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Background To determine by multi-omic analysis changes in metabolites, lipids, and proteins as a consequence of transient viral rebound (tVR) in children with perinatally acquired HIV-1 (PHIV). Methods Plasma samples from children with PHIV and with tVR (first episode of transient RNA-HIV viral load >20 copies/ml followed by suppression) on the time-point immediately before (pre-tVR) and after (post-tVR) the tVR were assessed. Multi-omic analyses were performed using nLC-Orbitrap, GC-qTOF-MS, and LC-qTOF-MS. Results Comparing pre- and post-tVR time-points, HIV-1 children with tVR (n = 5) showed a trend to a decrease in ratio CD4/CD8 (p = 0.08) but no significant differences were observed in plasma metabolites, lipids, or proteins. Post-tVR condition was compared with a reference group of children with PHIV with persistent viral control (n = 9), paired by sex, age, and time under antiretroviral treatment. A total of 10 proteins, 8 metabolites, and 2 lipids showed significant differences (p < 0.05): serotransferrin, clusterin, kininogen-1, succinic acid, threonine, 2-hydroxyisovaleric acid, methionine, 2-hydroxyglutaric, triacylglyceride 50:0 (TG50:0), and diacylglyceride 34:1 (DG34:1) were upregulated while alpha-2-macroglobulin, apolipoprotein A-II, carboxylic ester hydrolase, apolipoprotein D, coagulation factor IX, peptidase inhibitor 16, SAA2-SAA4 readthrough, oleic acid, palmitoleic acid, and D-sucrose downregulated on post-tVR time-point compared to the reference group. Ratio CD4/CD8 correlated with apolipoprotein A-II, DG34:1, and methionine (p = 0.004; ρ = 0.71, p = 0.016; ρ = −0.63; and p = 0.032; ρ = −0.57, respectively). Nadir CD4+ correlated inversely with kininogen-1 (p = 0.022; ρ = −0.60) and positively with D-sucrose (p = 0.001; ρ = 0.77). Conclusions tVR followed by suppression implies changes in soluble proteins, lipids, and metabolites that correlate with immunological parameters, mainly ratio CD4/CD8, that decreased after tVR. These distinct soluble biomarkers could be considered potential biomarkers of immune progression.

RationaleIn 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB).ObjectivesThis study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe.MethodsMulticentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases Measurements and main results1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4–12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TBin 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively).ConclusionsThe results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

IntroductionThe QuantiFERON-TBGold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting.MethodsCross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients ResultsOf 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations.ConclusionsOur non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially.

