transition process. RESULTS: Eighty-two patients with IBD were enrolled, with a mean age at transition of 20.2±2.7 years. Before transition, 40.2% of patients already had major surgery and 64.6% started biologics. At transition, 24% of patients were in moderate to severe active phase of their disease and 40% of them had already been treated with ≥ 2 biologics. The mean score of the TRAQ questionnaires collected is 3.4±1.5 and the mean score of SIBDQ is 53.9±9.8. A significant association was found between a TRAQ mean score > 3 and a SIBDQ > 50 (p=0.0129). Overall, 75% of patients had a positive opinion of the transition model adopted. CONCLUSIONS: A strong association has been found between TRAQ and SIBDQ questionnaires, showing how transition readiness has a direct impact on the quality of life of the young adult with IBD.

Autoimmune liver diseases and inflammatory bowel diseases in children: current issues and future perspectives.

Inflammatory bowel diseases (IBDs) represent a group of intestinal disorders with a chronic and relapsing inflammation of the gut, and with a potential risk of systemic involvement of other organs and systems. Over the pediatric age, an incidence higher than 20% of developing extraintestinal manifestation during follow-up has been reported. The liver and the biliary system are frequently involved, and primary sclerosing cholangitis (PSC) is the most predominant entity with an incidence rate of 6.4-7.8% in children. PSC recognizes a multifactorial pathogenesis, and so far a not fully known mechanism for this association. The peculiar phenotype and the distinct clinical course of patients with IBD and PSC-associated make this 'linkage' an attractive study model to better understand mechanisms underlying these diseases. Approaching to these patients is complex and multidisciplinary, and a unique therapeutic strategy has not been standardized yet. New medications are being studied; however, further studies are needed to fully understand the pathogenesis and to improve the care of these patients. The aim of this paper is to review the recent literature regarding hepatobiliary involvement in IBD patients, with particular attention to PSC, and to provide the latest information for a correct diagnosis and appropriate management.

Pediatric inflammatory bowel disease: specificity of very early onset.

INTRODUCTION: The incidence of inflammatory bowel disease (IBD) has increased over the last 50 years. It is now recognized that several genetic defects can express an IBD-like phenotype at very early onset (<6 years). AREAS COVERED: The aim of this review was to update knowledge concerning the specificity of IBD at onset <6 years, which can include conventional/standard IBD as well as monogenic IBD-like diseases. Expert commentary: We found that females are less prone than males to develop monogenic disorders, which have X-linked heritability in several cases. Furthermore, the Crohn's Diseases (CD) subtype seems to be suggestive of monogenic disorders while Unclassified IBD (IBDU) subtype is predominantly found in conventional/standard IBD at onset <6 years. Isolated colonic location is prevalent in both the subsets of IBD at onset <6 years if compared to IBD at later onset. Monogenic disorders require more aggressive medical and surgical treatments and can be complicated by the occurrence of lymphomas.

The clinical implications of thalidomide in inflammatory bowel diseases.

Thalidomide has anti-inflammatory and anti-angiogenetic activity that makes it suitable for treating inflammatory bowel diseases (IBD). The recent guidelines from the European Crohn's and Colitis Organization/European Society for Pediatric Gastroenterology Hepatology and Nutrition conclude that thalidomide cannot be recommended in refractory pediatric Crohn's disease but that it may be considered in selected cohorts of patients who are not anti-TNFα agent responders. The main adverse effect is the potential teratogenicity that renders the long-term use of thalidomide problematic in young adults due to the strict need for contraceptive use. In short-term use it is relatively safe; the most likely adverse effect is the neuropathy, which is highly reversible in children. So far the use of thalidomide is reported in 223 adult and pediatric IBD patients (206 with Crohn's disease). In the following sections, the authors will discuss efficacy and safety of thalidomide, in the short-term treatment of IBD.

Chronic pancreatitis as presentation of Crohn's disease in a child.

It is reported that a pancreatic disease may precede the diagnosis of inflammatory bowel disease (IBD) both in children and in adults. Idiopathic chronic pancreatitis, however, occasionally co-exists with the IBD, mainly at pediatric age. We report a case of a patient who progressively developed the features of a chronic pancreatitis, before the diagnosis of Crohn's Disease (CD). Ten months after the onset of the first episode of pancreatitis the patient developed bloody diarrhea, mucus stools and biochemical findings of inflammation. The colonoscopy revealed a diffuse colitis without involvement of the last loop and the gastroscopy showed inflammation of the iuxta-papillary area. The histological findings confirmed the diagnosis of CD that involved the colon and the duodenum. In conclusion, in children the idiopathic chronic pancreatitis may be an unusual presentation of CD. Thus, if other known cause of chronic pancreatitis are not found, a not invasive work up to exclude the IBD should be warranted. An early coincidental diagnosis of the IBD may delay the progression of the pancreatic disease.

