Anti-tumor necrosis factor therapy in Bulgarian pediatric patients with inflammatory bowel disease - an 8-year experience of a referral center.

INTRODUCTION: Anti-tumor necrosis factor (anti-TNF) therapy has become a mainstay in the treatment of patients with inflammatory bowel disease over the past few decades.

Risk Factors for Surgery in Pediatric Patients with Crohn's Disease.

OBJECTIVE: Pediatric Crohn's disease (CD) has a more aggressive phenotype and course than in adults. Many patients develop complications that require surgery. The aim of this study was to identify the factors associated with increased risk for surgical intervention in pediatric patients with CD. SUBJECTS AND METHODS: This study is a retrospective review of medical records. We analyzed the following variables: sex, age at diagnosis, presenting symptoms, duration of symptoms before diagnosis, disease location and severity, the presence of extraintestinal manifestations, and the presence of anti-Saccharomyces cerevisiae antibodies. Univariate analysis using the Mann-Whitney test and Fisher's exact test was performed to detect the factors associated with surgery. Potential risk factors with p < 0.05 were further analyzed using a multivariate binary logistic regression model. RESULTS: Fifty-seven patients (27 girls and 30 boys) were included in the analysis. More than one-fourth of them (28.1%) required surgical management. Female sex (p = 0.043), disease behavior (p = 0.012), and the presence of perianal disease at diagnosis (p < 0.001) were the variables associated with surgical intervention. Stricturing disease (B2) (odds ratio [OR], 24.944; p = 0.016), stricturing and penetrating disease (B2B3) (OR, 28.276; p = 0.011), and the presence of perianal disease at diagnosis (OR, 95.802; p = 0.001) were independent risk factors for surgery. Female sex was associated with surgery without being an independent risk factor. CONCLUSION: Females with B2 or B2B3 or the presence of perianal disease at diagnosis are at a higher risk for surgery and should be considered for more aggressive medical treatments.

Surrogate Markers of Intestinal Inflammation in Paediatric Patients with Inflammatory Bowel Disease.

BACKGROUND: Endoscopic evaluation is the gold standard for monitoring the disease activity in inflammatory bowel disease (IBD) but the procedure is invasive and not appropriate for frequent use, especially in the paediatric population. The aim of the present study was to assess the correlation between the levels of several inflammatory biomarkers and the degree of intestinal inflammation in paediatric patients with IBD. MATERIALS AND METHODS: A single center study including 31 children with ulcerative colitis (UC) and 22 children with Crohn's disease (CD) with different disease duration and activity. All participants provided blood samples to measure the levels of white blood cell count, platelets, C-reactive protein, erythrocyte sedimentation rate, albumin and fibrinogen, and faecal samples for measurement of faecal calprotectin and faecal alpha-1 antitrypsin. All participants underwent endoscopic evaluation. Endoscopic disease activity was assessed according to the Mayo Endoscopic Subscore and Simple Endoscopic Score for Crohn's Disease in UC and CD patients, respectively. RESULTS: 135 visits were included: 73 for UC patients and 62 for CD patients. In UC patients the strongest correlation was between the Mayo Endoscopic Subscore and the faecal calprotectin (r=0.867, p<0.001) followed by the albumin (r=0.523, p<0.001) and the C-reactive protein (r=0.487, p<0.001). In CD the strongest correlation was between the Simple Endoscopic Score for Crohn's disease and the faecal calprotectin (r=0.872, p<0.001) followed by the C-reactive protein (0.708, p<0.001) and the erythrocyte sedimentation rate (0.605, p<0.001). CONCLUSIONS: The faecal calprotectin is a valuable surrogate marker of intestinal inflammation that is useful for monitoring of a disease activity in paediatric patients with IBD.

