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Pneumonia is a frequent manifestation of COVID-19 in hospitalized children. Methods The study involved 80 hospitals in the SARS-CoV-2 Spanish Pediatric National Cohort. Participants were children

Purpose:Bladder cancer is a clinical and social problem due to its high incidence and recurrence rates. It frequently appears in elderly patients showing other medical comorbidities that hamper the use of standard chemotherapy. We evaluated the activity of CDK4/6 inhibitor as a new therapy for patients unfit for cisplatin (CDDP).Experimental Design:Bladder cancer cell lines were tested for in vitro sensitivity to CDK4/6 inhibition. A novel metastatic bladder cancer mouse model was developed and used to test its in vivo activity.Results:Cell lines tested were sensitive to CDK4/6 inhibition, independent on RB1 gene status. Transcriptome analyses and knockdown experiments revealed a major role for FOXM1 in this response. CDK4/6 inhibition resulted in reduced FOXM1 phosphorylation in vitro and in vivo and showed synergy with CDDP, allowing a significant tumor regression. FOXM1 exerted important oncogenic roles in bladder cancer.Conclusions:CDK4/6 inhibitors, alone or in combination, are a novel therapeutic strategy for patients with advanced bladder cancer previously classified as unfit for current treatment options.

Supplementary Table 4: Spreadsheet of transcriptomic data

Includes Supplementary Figures 1-13; Supplementary Tables 1, 2, 3, 7 and 8; and Supplementary References

Supplementary Table 5: Spreadsheet of transcriptomic data

Resumen Introduccion Los objetivos principales del estudio fueron dos: a) identificar la prevalencia de sintomas depresivos y de ansiedad y trastornos del sueno en pacientes jovenes con infeccion por VIH de transmision vertical en comparacion con un grupo de pares no infectados, y b) identificar factores sociodemograficos, psicosociales y relacionados con la medicacion y otros factores de riesgo y protectores relacionados con los sintomas psicologicos. Metodos Estudio transversal en dos grupos con medidas independientes: 36 sujetos con VIH (transmision vertical) y 39 sin VIH (no infectados). Se emplearon tres instrumentos de evaluacion estandarizados y un cuestionario sociodemografico/psicosocial (STAI, BDI, PSQI y test sociodemografico adaptado). Se realizo analisis univariante y multivariante. Resultados El analisis univariante no revelo diferencias significativas entre los dos grupos en las variables psicosociales o las escalas clinicas. El analisis multivariante encontro que los sintomas psicologicos se asociaban con fuerza a factores sociodemograficos y experiencias del pasado. Conclusiones El entorno y las variables psicosociales parecen estar asociados mas estrechamente con los sintomas psicologicos que el estado de VIH y podrian explicar mejor el estado psicologico actual del individuo.

Introduction The aim of the study was twofold: a) to determine the prevalence of symptoms of depression and anxiety and sleep disturbances in young patients with vertically-transmitted HIV infection compared to uninfected peers, and b) to identify sociodemographic, psychosocial and medication-related variables and other clinical risk and protective factors related to psychological symptoms. Methods We conducted a cross-sectional study in two groups with independent measures (36 youth with vertically transmitted HIV infection and 39 HIV-negative peers). We used 3 standardised assessment tools and a sociodemographic/psychosocial questionnaire (STAI, BDI, PSQI and adapted sociodemographic test). We performed univariate and multivariable analyses. Results The univariate analysis did not find significant differences between groups either in psychosocial factors or in the clinical scores. The multivariable analysis found that the presence of psychological symptoms was strongly associated with sociodemographic factors and past events. Conclusions Psychosocial factors and the social environment seemed to correlate more strongly to psychological symptoms than HIV status and to explain better the current psychological state of individuals.