Introduction: In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SERPE-SEOP) was published to help in the diagnosis and treatment of osteoarticular infections (OAI). In 2015 the RIOPed was considered as a multidisciplinary national network for the investigation into OAI. The aim of this study was to assess the level of adaption to the recommendations established in the Consensus during one year of follow-up. Material and methods: A prospective, national multicentre study was carried out in 37 hospitals between September 2015 and September 2016. The study included patients >16 years-old with a diagnosis of OAI, confirmed by microbiological isolation, or probable: septic arthritis (SA) with >40,000 white cells in synovial fluid, or osteomyelitis (OM)/spondylodiscitis (SD) with a compatible imaging test. The results were compared with those obtained in a retrospective study conducted between 2008 and 2012. Results: A total of 235 cases were included, of which 131 were OM, 79 SA, 30 OA, and 15 SD. As regards the complementary tests that the Consensus considered mandatory to perform, radiography was carried out on 87.8% of the cases, a blood culture on 91.6%, and culture of the synovial fluid in 99% of SA. A magnetic resonance (MR) was performed on 71% of the OM cases. The choice of intravenous empirical antibiotic treatment was adapted to the recommendations in 65.1% of cases, and in 62.3% for the oral treatment. Surgery was performed in 36.8% of SA cases (85.7% arthrotomy), with a significant decrease compared to the retrospective study (P = .014). Only 58.5% of cases followed the recommendations on the duration of the treatment; however, a lower duration of intravenous treatment was observed. Conclusions: In general, the level of adaptation to the recommendations that were set by the Expert Group, is good for the complementary tests, and acceptable as regards the choice of antibiotic treatment, although inadequate in almost 40% of cases. A decrease in hospital stay was achieved. Resumen: Introducción: En 2014 se publicó el Documento de Consenso desarrollado por SEIP-SERPE-SEOP para el diagnóstico y el tratamiento de las infecciones osteoarticulares (IOA). En 2015 se constituyó RIOPed como red nacional multidisciplinar para la investigación en IOA. El objetivo del estudio ha sido valorar el grado de adecuación a las recomendaciones establecidas en el consenso durante un año de seguimiento. Material y métodos: Estudio prospectivo multicéntrico nacional realizado entre septiembre de 2015 y septiembre de 2016 en 37 hospitales con inclusión de pacientes menores de 16 años diagnosticados de IOA, confirmada mediante aislamiento microbiológico, o probable: artritis séptica (AS) con >40.000 leucocitos en líquido sinovial u osteomielitis (OM)/osteoartritis (OA)/espondilodiscitis (ED) con prueba de imagen compatible. Los resultados se compararon con los obtenidos en el estudio retrospectivo realizado entre 2008 y 2012. Resultados: Se incluyeron 255 casos: 131 OM, 79 AS, 30 OA y 15 ED. Respecto a las pruebas complementarias que el consenso consideró de obligada realización, la radiografía se llevó a cabo en el 87,8% de los casos, el hemocultivo en el 91,6% y el cultivo de líquido sinovial en el 99% de AS. Se realizó RM en el 71% de las OM. La elección del tratamiento antibiótico intravenoso empírico se adecuó a las recomendaciones en el 65,1% de los casos, y en el 62,3% para el tratamiento oral. Se llevó a cabo cirugía en el 36,8% de las AS (85,7% artrotomía), con un descenso significativo respecto al estudio retrospectivo (P = ,014). Solo el 58,5% de casos se ajustaron a las recomendaciones de duración del tratamiento; sin embargo, se comprobó una menor duración del tratamiento intravenoso. Conclusiones: En general, el grado de adecuación a las recomendaciones que marcaron el grupo de expertos es bueno para las pruebas complementarias y aceptable respecto a la elección del tratamiento antibiótico, aun detectándose casi un 40% de inadecuación. Se ha conseguido un descenso de la estancia hospitalaria.

