Publications by authors named "Nicholas M Croft"

Current first-line treatments of paediatric ulcerative colitis (UC) maintain a 6-month remission in only half of the patients. Relapse prediction at diagnosis could enable earlier introduction of immunosuppressants. We collected intestinal biopsies from 56 treatment-naïve children, combining mucosal quantitative microbial profiling with host epigenomics, transcriptomics, genotyping, and in vitro and in vivo experiments on selected bacteria.

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Background: Environmental enteropathy (EE) is an asymptomatic lesion of the small intestine, likely an adaptive response to environmental noxa, including enteropathogens, leading to recurrent intestinal injury, mucosal inflammation, and microbial translocation. Inflammatory bowel disease (IBD) is increasing in incidence in newly industrialised countries. Given that EE is seen in individuals living in insanitary environments in low-income countries (LICs) and IBD has traditionally been viewed as a disease of developed countries, we hypothesised that these two conditions would not co-exist.

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Article Synopsis
  • CD4 memory T cell reactivation is linked to chronic inflammatory bowel disease (IBD), affecting conditions like Crohn's disease (CD) and ulcerative colitis, with unclear differences in T cell regulation among patients.
  • In a study of pediatric IBD patients, a specific subgroup of therapy-naïve CD patients showed higher frequencies of a particular inflammatory T cell type (TIGITCD38T) associated with severe disease and elevated IFN-γ levels.
  • The research identified IL-12 as a key driver of this inflammatory response, with increased IL-12 signaling linked to the transformation of T cells into more pathogenic forms, correlating with worsened intestinal inflammation.
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Background: Recent studies of children with inflammatory bowel disease (IBD) demonstrate an increased venous thromboembolism (VTE) risk. However, estimates of risk are variable and case numbers are limited. The aim of this study was to provide national estimates of the risk of VTE in children with IBD.

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Background: The genetic contribution to inflammatory bowel disease (IBD), encompassing both Crohn's disease (CD) and ulcerative colitis (UC), accounts for around 20% of disease variance, highlighting the need to characterize environmental and epigenetic influences. Recently, considerable progress has been made in characterizing the adult methylome in epigenome-wide association studies.

Methods: We report detailed analysis of the circulating methylome in 86 patients with childhood-onset CD and UC and 30 controls using the Illumina Infinium Human MethylationEPIC platform.

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Inflammatory bowel disease (IBD) chronicity results from memory T helper cell (Tmem) reactivation. Identifying patient-specific immunotypes is crucial for tailored treatment. We conducted a comprehensive study integrating circulating immune proteins and circulating Tmem, with intestinal tissue histology and mRNA analysis, in therapy-naïve pediatric IBD (Crohn's disease, CD: n = 62; ulcerative colitis, UC: n = 20; age-matched controls n = 43), and after 10-12 weeks' induction therapy.

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Article Synopsis
  • There's a lack of information about inflammatory bowel disease (IBD) in Africa.
  • To tackle this, a network of doctors working on IBD was created in sub-Saharan Africa.
  • The report covers 175 cases from 12 different countries collected over a span of 2 years.
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Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab.

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Article Synopsis
  • The study aimed to create a method for reporting rare and severe adverse events in children with inflammatory bowel disease (IBD) to establish incidence rates, compare different regions, and benchmark against overall children’s adverse event rates.
  • Researchers utilized data from the PIBD-SETQuality Safety Registry, which collected information on ten specified adverse events among children under 19 diagnosed with IBD, reported by pediatric gastroenterologists.
  • The registry gathered monthly reports from doctors participating in a network, focusing only on recent events and excluding events that didn’t meet specific criteria or involved unverified IBD diagnoses.
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Objectives: The objective of this study was to explore the correlation between paediatric Crohn's disease (CD) characteristics, bone health and growth parameters at diagnosis and follow-up.

Methods: Retrospective data was collected for 47 children aged 4-16 who were newly diagnosed with CD between January 2018 and December 2019. Mean follow-up time was 2.

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Visceral pain is a leading cause of morbidity in inflammatory bowel disease (IBD), contributing significantly to reduced quality of life. Currently available analgesics often lack efficacy or have intolerable side effects, driving the need for a more complete understanding of the mechanisms causing pain. Whole transcriptome gene expression analysis was performed by bulk RNA sequencing of colonic biopsies from patients with ulcerative colitis (UC) and Crohn's disease (CD) reporting abdominal pain and compared with noninflamed control biopsies.

