RESUMEN
Microvillus inclusion disease (MVID) is a congenital enteropathy characterized by accumulation of vesiculo-tubular endomembranes in the subapical cytoplasm of enterocytes, historically termed "secretory granules." However, neither their identity nor pathophysiological significance is well defined. Using immunoelectron microscopy and tomography, we studied biopsies from MVID patients (3× Myosin 5b mutations and 1× Syntaxin3 mutation) and compared them to controls and genome-edited CaCo2 cell models, harboring relevant mutations. Duodenal biopsies from 2 patients with novel Myosin 5b mutations and typical clinical symptoms showed unusual ultrastructural phenotypes: aberrant subapical vesicles and tubules were prominent in the enterocytes, though other histological hallmarks of MVID were almost absent (ectopic intra-/intercellular microvilli, brush border atrophy). We identified these enigmatic vesiculo-tubular organelles as Rab11-Rab8-positive recycling compartments of altered size, shape and location harboring the apical SNARE Syntaxin3, apical transporters sodium-hydrogen exchanger 3 (NHE3) and cystic fibrosis transmembrane conductance regulator. Our data strongly indicate that in MVID disrupted trafficking between cargo vesicles and the apical plasma membrane is the primary cause of a defect of epithelial polarity and subsequent facultative loss of brush border integrity, leading to malabsorption. Furthermore, they support the notion that mislocalization of transporters, such as NHE3 substantially contributes to the reported sodium loss diarrhea.
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Enterocitos/metabolismo , Síndromes de Malabsorción/metabolismo , Microvellosidades/patología , Mucolipidosis/metabolismo , Vesículas Secretoras/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Células CACO-2 , Membrana Celular/metabolismo , Enterocitos/ultraestructura , Humanos , Síndromes de Malabsorción/genética , Masculino , Microvellosidades/genética , Microvellosidades/metabolismo , Mucolipidosis/genética , Mutación , Miosina Tipo V/genética , Transporte de Proteínas , Proteínas Qa-SNARE/genética , Vesículas Secretoras/ultraestructuraRESUMEN
OBJECTIVES: The aim of the study was to summarize short-term effectiveness, safety, and cost of using infliximab biosimilar (IFX-B) drugs, (Inflectra [Hospira] and Remsima [NAAP]) compared to originator infliximab (IFX-O) (Remicade [MSD]) in biologic naive pediatric inflammatory bowel disease in the United Kingdom. METHODS: Prospective audit of patients starting anti-tumour necrosis factor (TNF) therapy. Disease severity, response to treatment, and remission rate was measured by Pediatric Crohn's Disease Activity Index (PCDAI) and/or Physician Global Assessment. RESULTS: Between March 2015 and February 2016, 278 patients (175 IFX-O, 82 IFX-B, and 21 Adalimumab) were started on anti-TNF therapy. This was compared with collected data on 398 patients started on IFX-O from 2011 to 2015. At initiation, median PCDAI was 36 (20,48) (nâ=â42) in the IFX-O group and 28 (20,40) (nâ=â29) in the IFX-B group, (Pâ=â0.08). Immunosuppression rates were similar: 150/175 (86%) for IFX-O and 65/82 (79%) for IFX-B (Pâ>â0.05). Post induction, median PCDAI score was 5 (0,11) (nâ=â19) and 0 (0,8) (nâ=â15) in the IFX-O and IFX-B groups, respectively (Pâ=â0.35). There was no difference in response to treatment using Physician Global Assessment 85% (nâ=â28) in IFX-O group and 86% (nâ=â19) in IFX-B group (Pâ>â0.05). Adverse events at initiation and post induction were not different between both groups (Pâ>â0.05). Using conservative calculations, £875,000 would have been saved for a 1-year period with universal adoption of biosimilars in patients who were instead treated with IFX-O. CONCLUSIONS: IFX-B is likely as effective as IFX-O in treating IBD in comparable pediatric populations. Sites should adopt infliximab biosimilar for new starts due to cost reduction with no difference in other parameters.
