The Impact of Biologic Therapies on Rate of Colectomy in Paediatric-onset Ulcerative Colitis - A Population-Based Cohort Study.

AIM: Biologic therapies have been associated with reduced rate of colectomy in ulcerative colitis (UC) in adults, but data are limited in paediatric-onset UC. Our aim was to define the rate of colectomy in paediatric-onset UC, including post-transition into adult care, and to evaluate the impact of biologic therapies on rate of colectomy. METHOD: All prevalent patients diagnosed with paediatric-onset UC in South-East Scotland were identified from a prospectively accrued database at our regional tertiary centre. Patients exposed to biologics or surgery were identified and further data collected from health records. Kaplan-Meier analysis was used to calculate cumulative risk of colectomy over time. RESULTS: 145 prevalent patients were identified between 2000 and 2021. Median follow-up was 7.9 years (IQR 4.1-13.1). 23 patients (16 %) underwent a colectomy. 50/145 (34 %) patients received biologic therapy, and 13/23 (57 %) patients who underwent colectomy received biologics. The cumulative risk of colectomy across the whole cohort at 1, 5, and 10 years was 3 %, 13 % and 16 %, respectively. Patients exposed to biologics had a higher colectomy rate at 5 and 10 years (22 % and 34 %). Patients in the pre-biologic era (2000-2008) had non-significantly reduced time from diagnosis to colectomy (2.4 vs 3.7 years, p = 0.204). CONCLUSION: We have defined the 1-, 5-, and 10-year colectomy rate in a population-based cohort of Paediatric-onset UC patients. Patients who received biologic therapy had a significantly increased risk of colectomy. Increased severity of disease in these patients may account for the greater colectomy risk. LEVEL OF EVIDENCE: Level 1.

Improved clinical outcomes with early anti-tumour necrosis factor alpha therapy in children with newly diagnosed Crohn's disease: real world data from the international prospective PIBD-SETQuality inception cohort study.

BACKGROUND & AIMS: Treatment guidelines for paediatric Crohn's disease (CD) suggest early use of anti-tumour necrosis factor alpha (anti-TNF) in high-risk individuals. The aim is to evaluate the effect of early anti-TNF in a real-world cohort. METHODS: Children with newly-diagnosed CD were prospectively recruited at 28 participating sites of the international observational PIBD-SETQuality study. Outcomes were compared at 3 months, 1 and 2 years between patients receiving early anti-TNF (<90 days after diagnosis) and those not receiving early anti-TNF. Outcomes included sustained steroid-free remission (SSFR) without treatment intensification (specified as SSFR*) and sustained steroid-free mild/inactive disease without treatment intensification (specified as SSFMI*). Penalised logistic regression model-based standardisation was applied to estimate the relative risks (RR) of early therapy on outcomes. RRs were estimated for high-risk and low-risk patients based on presence of predictors of poor outcome (POPOs) and disease activity at diagnosis. RESULTS: In total, 331 children (median age 13.9 years [IQR 12.2 - 15.3]) were enrolled, with 135 (41%) receiving early anti-TNF. At 1 year, patients on early anti-TNF had higher rates of SSFR* (30% vs. 14%, p<0.001) and SSFMI* (69% vs. 33%, p<0.001), with RRs of 2.95 (95%CI 1.63-5.36) and 4.67 (95%CI 2.46-8.87) respectively. At 1 year, the RRs for SSFMI* were higher, and statistically significant in high-risk patients, i.e. those with moderate/severe disease compared to mild/inactive disease at diagnosis (5.50 [95%CI 2.51-12.05]) vs. 2.91 [95%CI 0.92-9.11]), and those with any POPO compared to no POPO (5.05 [95%CI 2.45-10.43] vs. 3.41 [95%CI 0.54-21.7]). CONCLUSION: In this cohort of children with newly-diagnosed CD, early anti-TNF demonstrated superior effectiveness in high-risk patients.