Role of faecal calprotectin as a predictor of endoscopic activity in paediatric patients with ulcerative colitis / Papel de la calprotectina fecal como predictor de la actividad endoscópica en pacientes pediátricos con colitis ulcerosa

Introduction: Colonoscopy is currently considered to be the gold standard for evaluation of colonic mucosa inflammation in patients with ulcerative colitis (UC), but the procedure is invasive and cannot be repeated frequently, especially in the paediatric population. The aim of this study was to assess the role of faecal calprotectin (FC) as a predictor of endoscopic disease activity in paediatric patients with UC in clinical remission. Material and methods: Single-centre prospective study. Clinical remission was defined as Paediatric Ulcerative Colitis Activity Index <10. Endoscopic findings were assessed according to the Mayo Endoscopic Subscore (MES). MES≤1 was defined as endoscopic remission. All participants provided fresh faecal samples for measurement of FC. Results: A total of 34 visits of 24 children with UC were included in the study. There was a strong positive correlation between FC levels and endoscopic disease activity (n=34, r=0.83, p<0.001). The median FC levels in the subgroup with endoscopic activity (MES 2-3) were significantly higher than the median FC levels in the subgroup without endoscopic activity (MES≤1) (1000μg/g, IQR 575-1800μg/g vs. 100μg/g, IQR 80-223μg/g, p<0.001). At a cut-off of 298.5μg/g, FC had 92.3% sensitivity, 95.2% specificity and an AUROC 0.974 (SE 0.023, 95% CI 0.93-1, p<0.001) to predict endoscopic activity. Discussion: FC is an accurate surrogate marker of endoscopic activity in children with clinically quiescent UC

Introducción: Actualmente, la colonoscopia es considerada como el gold standard para la evaluación de la inflamación de la mucosa colónica en pacientes con colitis ulcerosa (CU), pero este procedimiento es invasivo y no se puede repetir frecuentemente, especialmente en la población pediátrica. El objetivo de este estudio es evaluar el papel de la calprotectina fecal (CF) como predictor de la actividad endoscópica de la enfermedad en pacientes pediátricos con CU en remisión clínica. Material y métodos: Estudio prospectivo monocéntrico. La remisión clínica se definió según el Índice de Actividad Pediátrico de Colitis Ulcerosa (Paediatric Ulcerative Colitis Activity Index) <10. Los hallazgos endoscópicos fueron evaluados según el Subscore Endoscópico de Mayo (SEM). SEM≤1 se definió como remisión endoscópica. En todos los participantes se obtuvo una muestra de heces para medición de la CF. Resultados: Un total de 34 visitas de 24 niños con CU se incluyeron en el estudio. Hubo una fuerte correlación positiva entre la CF y la actividad endoscópica de la enfermedad (n=34, r=0,83, p <0,001). La mediana de los niveles de CF en el subgrupo con actividad endoscópica (SEM 2-3) fue significativamente superior a la mediana de los niveles de CF en el subgrupo sin actividad endoscópica (MES≤1) (1.000 μg/g, IQR 575 μg/g-1.800 μg/g vs. 100 μg/g; IQR 80 μg/g-223 μg/g; p <0,001). Al nivel de corte de 298,5 μg/g la CF obtuvo una sensibilidad del 92,3%, una especificidad del 95,2% y un área bajo la curva de 0,974 (SE 0,023; IC del 95%, 0,93-1; p <0,001) para predecir actividad endoscópica. Discusión: La CF es un marcador indirecto preciso para actividad endoscópica en niños con CU clínicamente quiescente

Role of faecal calprotectin as a predictor of endoscopic activity in paediatric patients with ulcerative colitis.

