Disease Activity In Pediatric Patients Research Articles

Assay for interferon gamma release as a novel marker in pediatric patients with systemic lupus erythematosus

BackgroundThe interferon-gamma (IFN-γ) release assay (IGRA) is an important laboratory diagnosis for latent Mycobacterium tuberculosis (TB) infection. The TB-IGRA measures the release of IFN-γ from peripheral blood cells, who are exposed to TB antigen (Ag), mitogen (MT), or negative/nil control (NL) in vitro. While, an exceptional higher TB Ag-NL level will reflect an elevation of peripheral lymphocytes released IFN-γ in a same condition. Therefore, we found that the elevated levels of TB Ag-NL could become a new biomarker for the diagnosis and treatment of pediatric systemic lupus erythematosus (SLE) patients.MethodsWe have analyzed the clinical data of 776 children who are underwent TB-IGRA testing in the Department of Allergy and Rheumatology of Guangzhou Women and Children’s Medical Center from 2018 to 2020. To investigate the association between TB Ag-NL and SLE, we have analyzed the clinical data of 47 SLE patients and TB Ag-NL testing results, and then evaluated the association between TB Ag-NL and SLE disease activity.ResultsThe TB Ag-NL levels were significantly higher in patients with active SLE than those in inactive SLE (p = 0.0002). The TB Ag-NL levels were positively correlated with the SLE disease activity index (SLEDAI) and laboratory diagnosis parameters. The mean value of TB Ag-NL in SLE patients (0.04191 ± 0.07955, IU/mL) were significantly higher than those in patients with juvenile dermatomyositis (JDM) (0.0158 ± 0.0337, IU/mL, p = 0.036), juvenile idiopathic arthritis (JIA) (0.0162 ± 0.0388, IU/mL, p = 0.001), and healthy controls (HC) (0.0001 ± 0.0027, IU/mL, p = 0.0003). Therefore, the elevated TB Ag-NL levels could serve as a potential diagnostic biomarker of SLE, especially for the active SLE.ConclusionThe detection of IFN-γ release levels by the TB-IGRA may be useful to assess SLE disease activity in pediatric patients with active SLE.

Evaluation of bowel wall flow by color Doppler ultrasound in the assessment of inflammatory bowel disease activity in pediatric patients

Resumo Objetivo: Avaliar a atividade da doença inflamatória intestinal (DII) por ultrassonografia (US) com Doppler em cores, comparada à concentração de calprotectina fecal (CF) em pacientes pediátricos. Materiais e Métodos: Em uma série consecutiva, no período entre 2014 e 2020, foram avaliados 53 exames de 44 pacientes pediátricos: 28 casos de doença de Crohn, 15 de colite ulcerativa e um de colite indeterminada. O diagnóstico da DII foi feito pelos critérios de Porto. O fluxo parietal foi a alteração estudada mais detalhadamente e classificada pelo pesquisador principal e por dois radiologistas pediátricos cegados aos valores de CF e de US Doppler. Baixo fluxo parietal foi definido pela captação de até 2 sinais de US Doppler/cm2, fluxo moderado entre 3 e 5 sinais/cm2 e alto fluxo mais de 5 sinais/cm2. Resultados: Houve concordância substancial entre os radiologistas (kappa = 0,73). Nos exames com baixo fluxo parietal a CF média foi 92 μg/g (intervalo interquartil: 33-661 μg/g) e nos exames com alto fluxo a CF média foi 2.286 μg/g (intervalo interquartil: 1.728-5.612 μg/g). Na amostra total, a US demonstrou sensibilidade de 89,7% e especificidade de 92,0% para detecção da atividade inflamatória, 95,5% e 90,9% na doença de Crohn e 81,3% e 100,0% na colite ulcerativa, respectivamente. Conclusão: Houve forte correlação entre a US da parede intestinal e os valores da concentração de CF na avaliação da atividade inflamatória na DII de pacientes pediátricos.

Evaluation of bowel wall flow by color Doppler ultrasound in the assessment of inflammatory bowel disease activity in pediatric patients.