Nationwide Real-World Exclusive Enteral Nutrition Practice Over Time: Persistence of Use as Induction for Pediatric Crohn's Disease and Emerging Combination Strategy With Biologics.

BACKGROUND: Exclusive enteral nutrition (EEN) is the recommended first-line induction treatment in pediatric patients with active luminal Crohn's disease (CD). We aimed to provide a nationwide overview of evolving EEN practices during an era of increasing biologic use. METHODS: We analyzed a prospectively identified nationwide cohort of newly diagnosed pediatric patients with CD in Scotland between January 1, 2015, and June 30, 2022. Patients who received EEN for any indication were divided into 6-monthly epochs and examined over time. Differences during the COVID-19 pandemic (March 16, 2020, to July 19, 2021) were examined. Data were retrospectively collected from electronic medical records: demographics, anthropometrics, concomitant treatments, aspects of EEN administration, and remission/response rates. Descriptive statistics and linear regression were used for analyses. RESULTS: A total of 649 patients with CD were identified (63% male; median age 12.6 [interquartile range, 10.8-14.8] years); 497 (77%) of 649 received EEN as postdiagnosis induction therapy with a median course length of 7.7 (interquartile range, 5.9-8.0) weeks. Including repeat courses, 547 EEN courses were examined. An increasing incidence of CD was observed over time with no significant changes in EEN usage, remission or response rates, nasogastric tube usage, or course completion (all P > .05). Increasing use of EEN combined with biologics (combination induction) as first-line induction was observed over time (P < .001). Considering COVID-19, lower rates of EEN usage were observed (P = .008) with no differences in remission, oral administration, and course completion rates (all P > .05). CONCLUSIONS: Over the past 7.5 years, except during the COVID-19 pandemic, EEN usage rates have not changed despite an increase in biologic use, although combination induction is an emerging trend.

Clinical Features and Natural History of Paediatric Patients with Ulcerative Proctitis: A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND AIMS: Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. METHODS: This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. RESULTS: We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. CONCLUSION: Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.

Effectiveness of Switching to Subcutaneous Infliximab in Pediatric Inflammatory Bowel Disease Patients on Intravenous Maintenance Therapy.

No real-world data are available on subcutaneous infliximab (SC-IFX) in pediatric inflammatory bowel disease (PIBD). We report a single-center cohort experience of an elective switching program from biosimilar intravenous infliximab to SC-IFX, 120 mg fortnightly, as maintenance. Clinical and laboratory data were collected for 7 patients with infliximab trough levels collected prior and at 6 and 40 weeks after the switch. High treatment persistence was registered with a single patient discontinuing the treatment due to high IFX antibodies, already present before switching. All patients remained in clinical remission with no significant changes in laboratory markers and median infliximab trough levels (12.3 µg/mL at baseline; 13.9 and 14.0 µg/mL at 6 and 40 weeks respectively). No newly-developed IFX antibodies were detected and no adverse reactions or rescue therapies were recorded. Our real-world data support the feasibility of an elective switch to SC-IFX in PIBD as maintenance with potential advantages concerning medical resources and patient satisfaction.

Adeno-associated virus 2 infection in children with non-A-E hepatitis.

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.

The inexorable increase of biologic exposure in paediatric inflammatory bowel disease: a Scottish, population-based, longitudinal study.