Resumen: Introducción: En 2014 se publicó el Documento de Consenso desarrollado por SEIP-SERPE-SEOP para el diagnóstico y el tratamiento de las infecciones osteoarticulares (IOA). En 2015 se constituyó RIOPed como red nacional multidisciplinar para la investigación en IOA. El objetivo del estudio ha sido valorar el grado de adecuación a las recomendaciones establecidas en el consenso durante un año de seguimiento. Material y métodos: Estudio prospectivo multicéntrico nacional realizado entre septiembre de 2015 y septiembre de 2016 en 37 hospitales con inclusión de pacientes menores de 16 años diagnosticados de IOA, confirmada mediante aislamiento microbiológico, o probable: artritis séptica (AS) con > 40.000 leucocitos en líquido sinovial u osteomielitis (OM)/osteoartritis (OA)/espondilodiscitis (ED) con prueba de imagen compatible. Los resultados se compararon con los obtenidos en el estudio retrospectivo realizado entre 2008 y 2012. Resultados: Se incluyeron 255 casos: 131 OM, 79 AS, 30 OA y 15 ED. Respecto a las pruebas complementarias que el consenso consideró de obligada realización, la radiografía se llevó a cabo en el 87,8% de los casos, el hemocultivo en el 91,6% y el cultivo de líquido sinovial en el 99% de AS. Se realizó RM en el 71% de las OM. La elección del tratamiento antibiótico intravenoso empírico se adecuó a las recomendaciones en el 65,1% de los casos, y en el 62,3% para el tratamiento oral. Se llevó a cabo cirugía en el 36,8% de las AS (85,7% artrotomía), con un descenso significativo respecto al estudio retrospectivo (p = 0,014). Solo el 58,5% de casos se ajustaron a las recomendaciones de duración del tratamiento; sin embargo, se comprobó una menor duración del tratamiento intravenoso. Conclusiones: En general, el grado de adecuación a las recomendaciones que marcaron el grupo de expertos es bueno para las pruebas complementarias y aceptable respecto a la elección del tratamiento antibiótico, aun detectándose casi un 40% de inadecuación. Se ha conseguido un descenso de la estancia hospitalaria. Abstract: Introduction: In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SERPE-SEOP) was published to help in the diagnosis and treatment of osteoarticular infections (OAI). In 2015 the RIOPed was considered as a multidisciplinary national network for the investigation into OAI. The aim of this study was to assess the level of adaption to the recommendations established in the Consensus during one year of follow-up. Material and methods: A prospective, national multicentre study was carried out in 37 hospitals between September 2015 and September 2016. The study included patients > 16 years-old with a diagnosis of OAI, confirmed by microbiological isolation, or probable: septic arthritis (SA) with > 40,000 white cells in synovial fluid, or osteomyelitis (OM)/spondylodiscitis (SD) with a compatible imaging test. The results were compared with those obtained in a retrospective study conducted between 2008 and 2012. Results: A total of 235 cases were included, of which 131 were OM, 79 SA, 30 OA, and 15 SD. As regards the complementary tests that the Consensus considered mandatory to perform, radiography was carried out on 87.8% of the cases, a blood culture on 91.6%, and culture of the synovial fluid in 99% of SA. A magnetic resonance (MR) was performed on 71% of the OM cases. The choice of intravenous empirical antibiotic treatment was adapted to the recommendations in 65.1% of cases, and in 62.3% for the oral treatment. Surgery was performed in 36.8% of SA cases (85.7% arthrotomy), with a significant decrease compared to the retrospective study (P = .014). Only 58.5% of cases followed the recommendations on the duration of the treatment; however, a lower duration of intravenous treatment was observed. Conclusions: In general, the level of adaptation to the recommendations that were set by the Expert Group, is good for the complementary tests, and acceptable as regards the choice of antibiotic treatment, although inadequate in almost 40% of cases. A decrease in hospital stay was achieved.

The aim of this transversal study was to describe the virological and immunological features of HIV-infected youths transferred from pediatric to adult care units since 1997 vs. the non-transferred patients from the Madrid Cohort of HIV-infected children and adolescents in Spain. We included 106 non-transferred and 184 transferred patients under clinical follow-up in 17 public hospitals in Madrid by the end of December 2017. Virological and immunological outcomes were compared in transferred vs. non-transferred patients. ART drug resistance mutations and HIV-variants were analyzed in all subjects with available resistance pol genotypes and/or genotypic resistance profiles. Among the study cohort, 133 (72.3%) of 184 transferred and 75 (70.7%) of 106 non-transferred patients had available resistance genotypes. Most (88.9%) of transferred had ART experience at sampling. A third (33.3%) had had a triple-class experience. Acquired drug resistance (ADR) prevalence was significantly higher in pretreated transferred than non-transferred patients (71.8% vs. 44%; p = 0.0009), mainly to NRTI (72.8% vs. 31.1%; p

The QuantiFERON-Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients18 years who had a QFT-Plus performed between September 2016 and June 2020.Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2-, n=2; TB1-/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations.Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay's performance substantially.

Knowledge of thrombosis in children with SARS-CoV-2 is scarce. In this multicentre national cohort of children with SARS-CoV-2 involving 49 hospitals, 4 patients out of 537 infected children developed a thrombotic complication (prevalence of 0.7% (95% CI: 0.2% to 1.9%) out of the global cohort and 1.1% (95% CI: 0.3% to 2.8%) out of the hospitalised patients). We describe their characteristics and review other published paediatric cases. Three out of the four patients were adolescent girls, and only two cases had significant thrombotic risk factors. In this paediatric cohort, D-dimer value was not specific enough to predict thrombotic complications. Adolescence and previous thrombotic risk factors may be considered when initiating anticoagulant prophylaxis on children with SARS-CoV-2 disease (COVID-19). Instituto de Salud Carlos III y Fondos FEDER (PI20/00095) Sociedad Española de Pediatría (AEP) 4.973 JCR (2021) Q1, 16/130 Pediatrics 0.709 SJR (2021) Q2, 12/320 Pediatrics, Perinatology and Child Health No data IDR 2020 UEM