Contains fulltext : 291766.pdf (Publisher’s version ) (Open Access) BACKGROUND: Although super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment. METHODS: This was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r. RESULTS: In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough

Late presenters (LP) for HIV care are associated with higher morbidity and mortality rates. Our aim was to describe the characteristics associated with LP among adolescents in Spain. Identification of particular features may help in the design of strategies for improvement.Late-presenting adolescents diagnosed at 12-19 years of age and enrolled in the Spanish paediatric and adult HIV/AIDS cohorts (CoRIS-CoRISpe) from 2004 to 2019 were selected. LP were defined as those presenting with CD4 count350 cells/mmOf 410 adolescents newly diagnosed with HIV, 303 (73.9%) had available data for assessing late presentation. Of these, 34.7% were LP and 23.7% were cLP. The median CD4 count for cLP was 235 cells/mmOne-quarter of adolescents presented late for HIV care in Spain. Early adolescents, middle adolescents, and those born abroad presented a sevenfold, twofold, and twofold higher risk of being cLP, respectively. Enhancing the awareness of HIV risk and the access to care, especially for younger and foreign adolescents, could help reduce late presentation and tackle the adolescent HIV epidemic.

Background Knowledge about SARS-CoV-2 infection in pregnancy and newborns is scarce. The objective of this study is to analyse clinical and epidemiological characteristics of a cohort of women infected with SARS-CoV-2 during pregnancy and their newborns exposed to SARS-CoV-2 during gestation. Methods Multicentric observational study of Spanish hospitals from the GESNEO-COVD cohort, participants in RECLIP (Spanish Network of Paediatric Clinical Assays). Women with confirmed SARS-CoV-2 infection by PCR and/or serology during pregnancy, diagnosed and delivering during the period 15/03/2020–31/07/2020 were included. Epidemiological, clinical, and analytical data was collected. Results A total of 105 pregnant women with a median of 34.1 years old (IQR: 28.8–37.1) and 107 newborns were included. Globally, almost 65% of pregnant women had some COVID-19 symptoms and more than 43% were treated for SARS-COV-2. Overall, 30.8% of pregnant women had pneumonia and 5 (4.8%) women were admitted to the intensive care unit needing invasive mechanical ventilation. There was a rate of 36.2% of caesarean sections, which was associated with pneumonia during pregnancy (OR: 4.203, CI 95%: 1.473–11.995) and lower gestational age at delivery (OR: 0.724, CI 95%: 0.578–0.906). The prevalence of preterm birth was 20.6% and prematurity was associated with pneumonia during gestation (OR: 6.970, CI95%: 2.340–22.750) and having a positive SARS-CoV-2 PCR at delivery (OR: 6.520, CI95%: 1.840–31.790). All nasopharyngeal PCR in newborns were negative at birth and one positivized at 15 days of life. Two newborns died, one due to causes related to prematurity and another of unexpected sudden death during early skin-to-skin contact after delivery. Conclusions Although vertical transmission has not been reported in this cohort, the prognosis of newborns could be worsened by SARS-CoV-2 infection during pregnancy as COVID-19 pneumonia increased the risk of caesarean section deliveries and preterm births.

Asian scores developed to predict unresponsiveness to intravenous immunoglobulin (IVIG) or development of coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) are not appropriate in Western populations. The purpose of this study is to develop 2 scores, to predict unresponsiveness to IVIG and development of CAA, appropriate for Spanish population.Data of 625 Spanish children with KD collected retrospectively (2011-2016) were used to identify variables to develop the 2 scores of interest: unresponsiveness to IVIG and development of CAA. A statistical model selected best variables to create the scores, and scores were validated with data from 98 patients collected prospectively.From 625 patients of the retrospective cohort, final analysis was performed in 439 subjects: 37 developed CAA, and 212 were unresponsive to IVIG. For the score to predict CAA, a cutoff ≥ 8 was considered for high risk, considering a score system with a different weight for each of the eight variables. External validation showed a sensitivity of 22% and a specificity of 75%. The score to predict unresponsiveness to IVIG established a cutoff ≥ 8 for high risk, considering a score system with a different weight for each of the nine variables. External validation showed a sensitivity of 78% and a specificity of 50%.Two risk scores for KD were developed from Spanish population, to predict development of CAA and unresponsiveness to IVIG; validation in other cohorts could help to implement these tools in the management of KD in other Western populations.

Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) (PI20/00095) Fundacion para la Investigacion Biomedica del Hospital Universitario Infanta Sofia y del Hospital del Henares (FIIB HUIS HHEN) SERMAS-Fundacion para la Investigacion Biomedica del Hospital 12 de Octubre Universidad Europea de Madrid (UEM20/01) Spanish Society of Paediatrics (Asociacion Espanola de Pediatria) Covid-19 EPICO-AEP 2020 4.056 JCR (2021) Q1, 22/130 Pediatrics 0.922 SJR (2021) Q1, 539/2489 Medicine (Miscellaneous) No data IDR 2021 UEM

Background: Establishing the etiology of community-acquired pneumonia (CAP) in children at admission is challenging. Most of the admitted children with CAP receive antibiotics. We aimed to build and validate a diagnostic tool combining clinical, analytical and radiographic features to differentiate viral from bacterial CAP, and among bacterial CAP, typical from atypical bacteria. Methods: Design-observational, multi-center, prospective cohort study was conducted in 2 phases. Settings: 24 secondary and tertiary hospitals in Spain. Patients-A total of 495 consecutive hospitalized children between 1 month and 16 years of age with CAP were enrolled. Interventions-A score with 2 sequential steps was built (training set, 70% patients, and validation set 30%). Step 1 differentiates between viral and bacterial CAP and step 2 between typical and atypical bacterial CAP. Optimal cutoff points were selected to maximize specificity setting a high sensitivity (80%). Weights of each variable were calculated with a multivariable logistic regression. Main outcome measures-Viral or bacterial etiology. Results: In total, 262 (53%) children (median age: 2 years, 52.3% male) had an etiologic diagnosis. In step 1, bacterial CAPs were classified with a sensitivity = 97%, a specificity = 48%, and a ROC's area under the curve = 0.81. If a patient with CAP was classified as bacterial, he/she was assessed with step 2. Typical bacteria were classified with a sensitivity = 100%, a specificity = 64% and area under the curve = 0.90. We implemented the score into a mobile app named Pneumonia Etiology Predictor, freely available at usual app stores, that provides the probability of each etiology. Conclusions: This 2-steps tool can facilitate the physician's decision to prescribe antibiotics without compromising patient safety. Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) Instituto de Investigacion Hospital 12 de Octubre (i+12) AY191212-1 Universidad Europea de Madrid 2017/UEM03 Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS) Spanish Government Grant for emerging groups (PCAPE 2011_0025; 320/11) 3.806 JCR (2021) Q1, 31/130 Pediatrics 1.104 SJR (2021) Q1, 29/320 Pediatrics, Perinatology and Child Health No data IDR 2021 UEM

Objectives: To determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion. Study design: The Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (

[Objectives]: To describe the etiology of community-acquired pneumonia (CAP) in hospitalized children in Spain and analyze the predictors of the etiology., [Hypothesis]: The different etiological groups of pediatric CAP are associated with different clinical, radiographic, and analytical data., [Design]: Observational, multicenter, and prospective study., [Patient selection]: This study included children aged 1 month to 17 years with CAP, who were hospitalized between April 2012 and May 2019., [Methods]: An extensive microbiological workup was performed. The clinical, radiographic, and analytical parameters were analyzed for three etiological groups., [Results]: Among the 495 children included, at least one causative pathogen was identified in 262 (52.9%): pathogenic viruses in 155/262 (59.2%); atypical bacteria (AB), mainly Mycoplasma pneumonia, in 84/262 (32.1%); and typical bacteria (TyB) in 40/262 (15.3%). Consolidation was observed in 89/138 (64.5%) patients with viral CAP, 74/84 (88.1%) with CAP caused by AB, and 40/40 (100%) with CAP caused by TyB. Para-pneumonic pleural effusion (PPE) was observed in 112/495 (22.6%) patients, of which 61/112 (54.5%) presented a likely causative pathogen: viruses in 12/61 (19.7%); AB in 23/61 (37.7%); and TyB in 26/61 (42.6%). Viral etiology was significantly frequent in young patients and in those with low oxygen saturation, wheezing, no consolidation, and high lymphocyte counts. CAP patients with AB as the etiological agent had a significantly longer and less serious course as compared to those with other causative pathogens., [Conclusions]: Viruses and M. pneumoniae are the main causes of pediatric CAP in Spain. Wheezing, young age, and no consolidation on radiographs are indicative of viral etiology. Viruses and AB can also cause PPE. Since only a few cases can be directly attributed to TyB, the indications for antibiotics must be carefully considered in each patient., Instituto de Investigación Hospital 12 de Octubre (i+12), Grant/Award Number: AY191212‐1; Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and co‐funded by the European Regional Development Funds, Grant/Award Number: Project PI17/01458; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Grant/Award Number: PCAPE 2011_0025 Register 320/11; Research Project of Universidad Europea de Madrid, Grant/Award Number: 2017/UEM03