BACKGROUND: The use of biologics in paediatric-onset inflammatory bowel disease (PIBD) is rapidly changing. AIMS: To identify the incidence and prevalence of biologic use within Scottish PIBD services, and to describe patient demographics and outcomes for those patients who required escalation of therapy beyond anti-tumour necrosis factor alpha (anti-TNFα) agents METHODS: We captured a nationwide cohort of prospectively identified patients less than 18 years of age with PIBD (A1 phenotype; diagnosed <17 years of age) within paediatric services over a 4.5-year period (1 January 2015-30 June 2019). All patients who received infliximab, adalimumab, vedolizumab or ustekinumab during the study period and/or received their first dose of these biologics were audited retrospectively. RESULTS: Scotland-wide PIBD-prevalence cases increased from 554 to 644 over the study period. A total of 495 incident new-start biological therapies were commenced on 403 PIBD patients: 295 infliximab (60%), 161 adalimumab (32%), 24 vedolizumab (5%) and 15 ustekunumab (3%). The proportion of new-start biologics changed with infliximab initiation rates decreasing (87%-54%) while adalimumab (13%-31%), vedolizumab (0%-9%) and ustekinumab (0%-6%) all increased. The incidence rate (first dose of new biologic not including biosimilar switch) increased from 6.9% to 8.1% over the study period and point prevalence rates (any biologic use) increased from 20.2% to 43.5% - an average annual percentage increase of 20%. Biosimilar penetration of new-start anti-TNFα agents increased from 3% to 91%. Demographics and outcomes of those patients receiving vedolizumab and ustekinumab were similar. CONCLUSIONS: Complete accrual of Scottish nationwide biologic usage within paediatric services demonstrates a rapidly changing, inexorably increasing PIBD biologics landscape.

Bridge to nowhere: A retrospective single-center study on patients using chronic intravenous inotropic support as bridge therapy who do not receive surgical therapy.

Background: Many patients with advanced heart failure (HF) are administered chronic intravenous inotropic support (CIIS) as bridge to surgical therapy; some ultimately never receive surgery. We aimed to describe reasons patients "crossover" from CIIS as bridge therapy to palliative therapy, and compare end-of-life outcomes to patients initiated on CIIS as palliative therapy. Methods: Single-institution, retrospective cohort study of patients on CIIS as bridge or palliative therapy between 2010 and 2016; data obtained through review of health records and multi-disciplinary selection meeting minutes, was analyzed using descriptive and inferential statistics. Results: Of 246 patients discharged on CIIS as bridge therapy, 37 (16%) (male n = 28, 76%; African American n = 22, 60%) ultimately never received surgery. 67 matched patients on CIIS as palliative therapy were included for analysis (male n = 47, 70%; African American n = 47, 70%). The most common reasons for "crossover" from CIIS as bridge therapy to palliative therapy were frailty (n = 10, 27%), cardiac arrest (n = 5, 13.5%), and progressive non-cardiac illnesses (n = 6, 16.2%). A similar percentage of patients in the bridge (n = 28, 76%) and palliative (n = 48, 72%) groups died outside the hospital (P=0.66); however, fewer bridge patients received hospice care compared to the palliative group (35% vs 69%, P < 0.001). Comparing patients who died in the hospital, bridge patients (n = 9; 100%) were more likely to die in the intensive care unit than palliative patients (n = 8; 42%) (P < 0.001). Conclusion: Patients on CIIS as bridge therapy who do not ultimately receive surgical therapy "crossover" to palliative intention due to frailty, or development of or identification of serious illnesses. Nevertheless, these "bridge to nowhere" patients are less likely to receive palliative care or hospice and more likely to die in the intensive care unit than patients on CIIS as palliative therapy.

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Outcomes of paediatric patients with chronic liver disease in early adulthood: A heterogeneous, but representative, regional cohort study.

AIM: Advances in paediatric hepatology have led to the increasing survival of patients with paediatric-onset chronic hepatobiliary disease into adulthood. Data are lacking with regard to the outcomes of this heterogeneous group of patients and current transition models may be insufficient. This retrospective regional cohort study examined the outcomes of these patients cared for in a paediatric gastroenterology centre following transfer to adult services. METHODS: A prospective database of paediatric patients with liver disease identified those already transferred to adult services. Following exclusions, medical notes were examined and health parameters recorded including initial diagnoses, transplant status, fertility and mortality. Descriptive statistics were used to calculate follow-up data and transplant-free survival (TFS). RESULTS: Overall, 63 patients (52% male) entered the final analyses with a median follow-up of 27.5 years. The most common diagnosis was biliary atresia (19%); 27 different diagnoses were apparent within the cohort highlighting the heterogeneity within a single centre. Transplant prevalence at adult transfer was 41%; 14% of patients were lost to follow-up including 10% of transplant patients. TFS for biliary atresia was 17% after 37.4 years follow-up and was 54% for the total cohort. There were seven documented pregnancies and the prevalence of any psychological or psychiatric input was 44%. Transplant complications occurred in 38% of patients; there were two cancer diagnoses and two deaths following transfer. CONCLUSIONS: Although overall mortality was low, the health-care burden of patients with paediatric-onset chronic liver disease is high. This group is also very heterogeneous, making structured transition to adult services difficult.

