[Recurrent atelectasis in an infant : about one case of false-negative newborn screening for cystic fibrosis]. / Atélectasie récidivante chez un nourrisson : à propos d'un cas de faux-négatif du dépistage néonatal pour la mucoviscidose.

In infants as well as in older children, persistent or recurrent atelectasis remains a classic indication for sweat testing, even if neonatal screening for cystic fibrosis has been considered normal. Atelectasis is a common complication of cystic fibrosis. Yet, it has rarely been reported in infants. In cystic fibrosis, chronic atelectasis worsens the prognosis, especially when involving a lower lobe. Therefore, early and effective intervention is required. Antibiotic therapy, intensive chest physiotherapy together with inhaled mucolytics often allow to relieve bronchial obstruction but bronchoscopy with local aspiration and Dornase alpha instillation is sometimes necessary. In a two-month-old infant, we describe here the first reported case of false-negative cystic fibrosis newborn screening in Belgium.

Chez le nourrisson comme chez l'enfant plus âgé, une atélectasie persistante ou récidivante reste une indication classique de test à la sueur, même si le dépistage néonatal de la mucoviscidose a été considéré comme normal. Rarement rapportées chez le nourrisson, les atélectasies sont une complication commune de la mucoviscidose. Dans cette affection, l'atélectasie chronique d'un territoire péjore le pronostic, en particulier si elle concerne un lobe inférieur. Une intervention précoce et efficace est donc requise. Antibiothérapie, kinésithérapie respiratoire intensive et recours aux fluidifiants par voie de nébulisation suffisent souvent à lever l'obstruction bronchique, mais une endoscopie avec aspiration locale et instillation de dornase alpha est parfois nécessaire. Chez un nourrisson de 2 mois, nous rapportons ici le premier cas de faux-négatif du programme belge de dépistage néonatal de la mucoviscidose.

Diagnosing enterovirus meningitis via blood transcriptomics: an alternative for lumbar puncture?

BACKGROUND: Meningitis can be caused by several viruses and bacteria. Identifying the causative pathogen as quickly as possible is crucial to initiate the most optimal therapy, as acute bacterial meningitis is associated with a significant morbidity and mortality. Bacterial meningitis requires antibiotics, as opposed to enteroviral meningitis, which only requires supportive therapy. Clinical presentation is usually not sufficient to differentiate between viral and bacterial meningitis, thereby necessitating cerebrospinal fluid (CSF) analysis by PCR and/or time-consuming bacterial cultures. However, collecting CSF in children is not always feasible and a rather invasive procedure. METHODS: In 12 Belgian hospitals, we obtained acute blood samples from children with signs of meningitis (49 viral and 7 bacterial cases) (aged between 3 months and 16 years). After pathogen confirmation on CSF, the patient was asked to give a convalescent sample after recovery. 3' mRNA sequencing was performed to determine differentially expressed genes (DEGs) to create a host transcriptomic profile. RESULTS: Enteroviral meningitis cases displayed the largest upregulated fold change enrichment in type I interferon production, response and signaling pathways. Patients with bacterial meningitis showed a significant upregulation of genes related to macrophage and neutrophil activation. We found several significantly DEGs between enteroviral and bacterial meningitis. Random forest classification showed that we were able to differentiate enteroviral from bacterial meningitis with an AUC of 0.982 on held-out samples. CONCLUSIONS: Enteroviral meningitis has an innate immunity signature with type 1 interferons as key players. Our classifier, based on blood host transcriptomic profiles of different meningitis cases, is a possible strong alternative for diagnosing enteroviral meningitis.

Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule.

PURPOSE: Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection. MATERIALS AND METHODS: We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals. RESULTS: A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47). CONCLUSIONS: A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.

Blood transcriptomics to facilitate diagnosis and stratification in pediatric rheumatic diseases - a proof of concept study.

BACKGROUND: Transcriptome profiling of blood cells is an efficient tool to study the gene expression signatures of rheumatic diseases. This study aims to improve the early diagnosis of pediatric rheumatic diseases by investigating patients' blood gene expression and applying machine learning on the transcriptome data to develop predictive models. METHODS: RNA sequencing was performed on whole blood collected from children with rheumatic diseases. Random Forest classification models were developed based on the transcriptome data of 48 rheumatic patients, 46 children with viral infection, and 35 controls to classify different disease groups. The performance of these classifiers was evaluated by leave-one-out cross-validation. Analyses of differentially expressed genes (DEG), gene ontology (GO), and interferon-stimulated gene (ISG) score were also conducted. RESULTS: Our first classifier could differentiate pediatric rheumatic patients from controls and infection cases with high area-under-the-curve (AUC) values (AUC = 0.8 ± 0.1 and 0.7 ± 0.1, respectively). Three other classifiers could distinguish chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), and interferonopathies (IFN) from control and infection cases with AUC ≥ 0.8. DEG and GO analyses reveal that the pathophysiology of CRMO, IFN, and JIA involves innate immune responses including myeloid leukocyte and granulocyte activation, neutrophil activation and degranulation. IFN is specifically mediated by antibacterial and antifungal defense responses, CRMO by cellular response to cytokine, and JIA by cellular response to chemical stimulus. IFN patients particularly had the highest mean ISG score among all disease groups. CONCLUSION: Our data show that blood transcriptomics combined with machine learning is a promising diagnostic tool for pediatric rheumatic diseases and may assist physicians in making data-driven and patient-specific decisions in clinical practice.