INTRODUCTION: Colonoscopy is currently considered to be the gold standard for evaluation of colonic mucosa inflammation in patients with ulcerative colitis (UC), but the procedure is invasive and cannot be repeated frequently, especially in the paediatric population. The aim of this study was to assess the role of faecal calprotectin (FC) as a predictor of endoscopic disease activity in paediatric patients with UC in clinical remission. MATERIAL AND METHODS: Single-centre prospective study. Clinical remission was defined as Paediatric Ulcerative Colitis Activity Index <10. Endoscopic findings were assessed according to the Mayo Endoscopic Subscore (MES). MES≤1 was defined as endoscopic remission. All participants provided fresh faecal samples for measurement of FC. RESULTS: A total of 34 visits of 24 children with UC were included in the study. There was a strong positive correlation between FC levels and endoscopic disease activity (n=34, r=0.83, p<0.001). The median FC levels in the subgroup with endoscopic activity (MES 2-3) were significantly higher than the median FC levels in the subgroup without endoscopic activity (MES≤1) (1000µg/g, IQR 575-1800µg/g vs. 100µg/g, IQR 80-223µg/g, p<0.001). At a cut-off of 298.5µg/g, FC had 92.3% sensitivity, 95.2% specificity and an AUROC 0.974 (SE 0.023, 95% CI 0.93-1, p<0.001) to predict endoscopic activity. DISCUSSION: FC is an accurate surrogate marker of endoscopic activity in children with clinically quiescent UC.

Detecting inflammation in inflammatory bowel disease - how does ultrasound compare to magnetic resonance enterography using standardised scoring systems?

BACKGROUND: Magnetic resonance enterography (MRE) is the current gold standard for imaging in inflammatory bowel disease, but ultrasound (US) is a potential alternative. OBJECTIVE: To determine whether US is as good as MRE for the detecting inflamed bowel, using a combined consensus score as the reference standard. MATERIALS AND METHODS: We conducted a retrospective cohort study in children and adolescents <18 years with inflammatory bowel disease (IBD) at a tertiary and quaternary centre. We included children who underwent MRE and US within 4 weeks. We scored MRE using the London score and US using a score adapted from the METRIC (MR Enterography or Ultrasound in Crohn's Disease) trial. Four gastroenterologists assessed an independent clinical consensus score. A combined consensus score using the imaging and clinical scores was agreed upon and used as the reference standard to compare MRE with US. RESULTS: We included 53 children. At a whole-patient level, MRE scores were 2% higher than US scores. We used Lin coefficient to assess inter-observer variability. The repeatability of MRE scores was poor (Lin 0.6). Agreement for US scoring was substantial (Lin 0.95). There was a significant positive correlation between MRE and clinical consensus scores (Spearman's rho = 0.598, P=0.0053) and US and clinical consensus scores (Spearman's rho = 0.657, P=0.0016). CONCLUSION: US detects as much clinically significant bowel disease as MRE. It is possible that MRE overestimates the presence of disease when using a scoring system. This study demonstrates the feasibility of using a clinical consensus reference standard in paediatric IBD imaging studies.

Proteomics reveals that redox regulation is disrupted in patients with ethylmalonic encephalopathy.

Deficiency of the sulfide metabolizing protein ETHE1 is the cause of ethylmalonic encephalopathy (EE), an inherited and severe metabolic disorder. To study the molecular effects of EE, we performed a proteomics study on mitochondria from cultured patient fibroblast cells. Samples from six patients were analyzed and revealed seven differentially regulated proteins compared with healthy controls. Two proteins involved in pathways of detoxification and oxidative/reductive stress were underrepresented in EE patient samples: mitochondrial superoxide dismutase (SOD2) and aldehyde dehydrogenase X (ALDH1B). Sulfide:quinone oxidoreductase (SQRDL), which takes part in the same sulfide pathway as ETHE1, was also underrepresented in EE patients. The other differentially regulated proteins were apoptosis inducing factor (AIFM1), lactate dehydrogenase (LDHB), chloride intracellular channel (CLIC4) and dimethylarginine dimethylaminohydrolase 1 (DDAH1). These proteins have been reported to be involved in encephalopathy, energy metabolism, ion transport, and nitric oxide regulation, respectively. Interestingly, oxidoreductase activity was overrepresented among the regulated proteins indicating that redox perturbation plays an important role in the molecular mechanism of EE. This observation may explain the wide range of symptoms associated with the disease, and highlights the potency of the novel gaseous mediator sulfide.