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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.
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Infecciones por Adenovirus Humanos , Dependovirus , Hepatitis , Niño , Humanos , Enfermedad Aguda/epidemiología , Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/genética , Infecciones por Adenovirus Humanos/virología , Alelos , Estudios de Casos y Controles , Linfocitos T CD4-Positivos/inmunología , Coinfección/epidemiología , Coinfección/virología , Dependovirus/aislamiento & purificación , Predisposición Genética a la Enfermedad , Virus Helper/aislamiento & purificación , Hepatitis/epidemiología , Hepatitis/genética , Hepatitis/virología , Hepatocitos/virología , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/inmunología , Hígado/virologíaRESUMEN
OBJECTIVES: To evaluate the efficacy of standard and optimized infliximab induction dosing in attaining corticosteroid (CS) free clinical remission at week 52 and the effect that post-induction trough levels have on long-term outcome. METHODS: Inflammatory bowel disease (IBD) patients ≤18 years commenced on infliximab between August 1, 2016, and August 1, 2018, from Vancouver, Canada, and Glasgow, Scotland, were included. The Glasgow cohort followed standard induction while the Vancouver cohort undertook induction optimization based on clinical, biomarker, and proactive infliximab trough levels. Baseline characteristics and laboratory values were documented. RESULTS: In total, 140 children were included [median age 14.1 years (interquartile range (IQR) 12.0-16.0)]; 54% male. CS-free clinical remission at week 52 was higher in the optimized group compared to the standard cohort [65/78 (83%) vs. 32/62 (52%), P < 0.001]. Combined CS-free clinical and biomarker remission (CRP < 5 mg/L) was also higher in the optimized compared to the standard cohort [65/78 (83%) vs 25/62 (40%), P < 0.001]. The median post-induction trough level was higher in children who were in CS-free clinical remission at week 52 [3.6 mg/L (1.5-7.1)] vs. those who were not [2.0 mg/L (0.8-4.1), P = 0.04]. The odds of attaining a therapeutic post-induction trough level were almost 4-fold higher in the optimized group than the standard cohort (OR 3.97, 95% CI: 1.89-8.68, P < 0.001). CONCLUSIONS: Standard infliximab induction resulted in less favorable long-term outcomes for pediatric IBD patients. Optimizing induction using clinical, biomarker, and proactive trough levels resulted in higher post-induction trough levels and a greater odds of attaining long-term clinical remission.
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Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Masculino , Niño , Adolescente , Femenino , Infliximab/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Monitoreo de Drogas , Resultado del Tratamiento , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Inducción de Remisión , BiomarcadoresRESUMEN
On 31 March 2022, Public Health Scotland was alerted to five children aged 3-5 years admitted to hospital with severe hepatitis of unknown aetiology. Retrospective investigation identified eight additional cases aged 10 years and younger since 1 January 2022. Two pairs of cases have epidemiological links. Common viral hepatitis causes were excluded in those with available results. Five children were adenovirus PCR-positive. Other childhood viruses, including SARS-CoV-2, have been isolated. Investigations are ongoing, with new cases still presenting.
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COVID-19 , Hepatitis A , Niño , Preescolar , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Escocia/epidemiologíaRESUMEN
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.
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BACKGROUND: The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn's disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition. METHODS: Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn's disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. RESULTS: Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. CONCLUSIONS: This pilot study identified potential dietary triggers of gut inflammation in children with Crohn's disease after food reintroduction following treatment with exclusive enteral nutrition. TRIAL REGISTRATION: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).