To assess inflammatory bowel disease (IBD) activity with Doppler ultrasound in pediatric patients, comparing the accuracy of the ultrasound findings with that of the concentrations of fecal calprotectin (FC). In a consecutive series, we evaluated 53 examinations of 44 pediatric patients seen between 2014 and 2020: 28 with Crohn's disease, 15 with ulcerative colitis, and one with IBD unclassified. The diagnosis of IBD was made in accordance with the Porto criteria. The alteration studied in the greatest detail was bowel wall flow, which was classified by the lead investigator and two pediatric radiologists, all of whom were blinded to the FC concentrations and the other ultrasound findings. Bowel wall flow was categorized as low if there were up to 2 Doppler ultrasound signals/cm2, moderate if there were 3-5 signals/cm2, and high if there were more than 5 signals/cm2. The agreement among the radiologists was substantial (kappa = 0.73). In cases in which ultrasound showed low bowel wall flow, the median FC concentration was 92 µg/g (interquartile range, 33-661 µg/g), whereas it was 2,286 µg/g (interquartile range, 1,728-5,612 µg/g) in those in which ultrasound showed high bowel wall flow. In the sample as a whole, the sensitivity and specificity of ultrasound was 89.7% and 92.0%, respectively, for the detection of inflammatory activity; 95.5% and 90.9%, respectively, for the detection of Crohn's disease; and 81.3% and 100.0%, respectively, for the detection of ulcerative colitis. Ultrasound of the bowel wall showed a strong correlation with FC concentrations in the assessment of inflammatory activity in pediatric patients with IBD.

Echographic characterization of extraocular muscles in pediatric patients with thyroid dysfunction

ABSTRACT Purpose To characterize the size of extraocular muscles (EOMs) in a pediatric population with thyroid dysfunction using orbital echography. Methods Patients under age 18 with thyroid dysfunction who presented to an academic ophthalmology department from 2009 to 2020 and received orbital echography were included in this IRB-approved retrospective study. Data collected included age, clinical activity score (CAS), thyroid stimulating immunoglobulin (TSI), and extraocular recti muscle thickness on echography. Patients were organized into three age cohorts, after which statistical analysis compared recti measurements to previously reported normal ranges. Results Twenty patients with thyroid dysfunction were included. When comparing average recti muscle thicknesses of study patients to those of previously published normal children in similar age ranges, the levator-superior rectus complex was significantly increased in all age groups of children with thyroid dysfunction (p-values = <.004), and the levator-superior rectus complex was most frequently enlarged compared to published normal values (78% of eyes). CAS was not correlated with EOM size in the youngest group (5–10 years old, p-values >.315) but was significantly correlated in older groups (11–17 years old, p-values <.027). TSI was not correlated with EOM size in any group (p-values >.206). Conclusions Echographic reference ranges for EOMs in children with thyroid dysfunction were established. There are increased rates of levator-superior rectus complex enlargement in children with TED compared to adults with TED, and EOM size is correlated with CAS in children older than 10 years. Though limited, these findings may serve as an additional tool for ophthalmologists to ascertain disease activity in pediatric patients with thyroid dysfunction.

A14 TRANSABDOMINAL BOWEL ULTRASOUND AND CLINICAL OUTCOMES OVER ONE YEAR IN CHILDREN WITH NEWLY DIAGNOSED CROHN’S DISEASE

Abstract Background Transabdominal bowel ultrasound (TABUS) is an emerging non-invasive tool for monitoring inflammatory bowel disease (IBD). Its use is particularly increasing in pediatric IBD, given the need for anesthesia during endoscopy. The assessment of TABUS in pediatric IBD has been limited to small numbers of patients with no long-term follow-up. Purpose To describe TABUS findings and its relationship with clinical, biochemical, and endoscopic assessments in pediatric patients with Crohn’s disease up to one year post-diagnosis. Method Patients (0-18 years) with suspected IBD were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Those with Crohn’s disease were included. Patients underwent repeated TABUS, clinical assessments, blood work, fecal calprotectin (FCP) (baseline, 1-, 3-, 6-, 12-months), and endoscopy (baseline and 6-12 months). The weighted Pediatric Crohn’s Disease Activity Index (wPCDAI), Simple Endoscopic Score for Crohn’s Disease (SES-CD; rectum excluded), and Simple Ultrasound Activity Score for Crohn’s Disease (SUS-CD; rectum excluded) were used. Remission was defined as FCP&amp;lt;250mg/kg, CRP&amp;lt;4mg/L, wPCDAI&amp;lt;12, no upcoming surgery, and SES-CD score ≤2 for any bowel segment. Result(s) Fifty-six patients (68% male), median age 12.5 years (range 6-17), were followed for 6 months. Forty (71%) were followed up to 12 months. Median TABUS bowel wall thickness (BWT) and SUS-CD total scores improved in all bowel segments over time. SUS-CD total scores significantly correlated with SES-CD (baseline, 6-, 12-months), wPCDAI (baseline, 1-, 6-, 12-months), CRP (baseline, 1-, 3-, 6-months), ESR (baseline, 1-, 3-, 6-, 12-months), and FCP (baseline, 1-, 6-, 12-months) (rho ranged 0.302-0.732, p&amp;lt;0.05). Patients in remission had sustained significantly thinner BWT of their most affected bowel segment (Figure 1) starting at 1-month (median 3.1mm (IQR 2.7-3.7) vs. 4.1mm (IQR 2.9-5.6; p&amp;lt;0.05), and sustained significantly lower SUS-CD total scores starting at 6 months (median 0 (IQR 0-1) vs. median 2 (IQR 1-3); p&amp;lt;0.05). Seven patients had surgery (n=7/7 ileocecal, n=2/7 jejunal resection). All 7 patients had complex TI disease (n=6 strictures, n=1 long-segment disease &amp;gt;25cm) and proximal small bowel disease (n=2/2) on TABUS. Those with baseline ultrasound findings of a stricture with upstream bowel dilatation (n=7/56) had increased odds (OR=288, p&amp;lt;0.01) and relative risk (RR=42, p&amp;lt;0.01) of needing surgery (n=6/7 with baseline obstructive findings, n=1/49 without) within the first year. Image Conclusion(s) TABUS had significant correlations with clinical, biochemical, and endoscopic markers of Crohn’s disease activity in pediatric patients over one year. Bowel wall thickness of the most affected bowel segment is a helpful measurement, becoming significantly thinner as soon as 1-month post-diagnosis in those who obtain remission. Baseline findings of bowel narrowing and upstream dilation increase the odds and relative risk of needing surgery in the first year. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

