Climate change and biodiversity losses have necessitated innovative approaches to peatland management. This study examines pivotal historical landmarks and the recent forces of change that have affected peatlands in Finland, Ireland and Scotland, highlighting how national contexts, such as land ownership, forestry, agriculture and the need for domestic energy sources, have shaped the peatland use in those countries. We further introduce national and EU policies, which include, for example, national peatland strategies, and identify barriers to sustainable management of these important ecosystems. We propose six key solutions that could improve peatland persistence more broadly in northern Europe: (1) adoption of an integrated, landscape-scale strategy for rewetting and restoration with multi-stakeholder collaboration, (2) enhancement of monitoring to improve outcomes and refine best practices, (3) alignment of both national and EU policies across relevant sectors (energy, climate change, biodiversity, land use) to promote sustainable peatland management, (4) minimisation of trade-offs between green energy transition and sustainable peatland management, (5) engagement with local communities in restoration efforts for better acceptability and outcomes, and (6) wider leverage of market-based mechanisms, such as carbon, biodiversity and water credits, to finance peatland restoration. Together, these measures provide a pathway for the sustainable management of northern peatlands by balancing environmental integrity with socio-economic needs.

BACKGROUND:Very early-onset inflammatory bowel disease (VEOIBD) (diagnosed under 6 years of age) has attracted considerable attention in recent years, with monogenic forms providing insight into immune dysregulation. However, the majority of VEOIBD patients have a classical polygenic phenotype and a similar disease course to older children. METHODS:The study sought to assess the incidence trends of VEOIBD in Scotland from 1981 to 2014 and to describe the natural history, phenotype, and treatment burden of VEOIBD in a regional cohort from South-East Scotland (1997-2021). RESULTS:Nationally, 128 (8.1%) of 1567 incident pediatric inflammatory bowel disease (IBD) patients (<16 years of age at diagnosis) were VEOIBD; 10 (8%) of 128 were diagnosed <2 years of age. The incidence of VEOIBD rose from 0.64 per 100 000 per year (1981-1985) to 2.73 per 100 000 per year (2011-2014) (P = .002), an incidence rate ratio of 4.3 (95% confidence interval, 2.4-8.3). The average annual percentage change was 3.9% (95% confidence interval, 2.1%-5.7%) (P < .05). Crohn's disease was the most common subtype (63%); the median age at diagnosis was 4.4 years. The regional cohort (n = 46) had a median follow-up of 11.9 years. Crohn's disease cases presented with isolated colonic involvement in 47%, with pancolitis present in 64% of ulcerative colitis cases. Treatment exposures included immunosuppression (76%), corticosteroids (67%), and anti-tumor necrosis factor therapies (50%). A total of 11% were on no IBD-specific therapy at last follow-up, 11% required surgery and no patient had a diagnosis of monogenic IBD, cancer, or death. CONCLUSIONS:Scotland has a high incidence of VEOIBD, with monogenic IBD exceptionally rare. Although VEOIBD disease burden is high, treatment outcomes are broadly similar to those diagnosed later in childhood based on previous studies.

This article presents a national peatland database for the Republic of Ireland, covering not only undrained, near-intact bogs with absent land use and management at present but also peatlands that have been reclaimed for grassland, forestry and peat extraction (industrial and domestic) land uses. It presents peat substrate and vegetation data across the entire peat depth for peatland types raised bog (RB), lowland blanket bog (LLBB) and mountain blanket bog (MBB), the major land uses and most prevalent management types (a combination of drainage level and land use/grazing intensity) on these peatland types. It excludes 'near-intact' fens, which represent <2% of the total peatland area. Several key edaphic and vegetation properties, peatland classification information, physical features such as topography, elevation, and land use and management information are included in the database which consists of three major components: a 'Peatland Dataset' consisting of detailed site, non-composite soil profile and vegetation data, a 'CHNSO Dataset', containing results from elemental analysis of composite samples of the Peatland Dataset samples, and a collection of eight water table measurement records over the period November 2017 to January 2020. This new database fills a gap by integrating peat properties from the entire peat profile with a representative sampling design. It offers a valuable resource for peatland monitoring programs as well as planning and implementing sustainable management across Irish peatlands through restoration, rewetting and paludiculture ('wet agriculture') activities.