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Enfermedad de Crohn , Nutrición Enteral , Niño , Enfermedad de Crohn/terapia , Dieta , Humanos , Inflamación , Proyectos Piloto , Inducción de RemisiónRESUMEN
Prior studies have shown cannabis use is correlated with psychotic symptoms, but few have explored potential underlying mechanisms. The present study examined whether aberrant salience explains the association between cannabis use frequency and psychotic experiences (PE) while accounting for the mediating role of anxiety in this association. A US urban undergraduate sample of 816 racial and ethnic minorities contributed data used in linear regression models to determine associations between recent (3 months) cannabis use frequency, aberrant salience, anxiety, positive subscale Prodromal Questionnaire (PQ) items, and distressing positive PQ items. Results from hierarchical linear regression and mediation models using Hayes PROCESS application indicated the association between cannabis use frequency and PE was significantly explained by higher aberrant salience and anxiety. Furthermore, anxiety's indirect association with cannabis use frequency and PE significantly occurred through aberrant salience's indirect association with cannabis use frequency and PE (i.e., serial mediation). A similar pattern emerged for distressing PE. We also found earlier age of cannabis use onset (age 12-14) was associated with a higher number of PE and distressing PE and that this was partially explained by higher aberrant salience. Anxiety's indirect association between earlier age of onset and PE/distressing PE only occurred through aberrant salience (i.e., serial mediation). Aberrant salience may be the part of psychosis proneness most directly connected to why earlier initiation of cannabis use is a risk factor for psychotic disorders. This should be explored further in future longitudinal work with clinical high-risk populations and among minoritized youth.
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Cannabis , Trastornos Psicóticos , Adolescente , Ansiedad/epidemiología , Niño , Etnicidad , Humanos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/epidemiología , Encuestas y CuestionariosRESUMEN
ABSTRACT: The use of thiopurine therapy in Epstein-Barr virus (EBV)-naïve inflammatory bowel disease (IBD) patients remains controversial due to a risk of EBV-associated complications. We evaluated EBV status and outcomes within our paediatric IBD population over an 8-year period; finding that 217 of 409 (53%) screened patients were seropositive for EBV at IBD diagnosis; that thiopurines were used in 189 of 217 (87%) seropositive and 159 of 192 (83%) seronegative patients (Pâ=â0.22); and that 7 of 192 (4%) previously seronegative patients subsequently tested positive for EBV with 6 of 7 (86%) patients having concurrently recorded thiopurine use. All six patients continued thiopurine with/without a period of cessation; no EBV-associated lymphoproliferative disorders/serious complications were recorded within our cohort. A significant proportion of our patients would not receive thiopurine therapy should their use be avoided in EBV-negative patients (47%) or seronegative males (30%). The small but significant risks of thiopurine treatment must be balanced against the potential benefits of successful IBD management; further research into this is required.
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Infecciones por Virus de Epstein-Barr , Enfermedades Inflamatorias del Intestino , Trastornos Linfoproliferativos , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4 , Humanos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , MasculinoRESUMEN
OBJECTIVES: Following the disruption of normal paediatric inflammatory bowel disease (IBD) services during the peak of the COVID-19 pandemic, we prospectively audited the first-time use of home faecal calprotectin testing. We aimed to provide an alternative to laboratory tests and to assess the value of home testing as part of our regular services going forward. METHODS: Home test kits as well as accompanying user instructions were made available to our patients with paediatric IBD that required faecal calprotectin test between 17 April and 12 August 2020. Once the user completed the test, results were automatically uploaded to the result portal and clinical staff were alerted. A user feedback questionnaire was sent to users that had completed the home test. RESULTS: Of the 54 patients, 41 (76%) aged between 4.7 and 18.1 years used the home test. A total of 45 home tests were done, one of which produced an invalid result. The decision to modify management was made in 12 (29%) of the patients, while 14 (34%) had no changes made and 15 (37%) required further assessment. Twenty (48.8%) responded to the questionnaire and 85% stated that they preferred the home test to the laboratory testing method. CONCLUSIONS: Home calprotectin tests were useful in guiding clinical management during a time when laboratory testing was less available. They may offer benefits as part of routine paediatric IBD monitoring to help target appointments and reduce unnecessary hospital attendances in the future.