HIV infection results in a state of chronic immune activation leading to premature immune aging, B-cells dysfunction, that persists despite prolonged virological suppression. In this scenario, adolescence living with perinatally acquired HIV (PHIV), deserve a peculiar attention since potentially exposed for their entire life to chronic immune activation. Here we identified determinants of precocious aging B cells in 40 PHIV undergoing suppressive antiretroviral therapy (ART) for median 13.5 years. All individuals started ART by 2nd year of life and achieved virus suppression within the 1st year of ART, with majority of patient maintaining suppression until analysis and 5/40 experiencing viral Spike (transient elevation of HIV-1 VL, 50-999 copies/ml). We employed a multiomics approach including deep immunological B and T cell phenotype in PBMC, with aging B cells defined by the expression of T-bet and CD11c; plasma proteomics analysis by mass spectrometry and serum level of anti-measles antibodies as correlates of humoral response. We found that individuals with expansion of aging B cell, defined by the expression of T-bet+CD11c+, were those starting treatment later, presenting detectable levels of cell-associated HIV-1 RNA, history of Spikes, and a higher frequency of exhausted T-cells, including those expressing PD-1, LAG3, TIGIT. Accordingly, the proteomic analysis revealed that subjects with expansion of aging B cells and exhausted T cells had enrichment of proteins involved in immune inflammation and complement activation pathways, such as CLU and APCS which are also involved in tumor progression. Signs of precocious aging were associated with a reduced capacity to maintain virological memory against measles vaccination. To our knowledge, this is the first study focusing on precocious B-cell aging and dysfunctionality in PHIV with long-term virological suppression. Our experimental strategy enabled identification of clinical, viral, cellular and plasma soluble markers associated with B-cells aging. Our results pave the way to further define risk of disease progression or lymphoproliferative disorders in PHIV.Author summaryDespite a successful antiretroviral therapy (ART), adolescence living with perinatally acquired HIV (PHIV) experience B-cells dysfunction, including loss of vaccine-induced immunological memory and higher risk of developing B-cells associated tumors. It is thus paramount to define novel and precise correlates of precious aging B cell for the definition of novel therapeutic strategies. Here, we studied 40 PHIV who started treatment by 2nd year of life and maintain virological suppression for 13.5 years, with 5/40 patients experiencing transient elevation of the HIV-1 load in the plasma (Spike). We applied a multi-omics approach including immunological B and T cell phenotype, plasma proteomics analysis and serum level of anti-measles antibodies as functional correlates of vaccine-induced immunity. We found that levels of aging B cells were positively associated with age at ART start, cell associated HIV-1 RNA (caHIV-1 RNA) and the presence of Spikes. Individuals with increased proportions of aging B cells had concomitant expansion of exhausted T cells and were unable to maintain vaccine-induced immunity over time. B-cell aging, and T-cell exhaustion were also associated with proteins involved in immune inflammation. The factors found here to be associated with aging B-cell could inform further therapeutic studies.