P099 Serum proteomic analysis reveals novel biomarkers associated with disease activity in pediatric patients with Crohn’s disease

Abstract Background Although Crohn’s disease (CD) is associated with a marked hyper-inflammatory response, identifying serum biomarkers associated with disease activity and outcomes is considered challenging, given lack of sensitivity of different assays. Our aim was to identify novel markers using Olink, a novel technology based on proximity extension assay, enabling detection of minute amounts of proteins. Methods Serum samples were obtained from pediatric patients with CD at the time of diagnosis and following induction therapy, and from control subjects, consisting of pediatric patients with normal endoscopic procedures, without past or present history of an immune-mediated disorder (e.g. celiac, diabetes). Serums were subjected to Olink (two panels used, consisting of 184 proteins), and analysis was performed on a Normalized Protein eXpression file by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Benjamini-Hochberg and post-hoc Tukey analysis. Results Eighty-eight serum samples were collected: 30 from control subjects and 58 from 32 patients with CD (24 of them pre- and post-induction therapy). The median age of patients in the control and CD groups was 13.9 years (IQR 11.1–16.6) and 14.6 years (IQR 12.2–16.9), respectively (P=0.32). Twenty-four patients were treated with anti-TNFa agents and 8 with EEN. The median pediatric Crohn’s Disease Activity Index (PCDAI) decreased from 35 (22.5–42.5) to 5 (0–12.5, P&amp;lt;0.001) following induction therapy. We identified 72 proteins that significantly differed between patients and controls, and many of them were associated with CRP or ESR levels. String analysis identified several important nodes linking different proteins, including MMPs, MPO, EGFR and TNFRSF1A. Many proteins, such as resistin and different MMPs, showed a strong positive correlation with disease activity, based on PCDAI, while others, such as EGFR, showed a negative correlation. Several novel markers were identified to be highly expressed in the serum of patients with CD, including LRIG1, an intestinal stem cell marker, that was highly correlated with disease activity among the patients. Conclusion We identified novel serum markers that are associated with disease activity in pediatric patients with CD. These findings should be validated in future studies, and be complemented with expression and functional studies to define their role in mediating intestinal immune responses.

Serum levels of soluble HLA-G correlate with disease activity in pediatric patients with Crohn's disease.

Background:Human leukocyte antigen (HLA)-G, a member of the HLA family, is crucial for fetomaternal tolerance. Transmembrane or circulating/soluble HLA-G (sHLA-G) is elevated in autoimmune conditions and the tumor microenvironment. Circulating sHLA-G levels and their association with disease activity have not yet been assessed in pediatric patients with inflammatory bowel disease (IBD). This study aimed to quantify the serum sHLA-G levels of pediatric patients with IBD and assess the association of serum sHLA-G with disease activity.Methods:We enrolled 24 pediatric IBD patients Crohn's disease (CD) and ulcerative colitis (UC), n = 12 each] and 24 healthy controls. Based on the disease activity index, five and seven of the CD patients had mild and moderate/severe disease, respectively, whereas six of the UC patients were in remission and six had mild disease. Serum was collected and sHLA-G levels were determined by enzyme-linked immunosorbent assay (ELISA).Results:Pediatric patients with CD had significantly higher sHLA-G levels compared with patients with UC and healthy controls. Notably, serum sHLA-G levels were significantly higher in patients with moderate/severe CD than in those with mild CD.Conclusions:Serum sHLA-G levels correlate with disease activity in pediatric patients with CD and are higher in CD patients than in UC patients. Thus, sHLA-G is a potential biomarker for disease activity in CD.