I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations.

INTRODUCTION: The COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation and challenges of the ISPY COVID-19 trial during the first phase of trial activity from April 2020 until December 2021. METHODS AND ANALYSIS: The ISPY COVID-19 Trial is a multicentre open-label phase 2 platform trial in the USA designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID-19 Trial network includes academic and community hospitals with significant geographical diversity across the country. Enrolled patients are randomised to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes-time to recovery and mortality. The statistical design uses a Bayesian model with 'stopping' and 'graduation' criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrols to a maximum of 125 patients per arm and is compared with concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrolment and adaptation of the trial design are ongoing. ETHICS AND DISSEMINATION: ISPY COVID-19 operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT04488081.

Continuous Intravenous Inotropic Support for Advanced Heart Failure: Palliative Considerations.

The global prevalence of heart failure (HF) is increasing. Advancements in guideline-directed medical and device therapy have resulted in improved survival. Thus, there are more patients living - and living longer - with advanced HF. Only a small proportion of these patients are deemed appropriate for advanced surgical intervention (mechanical circulatory support or heart transplantation), and even if offered, some may decline such interventions if not aligned with their overall goals and values. Therefore, a growing number of patients with advanced HF receive chronic intravenous inotropic support (CIIS) for palliation of symptoms. Despite increased use, clinical evidence supporting use of palliative inotropes remains limited. However, available data suggest improvements in functional class, health-related quality of life (HRQoL) indicators, symptom burden, hemodynamic parameters, and possibly rehospitalization. While initial concerns regarding increased mortality have been assuaged in the modern era of guideline-directed medical therapy, palliative inotropes are certainly not without burden. Risks of infection and medication-related adverse effects, need for routine laboratory monitoring, frequent dressing changes, and presence of a reliable caregiver must be carefully considered prior to initiation. This review addresses pharmacology, guideline recommendations, benefits and burdens, considerations related to hospice and end-of-life care, and future directions of CIIS in advanced HF care.

Patterns of emergency admission for IBD patients over the last 10 years in Lothian, Scotland: a retrospective prevalent cohort analysis.

OBJECTIVE: It is unclear how the compounding prevalence of inflammatory bowel disease (IBD) has translated into the causes and rates of hospitalisation, particularly in an era of increased biologic prescribing. We aimed to analyse these trends in a population-based IBD cohort over the last 10 years. DESIGN: The Lothian IBD registry is a complete, validated, prevalent database of IBD patients in NHS Lothian, Scotland. ICD-10 coding of hospital discharge letters from all IBD patient admissions to secondary care between 1 January 2010 and 31 December 2019 was interrogated for admission cause, with linkage to local/national data sets on death and prescribed drugs. RESULTS: Fifty-seven per cent (4673/8211) of all IBD patients were admitted to secondary care for >24 h between 1 January 2010 and 31 December 2019. In patients <40 years, IBD was the commonest reason for admission (38% of admissions), whereas infection was the most common cause in those >60 years (19% of admissions). Three per cent (243/8211) of IBD patients accounted for 50% of the total IBD bed-days over the study period. Age-standardised IBD admission rates fell from 39.4 to 25.5 admissions per 100,000 population between 2010 and 2019, an average annual percentage reduction of 3% (95% CI -4.5% to -2.1%, p < 0.0001). Non-IBD admission rates were unchanged overall (145-137 per 100,000 population) and specifically for serious (hospitalisation) and severe (ITU admission or death) infection over the same period. CONCLUSION: Despite compounding prevalence and increased biologic use, IBD admission rates are falling. The cause of admission varies with age, with infection the predominant cause in older patients.