The SARS-CoV-2 pandemic has caused an increase in antibiotic use in different settings. We describe the antibiotic prescribing prevalence, associated factors and trends, as well as concomitant bacterial infections in children hospitalized with COVID-19 or multisystemic inflammatory syndrome related to SARS-CoV-2 in Spain. Instituto de Salud Carlos III (ISCIII) Unión Europea-Fondos FEDER (proyecto PI20/00095) Ministerio de Sanidad/ISCIII Sociedad Española de Pediatría Fondos FEDER (Contrato Río Hortega CM18/00100 y CM19/00015 ) 5.235 JCR (2021) Q1, 14/130 Pediatrics 1.236 SJR (2021) Q1, 66/301 Infectious Diseases No data IDR 2020 UEM

Limited data exist regarding sex bias and viral decay in children with HIV. We investigated the sex differences in viral decay in 25 perinatally HIV-infected children. Females presented faster phase I viral decay regardless of their age at antiretroviral therapy (ART) initiation, baseline CD4 percentages, or baseline RNA levels. Also, for each month elapsed under ART, females had faster viral decay than males.

Objetives. To perform a description of the etiology of hospitalized children with community-acquired pneumonia (CAP) in Spain and analyze predictors related to etiology. Hypothesis. The different etiological groups of pediatric CAP are associated to different clinical, radiographic and analytical data. Design. Observational, multi-center, prospective study. Patient selection. Patients from 1 month to 17 years admitted because of CAP from April 2012 to May 2019. Methods. An extensive microbiological workup was done. Clinical, radiographic and analytical parameters were analyzed in order to differentiate viral, atypical bacteria (AB) and typical bacteria (TyB) pneumonia. Results. 495 children were enrolled. At least one likely causative pathogen was identified in 262 (52.9%). Pathogenic viruses in 155/262 (59.2%), AB in 84/262 (32.1%) and TyB in 40/262 (15.3%). Consolidation was found in 89/138 (64.5%) CAP attributed to virus only, in 74/84 (88.1%) of CAP attributed to AB and 40/40 (100%) of CAP attributed to TyB. Para-pneumonic pleural effusion (PPE) was found in 112/495 (22.6%) patients, 61/112 (54.5%) with a likely causative pathogen: virus 12/61 (19.7%), AB 23/61 (37.7%) and TyB 26/61 (42.6%). Viral etiology was significantly more frequent in younger patients and those with lower oxygen saturation, wheezing, no-consolidation and higher lymphocyte counts. Patients with AB were significantly more likely to have more days of fever at admission and a higher rate of use of antibiotics before admission. Conclusions. Viruses and AB are the main cause of pediatric CAP in Spain. Wheezing, younger age and no-consolidation on the X-ray support viral etiology. Viruses and AB can also cause PPE. The use of antibiotic in pediatric CAP can be restricted.

Background and ObjectivesEstablishing the etiology of community-acquired pneumonia (CAP) in children at admission is challenging. As a result, most children receive antibiotics that do not need.This study aims to build and validate a diagnostic tool combining clinical, analytical and radiographical features to sequentially differentiate viral from bacterial CAP, and among bacterial CAP, typical from atypical bacteria, to improve choice of treatment.MethodsConsecutive hospitalized children between 1 month and 16 years of age with CAP were enrolled. An extensive microbiological workup was performed. A score was built with a training set of 70% patients, to first differentiate between viral and bacterial CAP and secondly, typical from atypical bacterial CAP. To select variables, a Ridge model was used. Optimal cut-off points were selected to maximize specificity setting a high sensitivity (80%). Weights of each variable were calculated with a multivariable logistic regression. The score was validated with the rest of the participants.ResultsIn total, 262 (53%) children (median age, 2 years, 52.3% male) had an etiological diagnosis.The step 1 discriminates viral from bacterial CAP. Bacterial CAPs were classified with a sensitivity=97%, a specificity=48%, and a ROC’s area under the curve (AUC)=0.81. If a CAP was classificated as bacterial, it was assessed with step 2. The step 2 differentiates typical vs. atypical bacterial CAP. Typical bacteria were classified with a sensitivity=100%, a specificity=64%, and AUC=0.90.ConclusionThis two-steps tool can facilitate the physician’s decision to prescribe antibiotics without compromising patient safety.Article summaryWe validated a clinical tool to predict the aetiology of CAP in children safely. This tool differentiates CAP into viral, atypical bacteria and typical bacteria.“What’s Known on This Subject”Establishing the aetiology of community-acquired pneumonia (CAP) in children at admission is challenging. As a result, most admitted children with CAP receive antibiotics.“What This Study Adds”We validated a clinical tool to predict the aetiology of pneumonia in children safely, differentiating among viral, atypical bacteria and typical bacteria.