P011 Serum adhesion G protein coupled receptor levels are associated with disease activity in pediatric patients with Crohn’s disease

Abstract Background Despite increasing number of therapies available for patients with Crohn’s disease (CD), response rates are generally not high. Therefore, there is a great need to identify novel targets in patients with active disease. Methods Serum samples were obtained from pediatric patients with CD at the time of diagnosis and following induction therapy with exclusive enteral nutrition (EEN) or anti-TNFa therapy, and from control subjects, defined as having normal colonoscopy without past or present history of inflammatory bowel diseases or other immune-mediated disorder. Associated clinical and laboratory data from these subjects was also collected. Serums were subjected to Olink technology (metabolism panel), based on proximity extension assay, enabling analysis of 92 proteins in each sample. Analysis was performed on a Normalized Protein eXpression (NPX) file comparing effect of different factors on the overall biomarker expression by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Benjamini-Hochberg and post-hoc Tukey analysis. Results Eighty-eight serum samples were collected: 30 from control subjects and 58 from 32 patients with CD. The median age of patients in the control and CD groups was 13.9 years (IQR 11.1–16.6) and 14.6 years (IQR 12.2–16.9), respectively (P=0.32). Twenty-four patients were treated with anti-TNFa agents and 8 with EEN. The median pediatric Crohn’s Disease Activity Index decreased from 35 (22.5–42.5) to 5 (0–12.5, P&amp;lt;0.001) following induction therapy. We identified 34 proteins that significantly differed between patients and controls. Moreover, within patients with CD, 8/34 of these proteins were differentially expressed in patients with active or non-active disease. Among these, adhesion G-protein coupled receptors E2 (ADGRE2) and G2 (ADGRG2), important for macrophage differentiation, were significantly lower among CD patients vs. controls. When stratifying according to disease activity, low levels of both markers were identified in CD patients with active disease (either patients that were treatment-naïve or those with primary non-response to anti-TNFa therapy) or with increased CRP levels. Principal component analysis showed that a combination of ADGRE2 and ADGRG2 showed good separation between control subjects and treatment naïve patients with active CD. Conclusion Serum levels of ADGRE2 and ADGRG2 are differentially regulated in patients with active CD, and should further be validated in additional Cohorts. The expression patterns and function of these receptors on different immune cells should be defined in future studies.

Is It Useful to Monitor Thiopurine Metabolites in Pediatric Patients with Crohn's Disease on Combination Therapy? A Multicenter Prospective Observational Study.

The additional value of azathioprine concomitant treatment on infliximab pharmacokinetics in children is not well described yet. In the present study, we aimed to describe the relationship between thiopurine metabolite levels, infliximab trough levels, anti-IFX antibody formation, and clinical and laboratory markers of disease activity in pediatric patients with Crohn's disease, and to assess non-adherence. Data were collected prospectively during repeated visits from pediatric patients followed for Crohn's disease in two Czech pediatric inflammatory bowel disease centers between January 2016 and June 2017. Thiopurine metabolites (6-thioguanine and 6-methylmercaptopurine) were measured by high-performance liquid chromatography. Infliximab trough levels and anti-IFX antibody serum levels were measured routinely by ELISA. The risk of loss of response to infliximab therapy was also assessed. A significant association between infliximab serum levels and 6-thioguanine erythrocyte levels was observed when tested as categorical variables (63 patients, 321 observations). To predict infliximab levels >5µg/mL, we propose a 6-thioguanine cutoff of 278pmol/8 × 108 erythrocytes (sensitivity, 0.799; specificity, 0.347). A higher loss-of-response-to-infliximab rate (tested in a subgroup of 51 patients) was observed in patients with undetectable 6-thioguanine levels than in those with detectable levels (p=0.026). Non-adherence to azathioprine therapy was suspected in 20% of patients. Thiopurine metabolite monitoring in pediatric patients with Crohn's disease is useful when optimizing combination therapy. Pediatric patients with undetectable 6-thioguanine levels are more likely to lose response to infliximab therapy. When targeting optimal infliximab levels, the 6-thioguanine cutoff levels in children appear to be higher than in adults.