Peatlands are the most efficient terrestrial ecosystems for long-term carbon (C) storage. In Ireland, approximately 84% of raised bogs are degraded, contributing an estimated emission of 1.9 Mt C year−1, nearly one-third of which originates from domestic peat extraction sites. Rewetting aims to reduce C emissions and restore sequestration capacity; however, immediate post-restoration effects remain poorly quantified. We investigated the short-term impact of rewetting on C fluxes over a 3-year period at a former domestic peat extraction site. CO2 and CH4 fluxes were measured across rewetted and adjacent unrestored areas with matched ecotopes (vegetation communities). Results show that rewetting led to substantial reductions in C emissions across all ecotopes. Compared to unrestored areas, the Sub-marginal and Facebank ecotopes had lower average annual C emissions by 0.88 and 0.74 t C ha−1, respectively. In the cutover bog, rewetting reduced emissions in Eriophorum and Molinia ecotopes by 2.17 and 0.59 t C ha−1 year−1, respectively. This study demonstrates that rewetting led to immediate carbon reduction, and can deliver immediate climate mitigation benefits. Expanding restoration to include undesignated domestic extraction bogs offers a cost-effective strategy to reduce emissions from degraded peatlands in the near term.

Objective Iron deficiency anaemia (IDA) is common in paediatric gastroenterology with intravenous iron increasingly utilised. While adult data are published for ferric derisomaltose (FDI), no paediatric data exist. Our aim was to assess the effectiveness and safety profile of FDI in paediatric gastroenterology. Design Retrospective cohort study. Setting Two UK referral centres (Edinburgh and Sheffield). Patients All paediatric gastroenterology patients who received FDI from June 2020 to June 2023. Main outcome measures Haematological and biochemical parameters were collected before and at 1, 3, 6 and 12 months after treatment, when available, together with the need for repeated FDI infusions and FDI adverse events. Results Sixty-five patients were identified (54% male; median age 12.8 years, IQR 9.6-15.2), receiving 78 FDI infusions. After a single infusion, 38/59 (64%) patients (effectiveness analysis) completely corrected their anaemia and 6/59 (10%) improved from moderate-severe to mild anaemia. Median haemoglobin increased from 92 (IQR 85-108) to 126 (IQR 115-132) g/L at 1 month (p<0.001) and peaked at 12 months (134 g/L, IQR 125-142; p<0.001) post infusion. A second infusion was performed in 12/59 (20%) patients with 9/12 correcting their anaemia. No significant biochemical alterations, including hypophosphataemia, were detected. Overall, 4/65 (6%) patients (safety analysis) experienced adverse events, with three discontinuing FDI infusion. Conclusions Our real-world data reveal FDI is rapidly and persistently effective in correcting IDA in paediatric gastroenterology. No significant biochemical alterations or new safety signals were identified.

BACKGROUND:Given the limited research on folate and ferritin status in children with cancer undergoing treatment, we investigated the prevalence of abnormalities and their impact on clinical outcomes and treatment complications. METHODS:This prospective cohort study enrolled children <18 years diagnosed with cancer between August 2010 and February 2014. Data collection occurred at diagnosis, 3, 6, 9, 12 and 18 months. Clinical outcomes were classified as event-free survival or events (relapse, death, the development of new metastasis, becoming palliative) and treatment complications. Micronutrient status was assessed through clinical and nutritional analyses. Binary logistic regression, multilevel model analysis explored relationships between micronutrient status and clinical outcomes. RESULTS:Eighty-two patients (median [interquartile range] 3.9 (1.9-8.8) years, 56% males) were recruited. Excess ferritin (85%) and folate deficiency (25.5%) were prevalent micronutrient abnormalities throughout the study. Decreased ferritin levels reduced the odds of events by 83.9% (odd ratios = 0.161, 95% CI = 1.000-1.002, p = 0.032). Higher ferritin was associated with increased number of treatment-related complications (B = 7.3E-5, 95% CI = 1.5E-5-0.000, p = 0.013). Folate status showed significant association with body mass index category (χ2 = 9.564, p = 0.008), indicating that overweight and obese patients were more prone to deficiency, and methotrexate (F(2.9); p = 0.06; -2LL (1381)). Haematological malignancies (F(2.8); p = 0.05; -2LL (4244)) and medium and high treatment intensity (F(2.4); p = 0.09; -2LL 4262)) were associated with higher ferritin levels over 18 months. CONCLUSIONS:Paediatric cancer patients undergoing treatment exhibit high ferritin and reduced folate levels. Elevated ferritin is linked to increased toxicity and negative clinical outcomes, highlighting the importance of regular assessment and monitoring of both folate and ferritin. Implementing routine monitoring for these biomarkers could help mitigate adverse effects associated with treatment. Large-scale population-based studies and clinical trials are now warranted.