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

A retrospective study that compared children younger than 6 months versus older children of a Spanish cohort of patients diagnosed with Kawasaki disease between 2011 and 2016 (Kawa-Race study). From the 598 patients recruited, 42 patients were younger than 6 months (7%) and presented more frequently with an incomplete diagnosis of Kawasaki disease (52.4 vs 27.9%, p = 0.001). Cardiac abnormalities detected by echocardiography were more common in younger patients (52.4 vs 30%, p = 0.002). These younger patients presented with a higher proportion of coronary aneurysms as well (19 vs 8.6%, p 0.001). Shock at diagnosis (9.5 vs 1.9%, p = 0.016) and admission to intensive care units (17.7 vs 4.1%, p = 0.003) were more frequent in patients younger than 6 months. There were no statistically significant differences in relation to infections, non-response to IVIG, or mid- or long-term outcomes.Conclusion: Data of the Spanish cohort are consistent with other American and Asian studies, although Spanish children younger than 6 months had a lower rate of non-response to IVIG and better clinical outcomes. A high index of suspicion should be considered for this population due to a higher risk of coronary abnormalities, presentation of shock, and admission to the intensive care unit. What is Known: •Children below 6 months of age with Kawasaki disease (KD) have different features compared to older. •Younger patients usually have an incomplete form of KD and coronary artery abnormalities. What is New: •Younger than 6 months with KD presented with shock and required admission to PICU more frequently compared to older. •Infections play a similar role in KD despite the age of the patients.

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

Background: Scarce evidence exists about the best treatment for multi-system inflammatory syndrome (MIS-C). We analysed the effects of steroids, intravenous immunoglobulin (IVig), and their combination on the probability of discharge over time, probability of switching to second-line treatment over time, and persistent fever after 2 days of treatment. Methods: We did a retrospective study to investigate the effect of treatments (IVig plus steroids, steroids alone or IVig alone) on children with MIS-C from 1 March to 1 June 2021. We estimated the time-to-event probability using a Cox model weighted by propensity score to balance the baseline characteristics. Findings: 30/132 (22·7%) patients were initially treated with steroids alone, 29/132 (21·9%) with IVig alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVig than with IVig plus steroids (hazard ratio [HR] 1·65, 95% CI 1·11–2·45, p=0·013), but with a higher probability of needing second-line therapy versus IVig plus steroids (HR 3·05, 95% CI 1·12-8·25, p=0·028). Patients on steroids had a lower probability of persistent fever after 2 days of treatment (odds ratio [OR] 0·55, 95% CI, 0·28–1·05, p=0·081) versus patients on IVig plus steroids, and those on the combination had a lower probability versus IVig alone (OR 0·21, 95% CI, 0·09–0·46, p=0·0001). Interpretation: The benefits of each approach may vary depending on the outcome assessed. IVig seemed to increase the probability of earlier discharge over time but also of needing second-line treatment over time. Steroids seemed to reduce persistent fever after 2 days of treatment, and combination therapy reduced the need for escalating treatment. Funding Information: Instituto Salud Carlos III, PI20/00095, SERMAS-Fundacion para la Investigacion Biomedica Hospital 12 de Octubre, Spanish Society of Paediatrics, SERMAS-Fundacion para la Investigacion Biomedica Hospitales Infanta Sofia y Henares, Fundacion Universidad Europea de Madrid. Declaration of Interests: No conflicts of interest. Ethics Approval Statement: The study was approved by the Ethics Committee of Hospital 12 de Octubre, Madrid (code 20/101), and other participating hospitals. Participants were enrolled after signed or verbal consent from parents/guardians and by the consent of patients older than 12 years.