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Biosimilares Farmacéuticos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , Adolescente , Niño , Femenino , Humanos , Quimioterapia de Inducción , Masculino , Auditoría Médica , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Reino UnidoRESUMEN
OBJECTIVE: The aim of this study was to measure the effectiveness, safety, and use of anti-tumor necrosis Factor (TNF) therapy in pediatric inflammatory bowel disease in the United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment +/or the Paediatric Crohn Disease Activity Index. RESULTS: A total of 37 centers participated (23/25 specialist pediatric inflammatory bowel disease sites). A total of 524 patients were included: 429 with Crohn disease (CD), 76 with ulcerative colitis (UC), and 19 with IBD unclassified (IBDU). Eighty-seven percent (488/562) of anti-TNF was infliximab; commonest indication was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95); 79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median time from diagnosis to treatment was 1.42 years (interquartile range 0.63-2.97). Disease (at initiation) was moderate or severe in 91% (156/171) by Physician Global Assessment compared to 41% (88/217) by Paediatric Crohn Disease Activity Index (Kappa (κ) 0.28â=âonly "fair agreement"; Pâ<â0.001.Where documented, 77% (53/69) of patients with CD responded to induction; and 65% (46/71) entered remission. A total of 2287 infusions and 301.96 years of patient' follow-up (nâ=â385) are represented; adverse events affected 3% (49/1587) infliximab and 2% (2/98) adalimumab infusions (no deaths or malignancies). Peri-anal abscess drainage was less common after anti-TNF initiation (CD), that is 26% (27/102) before, 7% (3/42) after (Pâ=â0.01); however, pre and post anti-TNF data collection was not over equal time periods. CONCLUSIONS: Anti-TNFs are effective treatments, usually given with thiopurine co-immunosuppression. This study highlights deficiencies in formal documentation of effect and disparity between disease severity scoring tools, which need to be addressed to improve ongoing patient care.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Terapia de Inmunosupresión/métodos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Anticuerpos Monoclonales Humanizados/efectos adversos , Niño , Preescolar , Auditoría Clínica , Femenino , Fármacos Gastrointestinales/efectos adversos , Humanos , Terapia de Inmunosupresión/efectos adversos , Lactante , Masculino , Estudios Prospectivos , Inducción de Remisión , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Reino UnidoRESUMEN
Gorlin-Goltz syndrome (GGS), also known as nevoid basal cell carcinoma syndrome (MIM 109 400), is a rare genetic condition with a prevalence between 1/56 000 and 1/256 000. Clinical presentation is usually characterized by multiple basal cell carcinomas, odontogenic jaw keratocysts, palmar or plantar pitting and skeletal anomalies. It is furthermore associated with the development of various tumors beside basal cell carcinoma, among which medulloblastoma is the most frequent. Increased incidence of other mesenchymal neoplasms, however, is also well known: recently the first adult case of gastric leiomyoma in GGS was reported, and the inclusion of "fibromas and leiomyomas of other organs" in the minor criteria for the diagnosis was suggested. We report the first case of a pediatric patient with GGS who also developed a gastric leiomyoma: the present case illustrates the need for this change to the diagnostic criteria to encompass the highly variable presentations and phenotype in GGS.
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Síndrome del Nevo Basocelular/diagnóstico , Neoplasias Cerebelosas/diagnóstico , Gastroscopía/métodos , Leiomioma/diagnóstico , Neoplasias Primarias Múltiples , Neoplasias Gástricas/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Adolescente , Humanos , MasculinoRESUMEN
The management of inflammatory bowel disease represents a key component of clinical practice for members of the British Society of Gastroenterology (BSG). There has been considerable progress in management strategies affecting all aspects of clinical care since the publication of previous BSG guidelines in 2004, necessitating the present revision. Key components of the present document worthy of attention as having been subject to re-assessment, and revision, and having direct impact on practice include: The data generated by the nationwide audits of inflammatory bowel disease (IBD) management in the UK in 2006, and 2008. The publication of 'Quality Care: service standards for the healthcare of people with IBD' in 2009. The introduction of the Montreal classification for Crohn's disease and ulcerative colitis. The revision of recommendations for the use of immunosuppressive therapy. The detailed analysis, guidelines and recommendations for the safe and appropriate use of biological therapies in Crohn's disease and ulcerative colitis. The reassessment of the role of surgery in disease management, with emphasis on the importance of multi-disciplinary decision-making in complex cases. The availablity of new data on the role of reconstructive surgery in ulcerative colitis. The cross-referencing to revised guidelines for colonoscopic surveillance, for the management of metabolic bone disease, and for the care of children with inflammatory bowel disease. Use of the BSG discussion forum available on the BSG website to enable ongoing feedback on the published document http://www.bsg.org.uk/forum (accessed Oct 2010). The present document is intended primarily for the use of clinicians in the United Kingdom, and serves to replace the previous BSG guidelines in IBD, while complementing recent consensus statements published by the European Crohn's and Colitis Organisation (ECCO) https://www.ecco-ibd.eu/index.php (accessed Oct 2010).