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Article Synopsis
  • The study assessed the impact of early anti-TNF treatment for children diagnosed with Crohn's disease, focusing on high-risk individuals.
  • It involved tracking the health outcomes of 331 children over 2 years, comparing those who started anti-TNF therapy within 90 days of diagnosis to those who did not.
  • Results showed that early anti-TNF users had significantly better rates of achieving remission and mild/inactive disease at one year, especially among high-risk patients.
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Background: Previous studies have demonstrated the tolerability and efficacy of multimatrix mesalamine in inducing and maintaining remission in adults with mild-to-moderate ulcerative colitis (UC). We evaluated the safety and efficacy of low-dose and high-dose once-daily multimatrix mesalamine in children and adolescents with mild-to-moderate UC or those in remission.

Methods: This prospective, randomised, parallel-group, phase 3 study (8-week double-blind acute [DBA] phase; 26-week double-blind maintenance [DBM] phase; and an additional 8-week, open-label acute [OLA] phase) was conducted in 33 sites across North America, Europe, and the Middle East between December 12, 2014, and November 28, 2018.

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Background: Several studies have proposed models to predict disease outcomes in paediatric ulcerative colitis (UC), notably PROTECT, Schechter and PIBD-ahead, but none has been validated by external cohorts AIM: To explore these models in a prospective multicentre inception cohort METHODS: Children newly diagnosed with UC in 17 centres were followed at disease onset and 3 and 12 months thereafter, as well as at last visit. Outcomes included steroid-free remission (SFR) and acute severe colitis (ASC).

Results: Of the 223 included children, 74 (34%), 97 (43%) and 52 (23%) presented with mild, moderate and severe disease, respectively.

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Background & Aims: The TUMMY-UC is a patient-reported outcome measure for pediatric ulcerative colitis (UC) with an observer-reported outcome version for children aged <8 years. It includes eight items selected by concept elicitation interviews. We aimed to finalize the TUMMY-UC by cognitive interviews (stage 2) and to evaluate the index for its psychometric properties (stage 3).

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Article Synopsis
  • There are only two approved advanced treatment options for children with inflammatory bowel disease (IBD), despite new drugs for adults being available.
  • A virtual meeting involving various stakeholders was held to discuss improving the approval process for pediatric IBD drug development.
  • Collaborative actions among clinical experts, patient groups, pharmaceutical companies, and regulators are essential to speed up the approval of new medications for children with IBD.
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Background And Aims: Thromboprophylaxis use in paediatric inflammatory bowel disease [IBD] is inconsistent. Current guidelines only support treating children with acute severe colitis with risk factors. We convened an international RAND panel to explore thromboprophylaxis in paediatric IBD inpatients in the context of new evidence.

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Objectives: To evaluate the longitudinal evolution of work productivity loss and activity impairment in caregivers of children with inflammatory bowel disease (IBD). We also evaluated the associations between these impairments, IBD-related factors, and caregivers' health-related quality of life (HRQOL) and estimated the indirect costs related to work absenteeism.

Study Design: Since January 2017, children with newly diagnosed IBD were enrolled prospectively in the Pediatric Inflammatory Bowel Disease Network for Safety, Efficacy, Treatment and Quality improvement of care study.

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Background And Aims: To date, there are no systematic pharmacokinetic [PK] data on vedolizumab in paediatric inflammatory bowel disease [IBD]. We report results from HUBBLE, a dose-ranging, phase 2 trial evaluating the PK, safety and efficacy of intravenous vedolizumab for paediatric IBD.

Methods: Enrolled patients [aged 2-17 years] with moderate to severe ulcerative colitis [UC] or Crohn's disease [CD] and body weight ≥10 kg were randomized by weight to receive low- or high-dose vedolizumab [≥30 kg, 150 or 300 mg; <30 kg, 100 or 200 mg] on Day 1 and Weeks 2, 6 and 14.

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Objectives: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2.

Methods: Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time-points.

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Background And Aims: Guidelines regarding thromboprophylaxis for venous thromboembolisms [VTEs] in children with inflammatory bowel disease [IBD] are based on limited paediatric evidence. We aimed to prospectively assess the incidence of VTEs in paediatric-onset IBD [PIBD], characterize PIBD patients with a VTE and identify potential IBD-related risk factors.

Methods: From October 2016 to September 2020, paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD.

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Introduction: High-quality procedure reports are a cornerstone of high-quality pediatric endoscopy as they ensure the clear communication of procedural events and outcomes, guide patient care and facilitate continuous quality improvement. The aim of this document is to outline standardized reporting elements that achieved international consensus as requirements for high-quality pediatric endoscopy procedure reports.

Methods: With support from the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used Delphi methodology to identify key elements that should be found in all pediatric endoscopy reports.

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