Laboratory Assessment of Disease Activity in Pediatric Patients with Inflammatory Bowel Disease: What’s New?

Laboratory tests are an integral part of both the diagnostic and follow-up algorithm of patients with inflammatory bowel disease (IBD). Their advantages over other non-invasive methods for assessing disease activity are greater objectivity than clinical activity indices and imaging studies. This review aims to analyze shortly the most common laboratory tests used to assess disease activity in pediatric patients with IBD. In addition to the conventional blood and serum markers that are not specific for gut inflammation, although routinely used, we also reviewed the established fecal markers such as calprotectin, lactoferrin, M2-pyruvate kinase, osteoprotegerin, HMGB1, chitinase 3-like 1, and the promising non-coding microRNA. In conclusion, neither marker is unique to the pediatric IBD. More clinical data are required to assess biomarkers’ full potential for diagnosis, management, and follow-up of pediatric IBD patients.

Serum neurofilament light chain in pediatric MS and other acquired demyelinating syndromes.

To explore the correlation between serum and CSF neurofilament light chain (NfL) and the association of NfL levels and future disease activity in pediatric patients with a first attack of acquired demyelinating syndromes (ADS). In total, 102 children <18 years with a first attack of CNS demyelination and 23 age-matched controls were included. Clinically definite multiple sclerosis (CDMS) was set as an endpoint for analysis. CSF NfL was tested by the commercially available ELISA (UmanDiagnostics); serum NfL (sNfL) was tested with a Simoa assay. Hazard ratios (HR) were calculated with Cox regression analysis. Of the 102 patients, 47 (46%) were tested for CSF NfL. CSF and serum NfL correlated significantly in the total group (ρ 0.532, p < 0.001) and even more significantly in the subgroup of patients with future CDMS diagnosis (ρ 0.773, p < 0.001). sNfL was higher in patients than in controls (geometric mean 6.1 pg/mL, p < 0.001), and was highest in ADS presenting with encephalopathy (acute disseminated encephalomyelitis, n = 28, 100.4 pg/mL), followed by patients without encephalopathy (ADS-) with future CDMS diagnosis (n = 40, 32.5 pg/mL), and ADS- who remained monophasic (n = 34, 17.6 pg/mL). sNfL levels higher than a median of 26.7 pg/mL at baseline are associated with a shorter time to CDMS diagnosis in ADS- (p = 0.045). HR for CDMS diagnosis was 1.09 for each 10 pg/mL increase of sNfL, after correction for age, oligoclonal bands, and MRI measures (p = 0.012). The significant correlation between CSF and serum NfL strengthens its reliability as a peripheral marker of neuroaxonal damage. Higher sNfL levels at baseline were associated with higher probability of future CDMS diagnosis in ADS-.

The Relationship Between Sleep Disturbance and Disease Activity in Pediatric Patients With Inflammatory Bowel Disease.

The aim of this prospective cross sectional study was to assess the prevalence of sleep disturbance in children with inflammatory bowel disease (IBD), including the relationships between sleep, inflammatory markers, and disease activity of pediatric patients with IBD. Pediatric patients with IBD and parents were enrolled in the study. Patients completed the Pittsburgh Sleep Quality Index (PSQI), the Pediatric Daytime Sleepiness Scale, and the Adolescent Sleep Wake Scale (ASWS) surveys. Parents completed the Child Sleep Habits Questionnaire (CSHQ). Disease activity for Crohn disease (CD) was determined by the Pediatric Crohn Disease Activity Index and the Pediatric Ulcerative Colitis Activity Index was used to define disease activity in ulcerative colitis (UC)/indeterminate colitis patients. Fifty-three pediatric patients with IBD (38 CD, 12 UC, and 3 indeterminate colitis) participated in the study. The significant correlations between the CSHQ and Pediatric Crohn Disease Activity Index (P = 0.002) and the PSQI and Pediatric Ulcerative Colitis Activity Index (P = 0.04) were found. Youth with UC and indeterminate colitis significantly reported more sleep disturbance than patients with CD, (P = 0.03, 0.05, and 0.04; PSQI, Pediatric Daytime Sleepiness Scale, ASWS, respectively). Patients self-reported significantly more sleep disturbance than was observed by parents (P < 0.0001). This study showed the significant correlations between CSHQ score compared to erythrocyte sedimentation rate and albumin (P = 0.001 and 0.03, respectively). Results suggest that increased disease activity is associated with adverse effects on sleep quality. Based on the results of this study, pediatric patients with IBD should be screened for sleep disturbance.

