关键词： Calprotectin   lactoferrin   inflammatory bowel disease   primary care   paediatrics   point-of-care test  

摘要： Background. Faecal calprotectin is considered to be a valid test for ruling out inflammatory bowel disease (IBD) in children with chronic gastrointestinal symptoms in specialist care. In contrast, faecal lactoferrin has higher specificity. The recent availability of both as point-of-care tests (POCTs) makes them attractive for use in primary care. Objective. To evaluate the test characteristics of calprotectin and lactoferrin POCTs for diagnosing IBD in symptomatic children. Methods. We defined two prospective cohorts of children with chronic gastrointestinal symptoms: (i) children presenting to primary care (primary care cohort);(ii) children referred for specialist care (referred cohort). Baseline POCT results were compared with the outcome of either endoscopic assessment or 12 months follow-up. Clinicians were blinded to the POCT results. Results. In the primary care cohort, none of the 114 children had IBD, and the calprotectin and lactoferrin POCTs had specificities of 0.95 (0.89-0.98) and 0.98 (0.93-0.99), respectively. In the referred cohort, 17 of the 90 children had IBD: the sensitivity of POCT calprotectin and POCT lactoferrin were both 0.94 (0.72-0.99);and the specificity was 0.93 (0.84-0.97) and 0.99 (0.92-1.00), respectively. The POCT calprotectin could reduce the referral rate by 76% and POCT lactoferrin by 81%, while missing one child with IBD (6%). Conclusion. A diagnostic test strategy in primary care using a simple POCT calprotectin or lactoferrin has the potential to reduce the need for referral for further diagnostic work-up in specialist care, with a low risk of missing a child with IBD.

关键词： Medical Home   Inflammatory Bowel Diseases   Intestinal Diseases  

关键词： C-reactive protein   Crohn disease   erythrocyte sedimentation rate   inflammatory bowel disease   ulcerative colitis  

摘要： We aimed to examine correlation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with diagnosis of inflammatory bowel disease and with clinical, endoscopic, histological, and radiographic disease activity during follow-up. We reviewed charts of 135 children with inflammatory bowel disease and correlated their ESR and CRP values with disease activity in various encounters during 5 years. Normal ESR and CRP values were observed in up to 28% of children with Crohn disease and 42% of children with ulcerative colitis at diagnosis, respectively. Correlation of ESR and CRP with Crohn disease clinical, endoscopic, and histologic activity during follow-up depended on their value at diagnosis and mode of analysis (continuous or dichotomous). Both markers were not useful in predicting clinical, endoscopic, or histologic ulcerative colitis disease activity and radiographic small bowel Crohn disease during follow-up.

关键词： Familial aggregation   Disease severity   Treatment requirements  

摘要： Several studies demonstrate an increased prevalence and concordance of inflammatory bowel disease among the relatives of patients. Other studies suggest that genetic influence is over-estimated. The aims of this study are to evaluate the phenotypic expression and the treatment requirements in familial inflammatory bowel disease, to study the relationship between number of relatives and degree of kinship with disease severity and to quantify the impact of family aggregation compared to other environmental factors. Observational analytical study of 1211 patients followed in our unit. We analyzed, according to the existence of familial association, number and degree of consanguinity, the phenotypic expression, complications, extraintestinal manifestations, treatment requirements, and mortality. A multivariable analysis considering smoking habits and non-steroidal-anti-inflammatory drugs was performed. 14.2% of patients had relatives affected. Median age at diagnosis tended to be lower in the familial group, 32 vs 29, p = 0.07. In familial ulcerative colitis, there was a higher proportion of extraintestinal manifestations: peripheral arthropathy (OR = 2.3, p = 0.015) and erythema nodosum (OR = 7.6, p = 0.001). In familial Crohn's disease, there were higher treatment requirements: immunomodulators (OR = 1.8, p = 0.029);biologics (OR = 1.9, p = 0.011);and surgery (OR = 1.7, p = 0.044). The abdominal abscess increased with the number of relatives affected: 5.1% (sporadic), 7.0% (one), and 14.3% (two or more), p=0.039. These associations were maintained in the multivariate analysis. Familial aggregation is considered a risk factor for more aggressive disease and higher treatment requirements, a tendency for earlier onset, more abdominal abscess, and extraintestinal manifestations, remaining a risk factor analyzing the influence of some environmental factors.

关键词： WEIGHT gain in pregnancy   INFLAMMATORY bowel diseases   CROHN'S disease   ULCERATIVE colitis   PREGNANCY complications  

关键词： Hedgehog signaling pathway   Inflammatory bowel disease   Epithelial cell apoptosis   Crohn's disease  

摘要： Hedgehog (Hh) signaling is essential for intestinal homeostasis and has been associated with inflammation and tissue repair. We hypothesized that Hh signaling could affect the inflammatory process in inflammatory bowel disease (IBD). For this purpose, colon specimens from the inflamed and non-inflamed mucosa of 15 patients with Crohn's disease (CD), 15 with ulcerative colitis, and 15 controls were analyzed by immunohistochemistry and real-time PCR. The production and modulation of cytokines were measured by ELISA from culture explants. Apoptosis was assessed by TUNEL and caspase-3 activity assays. Chemotaxis was evaluated using a transwell system. Primary human intestinal and skin fibroblasts were used for analyzing migration and BrdU incorporation. Hh proteins were generally expressed at the superficial epithelium, and a marked reduction was observed in CD. In the lamina propria, Gli-1 predominantly co-localized with vimentin- and alpha-smooth muscle actin-positive cells, with lower levels observed in CD. In colon explants, Hh stimulation resulted in reduction, while blockade increased, TNF alpha, IL-17, and TGF beta levels. Apoptotic rates were higher in inflamed samples, and they increased after Hh blockade. Levels of Gli-1 mRNA were negatively correlated with caspase-3 activity. Hh blockade increased chemoattraction of monocytes. Primary fibroblasts incorporated more BrdU, but migrated less after Hh blockade. These results suggest that Hh signaling provides a negative feedback to the lamina propria, down-regulating inflammatory cytokines, and inhibiting leukocyte migration and fibroblast proliferation, while favoring fibroblast migration. Therefore, Hh signaling is strongly implicated in the pathogenesis of intestinal inflammation, and it may represent a novel therapeutic target for IBD.