Peatland research has expanded rapidly in the last two decades encompassing a diverse, multi-disciplinary evidence base, as countries seek to manage this resource sustainably along with meeting climate and biodiversity targets. There is growing global interest in the role of peatlands in carbon and water cycles, leading to more interdisciplinary research that applies ecosystem services and other integrative frameworks to generate knowledge and provide guidance for action. These trends have been replicated in Ireland with increasing research in peatland science, applied work on these degraded ecosystems, and a growing interest from civil society, landowners, and communities in the stewardship of this resource. This paper presents evidence-based insights from over two decades of Irish peatland research, with practical lessons for peatland policy and management in other national contexts. Analyses of the evidence from the literature, specialist expertise, and stakeholder knowledge were carried out under ten themes: biodiversity, soil, climate change, water, archaeology and palaeoenvironment, technology and mapping, society and culture, management, growing media and policy and law. The research identified four foundational pillars (accountability, longevity, equity and holistic knowledge) as critical to achieving sustainable peatland management in Ireland, with broader application to other regions. Peatland restoration is widely recognised across research disciplines as a key tool to meet regulatory targets related to climate, biodiversity, and water quality, while also delivering societal benefits. The findings of this research provide accessible, reliable and up-to-date evidence for sustainable peatland management. This study addresses a critical global knowledge gap by developing a novel, interdisciplinary evidence synthesis framework—applied here to Ireland but replicable worldwide—that systematically integrates 20 years of multi-disciplinary peatland research, expert insights, and stakeholder perspectives across ten thematic pillars.

Abstract Background Oral vancomycin has had limited use in paediatric Inflammatory Bowel Disease (PIBD), with reported efficacy in primary sclerosing cholangitis (PSC-PIBD)1, acute severe colitis as part of a quadruple antibiotic regimen2, and very early onset IBD3. This study evaluates its effectiveness and safety as single-agent therapy in non-PSC PIBD patients. Methods This single-centre retrospective cohort study included PIBD patients started on oral vancomycin for active IBD or steroid/topical therapy dependency from 01/2017 to 08/2024. Exclusion criteria were PSC diagnosis, positive/equivocal stool test for C. difficile, another induction treatment started within 3 weeks prior and vancomycin use solely in a quadruple regimen2. Disease activity was assessed using PUCAI/wPCDAI, faecal calprotectin (FC), blood parameters at baseline, 1, 3, 6 and 12 months. Treatment regimen, duration, reasons for discontinuation and adverse events (AEs) were recorded. Vancomycin was started at 250mg in patients ≥30kg or 125mg in those <30kg TDS/QDS and tapered in responders after ≥1 month. Results Of 72 patients identified, 31 were included (16 males): 23 (74%) had Ulcerative Colitis (UC), 4 (13%) IBD unclassified (IBDU), 4 (13%) Crohn’s Disease (CD). At baseline, 5/31 were in clinical remission, with 2 also in biochemical remission but drug dependent. Initial vancomycin dosage was 17.5mg/kg/day (IQR 15.3-21.6), with a median duration of 4 (IQR 1-9) months. Concomitant medications are shown in Table 1: 10/31 (32%) were on biologics, with 4 able to discontinue and 2 to reduce biologic doses later. Overall, 17/31 (55%) patients (13 UC, 3 IBDU, 1 CD) achieved/maintained clinical and biochemical remission (Group 1), with 15 reducing/stopping other treatments. Conversely, 14/31 (45%) discontinued vancomycin due to non-response (11) or intolerance (3) (Group 2), with 11 stopping within 1 month. At baseline, Group 1 had lower disease activity score and platelet count than Group 2 (Table 1). A striking difference in response was noticed at 1 month (Figure 1), with FC in Group 1 dropping from 686μg/g (IQR 376-1143) at baseline to 60μg/g (IQR 25-160) at 1 month (p=0.001), while remaining high in Group 2 (p=0.52). In Group 1, 5/17 (29%) stopped vancomycin while in stable remission after 4 (IQR 2-9) months, with 3 restarted due to relapse, recapturing remission in 2/3. No severe AEs were reported. Conclusion Oral vancomycin was rapidly effective and safe, with 55% of non-PSC PIBD patients achieving/maintaining remission and 48% able to reduce/stop concomitant treatments. It was most effective in mildly active disease, especially UC/IBDU, and may offer a medium to long-term treatment option, with promising results in biologic-resistant but antibiotic-responsive PIBD patients. References 1.Ricciuto A, Liu K, El-Matary W, et al. Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium. Aliment Pharmacol Ther. 2024;59(10):1236-1247. doi:10.1111/apt.17936. 2.Turner D, Bishai J, Reshef L, et al. Antibiotic cocktail for pediatric acute severe colitis and the microbiome: The PRASCO randomized controlled trial. Inflamm Bowel Dis. 2020;26(11):1733-1742. doi:10.1093/ibd/izz298. 3.Lev-Tzion R, Ledder O, Shteyer E, Tan MLN, Uhlig HH, Turner D. Oral Vancomycin and Gentamicin for Treatment of Very Early Onset Inflammatory Bowel Disease. Digestion. 2017;95(4):310-313. doi:10.1159/000475660