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COVID-19/epidemiología , Heces/química , Enfermedades Inflamatorias del Intestino/terapia , Complejo de Antígeno L1 de Leucocito/análisis , Pandemias , Pruebas en el Punto de Atención , Adolescente , Biomarcadores/análisis , Niño , Preescolar , Pruebas de Química Clínica/estadística & datos numéricos , Retroalimentación , Femenino , Servicios de Atención de Salud a Domicilio , Humanos , Masculino , Portales del Paciente , Prioridad del Paciente/estadística & datos numéricos , Estudios Prospectivos , Juego de Reactivos para Diagnóstico/estadística & datos numéricos , Valores de Referencia , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Patients with paediatric inflammatory bowel disease (IBD) constitute one of the largest cohorts requiring transition from paediatric to adult services. Standardised transition care improves short and long-term patient outcomes. This study aimed to detail the current state of transition services for IBD in the United Kingdom (UK). METHODS: We performed a nationwide study to ascertain current practice, facilities and resources for children and young people with IBD. Specialist paediatric IBD centres were invited to contribute data on: timing of transition/transfer of care; transition resources available including clinics, staff and patient information; planning for future improvement. RESULTS: Twenty of 21 (95%) of invited centres responded. Over 90% of centres began the transition process below 16âyears of age and all had completed transfer to adult care at 18âyears of age. The proportion of patients in the transition process at individual centres varied from 10% to 50%.Joint clinics were held in every centre, with a mean of 12.9 clinics per year. Adult and paediatric gastroenterologists attended at all sites. Availability of additional team members was patchy across the UK, with dietetic, psychological and surgical attendance available in <50% centres. A structured transition tool was used in 75% of centres. Sexual health, contraception and pregnancy were discussed by <60% of teams. CONCLUSIONS: This study provides real-world clinical data on UK-wide transition services. These data can be used to develop a national strategy to complement current transition guidelines, focused on standardising services whilst allowing for local implementation.
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Colitis , Enfermedades Inflamatorias del Intestino , Cuidado de Transición , Adolescente , Adulto , Niño , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Embarazo , Reino UnidoRESUMEN
We describe the case of a patient with congenital chloride-losing diarrhoea (CCLD), global developmental delay and intermittent transaminitis who was diagnosed with Crohn's disease after persistent anaemia and onset of rectal bleeding. CCLD is a rare autosomal recessive condition causing large-volume chloride-rich diarrhoea, metabolic alkalosis and potentially life-threatening electrolyte disturbance. A possible association between CCLD and inflammatory bowel disease (IBD) has recently become apparent; however, the underlying mechanism has not been identified, with the role of increased expression of tumour necrosis factor-alpha hypothesised. Early diagnosis and management are key for favourable outcomes within both CCLD and IBD, and understanding a potential link between the two conditions may lead to development of novel therapies and management strategies. We aim to highlight the pathophysiology, diagnosis and management of CCLD; its potential association with IBD; and the potential therapeutic difficulties within the management of patients with comorbid CCLD and IBD.
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This case series describes the cases of three adolescent patients with established inflammatory bowel disease (IBD) who experienced significant hypophosphataemia following intravenous infusion of ferric carboxymaltose as treatment for iron deficiency anaemia. Hypophosphataemia may cause a diverse range of symptoms and may be difficult to diagnose clinically due to their non-specific nature. Checking a baseline phosphate (PO4) prior to intravenous iron infusion may identify patients at higher risk for significant hypophosphataemia and perhaps allow the selection of an alternative iron preparation. The routine monitoring of PO4 levels postinfusion presents a greater challenge; with cases of asymptomatic hypophosphataemia likely to be uncovered, as in case 3. Clinicians, patients and families should be aware of the symptoms of hypophosphataemia, and symptomatic patients should have bloods checked to allow prompt identification and correction of abnormalities where required. Review of guidelines surrounding intravenous iron infusion and management of hypophosphataemia in paediatric patients is now required.