Objectives: To evaluate electrocardiogram markers to predict coronary involvement in patients with Kawasaki disease by assessing measures of ventricular repolarization parameters on the 12-lead electrocardiogram. Study design: This cross-sectional study included 180 Spanish and Japanese patients ≤14 years of age with Kawasaki disease, with or without coronary involvement, from 2011 to 2016. We manually measured the Tp-Te/QT ratio and QTc interval (with Bazett's formula) in 12-lead electrocardiogram in the acute and recovery period and explored their potential association with coronary involvement. Results: No association was found between Tp-Te/QT ratio obtained manually in V5 and V6 leads and coronary involvement in the acute (V5:0.25 [IQR, 0.21-0.27] vs 0.25 [IQR, 0.20-0.27], P = .80; V6:0.24 [IQR, 0.21-0.27] vs 0.25 [IQR, 0.20-0.27], P = .86) or the recovery (V5: 0.23 [IQR, 0.20-0.25] vs 0.23 [IQR, 0.19-0.25], P = .68; V6: 0.23 [IQR, 0.20-0.25] vs 0.23 [IQR, 0.17-0.25], P = .50) period. By contrast, QTc in V5 and V6 was significantly lower in patients with Kawasaki disease and coronary involvement in the acute period (V5: 378 ms [IQR, 364-395 ms] vs 390 ms [IQR, 371-411 ms], P = .04; V6: 377 ms [IQR, 364-392 ms] vs 390 ms [IQR, 371-410 ms], P = .01). A QTc interval of

In this cross-sectional study of 284 children and adolescents with clinically or radiologically suspected tuberculosis in a low-endemic country, the QuantiFERON-TB Gold Plus assay specificity, sensitivity, positive predictive value and negative predictive value were 91.5%, 87.3%, 86.4%, and 91.2%, respectively. The specificity was higher than that observed in tuberculin skin tests performed simultaneously, but similar to previous-generation interferon-gamma release assays. Sin financiación 3.806 JCR (2021) Q3, 105/161 Inmunology 1.104 SJR (2021) Q1, 29/320 Pediatrics, Perinatology and Child Health No data IDR 2021 UEM

Acute mastoiditis is an infection that affects the mastoid air-cell system, usually due to the progression of an acute otitis media. The bacteria most frequently isolated in acute mastoiditis are Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus. The mastoid infection can extend affecting contiguous structures and producing intra or extracranial complications. The most frequent ones are intracranial complications, including meningitis, temporal lobe or cerebellar abscess, epidural or subdural abscess and venous sinus thrombosis. We present the case of a 4-year-old girl who developed two intracranial complications (intracranial epidural abscess and transverse and sigmoid sinus thrombosis) initiated in an acute mastoiditis produced by Streptococcus pyogenes.La mastoiditis aguda es una infección de las celdillas mastoideas, generalmente, secundaria a la progresión de una otitis media aguda. Las bacterias aisladas con más frecuencia en las mastoiditis son Streptococcus pneumoniae, Streptococcus pyogenes y Staphylococcus aureus. La infección mastoidea puede extenderse por contigüidad, afectar a estructuras vecinas y dar lugar a complicaciones intra- o extracraneales. Las más frecuentes son las intracraneales, entre las que se incluyen la meningitis, el absceso cerebeloso o del lóbulo temporal, el absceso epi- o subdural y la trombosis de senos venosos. Se presenta el caso de una niña de 4 años que desarrolló dos complicaciones intracraneales (absceso epidural y trombosis de senos venosos transverso y sigmoideo) a partir de una mastoiditis aguda producida por

Acute mastoiditis is an infection that affects the mastoid air-cell system, usually due to the progression of an acute otitis media. The bacteria most frequently isolated in acute mastoiditis are Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus. The mastoid infection can extend affecting contiguous structures and producing intra or extracranial complications. The most frequent ones are intracranial complications, including meningitis, temporal lobe or cerebellar abscess, epidural or subdural abscess and venous sinus thrombosis. We present the case of a 4-year-old girl who developed two intracranial complications (intracranial epidural abscess and transverse and sigmoid sinus thrombosis) initiated in an acute mastoiditis produced by Streptococcus pyogenes.