Numerous tools/software exist to gap-fill missing eddy covariance (EC) data, with varying performance depending on study-site dynamics. Disturbed ecosystems like former cutaway-peatlands may be challenging for gap-filling. Researchers using gap-filling spreadsheets may benefit from transitioning to R, but may face challenges if they lack programming skills. To address these, we introduce 'miniRECgap', a user-friendly tool in R for effortless gap-filling of EC carbon dioxide flux data using well-known temperature- and light-response functions. 'miniRECgap' can model net ecosystem exchange (NEE) via GUI-supported scripts with only five code-lines and minimal inputs. A case-study on one 'classic' (forest) and one 'challenging' (rehabilitating cutaway-peatland) ecosystem indicated that standard gap-filling (MDS) performed better for the 'classic', but not for the 'challenging' ecosystem (MDS R2 = 0.24; 'miniRECgap' R2 = 0.57). For the rehabilitating-peatland, an optimised shallow Artificial Neural Network outperformed other two approaches (R2 = 0.68). These findings demonstrate the importance of NEE gap-filling for assessing ecosystem-level carbon-dynamics, important for rehabilitatingpeatlands.

OBJECTIVE:Pediatric inflammatory bowel diseases (PIBDs), despite being more prevalent in westernized nations, show an increasing incidence worldwide. Accurate evaluation, diagnosis, therapy, and monitoring are mandatory for the adequate management of patients, as is a sensible use of expensive resources, which may be limited in some parts of the world. This limitation often poses challenges to diagnose and treat patients. As the long-term prognosis very much depends on early diagnosis and remission of active disease, it is important to consider reasonable alternatives that may help clinicians to act accordingly within resource constraints, without downgrading previously published guidelines. METHODS:A group of experts from the "Paediatric IBD Porto Group" of European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) as well as pediatric and adult IBD experts, trained in IBD centers and having working experience in limited-resource settings (LR settings), joined efforts to suggest alternative options in settings where resources are limited, while prioritizing an acceptable cost-effectiveness ratio. Almost all recently published ESPGHAN guidelines and position papers on PIBD were evaluated, and the writing group framed proposals for adaptation in situations with limited access to more expensive resources or tools. RESULTS:Ninety consensus-based recommendations, derived from the available evidence, were formulated. Diagnostic protocol, biochemical evaluation, imaging and endoscopy, monitoring and options for nutritional, medical and surgical treatment were addressed. Cooperation between professionals and institutions was suggested to improve quality of care and optimize use of available expertise. Patient education, counseling, mental health and transition of care were also addressed. CONCLUSION:Diagnosis and management of PIBD are complex and costly in medical resources, but some alternative protocols could provide acceptable results and help with accurate diagnosis and management. These recommendations and practice points may offer useful guidance in settings where resources may be limited while still providing good medical practice.