Procalcitonin is a predictor for high-grade vesicoureteral reflux in children: meta-analysis of individual patient data.

OBJECTIVE: To assess the predictive value of procalcitonin, a serum inflammatory marker, in the identification of children with first urinary tract infection (UTI) who might have high-grade (≥3) vesicoureteral reflux (VUR). STUDY DESIGN: We conducted a meta-analysis of individual data, including all series of children aged 1 month to 4 years with a first UTI, a procalcitonin (PCT) level measurement, cystograms, and an early dimercaptosuccinic acid scan. RESULTS: Of the 152 relevant identified articles, 12 studies representing 526 patients (10% with VUR ≥3) were included. PCT level was associated with VUR ≥3 as a continuous (P = .001), and as a binary variable, with a 0.5 ng/mL preferred threshold (adjusted OR, 2.5; 95% CI, 1.1 to 5.4). The sensitivity of PCT ≥0.5 ng/mL was 83% (95% CI, 71 to 91) with 43% specificity rate (95% CI, 38 to 47). In the subgroup of children with a positive results on dimercaptosuccinic acid scan, PCT ≥0.5 ng/mL was also associated with high-grade VUR (adjusted OR, 4.8; 95% CI, 1.3 to 17.6). CONCLUSIONS: We confirmed that PCT is a sensitive and validated predictor strongly associated with VUR ≥3, regardless of the presence of early renal parenchymal involvement in children with a first UTI.

Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.

The clinical phenotype of interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rbeta1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rbeta1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.

Submandibular lymphadenitis caused by Mycobacterium interjectum: contribution of new diagnostic tools.

Mycobacterium interjectum is a rare causative agent of cervical lymphadenitis. We describe a 2-year-old girl with suspected tuberculous cervical lymphadenitis.Sequencing of the 16S rRNA gene allowed the correct identification of Mycobacterium interjectum. As yet, only nine case reports of infections due to M. interjectum in children have been reported in the literature, and in all of them a correct identification could only be obtained using gene sequencing.

Prediction of Lyme meningitis based on a logistic regression model using clinical and cerebrospinal fluid analysis: a European study.

BACKGROUND: A prediction model based on clinical and cerebrospinal fluid (CSF) analysis has been proposed for the differentiation of Lyme meningitis (LM) from non-Lyme aseptic meningitis (NLAM) in the United States. No similar model has ever been proposed for European patients. The objective of our study was to develop a prediction model to differentiate LM from NLAM based on clinical and CSF biologic data. METHODS: The medical charts of all children older than 2 years of age admitted to our hospital from 1996 through 2006 with a definite diagnosis of LM were analyzed and compared retrospectively with those having a diagnosis of NLAM. Chart review included the duration of symptoms, the presence of cranial neuropathy, and CSF analysis. RESULTS: A total of 93 patients were included (LM: 26 patients; NLAM: 67 patients) in the study. Patients with LM had statistically more frequent cranial neuropathy (73% vs. 4%), displayed a longer duration of symptoms before admission (8.8 vs. 1.8 days), had a higher CSF protein (71 vs. 38 mg/d), and had a lower percentage of neutrophil cells in the CSF (3.4% vs. 51%) than patients with NLAM. A predicted probability was derived from these 4 variables. At a cutoff point of >0.432, the model had a negative predictive value of 100% and a positive predictive value of 92.3%, with a sensitivity of 100% and a specificity of 97%. CONCLUSIONS: We report the first European prediction model for LM. Owing to its high negative predictive value, this model may assist physicians in managing aseptic meningitis (AM) while awaiting serologic tests, especially in Lyme endemic regions.

Severe ostial stenosis of the left coronary artery in a 12-year-old girl as the first manifestation of Takayasu's arteritis.

We report the case of a 12-year-old girl who presented with isolated chest pain on minimal exertion over the last 2 months. A coronary angiography revealed severe narrowing of the left coronary artery ostium and increased thickness of the ascending aortic wall was demonstrated by transoesophageal echocardiography, suggesting the diagnosis ofTakayasu's arteritis. The patient was successfully treated with corticosteroids and coronary artery bypass graft surgery.