27 research outputs found

    Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseus Heteroplasia

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    Progressive osseous heteroplasia (POH; OMIM 166350) is a rare autosomal-dominant genetic disorder in which extra-skeletal bone forms within skin and muscle tissue. POH is one of the clinical manifestations of an inactivating mutation in the GNAS gene. GNAS gene alterations are difficult matter to address, as GNAS alleles show genetic imprinting and produce several transcript products, and the same mutation may lead to strikingly different phenotypes. Also, most of the publications concerning POH patients are either clinical depictions of a case (or a case series), descriptions of their genetic background, or a tentative correlation of both clinical and molecular findings. Treatment for POH is rarely addressed, and POH still lacks therapeutic options. We describe a unique case of POH in two monochorionic twins, who presented an almost asymptomatic vs. the severe clinical course, despite sharing the same mutation and genetic background. We also report the results of the therapeutic interventions currently available for heterotopic ossification in the patient with the severe course. This article not only critically supports the assumption that the POH course is strongly influenced by factors beyond genetic background but also remarks the lack of options for patients suffering an orphan disease, even after testing drugs with promising in vitro resultsThis study received support from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): project GePEM ISCIII/PI16/01478/Cofinanciado FEDER) (AS) and project ReSVinext ISCIII/PI16/01569/Cofinanciado FEDER (FM-T); Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007–2012, PI16/01569), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del plan nacional de I + D + I and fondos FEDER (FM-T), and 2016-PG071 Consolidación e Estructuración REDES 2016GI-1344 G3VIP (Grupo Gallego de Genética Vacunas Infecciones y Pediatría, 3) (AS and FM-T)S

    Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

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    Background The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. Methods A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. Results 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). Conclusion Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe casesThis work was supported by the Spanish Government (Research Program Health Research Fund (FIS; PI10/00540 y PI13/02382) National Plan I + D + I and FEDER funds) and Regional Galician funds (Promotion of Research Project 10 PXIB 918 184 PR) (FMT), and Ministerio de Ciencia e Innovación (SAF2011-26983) and the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (AS). MC’s research activities had been supported by grants from Instituto de Investigación Sanitaria de Santiago de Compostela. FMT’s research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora). Investigators received funding from the European Union’s Seventh Framework Program under ECGA no. 279185 (EUCLIDS) during the production of this paperS

    Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

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    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective roleThis work was supported by the Spanish Government (Research Program Health Research Fund (FIS; PI10/00540) National Plan I + D + I and FEDER funds), by Regional Galician funds (Promotion of Research Project 10 PXIB 918 184PR) (FMT), by Ministerio de Ciencia e Innovación (SAF2011-26983), and by the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (AS). A grant was received from the Sistema Universitario Gallego -Modalidad REDES (2014-PG139) from the Xunta de Galicia (to AS and FMT). MCL research activities have been supported by grants from Instituto de Investigación Sanitaria de Santiago de Compostela. FMT research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora). Investigators received funding from the European Union’s seventh Framework program under ECGA no. 279185 (EUCLIDS) during the production of this paper. JH was supported by the Imperial College Comprehensive Biomedical Research Centre and the Wellcome Trust Centre for Respiratory Infection at Imperial College (DMPED P26077 to JH). Micropathology Ltd. provided support in the form of salaries for authors ES and CF, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ sectionS

    Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection

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    The IFI27 interferon gene expression has been found to be largely increased in rotavirus (RV)-infected patients. IFI27 gene encodes for a protein of unknown function, very recently linked to epidermal proliferation and related to the epidermal growth factor (EGF) protein. The EGF is a low-molecular-weight polypeptide that is mainly produced by submandibular and parotid glands, and it plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. Our aim was to determine salivary EGF levels in RV-infected patients in order to establish its potential relationship with IFI27 increased expression and EGF-mediated mucosal protection in RV infection. We conducted a prospective comparative study using saliva samples from 27 infants infected with RV (sampled at recruitment during hospital admission and at convalescence, i.e. at least 3 months after recovery) and from 36 healthy control children. Median (SD) EGF salivary concentration was 777 (529) pg/ml in RV-infected group at acute phase and 356 (242) pg/m at convalescence, while it was 337 (119) pg/ml in the healthy control group. A significant association was found between EGF levels and hospitalization length of stay (P-value = 0.022; r(2) = -0.63). The salivary levels of EGF are significantly increased during the acute phase of natural RV infection, and relate to length of hospitalization. Further assessment of this non-invasive biomarker in RV disease is warranted.Instituto de Salud Carlos IIIXunta de Galicia. Consellería de Sanidad