Objective: To study the epidemiology, clinical features, diagnosis, therapeutic management, and outcome of non-tuberculous mycobacterial lymphadenitis in a paediatric population of Aragón (Spain). Material and methods: A retrospective study was conducted on patients under 15 years-old diagnosed with non-tuberculous mycobacterial lymphadenitis between the years 2000 and 2015. Inclusion criteria: patients with lymphadenitis and positive culture. Quantitative values are shown as mean, rank, and standard deviation, and qualitative data as frequencies. Results: Twenty-seven cases were registered, with a mean age of presentation of 39.9 months (range 10 months–8 years). The mean time between the symptoms onset and first consultation was 1.7 ± 1.1 months. The most frequent location was sub-maxilar in 17/27 cases (63%), on the right side in 59.3%, and size 2.96 ± 1.26 cm. Fistulae were observed in 16/27 cases. Tuberculin test was greater than 10 mm in 7/24 (29.1%). Microbiological cultures were positive for Mycobacterium avium in 14/27 (51.9%), Mycobacterium intracellulare 3/27 (11.1%), and Mycobacterium lentiflavum 3/27 (11.1%). Combined treatment of antibiotics and surgery was given in 16/27 cases (59.8%), medical treatment only in 7/27 (25.9%), and surgical exeresis alone in 4/27 (14.8%). Two patients required a new surgery, and one showed severe neutropenia secondary to rifabutin. Only one case (3.7%) suffered from temporary facial palsy as sequel. Conclusions: The most frequent treatment was the combination of antibiotics and surgery. Delay in diagnosis seemed to be responsible for the limited number of exeresis as first option, only one for every seven patients. Resumen: Objetivo: Estudiar la epidemiología, las manifestaciones clínicas, el manejo diagnóstico-terapéutico y la evolución de las linfadenitis por micobacterias no tuberculosas en la población pediátrica de Aragón. Material y métodos: Estudio retrospectivo de pacientes menores de 15 años diagnosticados de linfadenitis por micobacteria no tuberculosa entre 2000 y 2015. Criterios de inclusión: pacientes con linfadenitis y cultivo positivo. Los resultados se expresan como medias, rango y desviación típica para las variables cuantitativas, y porcentajes para las cualitativas. Resultados: Se detectan 27 casos, edad media de presentación 39,9 meses (rango 10 meses-8 años). El tiempo desde inicio de los síntomas hasta la primera consulta especializada es 1,7 ± 1,1 meses. La localización más frecuente es submaxilar en 17/27 casos (63%), lado derecho en el 59,3%, con tamaño de 2,96 ± 1,26 cm. Solo 16/27 presentan fistulización. Prueba de tuberculina superior a 10 mm en 7/24 (29,1%). El cultivo es positivo para Mycobacterium avium en 14/27 (51,9%), Mycobacterium intracellulare 3/27 (11,1%), Mycobacterium lentiflavum 3/27 (11,1%). El 92,6% (23/27) es tratado inicialmente con amoxicilina-clavulánico. La combinación de antibióticos y cirugía se aplica en 16/27 casos (59,3%), solo antibioterapia 7/27 (25,9%) y únicamente exéresis 4/27 (14,8%). Dos pacientes precisan reintervención y un caso desarrolla neutropenia grave secundaria a rifabutina. Solo un caso (3,7%) presenta parálisis facial transitoria como secuela. Conclusiones: La combinación de antibioterapia y cirugía es el tratamiento más frecuente. El retraso en el diagnóstico hace que la exéresis como primera opción terapéutica se realice únicamente en uno de cada 7 pacientes.

