Differentiation between pediatric irritable bowel syndrome and inflammatory bowel disease based on fecal scent : proof of principle study

The diagnostic work-up of pediatric irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) commonly includes invasive tests for discrimination from inflammatory bowel disease (IBD). As this carries a high burden on patients, an ongoing need exists for development of noninvasive diagnostic biomarkers for IBS and FAP-NOS. Several studies have shown microbiota alterations in IBS/FAP, which are considered to be reflected by fecal volatile organic compounds (VOCs). The object of the study was to evaluate whether pediatric IBS/FAP-NOS could be discriminated from IBD and healthy controls by fecal VOC analysis. IBS/FAP-NOS was diagnosed according to the ROME IV criteria, and de novo IBD patients and healthy controls (HCs) aged 4 to 17 years were matched on age and sex. Fecal VOCs were analyzed by means of field asymmetric ion mobility spectrometry. Fecal VOCs of 15 IBS/FAP-NOS, 30 IBD (15 ulcerative colitis, 15 Crohn's disease) patients and 30 HCs were analyzed and compared. Differentiation between IBS/FAP-NOS and IBD was feasible with high accuracy (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.88-1; P < 0.00001). IBS/FAP-NOS profiles could not be differentiated from HCs (AUC, 0.59; 95% CI, 0.41-0.77; P = 0.167), whereas IBD profiles could with high accuracy (AUC, 0.96; 95% CI, 0.93-1; P < 0.00001). Pediatric IBS/FAP-NOS could be differentiated from IBD by fecal VOC analysis with high accuracy, but not from healthy controls. The latter finding limits the potential of fecal VOCs to serve as a diagnostic biomarker for IBS/FAP-NOS. However, VOC could possibly serve as additional noninvasive biomarker to differentiate IBS/FAP-NOS from IBD

Polymorphisms in the mannose-binding lectin gene as determinants of age-defined risk of coronary artery lesions in Kawasaki disease

OBJECTIVE: To evaluate the relationship between polymorphisms in the gene coding for mannose-binding lectin (MBL) and the occurrence of coronary artery lesions (CALs) among different age groups of patients with Kawasaki disease. METHODS: The frequencies of the genotypes, defined as mutations in codons 52, 54, and 57, and the functional promoter variants of the MBL2 gene were determined in 88 patients with acute Kawasaki disease (median age at onset 1.9 years). The possible influence of the MBL2 genotype on the development and progression of CALs in Kawasaki disease was assessed according to age categories and MBL genotypes in univariate and multivariate analyses. RESULTS: In patients younger than age 1 year, we found an increased risk of developing CALs in the presence of a variant MBL2 genotype (P = 0.008). In contrast, in patients older than age 1 year, we found an increased risk of CALs in those patients with the wild-type genotype (P = 0.005). CONCLUSION: Our findings indicate that MBL has an ambiguous role in Kawasaki disease and contributes differently to the pathophysiologic development of CALs, being protective in infants but potentially harmful in patients of older age. The data also imply that the standard treatment of intravenous immunoglobulins to reduce the development of lesions may not be as effective in the very young as it is in the older patients. For the very young, alternative or adjuvant treatment may be indicated, particularly in infants who are MBL-deficien

Association of mannose-binding lectin genotype with cardiovascular abnormalities in Kawasaki disease

Kawasaki disease is an acute vasculitis of possible infectious cause, which in particular affects the coronary arteries. Young children rely mostly on their innate immune system for protection against invading microorganisms, of which mannose-binding lectin is an important component. We aimed to investigate the possible role of the gene for this molecule (MBL) in white Dutch patients with Kawasaki disease. In 90 patients, frequency of mutations in the MBL gene was higher than in healthy children. In children younger than I year, those with mutations were at higher risk of development of coronary artery lesions than were those without (odds ratio 15-7, 95% CI 1.4-176.5, p=0.026). Our findings suggest that the innate immune system contributes differently to pathophysiology of Kawasaki disease at various age

Effect of dexamethasone on tracheal viral load and interleukin-8 tracheal concentration in children with respiratory syncytial virus infection

Background. Lower respiratory tract infection caused by respiratory syncytial virus (RSV) is in part an immune-mediated disease. For that reason corticosteroids might be effective, especially in patients with severe RSV lower respiratory tract infection. Our aim was to assess the effect of dexamethasone on tracheal viral load and airway inflammation in patients with RSV infection. Methods. Mechanically ventilated children with proven RSV infection were randomized to receive dexamethasone (0.6 mg/kg/day in four doses for 48 h) or placebo. Daily tracheal aspirates were analyzed for viral load (by quantitative polymerase chain reaction), interleukin (IL)-8 and white blood cell count. Results. The RSV RNA concentrations decreased in a similar manner from baseline in the dexamethasone (9 patients) and in the placebo group (13 patients). IL-8 decreased from baseline in the dexamethasone group but increased in the placebo group during the first 48 h [change from baseline at 24 h, -2.3 vs. 0.9 ln ng/ml (95% confidence interval for difference, -4.2 to 0.3, P = 0.02) and at 48 h, -4.2 vs. 0.4 ln mg/ml (95% confidence interval for difference, -5.3 to -0.3; P = 0.03), respectively], without effect on the tracheal white blood cell count. Conclusion. Dexamethasone does not cause an impaired decline of tracheal RSV but lowers IL-8 of children mechanically ventilated for RSV lower respiratory tract infection, potentially leading to less inflammation and reduced phagocyte activatio

Longstanding obliterative panarteritis in Kawasaki disease: Lack of cyclosporin A effect