关键词： INFLAMMATORY bowel disease diagnosis   IMMIGRANTS -- United States   DISEASES   HISPANIC Americans   GASTROENTEROLOGY   COHORT analysis  

摘要： Background: Despite a rising incidence of inflammatory bowel disease (IBD) in Hispanics in the United States, there are no studies examining the relationship between immigrant generation and IBD onset among Hispanics. Aims: To determine whether age of IBD diagnosis, time from immigration to IBD diagnosis and IBD phenotype, differed across immigration periods in South Florida Cuban immigrants. Methods: This was a cohort of consecutively identified Cuban-born adults who developed IBD in the United States and were followed in gastroenterology (GI) clinic. We divided time cohorts of immigration by historical relevance: before 1980, 1980-1994 and 1995-to-present. We examined differences across time cohorts in diagnosis age, time from immigration to IBD diagnosis, and IBD phenotype (ie, IBD type, disease location). Results: A total of 130 Cuban patients with IBD were included. Age of IBD diagnosis was older in Cubans arriving before 1980 than in those arriving between 19801994 or after 1995 (44.7 vs 33.79 and 33.71, respectively, P<.0001). Time between immigration and diagnosis was shorter in patients arriving to the US after 1980 (31.77 years, Standard deviation (SD) 12.83 (<1980) vs 17.13 years, SD 8.55 (1980-1994) and 8.30 years, SD 4.72 (1995-to-present). IBD phenotype, including type of IBD, disease location and surgeries, did not differ significantly across time cohorts. Conclusions: Our study describes changing patterns of IBD onset following immigration in Cubans, suggesting that environmental changes either in the United States, Cuba or both are resulting in faster IBD onset in younger immigrant generations. These studies can inform the search for environmental triggers that may result in IBD.

关键词： Crohn Disease   Inflammatory Bowel Diseases   Probiotics   Review, Systematic   Meta-Analysis   Intestinal Diseases   Functional foods  

摘要： Background: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. Aim: To perform a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. Methods: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). Results: The search identified 12 253 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86;95% CI=0.68-1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74;95% CI=0.63-0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR=1.02;95% CI=0.85-1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission. Conclusions: VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.

关键词： irritable bowel syndrome   pediatric inflammatory bowel disease   predictors   quality of life  

摘要： Objectives: We sought to describe the prevalence of the overlap of functional abdominal pain disorders (FAPDs) in children with inflammatory bowel diseases (IBDs), a condition we have designated as IBD-FAPD. We also aimed to describe the psychological profile of this group, and to assess predictors of disease and the impact of IBD-FAPD on quality of life. Methods: This cross-sectional prospective study included patients ages 8 to 18 years with a diagnosis of IBD. Disease activity was assessed by physician's global assessment, laboratory studies, and abbreviated Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index scoring. Age-appropriate validated questionnaires were used to diagnose FAPDs according to the Rome III criteria, depression, anxiety symptoms, and quality of life. Results: There were 128 patients recruited. Eighty-one (63%) completed questionnaires (36 girls;45 boys;mean age 14.42.6 years) (62 Crohn disease, 19 ulcerative colitis). The prevalence of IBD-FAPD in clinical remission was 26% (17 Crohn disease, 4 ulcerative colitis;95% confidence interval: 20.6%-79.4%), with significantly more girls having IBD-FAPD (P = 0.038). Anxiety symptoms were in 14.3% of patients with IBD-FAPD (P = 0.06) and depression in 23.8% (P = 0.006). The average Pediatric Quality of Life Inventory Gastrointestinal Symptoms score for the IBD-FAPD group was significantly lower than those without FAPDs (71 vs 86.5, P = 0.008). Conclusions: In our cohort, the prevalence of IBD-FAPD was 26%. This is the first study to assess all FAPDs using the Rome III criteria and to demonstrate increased anxiety, depression, and worse quality of life in children with IBD-FAPD. The identification of patients predisposed to IBD-FAPD may allow implementing strategies that could improve symptoms and quality of life.

关键词： case series   diagnostic algorithm   immunologic workup   inflammatory bowel disease   primary immunodeficiency   very-early-onset inflammatory bowel disease  

摘要： Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis have a multifactorial pathogenesis with complex interactions between polygenetic predispositions and environmental factors. However, IBD can also be caused by monogenic diseases, such as primary immunodeficiencies (PID). Recently, an increasing number of these altogether rare diseases have been described to present often primarily, or solely, as IBD. Early recognition of these conditions enables adaption of therapies and thus directly benefits the course of IBDs. Here, we discuss the different clinical presentations in IBD and characteristic features of patient's history, clinical findings, and diagnostic results indicative for a causative PID. Possible predictors are early onset of disease, necessity of parenteral nutrition, failure to respond to standard immunosuppressive therapy, parental consanguinity, increased susceptibility for infections, certain histopathologic findings, and blood tests that are atypical for classic IBD. We illustrate this with exemplary case studies of IBD due to NEMO deficiency, chronic granulomatous disease, common variable immunodeficiency, CTLA-4 and LRBA deficiency. Taking these factors into account, we propose a diagnostic pathway to enable early diagnosis of IBD due to PID.