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Enfermedades Inflamatorias del Intestino/terapia , Adulto , Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Atención a la Salud/organización & administración , Técnicas de Diagnóstico del Sistema Digestivo , Medicina Basada en la Evidencia/métodos , Medicina Basada en la Evidencia/normas , Fármacos Gastrointestinales/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/diagnóstico , Apoyo Nutricional/métodos , Cese del Hábito de Fumar , Reino UnidoRESUMEN
Infantile hypertrophic pyloric stenosis (IHPS) has an incidence of 1-8 per 1000 live births and is inherited as a complex sex-modified multifactorial trait with a striking male preponderance. Syndromic and monogenic forms exist, and two loci have been identified. Infants present with vomiting due to gastric-outlet obstruction caused by hypertrophy of the smooth muscle of the pylorus. A genome-wide SNP-based high-density linkage scan was carried out on 81 IHPS pedigrees. Nonparametric and parametric linkage analysis identified loci on chromosomes 11q14-q22 (Z(max) = 3.9, p < 0.0001; HLOD(max) = 3.4, alpha = 0.34) and Xq23 (Z(max) = 4.3, p < 0.00001; HLOD(max) = 4.8, alpha = 0.56). The two linked chromosomal regions each harbor functional candidate genes that are members of the canonical transient receptor potential (TRPC) family of ion channels and have a potential role in smooth-muscle control and hypertrophy.
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Cromosomas Humanos Par 11/genética , Ligamiento Genético , Predisposición Genética a la Enfermedad , Genoma Humano/genética , Estenosis Hipertrófica del Piloro/genética , Mapeo Cromosómico , Femenino , Humanos , Lactante , Masculino , Linaje , Polimorfismo de Nucleótido Simple , Razón de MasculinidadRESUMEN
Generalised lymphatic dysplasia (GLD) is characterised by extensive peripheral lymphoedema with visceral involvement. In some cases, it presents in utero with hydrops fetalis. Autosomal dominant and recessive inheritance has been reported. A large, non-consanguineous family with three affected siblings with generalised lymphatic dysplasia is presented. One child died aged 5 months, one spontaneously miscarried at 17 weeks gestation, and the third has survived with extensive lymphoedema. All three presented with hydrops fetalis. There are seven other siblings who are clinically unaffected. Linkage analysis produced two loci on chromosome 18, covering 22 Mb and containing 150 genes, one of which is CCBE1. A homozygous cysteine to serine change in CCBE1 has been identified in the proband, in a residue that is conserved across species. High density SNP analysis revealed homozygosity (a region of 900 kb) around the locus for CCBE1 in all three affected cases. This indicates a likely ancestral mutation that is common to both parents; an example of a homozygous mutation representing Identity by Descent (IBD) in this pedigree. Recent studies in zebrafish have shown this gene to be required for lymphangiogenesis and venous sprouting and are therefore supportive of our findings. In view of the conserved nature of the cysteine, the nature of the amino acid change, the occurrence of a homozygous region around the locus, the segregation within the family, and the evidence from zebrafish, we propose that this mutation is causative for the generalised lymphatic dysplasia in this family, and may be of relevance in cases of non-immune hydrops fetalis.