Prematurity, Delivery Method, and Infant Feeding Type Are Not Associated with Paediatric-onset Inflammatory Bowel Disease Risk: A Scottish Retrospective Birth Cohort Study.

BACKGROUND AND AIMS: The incidence of paediatric-onset inflammatory bowel disease [PIBD] continues to rise globally. We aimed to determine whether mode of delivery, gestational age at birth, or type of infant feeding contribute to the development of PIBD in a nationwide cohort of Scottish children. METHODS: All children born in Scotland between 1981 and 2017 were identified using linked health administrative data to determine mode of delivery, gestational age at birth, and type of infant feeding. PIBD cases were defined as onset of Crohn's disease [CD], ulcerative colitis [UC], or IBD-unclassified [IBDU] before age 16 years. Validation was performed within an entire Scottish health board [16% of total population] via individual case-note verification. Hazard ratios [HR] were calculated for each exposure using Cox proportional hazards models. RESULTS: A study population of 2 013 851 children was identified including 1721 PIBD cases. Validation of 261 PIBD patients coded as CD and/or UC identified 242 [93%] as true positive. Children delivered vaginally did not have an altered risk of developing PIBD compared with those delivered by caesarean section, adjusted HR 0.95 [95% CI 0.84-1.08] [p = 0.46]. Compared with children born at term [≥37 weeks], children born prematurely did not have an altered risk of developing PIBD, i.e., at 24-31 weeks of gestation, HR 0.99 [95% CI 0.57-1.71] [p = 0.97] and at 32-36 weeks of gestation, HR 0.96 [95% CI 0.76-1.20] [p = 0.71]. Compared with children exclusively breastfed at age 6 weeks, children exclusively formula fed did not have an altered risk of developing PIBD: adjusted HR 0.97 [95% CI 0.81-1.15] [p = 0.69]. CONCLUSIONS: This population-based study demonstrates no association between mode of delivery, gestational age, or exclusive formula feeding at 6 weeks, and the development of PIBD.

Twenty-first Century Trends in the Global Epidemiology of Pediatric-Onset Inflammatory Bowel Disease: Systematic Review.

BACKGROUND & AIMS: The incidence of inflammatory bowel disease (IBD) is increasing internationally, particularly in nations with historically low rates. Previous reports of the epidemiology of pediatric-onset IBD identified a paucity of data. We systematically reviewed the global trends in incidence and prevalence of IBD diagnosed in individuals <21 years old over the first 2 decades of the 21st century. METHODS: We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from January 2010 to February 2020 to identify population-based studies reporting the incidence and/or prevalence of IBD, Crohn's disease, ulcerative colitis, and/or IBD-unclassified. Data from studies published before 2000 were derived from a previously published systematic review. We described the geographic distribution and trends in children of all ages and limiting to very early onset (VEO) IBD. RESULTS: A total of 131 studies from 48 countries were included. The incidence and prevalence of pediatric-onset IBD is highest in Northern Europe and North America and lowest in Southern Europe, Asia, and the Middle East. Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence. Data on the incidence and prevalence of VEO-IBD are limited to countries with historically high rates of IBD. Time trends in the incidence of VEO-IBD were visually heterogeneous. CONCLUSIONS: Rates of pediatric-onset IBD continue to rise around the world and data are emerging from regions where it was not previously reported; however, there remains a paucity of data on VEO-IBD and on pediatric IBD from developing and recently developed countries.

The Epidemiology of Pediatric Autoimmune Hepatitis in Scotland: A National Cohort Study.