Resumen: Objetivo: Estudiar la epidemiología, las manifestaciones clínicas, el manejo diagnóstico-terapéutico y la evolución de las linfadenitis por micobacterias no tuberculosas en la población pediátrica de Aragón. Material y métodos: Estudio retrospectivo de pacientes menores de 15 años diagnosticados de linfadenitis por micobacteria no tuberculosa entre 2000 y 2015. Criterios de inclusión: pacientes con linfadenitis y cultivo positivo. Los resultados se expresan como medias, rango y desviación típica para las variables cuantitativas, y porcentajes para las cualitativas. Resultados: Se detectan 27 casos, edad media de presentación 39,9 meses (rango 10 meses-8 años). El tiempo desde inicio de los síntomas hasta la primera consulta especializada es 1,7 ± 1,1 meses. La localización más frecuente es submaxilar en 17/27 casos (63%), lado derecho en el 59,3%, con tamaño de 2,96 ± 1,26 cm. Solo 16/27 presentan fistulización. Prueba de tuberculina superior a 10 mm en 7/24 (29,1%). El cultivo es positivo para Mycobacterium avium en 14/27 (51,9%), Mycobacterium intracellulare 3/27 (11,1%), Mycobacterium lentiflavum 3/27 (11,1%). El 92,6% (23/27) es tratado inicialmente con amoxicilina-clavulánico. La combinación de antibióticos y cirugía se aplica en 16/27 casos (59,3%), solo antibioterapia 7/27 (25,9%) y únicamente exéresis 4/27 (14,8%). Dos pacientes precisan reintervención y un caso desarrolla neutropenia grave secundaria a rifabutina. Solo un caso (3,7%) presenta parálisis facial transitoria como secuela. Conclusiones: La combinación de antibioterapia y cirugía es el tratamiento más frecuente. El retraso en el diagnóstico hace que la exéresis como primera opción terapéutica se realice únicamente en uno de cada 7 pacientes. Abstract: Objective: To study the epidemiology, clinical features, diagnosis, therapeutic management, and outcome of non-tuberculous mycobacterial lymphadenitis in a paediatric population of Aragón (Spain). Material and methods: A retrospective study was conducted on patients under 15 years-old diagnosed with non-tuberculous mycobacterial lymphadenitis between the years 2000 and 2015. Inclusion criteria: patients with lymphadenitis and positive culture. Quantitative values are shown as mean, rank, and standard deviation, and qualitative data as frequencies. Results: Twenty-seven cases were registered, with a mean age of presentation of 39.9 months (range 10 months–8 years). The mean time between the symptoms onset and first consultation was 1.7 ± 1.1 months. The most frequent location was sub-maxilar in 17/27 cases (63%), on the right side in 59.3%, and size 2.96 ± 1.26 cm. Fistulae were observed in 16/27 cases. Tuberculin test was greater than 10 mm in 7/24 (29.1%). Microbiological cultures were positive for Mycobacterium avium in 14/27 (51.9%), Mycobacterium intracellulare 3/27 (11.1%), and Mycobacterium lentiflavum 3/27 (11.1%). Combined treatment of antibiotics and surgery was given in 16/27 cases (59.8%), medical treatment only in7/27 (25.9%), and surgical exeresis alone in 4/27 (14.8%). Two patients required a new surgery, and one showed severe neutropenia secondary to rifabutin. Only one case (3.7%) suffered from temporary facial palsy as sequel. Conclusions: The most frequent treatment was the combination of antibiotics and surgery. Delay in diagnosis seemed to be responsible for the limited number of exeresis as first option, only one for every seven patients.

Spanish Pediatric TB Research Network (pTBred) and the European NontuberculouS MycoBacterial Lymphadenitis in childrEn (ENSeMBLE) Study., [Objectives] To assess the performance of interferon-gamma release assays (IGRAs) in the differential diagnosis between Mycobacterium avium complex (MAC) and tuberculosis (TB) in children affected with subacute/chronic submandibular/cervical lymphadenitis., [Study design] Multicenter observational study comparing children with microbiologically confirmed MAC lymphadenitis from the European NontuberculouS MycoBacterial Lymphadenitis in childrEn study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB database., [Results] Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44 out of 74 (59.5%) had positive tuberculin skin test (TST) results at the 5-mm cut-off, compared with 32 out of 33 (97%) TB cases (P < .001); at the 10-mm cut-off TST results were positive in 23 out of 74 (31.1%) vs 26 out of 31 (83.9%), respectively (P < .001). IGRA results were positive in only 1 out of 32 (3.1%) patients with MAC who had undergone IGRA testing, compared with 21 out of 23 (91.3%) TB cases (P < .001). Agreement between TST and IGRA results was poor in MAC (23.3%; κ = 0.017), but good in TB cases (95.6%; κ = 0.646). IGRAs had a specificity of 96.9% (95% CI 84.3%-99.8%), positive predictive value of 95.4% (95% CI 78.2%-99.8%), and negative predictive value of 93.9% (95% CI 80.4%-98.9%) for TB lymphadenitis., [Conclusions] In contrast to TST, IGRAs have high specificity, negative predictive value, and positive predictive value for TB lymphadenitis in children with subacute/chronic lymphadenopathy, and consequently can help to discriminate between TB and MAC disease. Therefore, IGRAs are useful tools in the diagnostic work-up of children with lymphadenopathy, particularly when culture and polymerase chain reaction results are negative.