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Proteínas de Unión al Calcio/genética , Análisis Mutacional de ADN/métodos , Ligamiento Genético , Predisposición Genética a la Enfermedad/genética , Linfedema/genética , Mutación , Proteínas Supresoras de Tumor/genética , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Humanos Par 18/genética , Salud de la Familia , Resultado Fatal , Femenino , Muerte Fetal , Genes Recesivos , Genotipo , Humanos , Lactante , Linfedema/patología , Masculino , Linaje , Polimorfismo de Nucleótido SimpleRESUMEN
AIM: To compare the diagnostic yield of small intestinal contrast ultrasonography (SICUS) with magnetic resonance enterography (MRE) in routine clinical practice in a cohort of pediatric patients investigated for Crohn's disease (CD) attending a UK tertiary center. METHODS AND RESULTS: Patients with suspected or established CD who underwent SICUS were identified retrospectively. SICUS was compared to conventional transabdominal ultrasound (TUS), ileocolonoscopy (IC), and MRE. The accuracy and agreement of SICUS in detecting small bowel lesions and CD-related complications were assessed using kappa (κ) coefficient statistics. A total of 93 patients (median age 15 years, range 2-17, 49 male) underwent SICUS; 58 had suspected and 35 had established CD. In suspected CD, sensitivity and specificity of SICUS in detecting CD small bowel lesions were 81.8 and 100% and for TUS 85.7 and 87.5%, respectively. In established CD, sensitivity and specificity of SICUS were 98.7 and 100% and TUS 80 and 100%, respectively. Agreement between SICUS and IC was substantial for the presence of lesions (κ = 0.73) but fair in TUS (κ = 0.31). Agreement between SICUS and IC was almost perfect for detecting strictures (κ = 0.84), with a sensitivity of 100% and specificity of 97.6%. When comparing SICUS and TUS with MRE, agreement for the presence of lesions was substantial (κ = 0.63) and moderate (κ = 0.53), respectively. Agreement between SICUS and MRE was substantial for detecting strictures (κ = 0.77) and dilatation (κ = 0.68). CONCLUSIONS: SICUS offers a radiation-free alternative for assessing pediatric small bowel CD, with diagnostic accuracy that is comparable to MRE and IC, supporting its wider use in routine practice.
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Familial non-Hodgkin lymphoma (NHL) is rare and in most cases, no underlying cause is identifiable. We report homozygous truncating mutations in the mismatch repair gene MSH2 (226C-->T; Q76X) in three siblings who each developed T-cell NHL in early childhood. All three children had hyperpigmented and hypopigmented skin lesions. Constitutional biallelic MSH2 mutations have previously been reported in five individuals, all of whom developed malignancy in childhood. Familial lymphoma has not been reported in this context or in association with biallelic mutations in the other mismatch repair genes MLH1, MSH6 or PMS2. In addition, hypopigmented skin lesions have not previously been reported in biallelic MSH2 carriers. Our findings therefore expand the spectrum of phenotypes associated with biallelic MSH2 mutations and identify a new cause of familial lymphoma. Moreover, the diagnosis has important management implications as it allows the avoidance of chemotherapeutic agents likely to be ineffective and mutagenic in the proband, and the provision of cascade genetic testing and tumour screening for relatives.
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Predisposición Genética a la Enfermedad , Linfoma de Células T/genética , Proteína 2 Homóloga a MutS/genética , Mutación/genética , Secuencia de Bases , Preescolar , Análisis Mutacional de ADN , Femenino , Humanos , Hipopigmentación/etiología , Linfoma de Células T/complicaciones , Masculino , Datos de Secuencia Molecular , LinajeRESUMEN
Background: Pediatric ulcerative colitis (UC) presents at an earlier age and increasing prevalence. Our aim was to examine morbidity, steroid sparing strategies, and surgical outcome in children with active UC. Methods: A national prospective audit was conducted for the inpatient period of all children with UC for medical or surgical treatment in the United Kingdom (UK) over 1 year. Thirty-two participating centers recruited 224 children in 298 admissions, comparisons over 6 years were made with previous audits. Results: Over 6 years, recording of Paediatric Ulcerative Colitis Activity Index (PUCAI) score (median 65)(23% to 55%, P < 0.001), guidelines for acute severe colitis (43% to 77%, P < 0.04), and ileal pouch surgery registration (4% to 56%, P < 0.001) have increased. Corticosteroids were given in 183/298 episodes (61%) with 61/183 (33%) not responding and requiring second line therapy or surgery. Of those treated with anti-TNFalpha (16/61, 26%), 3/16 (18.8%) failed to respond and required colectomy. Prescription of rescue therapy (26% to 49%, P = 0.04) and proportion of anti-TNFalpha (20% to 53%, P = 0.03) had increased, colectomy rate (23.7% to 15%) was not significantly reduced (P = 0.5). Subtotal colectomy was the most common surgery performed (n = 40), and surgical complications from all procedures occurred in 33%. In 215/224 (96%) iron deficiency anemia was detected and in 51% treated, orally (50.2%) or intravenously (49.8%). Conclusions: A third of children were not responsive to steroids, and a quarter of these were treated with anti-TNFalpha. Colectomy was required in 41/298 (13.7%) of all admissions. Our national audit program indicates effectiveness of actions taken to reduce steroid dependency, surgery, and iron deficiency. 10.1093/ibd/izy042_video1izy042.video15769503407001.