Acute severe colitis (ASC) is a relatively frequent manifestation in children with ulcerative colitis and one of the few emergencies in paediatric gastroenterology. A standardized proactive approach based on tight monitoring and timely medical and surgical interventions may improve patients' outcomes. We aimed to update the previous ASC guidelines using detailed recommendations and practice points, based on a systematic review of the literature and consensus of experts. These guidelines update is a joint effort of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organization. A systematic search was performed in Pubmed Ovid Medline, Embase and Cochrane databases using 13 predefined PICO (patient, intervention, comparison, outcomes) based questions and 30 non-PICO based questions. Grading methodology was based on the Oxford Centre for Evidence-Based Medicine-Levels of evidence. The questions were addressed by working subgroups following an iterative consensus voting process, including three online voting meetings and one face-to-face meeting. A total of 36 recommendations and 72 practice points were endorsed with a consensus rate of at least 88% for all statements, regarding initial evaluation, monitoring, medical and surgical treatment of ASC in children. Several topics have been revised since the previous 2018 guidelines and differ from corresponding published adult guidelines. These guidelines present a comprehensive overview of the management of ASC in children, offering practical recommendations and practice points aiming to standardize clinical and surgical treatment and improve outcomes of this severe scenario.

OBJECTIVES:Oral vancomycin (OV) has limited usage in paediatric inflammatory bowel disease (PIBD) with reported efficacy in primary sclerosing cholangitis (PSC-PIBD), acute severe colitis as part of quadruple-antibiotic regimen, and very early-onset IBD. This study evaluates OV effectiveness and safety as a single-agent in non-PSC PIBD. METHODS:This single-centre retrospective study included patients on OV for active disease or steroid/topical therapy dependency. Exclusion criteria were PSC diagnosis, Clostridioides difficile infection, induction treatment started <3 weeks prior, and OV as part of quadruple-antibiotic regimen. Disease activity was assessed at baseline, 1-, 3-, 6- and 12-months. OV was started at 250/125 mg (≥30/<30 kg), three or four times daily, and tapered in responders after ≥1 month. RESULTS:Thirty-one patients (16 males; median age 15.1 years, IQR:11.7-16.6) were included: 23 ulcerative colitis (UC), 4 IBD-unclassified (IBDU) and 4 Crohn's disease. OV dosing was 17.5 mg/kg/day (IQR: 15.3-21.6) for 4 months (IQR: 1-9). Clinical and biochemical remission was achieved or maintained in 17/31 (55%), with 15/17 reducing/stopping other treatments and two remaining on OV monotherapy. Conversely, 14/31 (45%) discontinued OV due to non-response (11/14) or intolerance (3/14), the majority (11/14) within 1 month. Responders had lower baseline clinical disease activity and platelet count (p < 0.05). At 1-month faecal calprotectin dropped from 686 to 60 μg/g in responders (p = 0.001) but remained high in nonresponders. No serious adverse events occurred. CONCLUSION:OV was rapidly effective in 55% of PIBD cases, enabling 48% to reduce or stop other treatments. It proved most beneficial in mildly active UC/IBDU as an induction strategy plus a maintenance option for some, with a role in others in treatment de-escalation.