The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.

The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.

Kawasaki disease (KD) is a multisystem vasculitis of small and medium vessels typical of childhood. Timely treatment with intravenous immunoglobulin (IVIG) has reduced the incidence of coronary artery abnormalities (CAAs) from 25% to approximately 4%.1 Asian studies have focused on infants under 3 months of age, but there are no published data about these patients from Western countries.2 3 We reviewed 621 patients under 16 years old with a diagnosis of KD between 2011 and 2016 from a multicentre study in Spain (KAWA-RACE study); 84 hospitals participated throughout the country. We found seven children under 90 days (1.13%), with a male predominance (6 of 7). Five presented irritability, but only two fulfilled the criteria for complete KD (table 1).1 The following were the main laboratory findings (median, IQR): highest C reactive protein (CRP) 24 mg/L (8.48–31.4), highest erythrocyte sedimentation rate 79 mm (70–105.5), maximum and minimum platelet count 900 ×10^9/L (682–1 117) and 506 ×10^9/L (449–612), minimum haemoglobin 10 g/dL (9–10.8), maximum leucocytes 21 ×10^9/L (16.45–23.37), minimum sodium 135.5 mEq/L (133–137.5), and minimum albumin 2.9 mg/dL (2.6–3.4). View this table: Table 1 Diagnosis, symptoms, cardiological and microbiological findings In three cases, a viral infection was diagnosed and four patients presented with CAA, but no other echocardiographic findings were detected (table 1). The median time interval since fever onset to IVIG administration was 8 days. All patients responded well to the first dose of IVIG, and only one received concomitant intravenous steroids because he was considered to be at high risk for IVIG resistance. All CAAs were transient and resolved during follow-up (table 1). Epidemiology is different in Western countries when compared with Asian …

Treatment with tumor necrosis factor α inhibitors is a risk factor for tuberculosis (TB). Despite previous treatment with isoniazid for latent TB, a 9-year-old girl with juvenile idiopathic arthritis developed disseminated TB after changing therapy with etanercept to adalimumab and after new contact with a smear-positive relative. Genotyping strain matches and susceptibility to isoniazid make reinfection more likely than reactivation in our patient.

Lymphadenitis is the most common clinical feature in nontuberculous mycobacterium infection in immunocompetent children. We present two case reports of M. lentiflavum lymphadenitis diagnosed in a tertiary hospital in the last 10 years. Routine tests were performed after persistent adenopathy, and a sample for culture was obtained, being positive for this microorganism. Both patients received oral antibiotics during several weeks. Case 1 needed complete excision after five months of treatment, whilst Case 2 was cured by medical therapy. M. lentiflavum is considered, among the newly described nontuberculous mycobacterial species, an emergent pathogen in our environment. It has its own microbiological and clinical characteristics, different from the rest of nontuberculous mycobacteria. Case reports are limited in the literature since the infection was described for the first time in 1997.

