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.

[Risk of thrombosis in reactive thrombocytosis]. / Risico op trombose bij reactieve trombocytose.

Reactive thrombocytosis (RT; thrombocyte count: > 450 x 109/l) is a condition in which an increase in platelet production, stimulated by cytokines in the bone marrow, is secondary to some condition or circumstance. Although RT does often occur in children, the risk of thromboembolic complications is negligible in this group if they have no other risk factors for thrombosis. In the absence of additional risk factors for thrombosis it seems as though RT in adults does not predispose them to thromboembolic complications either. Patients with RT caused by a non-myeloproliferative malignancy do have an increased risk of thromboembolic complications; antithrombotic prophylaxis might be effective in this group, but there is no scientific evidence for this. We advise a watch-and-wait approach in children and adults with RT who have no other risk factors for thromboembolism, even in patients with extreme thrombocytosis (thrombocyte count: > 1000 x 109/l). In patients who do have an increased risk of thromboembolic complications we advise tailoring prescription or non-prescription of antithrombotic prophylaxis to the individual patient.

Differentiation Between Pediatric Irritable Bowel Syndrome and Inflammatory Bowel Disease Based on Fecal Scent: Proof of Principle Study.

Background: 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. Methods: 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. Results: 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). Conclusion: 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. 10.1093/ibd/izy151_video1izy151.video15786446046001.

Elastase and granzymes during meningococcal disease in children: correlation to disease severity.

OBJECTIVE: To investigate the levels of human neutrophil elastase and lymphocyte-derived granzymes A and B in relation to disease severity in children with meningococcal disease. DESIGN: Clinical observational cohort study. SETTING: Paediatric intensive care unit. PATIENTS: All patients with meningococcal disease during the study period were included. MEASUREMENTS AND RESULTS: Blood sampling was done on the day of admission and on days 3 and 7. Assays for elastase and granzymes were done with ELISA. Sixty-one patients were included: 19 having distinct meningitis; 17 meningitis and shock; and 25 fulminant septicaemia. On admission levels of elastase were increased in all patients, being highest in those with fulminant septicaemia and lowest in those with distinct meningitis. Granzyme A (although marginally) and granzyme B levels were only increased in patients with shock. In 20 of the 28 patients admitted for > or = 3 days elastase decreased from admission ("rapid-decrease" group). In the remaining 8 patients, elastase started to decrease after 2 days ("slow-decrease" group). Patients of the "slow-decrease" group had a higher temperature up to day 4, needed more respiratory support (mean airway pressure in cm H2O on days 3 and 4: p=0.02 and p<0.01, respectively), and more circulatory support (>2 inotropic agents on day 3; p=0.04) compared with the "rapid-decrease" group. CONCLUSIONS: Human neutrophil elastase and granzyme B are related with disease severity during the initial phase of meningococcal disease and prolonged neutrophil activation is associated with the extent of organ dysfunction during the period thereafter.

Facial nerve palsy in a thirteen-year-old male youth with Kawasaki disease.

A 13-year-old male youth was hospitalized with Kawasaki disease. In the course of the disease he developed a facial nerve palsy and an aneurysm of the right coronary artery. After treatment with immunoglobulins both complications disappeared within 10 days and 1 month, respectively.

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 activation.

[Kawasaki disease: description of a Dutch cohort of 392 patients]. / De ziekte van Kawasaki. Beschrijving van een Nederlands cohort van 392 patiënten.

AIM: To describe the patient characteristics, management and cardiovascular sequelae of Kawasaki disease (KD) in patients taking part in a multidisciplinary follow-up in the Emma Children's Hospital during the period January 1999-June 2010. DESIGN: Retrospective, observational study. METHODS: We included 392 patients who were diagnosed with complete or incomplete KD. Clinical and outpatient statuses were used to collect clinical data. RESULTS: The median age at onset of the disease was 3.2 years (range: 0.1-16.4). The male-to-female ratio was 1.6 : 1. Complete KD was diagnosed in 83.9% of patients. Patients with incomplete KD were younger than those with complete KD: 2.2 versus 3.4 years (both SD: 3.0; p < 0.01). 357 patients (91.1%) were treated with intravenous immunoglobulins; 65 patients (16.6%) received a second intravenous dose. Coronary artery aneurysms were diagnosed in 83 patients (21.2%). Male gender, age < 1 year, incomplete presentation and late start of treatment (> 10 days after start of fever) were shown to be independent risk factors for developing aneurysms. These abnormalities normalized in 50 of the 83 patients. 2 patients died of the disease within a year. 5 patients underwent coronary artery bypass grafting during the follow-up period. CONCLUSION: Kawasaki disease is a rare form of vasculitis seen in children, in which aneurysms of the coronary artery can develop. Clinicians should be alert to the possibility of KD in cases of persistent inexplicable fever, especially in young children, even in the absence of complete clinical disease. A timely start to treatment reduces the risk of developing coronary artery aneurysms.

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-deficient.

Absence of circulating natural killer and primed CD8+ cells in life-threatening varicella.

Five pediatric patients with no history of immunodeficiency had a life-threatening course of varicella. Strikingly, natural killer (NK) cells were absent from the circulation in all children, and, despite active viral infection, up to 98% of the CD8(+) cells were naive. Primary immunodeficiencies were excluded--NK cells and primed CD8(+) cells reappeared in the circulation, granzymes were detectable in plasma early during infection, and no abnormalities could be detected in interleukin-15 receptor function. Our data indicate that varicella-zoster virus (VZV) has a unique capability to seclude primed CD8(+) cells and NK cells from the circulating lymphocyte pool. This may be the consequence of an overwhelming immune response to VZV that is influenced by factors such as infectious dose, age, and the presence of maternal antibodies during infancy. Because both homozygous twin sisters in the study had a severe course of varicella, particular genetic factors may contribute to severe varicella.

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 1 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 ages.