Autoimmune hepatitis (AIH) is a rare, but potentially severe, cause of liver disease in children. We aimed to summarize how children with AIH in Scotland presented, were investigated and managed in addition to producing novel epidemiological data and outcomes. Methods: All prevalent pediatric patients with AIH cared for in pediatric services between January 2013 and September 2018 were included. Individual patient data were obtained from electronic patient records in the 3-main academic pediatric centers in Scotland covering the entire population. Results: Thirty-eight patients were included (25 female) with median follow-up of 33 months (range, 2-145 mo) and 136 total patient years. The incidence between 2014 and 2017 was 0.49/100 000/y (95% confidence interval, 0.29-0.78) and point prevalence between 2013 and 2018 was 1.75/100 000 (95% confidence interval, 1.42-2.13). Thirty-five (92%) patients were autoantibody positive, most commonly anti-nuclear antibody (63%) and anti-smooth muscle antibody (42%). Thirty-seven (97%) patients had induction therapy with oral corticosteroids, 30 (79%) required maintenance treatment with azathioprine, and 23 (61%) received ursodeoxycholic acid. There were 1.4 disease flares per 10 patient years and 3 patients required liver transplantation with an overall 5-year survival rate without the need for transplantation of 95%. Conclusions: We calculated a novel incidence and prevalence rate for pediatric AIH in Scotland. Nearly all were invariably treated initially with corticosteroids with most placed-on azathioprine as maintenance therapy. Outcomes were generally favorable with low rates of disease flares and the need for transplantation being rare.

Recognising and Treating Complicated Fissuring Perianal Crohn Disease: A South-East Scotland Cohort Study.

ABSTRACT: Fissuring perianal Crohn disease (CD) is not recognised as a perianal phenotype in Montreal/Paris inflammatory bowel disease classifications; however, can occasionally present as complicated disease with severe perianal pain driving increasingly intensive medical therapy despite well controlled luminal disease. We identified a regional cohort of prospectively acquired incident cases of paediatric CD diagnosed <16 years of age in South-East Scotland over a 19-year period (1999-2018), and conducted a retrospective review of complicated fissuring perianal CD causing severe pain related to anal sphincter complex spasm at defecation. Two hundred forty-seven new cases of paediatric CD were diagnosed with complicated fissuring perianal disease identified in 4 described cases (cumulative incidence 1.6%). These patients with marked fissuring and refractory anal sphincter complex spasm required neurostimulation-guided, 4-quadrant, anal intrasphincteric botulinum toxin (BT). All experienced immediate success, measured by cessation of spasms, with variable ongoing symptom relief after median (range) 3 (2-5) BT injections.

Combination Immunotherapy Use and Withdrawal in Pediatric Inflammatory Bowel Disease-A Review of the Evidence.

Evidence-based guidelines have been developed outlining the concomitant use of anti-tumor necrosis factor alpha (anti-TNF) agents and immunomodulators including azathioprine (AZA) and methotrexate (MTX) in both adult and pediatric populations. However, there exists a paucity of data guiding evidence-based strategies for their withdrawal in pediatric patients in sustained remission. This narrative review focuses on the available pediatric evidence on this question in the context of what is known from the larger body of evidence available from adult studies. The objective is to provide clarity and practical guidance around who, what, when, and how to step down pediatric patients with inflammatory bowel disease (IBD) from combination immunotherapy. Outcomes following withdrawal of either of the two most commonly used anti-TNF therapies [infliximab (IFX) or adalimumab (ADA)], or immunomodulator therapies, from a combination regimen are examined. Essentially, a judicious approach must be taken to identify a significant minority of patients who would benefit from treatment rationalization. We conclude that step-down to anti-TNF (rather than immunomodulator) monotherapy after at least 6 months of sustained clinical remission is a viable option for a select group of pediatric patients. This group includes those with good indicators of mucosal healing, low or undetectable anti-TNF trough levels, lack of predictors for severe disease, and no prior escalation of anti-TNF therapy. Transmural healing and specific human leukocyte antigen (HLA) typing are some of the emerging targets and tools that may help facilitate improved outcomes in this process. We also propose a simplified evidence-based schema that may assist in this decision-making process. Further pediatric clinical studies are required to develop the evidence base for decision-making in this area.