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INTRODUCTION: Increased risk of opportunistic infection-e.g., varicella zoster infection-secondary to therapies is a cause of morbidity in inflammatory bowel disease [IBD] patients. The UK vaccination schedule does not include varicella immunisation. We aimed to evaluate the varicella screening and immunisation programme in a paediatric IBD population. METHODS: Data regarding IBD diagnosis, varicella status, and consequent immunisations/treatment interventions were collected retrospectively from the records of patients diagnosed with IBD over a 10-year period [2009-2018]. RESULTS: In all, 520 IBD patients were diagnosed; 505/520 [97%] had varicella testing; 46/505 [9%] were naïve. Of 501 patients, 391[78%] were tested before or within 7 days of diagnosis; this increased in the second 5-year period compared with the first (229/268 [85%] versus 162/233 [70%]; pâ <0.00001). Median diagnosis age of naïve patients was lower [8.3 years versus 12.8 years; pâ <0.00001]. Where vaccination was feasible, 21/31 [68%] had two and 7/31 [23%] one immunisation. Prednisolone induction led to lower rates of vaccination (5/13 [39%] versus 23/33 [70%] for other induction therapies; pâ =0.02). Of 28 vaccinated patients, 5 [18%] had suspected breakthrough varicella; and 6/18 [33%] unimmunised patients required post-exposure prophylaxis or treatment for varicella. Immunisation was associated with a decrease in patients requiring post-exposure prophylaxis (0/28 [0%] versus 5/18 [28%]; pâ =0.0006) and varicella-related hospital admission (1/28 [4%] versus 4/18 [22%]; pâ =0.01). CONCLUSIONS: High rates of varicella screening and immunisation within a PIBD population are possible, resulting in a reduction in hospital admissions for varicella treatment. Varicella immunisation may be of increasing importance within the PIBD population with the emergence of novel therapeutic strategies.
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Varicela/diagnóstico , Varicela/prevención & control , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/prevención & control , Vacunación/estadística & datos numéricos , Antiinflamatorios/uso terapéutico , Anticuerpos Antivirales/sangre , Varicela/sangre , Varicela/complicaciones , Niño , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Huésped Inmunocomprometido , Inmunoglobulina G/sangre , Inmunosupresores/uso terapéutico , Quimioterapia de Inducción , Masculino , Infecciones Oportunistas/sangre , Infecciones Oportunistas/complicaciones , Profilaxis Posexposición/estadística & datos numéricos , Prednisolona/uso terapéutico , Estudios RetrospectivosRESUMEN
Exclusive enteral nutrition (EEN) is effective in inducing remission in paediatric Crohn Disease (CD) and has been shown to reduce inflammation and improve outcomes in adult CD patients when used before resectional surgery. This retrospective study demonstrates that preoperative EEN is achievable in paediatric CD patients undergoing right hemicolectomy and is associated with positive peri-operative outcomes. Seventeen patients (8 who received preoperative EEN and 9 who did not) were included in the study. Six of 8 (75.0%) managed EEN orally; 1 via nasogastric tube and another via a previously sited gastrostomy. Use of preoperative EEN was associated with a decreased rate of moderate/severe disease on resection pathology (5/8 [62.5%] vs 9/9 [100%]; Pâ=â0.04). Larger studies are required to determine the wider potential benefits of preoperative EEN on postoperative outcomes within paediatric practice.
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Enfermedad de Crohn , Adulto , Niño , Enfermedad de Crohn/terapia , Nutrición Enteral , Humanos , Ejercicio Preoperatorio , Inducción de Remisión , Estudios RetrospectivosRESUMEN
BACKGROUND: Our current understanding regarding the aetiology of infantile acute liver failure largely derives from studies conducted by regional liver units. This may introduce selection bias and therefore not provide a true reflection of the wider population. METHODS: Every coagulation screen with a prothrombin time ≥18 s in our centre was examined over one calendar year. All patients less than 1 year of age were included and their electronic records retrospectively reviewed. RESULTS: 24 patients were identified, from 9989 coagulation screens, that fit the current definition of acute liver failure. Hypoxic birth injury and ischaemic events were the most common aetiologies. Survival was 75%. CONCLUSION: The 'catch-all' methodology employed demonstrated that acute liver failure is more common than previously reported and suggests that current data may exclude large numbers who either have more minor self-resolving disease or conversely have severe disease leading to death prior to transfer.