Kawasaki disease is a childhood vasculitis of medium-sized vessels, affecting the coronary arteries in particular. We have treated a therapy-resistant child who met all diagnostic criteria for Kawasaki disease. After the boy was given intravenous immunoglobulins and salicylates, as well as several courses of pulsed methylprednisolone, disease recurred and coronary artery lesions became progressively detectable. Cyclosporin A was started and seemed clinically effective. In contrast to the positive effect on inflammatory parameters, ie, C-reactive protein and white blood cell counts, a novel plasma marker for cytotoxicity ( granzyme B) remained elevated. Coronary disease progressed to fatal obstruction and myocardial infarction. Echocardiography, electrocardiograms, and myocardial creatine phosphokinase did not predict impending death. At autopsy an obliterative panarteritis was observed resulting from massive fibrointimal proliferation, affecting the aorta and several large and medium-sized arteries. Immunophenotypic analysis of the inflammatory infiltrates in arteries revealed mainly granzyme-positive cytotoxic T cells and macrophages in the intima and media, as well as nodular aggregates of T cells, B cells, and plasma cells in the adventitia of affected arteries. These findings further endorse the role of specific cellular and humoral immunity in Kawasaki disease. Unremitting coronary arteritis and excessive smooth muscle hyperplasia resulted in coronary occlusion despite the use of cyclosporin

Young children with a minor traumatic head injury: clinical observation or CT scan?

Currently, in young children with minor traumatic head injuries (MTHI) classified as intermediate risk (IR), PECARN recommends clinical observation over computer tomography (CT) scan depending on provider comfort, although both options being possible. In this study, we describe clinicians’ choice and which factors were associated with this decision. This was a planned sub-study of a prospective multicenter observational study that enrolled 1006 children younger than 18 years with MTHI who presented to six emergency departments in The Netherlands. Of those, 280 children classified as IR group fulfilling one or more minor criteria, leaving the clinician with the choice between clinical observation and a CT scan. In our cohort, 228/280 (81%) children were admitted for clinical observation, 15/280 (5.4%) received a CT scan, 6/280 (2.1%) received a CT scan and were admitted for observation, and 31/280 (11%) children were discharged from the emergency department without any intervention. Three objective factors were associated with a CT scan, namely age above 2 years, the presence of any loss of consciousness (LOC), and presentation on weekend days. Conclusion: In children with MTHI in an IR group, clinicians prefer clinical observation above performing a CT scan. Older age, day of presentation, and any loss of consciousness are factors associated with a CT scan.What is Known:• Clinical decision rules have been developed in the management of children of different risk groups with minor traumatic head injury (MTHI).• According to the Dutch national, clinical decision rules in children under 6 years of age up to 50% of children classify as intermediate risk (IR) and clinicians may choose between clinical observation and computed tomography (CT).What is New:• In this IR group, clinical observation is chosen in 81% children with MTHI.• In the subgroup where clinicians performed a CT scan, children were older and presented more frequently on a weekend day, and more frequently consciousness was lost

Peanut thresholds in peanut‐allergic children are related to dietary composition

Abstract Background There is no clear explanation for the large variation in threshold levels among peanut‐allergic children. We hypothesized that diet composition can partly explain this variation in thresholds, as nutrients and foods influence the intestinal barrier function and microbiota. Aim to explore the relationship between the threshold levels for peanut and nutritional intake and gut microbial composition in peanut‐allergic children. Methods In this explorative cross‐sectional study the cumulative threshold levels for peanut were determined by oral food challenge tests. Data on nutrients and foods consumed were obtained from 3‐day food diaries. Microbial composition of faeces and saliva were determined by molecular microbiota detection technique. Multivariable linear regression analysis and multiple logistic regression were used to explore the associations, adjusted for energy and senitization. Results Sixty‐five children were included, of whom 32 (49%) (median age 50 months, IQR 28.0–96.5) had a positive oral food challenge. Significant positive associations were found between the intake of total carbohydrates, vitamin A and cumulative threshold levels for peanut, while significant negative associations were found for long‐chain polyunsaturated fatty acids, linoleic acid and omega‐6 fatty acids. No associations were found between threshold levels and microbial composition of faeces and saliva. However, a significant higher abundance of Proteobacteria and Bacteroidetes in saliva (p = 0.011 and 0.04, respectively) and of Proteobacteria in faeces (p = 0.003) were found in children with a positive peanut challenge compared to children with a negative peanut challenge. Conclusion As a novel concept, this study showed that dietary composition is related to threshold levels for peanut

Multi-centre study found that strict adherence to guidelines led to computed tomography scans being overused in children with minor head injuries

Aim: Our primary aim was to calculate the head computed tomography (CT) scan rate in children with a minor head injury (MHI) when the Dutch National guidelines were followed in clinical practice. The secondary aim was to determine the incidence of CT abnormalities and the guideline predictors associated with traumatic abnormalities. Methods: We performed a multi-centre, prospective observational cross-sectional study in the emergency departments of six hospitals in The Netherlands between 1 April 2015 and 31 December 2016. Results: Data on 1002 patients were studied and 69% of cases complied with the guidelines. The overall CT rate was 44% and the incidence of traumatic abnormal CT findings was 13%. CT scans were performed in 19% of children under two years of age, 48% of children between two and five years and 63% of children aged six years or more. Multivariate regression analysis for all age categories showed that CT abnormalities were predicted by a Glasgow Coma Scale of less than 15, suspicion of a basal skull fracture, vomiting and scalp haematomas or external lesions of the skull. Conclusion: Strict adherence to the Dutch national guidelines resulted in CT overuse. New guidelines are needed to safely reduce CT scan indications