Association of Vitamin D with Inflammatory Bowel Disease Activity in Pediatric Patients.

BackgroundIt has been known that vitamin D level (serum 25[OH]D) has correlation with inflammatory bowel disease (IBD). The purpose of this study is to investigate changes of serum 25[OH]D in pediatric IBD patients according to the disease activity.MethodsA total of 96 children and adolescent with IBD were enrolled in this retrospective study. Serologic inflammatory markers and clinical disease activity scores of the patients were collected, and their correlations with serum 25[OH]D were analyzed. Seasonal variations of serum 25[OH]D were also investigated both in active disease state and remission state.ResultsOf the 96 patients, 41 (43%) were women and patients with a vitamin D deficiency (< 20 ng/mL) at diagnosis were 77 (80.2%). There was no significant difference between Crohn's disease and ulcerative colitis for serum 25[OH]D. Serum 25[OH]D was higher in remission group than in active disease group (12.4 [8.8–29] ng/mL vs. 17.9 [12.3–34.4] ng/mL; P < 0.001) and the difference was more significant than other micronutrients. There was no significant difference in serum 25[OH]D concentration between patients with ileal involvement and patients without ileal involvement. There were seasonal variations in the active phase, but there was no significant difference by season in the remission phase.ConclusionSerum 25[OH]D is inversely correlated with disease activity in IBD. Monitoring and supplementation is required especially for active disease status and in winter and spring season.

Free and Bioavailable 25-Hydroxyvitamin D Concentrations are Associated With Disease Activity in Pediatric Patients With Newly Diagnosed Treatment Naïve Ulcerative Colitis.

Vitamin D regulates intestinal epithelial and immune functions, and vitamin D receptor deficiency increases the severity of murine colitis. Bioavailable 25-hydroxyvitamin D (25(OH)D) is available to target tissues and may be a driver of immune function. The aim is to evaluate the relationship of bioavailable 25(OH)D to the clinical expression of treatment naive pediatric ulcerative colitis (UC). The PROTECT (Predicting Response to Standardized Pediatric Colitis Therapy) study enrolled children ≤17 years newly diagnosed with UC. Free and total 25(OH)D were directly measured and 25(OH)D fractions were compared with disease activity measures. Data were available on 388 subjects, mean age 12.7 years, 49% female, 84% with extensive/pancolitis. The median (IQR) total 25(OH)D concentration was 28.5 (23.9, 34.8) ng/mL, and 57% of subjects demonstrated insufficient vitamin D status (25(OH)D < 30 ng/mL). We found no evidence of association between total 25(OH)D and disease activity. Regression models adjusted for age, sex, race, and ethnicity demonstrated that an increase from 25th to 75th percentile for bioavailable and free 25(OH)D were associated with a mean (95th CI) decrease in the Pediatric Ulcerative Colitis Activity Index (PUCAI) of -8.7 (-13.7, -3.6) and -3.1 (-5.0, -1.2), respectively. No associations were detected between 25(OH)D fractions and fecal calprotectin or Mayo endoscopy score. Vitamin D insufficiency is highly prevalent in children with newly diagnosed UC. We found associations of free and bioavailable, but not total 25(OH)D, with PUCAI. Bioavailable vitamin D may contribute to UC pathophysiology and clinical activity.

Correlations of Plasma Citrulline Levels With Clinical and Endoscopic Score and Blood Markers According to Small Bowel Involvement in Pediatric Crohn Disease

Several studies have indicated that plasma citrulline levels reflect the extent of mucosal injury of the small intestine. This study was performed to determine whether plasma citrulline levels correlate with the disease activity in pediatric patients with Crohn disease (CD). A total of 63 CD and 23 ulcerative colitis (UC) patients were included in this study. Disease severity was assessed by pediatric CD activity index (PCDAI), pediatric UC activity index, simplified endoscopic activity score for CD, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The correlations among these variables and plasma citrulline levels were evaluated. We performed subgroup analysis whether correlations between plasma citrulline levels and disease activity depend on small bowel involvement in patients with CD. The plasma citrulline levels correlated negatively with CRP (r = -0.332, P = 0.008), ESR (r = -0.290, P = 0.022), and PCDAI (r = -0.424, P = 0.001) in patients with CD. The plasma citrulline levels were significantly lower in patients with jejunal involvement than in those without (P = 0.027). In subgroup analysis, patients with CD with jejunal involvement showed significantly negative correlations of plasma citrulline levels with CRP (r = -0.628, P = 0.016) and PCDAI (r = -0.632, P = 0.015); however, patients with CD without jejunal involvement revealed no correlations of plasma citrulline levels with CRP and PCDAI. There were no significant correlations between plasma citrulline levels and simplified endoscopic activity score for CD. There were no significant correlations of plasma citrulline levels with CRP, ESR, and pediatric UC activity index in patients with UC. Plasma citrulline levels correlated with disease severity as measured by PCDAI, CRP, and ESR in pediatric patients with CD with jejunal involvement.