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Fallo Hepático Agudo/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/etiología , Masculino , Estudios Retrospectivos , Factores de Riesgo , Escocia/epidemiología , Tasa de SupervivenciaRESUMEN
Exposure to traumatic life events (TLE) is a risk factor for psychosis. Yet, a dearth of studies examines factors linking TLE to psychosis, while considering differences in TLE frequency. This study investigated dissociation and aberrant salience as mediators and moderators of the relation between three TLE groups (none, 1-3 TLE and 4+ TLE) and psychotic-like experiences (PLE) in a multi-ethnic sample of 816 emerging adults. The participants completed self-report inventories of PLE (Prodromal Questionnaire), TLE (Life Events Checklist), dissociative experiences (Dissociative Symptoms Scale), and aberrant salience (Aberrant Salience Inventory). As expected, groups with higher TLE frequency endorsed higher PLE. Parallel mediation models indicated that, while aberrant salience mediated the relation between both levels of cumulative traumatic experiences (1-3 TLE and 4+ TLE) and PLE, dissociation only mediated the relation between exposure to at least four different traumatic experiences and PLE. The moderation results showed that risk of PLE was highest among individuals with 1-3 TLE who endorsed dissociation. Our results suggest that, while aberrant salience processing explains why TLE may relate to higher psychosis risk, dissociation's role in this relation is dependent on the number of different TLE exposures.
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OBJECTIVES: The aim of the study was to evaluate the use of steroids within the paediatric inflammatory bowel disease (PIBD) population at a tertiary paediatric centre over a year; to identify cases of steroid dependency; and assess factors associated with steroid excess. METHODS: The prevalent PIBD population (May 1, 2017-April 30, 2018) were reviewed. Data were collected retrospectively from patient records and entered into an online steroid assessment tool (modified for paediatrics). RESULTS: A total of 229 patients (181 Crohn disease, 31 ulcerative colitis [UC], and 17 inflammatory bowel disease-unclassified) were included. Of the 229 patients 38 (16.6%) received oral steroids; 12 of 38 (31.6%) receiving >3-month course. Eleven of 38 (28.9%) received >1 steroid course (maximum 2). Of the 229 patients 37 (16.2%) had exclusive enteral nutrition, with 26 of 37 (11.4% total cohort) avoiding steroid use during the study period.Quiescent disease activity had a negative correlation with steroid use (11/127 [8.7%] vs 27/102 [26.5%] Pâ<â0.01), and steroid dependency (3/127 [2.4%] vs 12/102 [11.8%] Pâ<â0.01). Patients with UC were more likely to be steroid dependent (5/31 [16.1%] UC vs 10/198 [5.1%]; Pâ=â0.02); as were network-managed patients (8/11 [72.7%] vs 7/27 [25.9%]; Pâ=â0.01). Fourteen of 15 (93.3%) of steroid-dependent patients had active steroid sparing strategies in place (eg, commencement, switching, or optimization of therapies). CONCLUSIONS: We have described rates of steroid use and dependency within our PIBD population. Exclusive enteral nutrition served as a steroid sparing tool in 11.4% of the total cohort. Replication of this study in other paediatric centres would allow comparative analysis.
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Corticoesteroides/administración & dosificación , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Encuestas y Cuestionarios , Administración Oral , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Registros Médicos , Estudios RetrospectivosRESUMEN
BACKGROUND: Faecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn's disease. It is unknown how faecal calprotectin changes during food re-introduction and the influence of maintenance enteral nutrition. AIMS: To study changes to faecal calprotectin during exclusive enteral nutrition and at food reintroduction, and explore associations with maintenance enteral nutrition. METHODS: Children with Crohn's disease were followed during exclusive enteral nutrition and during food-reintroduction. Faecal calprotectin was measured before, at 33 and 54 days of exclusive enteral nutrition, and at 17, 52 and 72 days after food-reintroduction. Maintenance enteral nutrition use was recorded with estimated weight food diaries. Data are presented with medians and Q1:Q3. RESULTS: Sixty-six patients started exclusive enteral nutrition and 41 (62%) achieved clinical remission (weighted paediatric Crohn's disease activity index <12.5). Baseline faecal calprotectin (mg/kg) decreased after 4 and 8 weeks of exclusive enteral nutrition (Start: 1433 [Q1: 946, Q3: 1820] vs 33 days: 844 [314, 1438] vs 54 days: 453 [165, 1100]; P < .001). Within 17 days of food reintroduction, faecal calprotectin increased to 953 [Q1: 519, Q3: 1611] and by 52 days to 1094 [660, 1625] (both P < .02). Fifteen of 41 (37%) children in remission used maintenance enteral nutrition (333 kcal or 18% of energy intake). At 17 days of food reintroduction, faecal calprotectin was lower in maintenance enteral nutrition users than non-users (651 [Q1: 271, Q3: 1781] vs 1238 [749, 2102], P = .049) and correlated inversely with maintenance enteral nutrition volume (rho: -0.573, P = .041), kcals (rho: -0.584, P = .036) and % energy intake (rho: -0.649, P = .016). Maintenance enteral nutrition use was not associated with longer periods of remission (P = .7). Faecal calprotectin at the end of exclusive enteral nutrition did not predict length of remission. CONCLUSIONS: The effect of exclusive enteral nutrition on faecal calprotectin is diminished early during food reintroduction. Maintenance enteral nutrition at ~18% of energy intake is associated with a lower faecal calprotectin at the early phase of food reintroduction but is ineffective in maintaining longer term remission.