Abstract Background Psychological and emotional stress can cause inflammation, leading to immune-mediated inflammatory diseases (IMID) and impact the disease course in adults with IBD but the relationship in children remains understudied. [1,2] In a population-based cohort study, we aimed to estimate the effect of childhood adversities on developing a severe disease course in paediatric-onset IBD (pIBD) and IMID (pIMID) Methods Using the Danish registries, we identified all individuals born between 1981 and 2001 who were diagnosed with pIMID before age 18 (defined as IBD [most common pIMID], autoimmune liver disease, juvenile idiopathic arthritis, systemic lupus erythematosus, or vasculitis). We used nationwide health and socioeconomic registries to model childhood adversity from ages 0 to 15. We divided it into 5 trajectories: low adversity, early-life material deprivation, persistent material deprivation, loss or threat of loss, and high adversity.[3] The trajectories were modelled based on poverty, unemployment, death or severe illness, parental drug or alcohol abuse, maternal separation, or foster care. The outcome was developing a severe disease course as defined by requiring biologics, steroid dependency, surgery (disease-specific), hospitalisation (>5 days), and complications indicative of disease progression. We used Cox regression to estimate sex-adjusted hazard ratios (aHR) with age as the underlying timescale. Person time started at pIMID diagnosis and ended at the earliest of the outcome, emigration, death, or 31 DEC 2021. The low adversity trajectory was used as comparator for all analyses. Results Of 5,847 incident pIMID patients (3,014 [52%] pIBD), 3,829 (65%) developed a severe pIMID disease course. Table 1 presents patient characteristics. Patients with persistent material deprivation were more likely to develop steroid dependency (aHR 1.15 [95%CI:1.01-1.30]), require surgery (1.30 [95%CI: 1.07-1.58)] and prolonged hospitalisation (aHR 1.67 [95%CI: 1.42-1.96]), and develop complications (aHR 1.32 [95%CI: 1.03-1.70]). Patients with persistent material deprivation and high adversity were less likely to receive biologics (aHR 0.86 [95%CI: 0.75-0.99] and aHR 0.65 [95%CI: 0.48-0.87], respectively). Figure 1 presents the cumulative risks of developing a severe disease course. Conclusion Childhood adversity, especially persistent material deprivation, is associated with developing a severe disease course in pIBD and pIMID, indicating substantial social inequality despite the universal free healthcare setting. It should be investigated whether this effect represents physiological changes or is mediated through socioeconomic factors such as poor family support. References 1:Schneider KM, Blank N, Alvarez Y, et al. The enteric nervous system relays psychological stress to intestinal inflammation. Cell. 2023;186(13):2823-2838.e20. doi:10.1016/j.cell.2023.05.001 2:Zhao J, Xue E, Zhou S, et al. Allostatic load increases the incidence and risk of adverse prognosis in inflammatory bowel disease. Aliment Pharmacol Ther. 2024;60(8):1062-1074. doi:10.1111/apt.18217 3:Rod NH, Bengtsson J, Budtz-Jørgensen E, et al. Trajectories of childhood adversity and mortality in early adulthood: a population-based cohort study. The Lancet. 2020;396(10249):489-497. doi:10.1016/S0140-6736(20)30621-8

Health administrative data (HAD) have significantly increased our knowledge of rare outcomes in inflammatory bowel disease (IBD), such as cancer and mortality. We aimed to assess the information bias imposed by misclassification of the IBD diagnosis in HAD studies by performing quantitative bias analysis (QBA). In a narrative review, we identified pediatric-onset IBD (PIBD) HAD studies assessing cancer risk in which the PIBD case identification was based on published validation studies. We then performed QBA to adjust for non-differential exposure misclassification using the sensitivity and specificity values from country or region-specific validation studies. We present QBA on four recent studies reporting on cancer outcomes. Generally, we found the reported cancer risks biased towards the null. In the most extreme example, the relative risk changed from 2.0 (95% CI, 1.2-3.4) to 5.8 (95%CI, 2.5-13.7) after bias adjustment. The risk difference for this example rose from 1.0% (95% CI, 0.1-1.9) to 3.8% (95%CI, 1.4-7.9) after bias adjustment. The results from this study indicate that most HAD-based studies on rare long-term consequences of IBD significantly underestimate the true risk of the outcomes. These results can be extrapolated to other HAD-based studies with imperfect specificity of the case assertion algorithms.

OBJECTIVES:Despite advances in the management of ambulatory paediatric ulcerative colitis (UC), challenges remain as many patients are refractory to therapy and some require colectomy. The aim of these guidelines is to provide an update on optimal care for UC through detailed recommendations and practice points. METHODS:These guidelines are an update to those published in 2018 and are a joint effort of the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation. An extensive literature search with subsequent evidence appraisal using the Oxford methodology was performed, followed by three online voting sessions and a consensus face-to-face meeting. Thirty-nine recommendations and 77 practice points were endorsed by the 25 experts with at least an 84% consensus rate. RESULTS:Robust evidence-based recommendations and detailed practice points are provided. In addition to reemphasising and updating the role of more 'traditional' UC therapies, these guidelines outline optimising the use of antitumour necrosis factor therapies and integrating newer biologics and small molecules, as well as supportive therapy, to improve outcomes and provide an updated management algorithm. Measurement and monitoring tools and decision aids are provided, and additional aspects, including nutritional support, extraintestinal manifestations, pouchitis, inflammatory bowel disease-unclassified and patient support, are discussed. Some aspects, including surgery and thromboprophylaxis, are covered in the acute severe UC guidelines. CONCLUSIONS:These guidelines serve as an aid in managing children with UC through a combination of evidence-based recommendations and more practical practice points in the ambulatory setting.