Second generation colon capsule endoscopy versus colonoscopy in paediatric ulcerative colitis

Background: Second generation colon capsule endoscopy (CCE-2) was proven to be accurate for the diagnosis of neoplastic lesions in adults. Although appealing, as it potentially may overcome invasiveness of colonoscopy, to date, CCE-2 in pediatric patients was never described. Primary aim of this study was to determine the accuracy of CCE-2 in evaluating disease activity in pediatric patients suffering from ulcerative colitis (UC). Disease extension, tolerability, inter-observer agreement, and safety were also evaluated.

Role of Pelvic Magnetic Resonance Imaging for Evaluation of Disease Activity in Pediatric Patients With Perianal Crohnʼs Disease

Approximately one-third of the patients with Crohn's Disease have perianal involvement. Cessation of drainage from the orifices of the fistula is still been used widely as an indicator for cure in the pediatric population. However, recent literature has shown us that cessation of drainage is not equivalent to healing of a fistula. Contrast-enhanced pelvic Magnetic Resonance Imaging has been used to diagnose and monitor perianal Crohn's Disease. Adult studies have used various radiologic parameters (T2 hyperintensity, rectal wall thickening, bowel stratification, Percentage Increase in T2 hyperintensity etc.) and scores (Van Assche Score) to monitor perianal Crohn's Disease. However, similar studies are lacking in pediatric population. We performed a retrospective chart review of children under the age of 18 years at initial diagnosis who underwent contrast-enhanced pelvic MRI for perianal Crohn's disease. We analyzed a total of 44 pelvic MRI images. Of those, 29 were baseline images, performed at the time of diagnosis and 15 were follow up images (while on treatment). We also noted down clinical (fistula drainage) and laboratory (hemoglobin, hematocrit, albumin, ESR and CRP). We compared various radiological parameters and scores amongst the two groups. We also compared the correlation of the radiological parameters to laboratory values at the time of MRI. We found that amongst individual parameters, the PI (percentage increase in intensity on contrast enhancement compared to fat) [2], was significantly higher in the baseline group compared to treatment group {318.97 ± 116.81 vs. 246.15 ± 74.89 P = 0.021}. There was no significant difference amongst the other individual parameters (T2 hyperintensity, rectal wall thickening, Park's classification, St James classification, presence of abscesses). However, the MRI based scores suggested by Van Assche et al [1] (15.28 ± 3.82 vs10.47 ± 4.62, P = 0.002) and Horsthius et al [1] (21.34 ± 4.74 vs 14.87 ± 6.02, P = 0.001) were significantly higher in the baseline group compared to treatment group. Also, MRI scores by Horstheus et al showed significant positive correlation to ESR (Pearson co-efficient = 0.398, P = 0.012) and negative correlation to serum albumin (Pearson co-efficient = -0.558, P = 0.00), hemoglobin (Pearson co-efficient = -0.317, P = 0.016) and hematocrit. (Pearson co-efficient = -0.383, P = 0.016). Similar results were seen with the Van Assche score. Authors suggest that the use of radiological parameters and scores described above will help the pediatric gastroenterologist to better monitor treatment of perianal Crohn's disease. To the best of authors' knowledge; this is the first study in pediatric population which demonstrates the value of using the above radiological parameters and scores to monitor perianal Crohn's disease. References 1) Horsthuis K, de Ridder L, Smets AM, van Leeuwen MS, Benninga MA, Houwen RH, et al. Magnetic resonance enterography for suspected inflammatory bowel disease in a pediatric population. J Pediatr Gastroenterol Nutr. Nov; 51(5):603-9. 2) Villa C, Pompili G, Franceschelli G, Munari A, Radaelli G, Maconi G, et al. Role of magnetic resonance imaging in evaluation of the activity of perianal Crohn's disease. Eur J Radiol. Apr; 81(4):616-22.