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Colectomía/estadística & datos numéricos , Colitis Ulcerosa/terapia , Inmunosupresores/uso terapéutico , Esteroides/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Niño , Preescolar , Colectomía/efectos adversos , Colitis Ulcerosa/epidemiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Resultado del Tratamiento , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: This study evaluated the safety, tolerability, and efficacy of natalizumab, a humanized monoclonal immunoglobulin-G4 antibody to [alpha]4 integrin, in adolescent patients with moderately to severely active Crohn disease (CD). PATIENTS AND METHODS: In a single-arm study, 38 adolescent patients (ages 12-17 y) with active CD (Pediatric Crohn Disease Activity Index [PCDAI] >30) received 3 intravenous infusions of natalizumab (3 mg/kg) at 0, 4 and 8 weeks. The primary analysis was safety, assessed by adverse events, laboratory results, and vital signs. Pharmacokinetic and pharmacodynamic measurements and formation of anti-natalizumab antibodies also were analyzed. Efficacy outcomes were assessed by changes in PCDAI, quality of life (IMPACT III), and levels of C-reactive protein and serum albumin. RESULTS: Thirty-one patients (82%) received 3 natalizumab infusions. The most common adverse events were headache (26%), pyrexia (21%) and CD exacerbation (24%). Clinical response (> or =15-point decrease from baseline PCDAI) and remission (PCDAI < or =10) rates were greatest at week 10 (55% and 29%, respectively). Three patients (8%) tested positive for anti-natalizumab antibodies. The peak level (61.0 and 66.3 microg/mL) and half-life (92.3 and 96.3 h) of natalizumab were comparable after the first and third infusions. Mean [alpha]4 integrin receptor saturation was 93% at 2 hours and <40% at 4 weeks after the first and third infusions. Increase from baseline in circulating lymphocytes ranged from 106% to 122% at 2 weeks and 45% to 65% at 4 weeks after each infusion. CONCLUSION: Natalizumab (3 mg/kg) was well tolerated in these adolescent patients with active CD, with a safety and efficacy profile similar to that of adult natalizumab-treated CD patients. Future studies should evaluate long-term safety and efficacy.
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Anticuerpos Monoclonales/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Adolescente , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados , Niño , Enfermedad de Crohn/inmunología , Femenino , Humanos , Inmunosupresores/inmunología , Inmunosupresores/farmacología , Integrina alfa4/inmunología , Masculino , Natalizumab , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. METHODS: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. RESULTS: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. CONCLUSIONS: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.
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Diarrea/etiología , Predisposición Genética a la Enfermedad , Enfermedades Inflamatorias del Intestino/genética , Edad de Inicio , Niño , Preescolar , Enfermedad Crónica , Femenino , Estudio de Asociación del Genoma Completo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Secuenciación del ExomaRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) is becoming more common in children. While treatment options remain limited the appropriate organisation and delivery of services are an integral part of good care. METHODS: All eligible UK paediatric sites were invited to submit data for organisation of paediatric IBD services as of 1 September 2010. Comparison, when relevant, was made with the previous paediatric audit (2008) and the concurrently running adult audit. RESULTS: 24/25 (96%) of sites submitted data. The median number of patients managed and the median number of new IBD (ulcerative colitis and Crohn's disease only) cases per annum was 178 (IQR 136-281) and 32 (IQR 23-50), respectively. There was an increase in the IBD workforce including whole-time equivalent (WTE) IBD nurses (1.0 vs 1.5 WTE nurses, p=0.02). 1023 patients 16â years and younger were looked after in the 202 adult sites who submitted data; only 78/202 sites indicated they cared for 16-year-old and younger children; approximately half of these 78 sites had age-appropriate support facilities. Most paediatric sites have access to urgent endoscopy (83%), telephone advice (100%) and urgent clinic appointments (91%). Most sites did not have: shared care pathways with primary care (74%), annual reviews (71%), real time patient management systems (83%) and research network trial participation (78%). CONCLUSIONS: Many aspects of paediatric IBD care in the UK are good and have shown significant improvement over recent years. There are areas in need of further change and specific regional and national action plans should address identified deficiencies before any future audit of paediatric and adult IBD services.