Plasma citrulline as surrogate marker of intestinal inflammation in pediatric and adolescent with Crohn's disease: preliminary report.

PURPOSE: Several researchers have found that plasma citrulline could be a marker of reduced enterocyte mass. The aim of this study was to assess the relationship between plasma citrulline and bowel inflammation and/or disease location in pediatric and adolescent Crohn's disease (CD) patients. METHODS: Between January 2008 and January 2010, 31 CD patients and 44 controls were included in our study, and 15 out of the 31 CD patients continued a prospective survey. We evaluated the differences between groups, at baseline, in plasma citrulline and glutamine and between their baseline and final values during the prospective survey, and correlation between baseline values of citrulline and duration of disease, C-reactive protein, and fecal calprotectin. RESULTS: Mean citrulline value was 33.0 ± 7.5 µmol/L in controls and 23.5 ± 8.4 µmol/L in CD patients (P < 0.0001). Plasma citrulline was significantly lower in patients with small bowel (SB) location than in patient with only ileo-colon disease (14.2 ± 5.5 and 24.7 ± 8.0, respectively; P = 0.0037). Citrulline ≤22 µmol/L reached sensitivity of 100% (95% confidence interval (CI) 54-100) and specificity of 98% (CI 89-99) in differentiating control subjects from CD with SB location. CONCLUSIONS: CD patients have reduced concentration of plasma citrulline than controls. Intestinal damage rather than inflammation seems to be responsible for the reduced biosynthesis of citrulline, which decreases particularly in CD patients with SB location. This finding suggests the potential role of citrulline as marker of disease location, but future works will be needed to confirm this suggestion.

Incidence, clinical presentation, and management of constipation in a pediatric ED.

OBJECTIVES: The study aimed to assess, in pediatric patients presenting to the emergency department (ED), the incidence of visit to the ED for functional constipation (FC), symptoms, signs of presentation, and management from ED physicians. DESIGN: This is a retrospective study of hospital records for a period of 1 year at the ED of "Bambino Gesù" Children's Hospital, Rome, Italy. Children younger than 15 years discharged from ED with a diagnosis of FC in the 1-year period were included. INTERVENTIONS: We analyzed medical records of 202 patients (<15 years) with FC diagnosis at discharge. Main outcome measures included incidence, demographic characteristics, clinical presentations of FC patients, and ED physicians' interventions. RESULTS: Two hundred two FC cases were studied in a 12-month study period. Compared with the total number of ED consultations, the incidence of FC was 0.4%. The number of patients 4 years or younger was much higher than patients older than 4 years (P < .0001). Bowel frequency of 3 bowel movements or less per day, acute abdominal pain, and stool retention were found to be significantly more frequent than the other presenting symptoms (P < .0001). The number of patients beginning a therapy after ED discharge was significantly higher compared with that already treated before ED visit (P < .0001). Discharged patients were referred to community pediatricians significantly more frequently than to pediatric gastroenterologists (P = .003). CONCLUSIONS: Emergency department physicians have an important role in the diagnosis and management of FC despite its relatively low incidence. Indeed, ED intervention in many cases leads not only to recognition this disease but also to an approach for therapeutic strategy, avoiding complications of chronic constipation.

Irreversible intestinal failure: prevalence and prognostic factors.

BACKGROUND AND AIM: Parenteral nutrition (PN) is the primary treatment for intestinal failure, which is considered irreversible in patients who remain partially or fully dependent on PN. Causes of irreversible intestinal failure are short bowel syndrome (SBS), motility disorders (MD), and severe protracted diarrhea (SPD). The aim of this study was to report the clinical outcome in these patients in relation to the underlying disease. PATIENTS AND METHODS: From January 1, 1989 to December 31, 2006, 218 intestinal failure patients were observed in our center, but only 96 (48 SBS, 39 SPD, and 9 MD) were included because they required at least 50% of their total calories as PN for not less than 3 months. In these patients, survival and complication rates were evaluated. RESULTS: The survival rate was significantly higher in SBS patients than in the other groups (P < 0.01). SBS patients showed a higher rate of major complications, although only intestinal failure-associated liver disease was significantly higher (P < 0.001). In our series, MD was the main cause of irreversible intestinal failure. CONCLUSIONS: The potential for bowel adaptation is higher in surgical than in medical causes of intestinal failure and does not seem to be influenced by complications of intestinal failure. SBS, although worsened by the major number of complications, was not the main category contributing to intestinal failure.