X-linked agammaglobulinemia is a primary humoral immunodeficiency. It is a recessive X-linked disorder characterized by low or absent circulating mature B cells, hypo/agammaglobulinemia and no humoral response to immunizations due to mutations along chromosome X. It is characterized by severe, recurrent and difficult treatment infections. It is diagnosed in the first 6 months of life in children; the only sign of alarm is the absent or decreased size of tonsils and lymph nodes, but it is not always present. The main cornerstones of treatment are immunoglobulin replacement therapy to maintain serum levels above 500-700 mg/dl and infection control; this allows these patients to do their day-to-day activities. We report a 2 year old boy with X-linked agammaglobulinemia, with no history of interest, who presented with P. aeruginosa sepsis. He had an excellent clinical improvement without further important infections after intravenous immunoglobulin replacement therapy.La agammaglobulinemia ligada al X es una inmunodeficiencia humoral primaria, recesiva y ligada al cromosoma X, en la que existe una disminución marcada de linfocitos B maduros, hipo-/agammaglobulinemia y escasa respuesta humoral a las inmunizaciones, debido a mutaciones en el brazo largo del cromosoma X. Se caracteriza por infecciones graves, recurrentes y difíciles de tratar, que ocurren, generalmente, a partir de los 6 meses. El único signo de alarma, no siempre presente, es la ausencia o disminución del tamaño de las amígdalas y los ganglios linfáticos. El tratamiento de elección es el sustitutivo con inmunoglobulina G intravenosa para mantener niveles séricos por encima de 500-700 mg/dl y el control de las infecciones, lo que permite que estos pacientes hagan sus tareas habituales. Se presenta un niño de 2 años sin antecedentes personales ni familiares relevantes diagnosticado con agammaglobulinemia ligada al X tras una sepsis por P. aeruginosa. Tuvo una evolución clínica adecuada sin nuevos episodios infecciosos importantes tras el inicio del tratamiento sustitutivo con inmunoglobulina G intravenosa mensual.

Lymphadenitis is the most common clinical feature in nontuberculous mycobacterium infection in immunocompetent children. We present two case reports of M. lentiflavum lymphadenitis diagnosed in a tertiary hospital in the last 10 years. Routine tests were performed after persistent adenopathy, and a sample for culture was obtained, being positive for this microorganism. Both patients received oral antibiotics during several weeks. Case 1 needed complete excision after five months of treatment, whilst Case 2 was cured by medical therapy. M. lentiflavum is considered, among the newly described nontuberculous mycobacterial species, an emergent pathogen in our environment. It has its own microbiological and clinical characteristics, different from the rest of nontuberculous mycobacteria. Case reports are limited in the literature since the infection was described for the first time in 1997.La linfadenitis es la manifestación clínica más frecuente de la infección por micobacterias no tuberculosas en niños inmunocompetentes. Se presentan dos casos de linfadenitis por M. lentiflavum diagnosticados en un hospital de tercer nivel en los últimos 10 años. Se realizaron pruebas complementarias de rutina ante adenopatía persistente y se obtuvo una muestra mediante drenaje para el cultivo, que resultó positivo para este germen. Ambos pacientes recibieron tratamiento antibiótico oral durante varias semanas. El caso 1 precisó exéresis completa al quinto mes de evolución, mientras que el caso 2 presentó resolución completa de la lesión a los 4 meses. M. lentiflavum es considerado, de entre las nuevas especies de micobacterias no tuberculosas recientemente descritas, un germen emergente en nuestro medio. Posee unas características microbiológicas y clínicas especiales, diferentes del resto de las micobacterias no tuberculosas. Son pocos los casos publicados hasta la fecha desde que se describió por primera vez la infección en 1997.

We report the epidemiology of invasive Haemophilus influenzae type B infections. The study is based on 58 children and was carried out during the years from 1981 to 1990. Sixty-three percent of the patients had meningitis, 10.3% had arthritis, 10.3% had epiglottitis, 8.6% had cellulitis and 6.9% had pneumonia. Thirteen percent of the cases were children who were less than 6 months old, 34.4% were less than 12 months old, 70.6% were less than 24 months of age and 93% were less than 4 years old. Among the latter, 90% of the children with epiglottis or pneumonia were 24 months or older compared with 16% of the patients with meningitis, arthritis or cellulitis (p0.001). Sixty-three percent of the isolated strains of Haemophilus influenzae type B were resistant to ampicillin and 19.2% of the strains were resistant to ampicillin and chloramphenicol.