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BACKGROUND: Pediatric ulcerative colitis (UC) care is variable with a lack of appropriate guidelines to guide practice until recently. METHODS: UC inpatients <17 years old admitted to 23 U.K. pediatric hospitals had clinical details collected between September 2010 and 2011. Comparative data for 248 patients were available from a previous audit in 2008. RESULTS: One hundred and seventy-six patients (98 males) of median age 13 years (interquartile range, 10-13) were analyzed; 23 were elective surgical admissions, 47 new diagnoses, and 106 needed acute medical care for established UC. Median length of stay was 6 days (interquartile range, 3-10) with no deaths. Eighty-eight of 126 patients (70%) with active disease had standard stool cultures performed (3 [2%] were positive), and 57 (45%) had Clostridium difficile toxin tested (none positive). Twenty-five of 66 (38%) emergency admissions had an abdominal x-ray on admission, and 13 of 66 patients (20%) had a Pediatric Ulcerative Colitis Activity Index score. There were 3 cases of toxic megacolon and 2 thromboses. Eighty-one of 116 patients (71%) responded to steroids. Nineteen patients who did not respond adequately to steroids received rescue therapy (7 infliximab, 11 ciclosporin, and 1 both) with overall response rate of 90%; 7 patients needed surgery acutely, 5 without previous rescue therapy. Compared with the 2008 data, stool culture rates improved significantly (86 of 121 [71%] versus 76 of 147 [52%], P = 0.001) as did heparinization rates (15 of 150 [10%] versus 5 of 215 [2%], P = 0.002) and rescue therapy usage (17 of 33 [52%] versus 10 of 38 [26%], P = 0.03). CONCLUSIONS: There were signs of improving UC care with significantly increased rates of stool culture and rescue therapy. The majority of sites, however, did not use Pediatric Ulcerative Colitis Activity Index scores.
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Colitis Ulcerosa/mortalidad , Colitis Ulcerosa/terapia , Heces/microbiología , Pacientes Internos/estadística & datos numéricos , Adolescente , Técnicas de Cultivo de Célula , Niño , Colitis Ulcerosa/diagnóstico , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Tiempo de Internación , Masculino , Tasa de Supervivencia , Resultado del Tratamiento , Reino UnidoRESUMEN
Inflammatory bowel disease (IBD) in children can cause significant impairment in linear growth, and delay in pubertal onset. The aim of this study was to assess the impact of surgery on linear growth in children with Crohn's disease (CD) who were resistant to medical therapy, and had documented evidence of growth impairment. We performed a retrospective study on eight consecutive patients with refractory disease who had attended the paediatric IBD clinic. All patients underwent surgery as part of their treatment. Height and weight were recorded at least 6 months prior to surgery, at the time of surgery, and 6 months post surgery. Growth velocities and height Z-scores were calculated. All patients had evidence of sustained growth suppression prior to surgery. Three patients had evidence of growth failure. There was a significant increase in height velocity from 0.15 cm/month before surgery to 0.54 cm/month after surgery (P = 0.006). There was also a significant decrease in the modified Harvey-Bradshaw index (HBI) of disease activity from 2.00 before surgery, to 0.84 after surgery (P = 0.003). Improvements in height Z-score and weight velocity after surgery were not significant on statistical analysis. Our study demonstrates that before surgery, children with CD refractory to therapy have sustained growth suppression, and in some cases may even have growth failure. Surgical intervention before puberty appears to result in a significant improvement in height velocity and disease activity. These findings need to be further investigated with carefully designed prospective studies.