    Development and Validation of a New Clinical Scale for Infants with Acute Respiratory Infection: The ReSVinet Scale

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    Background and Aims A properly validated scoring system allowing objective categorization of infants with acute respiratory infections (ARIs), avoiding the need for in-person assessment and that could also be used by non-health professionals is currently not available. We aimed to develop a new clinical assessment scale meeting these specifications. Methods We designed a clinical scale (ReSVinet scale) based on seven parameters (feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition, fever) that were assigned different values (from 0 to 3) for a total of 20 points.170 children under two years of age with ARI were assessed independently by three pediatricians using this scale. Parents also evaluated their offspring with an adapted version of the scale in a subset of 61 cases. The scale was tested for internal consistency (Cronbach’s alpha), Pearson correlation coefficient for the items in the scale, inter-observer reliability (kappa index) and floor-ceiling effect. Results Internal consistency was good for all the observers, with the lowest Cronbach’s alpha being 0.72. There was a strong correlation between the investigators (r-value ranged 0.76–0.83) and also between the results obtained by the parents and the investigators(r = 0.73). Light’s kappa for the observations of the three investigators was 0.74. Weighted kappa in the group evaluated by the parents was 0.73. The final score was correlated with length of hospital stay, PICU admission and Wood-Downes Score. Conclusions The ReSVinet scale may be useful and reliable in the evaluation of infants with ARI, particularly acute bronchiolitis, even with data obtained from medical records and when employed by parents. Although further studies are necessary, ReSVinet scale already complies with more score validation criteria than the vast majority of the alternatives currently available and used in the clinical practiceThis work was supported by the Spanish Government (Research Program Health Research Fund – [http://www.gendres.org] (FIS; PI10/00540 y PI13/02382) National Plan I + D + I and FEDER funds) and Regional Galician funds (Promotion of Research Project 10 PXIB 918 184 PR) (FMT), and Ministerio de Ciencia e Innovación (SAF2011-26983) and the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (AS). MC’s research activities have been supported by grants from Instituto de Investigación Sanitaria de Santiago de Compostela. FMT’s research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora- ISCIII/INT14/00245/ Cofinanciado FEDER), Spanish National Plan I + D + i and FEDER funds. Investigators received funding from the European Union’s Seventh Framework Program under ECGA no. 279185 (EUCLIDS – [http://www.euclids-project.eu]) during the production of this paper. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptS

    Respiratory Syncytial Virus Seasonality:A Global Overview

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    Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. By the age of 1 year, 60-70% of children have been infected by RSV. In addition, early-life RSV infection is associated with the development of recurrent wheezing and asthma in infancy and childhood. The need for precise epidemiologic data regarding RSV as a worldwide pathogen has been growing steadily as novel RSV therapeutics are reaching the final stages of development. To optimize the prevention, diagnosis and treatment of RSV infection in a timely manner, knowledge about the differences in the timing of the RSV epidemics worldwide is needed. Previous analyses, based on literature reviews of individual reports obtained from medical databases, have fail to provide global country seasonality patterns. Until recently, only certain countries have been recording RSV incidence through their own surveillance systems. This analysis was based on national RSV surveillance reports and medical databases from 27 countries worldwide. This is the first study using original source high-quality surveillance data to establish a global, robust and homogeneous report on global country-specific RSV seasonality

    Plasma lipid profiles discriminate bacterial from viral infection in febrile children

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    Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

    Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

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    Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

    Plasma lipid profiles discriminate bacterial from viral infection in febrile children

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    Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

    The ReSVinet Score for Bronchiolitis: A Scale for All Seasons

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    The ReSVinet Scale is a clinical score for the assessment of respiratory difficulty in infancy. Our aim was to provide an update on the characteristics that make this tool different to any other. We descriptively compared the characteristics of the ReSVinet Scale with other options that can be found in the current literature or mobile apps stores. The ReSVinet Scale has been devised for its use regardless of the age of the child, entity causing respiratory symptoms, and setting. To this date, it is the only pediatric respiratory scale for acute respiratory distress that provides a parental version, and it is also the first one to have undergone validation in primary care. The tool can be found either in paper format or can be downloaded via App stores for devices running on Android or iOS systems. It has also been adopted recently as the assessment instrument for several clinical trials and for an IMI2 initiative (RESCEU project). All the aforementioned characteristics of the ReSVinet Scale should help toward its dissemination, as currently no other clinical tool for the assessment of respiratory difficulty can offer those advantages
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