Background: Given the paucity of long-term longitudinal data for inflammatory bowel disease type unclassified (IBDU), we aimed to clarify IBDU disease course and reclassification rate by presenting nationwide data with up to 20 years of follow-up. Methods: We analyzed a prospectively identified 11-year cohort of pediatric patients diagnosed with IBDU between January 1, 2003 and December 31, 2013 at all Scottish pediatric IBD centers and followed up into adult services until December 31, 2022. Data were obtained from electronic medical records at fixed timepoints (5 and 10 years post-diagnosis) and at the final follow-up. Results: Overall, 102 patients were included in the analysis (57/102 [56%] male, median [interquartile range {IQR}] age at diagnosis: 11.5 [9.1-13.2] years) with a median (IQR) follow-up length of 10.5 (8.6-14.0) years. A change of diagnosis was made in 61 of 102 patients (60%); of these, 30 patients (29%) were reclassified to Crohn's disease (CD) and 31 patients (30%) to ulcerative colitis (UC). Patients who remained with IBDU had higher 1- to 5-year remission rates (IBDU 30/39 [77%] vs reclassified 16/57 [28%], P < .05), with lower rates of moderate-to-severe disease (IBDU 3/39 [8%] vs reclassified 31/57 [54%], P < .05) and less need for biologics across all timepoints (IBDU vs reclassified: first timepoint 1/39 [3%] vs 17/57 [30%], second timepoint 1/33 [3%] vs 26/56 [46%], third timepoint 0/18 [0%] vs 16/33 [49%]; all P < .05). Higher rates of surgical resections were observed in reclassified patients (reclassified 11/61 [18%] vs IBDU 1/41 [2%], P = .02). Conclusions: In our nationwide pediatric IBDU cohort, 60% of patients were reclassified to either UC or CD over 10.5 years of median follow-up; those who remained with IBDU had a milder disease course.

Abstract Background The application of -omics technology offers important opportunities for biomarker discovery to personalise management of patients with inflammatory bowel disease (IBD). In previous work, we reported a characteristic profile of genome-wide DNA methylation in peripheral blood leucocytes from children with paediatric IBD (pIBD) at diagnosis defining the IBD methylome. This characteristic pattern of genome-wide alterations was replicated in inception cohorts of adult patients in UK and Scandinavia. Methods Whole blood DNA methylation profiling was performed using the Illumina EPIC array on 86 pIBD patients and 30 non-IBD controls. Patients had a median age of 12 y and were prospectively recruited from gastroenterology clinics in Oxford and Cambridge, UK. In modelling, we utilised the paediatric BISCUIT and PICTS study cohorts from Scotland as our training data. Publicly available data from the RISK paediatric CD cohort from North America was accessed (GSE11261) to further assess accuracy of the model. The model was then subjected to further testing in an Oxford-based paediatric coeliac cohort and adult cohorts with IBD, and rheumatoid arthritis (RA)(Table 1). Results Genome-wide methylation changes in the Oxford/Cambridge cohort were highly consistent with the index BISCUIT and PICTS cohorts. Four single methylation sites were selected to make up a diagnostic model involving the genes, RPS6KA2, VMP1, CF1 and ARHGEF3 (Figure 1) in the index cohort and validated in the Oxford/Cambridge cohort. Following receiver operating characteristic (ROC) area under the curve (AUC) analyses the model demonstrated an AUC of 0.912 (95% CI: 0.86-0.96) (Table 1). To further validate our model, we compared pIBD who were CRP-positive (>5 mg/l) and CRP-negative (<5 mg/l) at presentation against non-IBD children. In the CRP-positive group, we found an AUC of 0.99 (95% CI: 0.99-1). Within the CRP-negative group an AUC of 0.90 was observed against controls (95% CI: 0.83-0.96). The model was further validated using methylation data at the baseline timepoint in the RISK cohort, with an AUC of 0.93 (95% CI: 0.90-0.96). In further analyses, we demonstrated specificity for IBD compared with paediatric coeliac disease; and accuracy higher in childhood-onset AUC than adult-onset disease AUC; the model is not accurate in diagnosis of RA. Conclusion We confirm a characteristic pattern of DNA methylation changes in childhood-onset IBD; and derive and validate a 4-probe model for diagnosis with high accuracy in both Europe and North America. The model is specific for pIBD compared with symptomatic children with no demonstrable pathology; and children with coeliac disease; and may provide an alternative to current markers in blood and stool, including calprotectin.

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. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn’s Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7–17.2) with a median follow-up of 7.4 months (IQR 5.6–11.8). Ninety-nine percent had received prior anti-TNF, 63