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Enfermedad de Crohn/dietoterapia , Nutrición Enteral , Heces/química , Alimentos , Complejo de Antígeno L1 de Leucocito/metabolismo , Adolescente , Niño , Ingestión de Energía , Femenino , Humanos , Masculino , Inducción de RemisiónRESUMEN
BACKGROUND & AIMS: Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD. METHODS: We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment. RESULTS: For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (µmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log10 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [P = .015] and 1.0 for CD-TREAT [P = .044] vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P = .002). CONCLUSION: CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246.
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Bacterias/crecimiento & desarrollo , Enfermedad de Crohn/dietoterapia , Nutrición Enteral , Microbioma Gastrointestinal , Valor Nutritivo , Adolescente , Adulto , Animales , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Carga Bacteriana , Niño , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/fisiopatología , Modelos Animales de Enfermedad , Heces/microbiología , Femenino , Antígeno HLA-B27/genética , Antígeno HLA-B7/genética , Humanos , Masculino , Estado Nutricional , Ratas Transgénicas , Recurrencia , Inducción de Remisión , Escocia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
We describe the case of a patient with ongoing weight loss, low mood and previously undisclosed gastrointestinal (GI) symptoms initially diagnosed with an eating disorder and subsequently diagnosed with ulcerative colitis over a year following initial presentation. This patient exhibited disordered eating secondary to the worsening symptoms of undiagnosed inflammatory bowel disease (IBD) and had altered her eating habits to reduce the diarrhoea and rectal bleeding she was experiencing, contributing to significant weight loss.The implications of a delayed diagnosis of IBD or incorrect diagnosis of eating disorder are severe both physically and psychologically. We discuss factors in the assessment of patients which may raise suspicion of organic GI disease such as IBD-an important differential diagnosis in those with non-specific GI symptoms and suspected eating disorder-and highlight baseline investigations which should be performed to ensure a diagnosis of IBD is not missed in these patients.
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Colitis Ulcerosa/diagnóstico , Dolor Abdominal/etiología , Niño , Diagnóstico Diferencial , Diarrea/etiología , Endoscopía del Sistema Digestivo , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Femenino , Hemorragia Gastrointestinal/etiología , Humanos , Leucocitosis/etiología , Pérdida de PesoRESUMEN
The safety, clinical efficacy, and cost-effectiveness of biosimilar infliximab in adult inflammatory bowel disease (IBD) have now been extensively shown. Limited data have been collected in the paediatric setting. We report nationwide, prospective, clinical safety and effectiveness data for patients from all 3 Scottish paediatric inflammatory bowel disease networks switching from originator to biosimilar infliximab. Prospective clinical data were collected for 33 patients. Information was collected from electronic patient records, laboratory reports, and patient case notes. There were no clinically significant changes to disease activity, biomarkers, antidrug antibodies, or trough drug levels (Pâ>â0.1) within a 12-month follow-up period; in addition, there were no significant adverse events reported. No infusion reactions were seen in the 264 infusions delivered. Switching from originator infliximab to the biosimilar (CT-P13) appears to be associated with neither an increase in infusion reactions nor significant loss of effectiveness in the short term.