Introduction Persistence of HIV‐1, causing chronic immune activation, is a key determinant of premature senescence. Early antiretroviral therapy (ART) has been associated with a reduced HIV‐1 reservoir in children with perinatally acquired HIV‐1 (PHIV), but its impact on the senescence process is an open question. We investigated the association between HIV‐1 reservoir and biological and immune ageing profile in PHIV enrolled in the multicentre cross‐sectional study CARMA (Child and Adolescent Reservoir Measurements on early suppressive ART) conducted within the EPIICAL (Early treated Perinatally HIV Infected individuals: Improving Children's Actual Life) consortium. Methods Between September 2017 and June 2018, CARMA enrolled 40 PHIV who started ART before 2 years of age and had undetectable viremia for at least 5 years before sampling date. Samples from 37 children with a median age of 13.8 years were available for this study. HIV‐1 DNA copies on CD4 cells, relative telomere length (marker of cellular senescence) and levels of T‐cell receptor rearrangement excision circle (TREC, marker of thymic output) on CD4 and CD8 cells were quantified by qPCR. Immunological profile was assessed by flow cytometry. Associations between molecular and phenotypic markers, HIV‐1 reservoir and age at ART initiation were explored using a multivariable Poisson regression. Results Higher HIV‐1 reservoir was associated (p

Background: We aimed to identify risk factors causing critical disease in hospitalized children with COVID-19 and to build a predictive model to anticipate the probability of need for critical care. Methods: We conducted a multicenter, prospective study of children with SARS-CoV-2 infection in 52 Spanish hospitals. The primary outcome was the need for critical care. We used a multivariable Bayesian model to estimate the probability of needing critical care. Results: The study enrolled 350 children from March 12, 2020, to July 1, 2020: 292 (83.4%) and 214 (73.7%) were considered to have relevant COVID-19, of whom 24.2% required critical care. Four major clinical syndromes of decreasing severity were identified: multi-inflammatory syndrome (MIS-C) (17.3%), bronchopulmonary (51.4%), gastrointestinal (11.6%), and mild syndrome (19.6%). Main risk factors were high C-reactive protein and creatinine concentration, lymphopenia, low platelets, anemia, tachycardia, age, neutrophilia, leukocytosis, and low oxygen saturation. These risk factors increased the risk of critical disease depending on the syndrome: the more severe the syndrome, the more risk the factors conferred. Based on our findings, we developed an online risk prediction tool (https://rserver.h12o.es/pediatria/EPICOAPP/, username: user, password: 0000). Conclusions: Risk factors for severe COVID-19 include inflammation, cytopenia, age, comorbidities, and organ dysfunction. The more severe the syndrome, the more the risk factor increases the risk of critical illness. Risk of severe disease can be predicted with a Bayesian model. Sin financiación 2.129 (2020) Q4,143/162 Inmunology 1.104 SJR (2021) Q1, 29/320 Pediatrics, Perinatology and Child Health No data IDR 2020 UEM

We conducted a multicenter clinical validity study of the Panbio coronavirus disease 2019 Antigen Rapid Test of nasopharyngeal samples in pediatric patients with coronavirus disease 2019-compatible symptoms of ≤5 days of evolution. Our study showed limited accuracy in nasopharyngeal antigen testing: overall sensitivity was 45.4%, and 99.8% of specificity, positive-predictive value was 92.5%.