Fecal Calprotectin Is a Useful Marker for Disease Activity in Pediatric Patients with Inflammatory Bowel Disease

Studies evaluating the correlation between endoscopic disease activity and noninvasive markers are scarce in inflammatory bowel disease (IBD). The aim of this study is to evaluate the accuracy of the fecal calprotectin (FC) assay as a marker of disease activity of IBD, as determined by an extensive endoscopic scoring system. Thirty-five children and adolescents with IBD [17 with ulcerative colitis (UC) and 18 with Crohn's disease (CD)] and 28 healthy volunteers were enrolled. FC levels were determined by ELISA. The sum of Matts' score for UC and the simple endoscopic score for Crohn's disease (SES-CD) were used. The ileal lesions were evaluated by ultrasonography. In UC patients, there was a strong correlation between FC levels and the sum of Matts' score (r=0.838, p<0.01). FC levels were significantly elevated in endoscopically active patients (median 1,562.5 μg/g) as compared to patients in endoscopic remission (median 38.9 μg/g) or healthy controls (median 19.9 μg/g). In CD patients, there was a strong correlation between FC levels and the SES-CD score (r=0.760, p<0.01). The FC levels were significantly higher in endoscopically active patients (median 2,037.5 μg/g) than in endoscopically inactive patients (median 172.5 μg/g) or healthy controls (median 19.9 μg/g), respectively. The FC levels of patients with ileal wall thickening (median 2,225.0 μg/g) were significantly higher than healthy controls (median 19.9 μg/g) and patients lacking ileal wall thickening (median 17.5 μg/g), respectively. The FC assay is a useful marker for the detection of mucosal inflammation in pediatric IBD patients.

Longitudinal Patterns of Predominant Asthma Disease Activity in Pediatric Patients Enrolled in an Asthma-Specific Disease Management Program

To determine if patterns of predominant asthma disease activity are more closely related than baseline asthma severity to measures of morbidity (acute asthma attack, emergency room visit/hospitalization, missed school days, and/or steroid burst). Retrospective analysis was performed for inner-city Los Angeles asthmatic children (3 to 18 years of age) during their first year of enrollment in an asthma-specific disease management program. All measures of morbidity were more closely related to patterns of predominant disease activity than baseline severity. We conclude that patterns of predominant disease activity are a more significant predictor of asthma morbidity than is baseline severity.

Fecal Lactoferrin Is a Sensitive and Specific Marker of Disease Activity in Children and Young Adults With Inflammatory Bowel Disease

Fecal lactoferrin (FLA) is a neutrophil-derived surrogate marker of intestinal inflammation that is elevated in patients with inflammatory bowel disease. However, the correlation between FLA levels and serological markers of disease activity has not been previously reported, to our knowledge. In the present study we evaluated the ability of FLA levels to reflect disease activity in pediatric patients with inflammatory bowel disease. We further assessed the relationship between FLA levels and customary laboratory and clinical measures of inflammation. Fecal specimens were collected from 148 consecutive pediatric patients (79 with Crohn disease, 62 with ulcerative colitis, and 7 with irritable bowel syndrome) and 22 healthy control individuals. Lactoferrin was measured by enzyme-linked immunosorbent assay (IBD-SCAN, TECHLAB, Inc). Disease activity was assessed at the time of sample provision by laboratory measures (including erythrocyte sedimentation rate [ESR] and albumin) and previously validated disease activity indices (Pediatric Crohn Disease Activity Index, Kozarek, Harvey Bradshaw Activity Index). Lactoferrin levels were significantly higher in patients with ulcerative colitis (1880 +/- 565 microg/mL) (mean +/- SE) or Crohn disease (1701 +/- 382 microg/mL) than in healthy control individuals under 21 years of age (1.17 +/- 0.47 microg/mL, P < 0.001). Lactoferrin levels correlated significantly with ESR, hematocrit, albumin, and platelet count (P < 0.001). Receiver operating characteristic curve analysis revealed that FLA levels were comparable to ESR in detecting patients with clinically active disease (P < 0.001). Patients who experienced a clinical flare within 2 months of specimen collection displayed higher lactoferrin levels (845 +/- 452 microg/mL) than did those who remained in clinical remission (190 +/- 90 microg/mL, P = 0.003). Data presented here demonstrate that FLA is a sensitive and specific biochemical marker of inflammation for use in the diagnosis and interval assessment of pediatric patients with IBD, and its level correlates well with both clinical disease activity indices and ESR. Elevated levels of FLA may also identify patients at greater risk for the development of subsequent clinical flares.