Background Strategies aimed at antiretroviral therapy (ART)–free remission will target individuals with a limited viral reservoir. We investigated factors associated with low reservoir measured as total human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells (PBMCs) in perinatal infection (PaHIV). Methods Children from 7 European centers in the Early Treated Perinatally HIV Infected Individuals: Improving Children’s Actual Life (EPIICAL) consortium who commenced ART aged 5 years were included. Total HIV-1 DNA was measured by quantitative polymerase chain reaction per million PBMCs. Factors associated with total HIV-1 DNA were analyzed using generalized additive models. Age, VL at ART initiation, and baseline CD4% effects were tested including smoothing splines to test nonlinear association. Results Forty PaHIV, 27 (67.5%) female 21 (52.5%) Black/Black African, had total HIV-1 DNA measured; median 12 (IQR, 7.3–15.4) years after ART initiation. Eleven had total HIV-1 DNA 6 logs. The effect of CD4% (coefficient = 0.03 ± 0.01, P = .049) was not maintained >40%. Conclusions In this PaHIV cohort, reduced total HIV-1 DNA levels were associated with younger age and lower VL at ART initiation. The impact of early-infant treatment on reservoir size persists after a decade of suppressive therapy., Initiation of antiretroviral therapy at a younger age and lower plasma viral load were associated with a lower HIV-1 viral reservoir in peripheral blood mononuclear cells after more than a decade of sustained virological suppression.

Pediatric National AIDS Research Network of Spain (CORISPE) integrated in the Translational Research Network in Pediatric Infectious Diseases (RITIP)., HIV co‐infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV‐infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co‐infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV–co‐infected patients and age‐ and sex‐matched vertically HCV–mono‐infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty‐seven co‐infected patients were compared with 67 matched HCV–mono‐infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co‐infected vs 20% mono‐infected had progressed to advanced fibrosis (P = .617). Peg‐IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P‐value < .001). At treatment initiation, co‐infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P < .001), and 47.1% vs 7.1% showed advanced fibrosis (P < .003), with no differences in hard‐to‐treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P = .122). In vertically HIV/HCV–co‐infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg‐IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct‐acting antivirals against HCV for vertically co‐infected patients., This study was supported by the Instituto de Salud Carlos III, FEDER—Spanish Ministry of Science an Innovation [The Spanish National Cohort of HIV‐infected Children (CoRISpe)], included in the Spanish National AIDS Research Network (RIS) [Grant no RD16/0025] and a Fellowship from Gilead 2014 [GLD 14/00264]. The study is part of the FARO project: characterization of young adults transitioned to adult care units (RIS‐EPICLIN‐06/2013). TS has been funded by the European Society of Pediatric Infectious Diseases (ESPID Research Fellowship) and is now funded by the Instituto de Salud Carlos III—Spanish Ministry of Health and Innovation [contratos Juan Rodés, Grant JR16/00021] cofunded by Fondos FEDER of the EU.

Pneumonia is a lung infection that causes 15% of childhood mortality (under 5 years old), over 800,000 children under five every year, around 2,200 every day, all over the world. This pathology is mainly caused by viruses or bacteria. X-rays imaging analysis is one of the most used methods for pneumonia diagnosis. These clinical images can be analyzed using machine learning methods such as convolutional neural networks (CNN), which learn to extract critical features for the classification. However, the usability of these systems is limited in medicine due to the lack of interpretability, because of these models cannot be used to generate an understandable explanation (from a human-based perspective), about how they have reached those results. Another problem that difficults the impact of this technology is the limited amount of labeled data in many medicine domains. The main contributions of this work are two fold: the first one is the design of a new explainable artificial intelligence (XAI) technique based on combining the individual heatmaps obtained from each model in the ensemble. This allows to overcome the explainability and interpretability problems of the CNN “black boxes”, highlighting those areas of the image which are more relevant to generate the classification. The second one is the development of new ensemble deep learning models to classify chest X-rays that allow highly competitive results using small datasets for training. We tested our ensemble model using a small dataset of pediatric X-rays (950 samples of children between one month and 16 years old) with low quality and anatomical variability (which represents one of the biggest challenges addressed in this work). We also tested other strategies such as single CNNs trained from scratch and transfer learning using CheXNet. Our results show that our ensemble model clearly outperforms these strategies obtaining highly competitive results. Finally we confirmed the robustness of our approach using another pneumonia diagnosis dataset (Kermany et al., 2018). Sin financiación 7.307 JCR (2021) Q1, 10/110 Computer Science, Theory & Methods 2.233 SJR (2021) Q1, 23/351 Computer Networks and Communications No data IDR 2021 UEM