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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.

Background Early combined antiretroviral treatment (cART) in perinatally acquired HIV-1 children has been associated with a rapid viral suppression, small HIV-1 reservoir size and reduced mortality and morbidity. Immunometabolism has emerged as an important field in HIV-1 infection offering both relevant knowledge regarding immunopathogenesis and potential targets for therapies against HIV-1. Objectives To characterize the proteomic, lipidomic and metabolomic profile of HIV-1-infected children depending on their age at cART initiation. Patients and methods Plasma samples from perinatally HIV-1-infected children under suppressive cART who initiated an early cART (first 12 weeks after birth, EARLY, n = 10) and late cART (12–50 weeks after birth, LATE, n = 10) were analysed. Comparative plasma proteomics, lipidomics and metabolomics analyses were performed by nanoLC-Orbitrap, UHPLC-qTOF and GC-qTOF, respectively. Results Seven of the 188 proteins identified exhibited differences comparing EARLY and LATE groups of HIV-1-infected children. Despite no differences in the lipidomic (n = 115) and metabolomic (n = 81) profiles, strong correlations were found between proteins and lipid levels as well as metabolites, including glucidic components and amino acids, with clinical parameters. The ratio among different proteins showed high discriminatory power of EARLY and LATE groups. Conclusions Protein signature show a different proinflammatory state associated with a late cART introduction. Its associations with lipid levels and the relationships found between metabolites and clinical parameters may potentially trigger premature non-AIDS events in this HIV-1 population, including atherosclerotic diseases and metabolic disorders. Antiretroviral treatment should be started as soon as possible in perinatally acquired HIV-1-infected children to prevent them from future long-life complications.

Inborn errors of intermediary metabolism (IEiM) are a group of monogenic disorders that affect a metabolic pathway of proteins, carbohidrates, or lipids; when not treated timely, IEiM are associated with high morbidity and mortality. To date, nutritional therapy is the cornerstone of treatment for patients with IEiM, which aims to prevent the accumulation of toxic metabolites by restricting the substrates involved in the affected pathway. Nutritional management in infants includes a metabolic formula free of the nutrients involved in IEiM and breastmilk or infant formula. Because of its amino acid profile, the content of essential fatty acids, and protection against disease, breast milk is an excellent food for patients with IEiM. This literature review on breastfeeding in some IEiM aims to serve as a guide for health care personnel involved in the medical care of these patients. Breastfeeding can be successfully carried out in patients with IEiM as long as there is a close and continuous follow-up, preferably in specialized centers. The nutrition professional and the pediatrician should individualize the recommendations to provide on-demand breastfeeding in conjunction with metabolic formula or quantified breastfeeding to achieve a good clinical evolution in this group of patients.Los errores innatos del metabolismo intermediario (EIMi) son un grupo de enfermedades monogénicas que afectan alguna vía del metabolismo de las proteínas, los hidratos de carbono o los lípidos; cuando no son tratados a tiempo, se asocian con una elevada morbimortalidad. A la fecha, la piedra angular del tratamiento de los EIMi ha sido la terapia nutricional, cuyo propósito es evitar la acumulación de metabolitos tóxicos al restringir los sustratos que están involucrados en la vía afectada. El manejo nutricional en lactantes incluye una fórmula metabólica sin los nutrimentos involucrados en el EIMi más el aporte de alimentación al seno materno o fórmula infantil. Por el perfil de aminoácidos, la proporción de ácidos grasos esenciales y la protección contra enfermedades, la leche materna resulta un alimento ideal para los pacientes con EIMi. El objetivo de esta revisión de la literatura sobre la lactancia materna en algunos EIMi es servir de guía para el personal de salud involucrado en la atención médica de estos pacientes. La lactancia materna puede ser llevada a cabo de forma exitosa en pacientes con EIMi siempre que exista un seguimiento estrecho y continuo, de preferencia en centros especializados. El profesional de la nutrición y el pediatra deben individualizar las recomendaciones para proporcionar una lactancia a libre demanda en conjunto con una fórmula metabólica o una lactancia materna cuantificada, y con ello lograr una adecuada evolución en estos pacientes.

Multicenter study designed to describe epidemiologic and clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive cases registered among children and adolescents living with HIV (CALWH). SARS-CoV-2 infection was confirmed in 13.3% of CALWH, with all patients presenting mild symptoms, and the outcome was good in all patients. None of the HIV- and antiretroviral treatment-related variables studied were associated with greater infection risk or could be considered protective.

Objectives We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. Methods We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA Results Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs sampling of 21.3 years (IQR: 15.6–23.1) with 4 years (IQR 2.1–6.5) of suppressed viral load (VL). Nine (75%) youths did not present M184V/I in pDNA after at least 1 year of viral suppression. In December 2019, the remaining three subjects carrying M184V/I in pDNA maintained suppressed viraemia, and two still used emtricitabine in ART. Conclusions The prevalence of resistance mutations to lamivudine and emtricitabine in pDNA in a cohort of youths perinatally infected with HIV who remain with undetectable VL, previously lamivudine and/or emtricitabine experienced, was infrequent. Our results indicate that ART including lamivudine or emtricitabine may also be safe and successful in youths with perinatal HIV with previous experience of and resistances to these drugs detected in plasma.

Pneumatoceles are rare complications of pulmonary tuberculosis in children. We present 2 cases in infants of disseminated tuberculosis complicated by pneumatoceles with different evolution. This complication should be considered if worsening of respiratory symptoms occurs after initiating anti-tuberculous treatment. Treatment of pneumatoceles is usually conservative and surgical treatment should be used in patients with giant cysts which cause respiratory distress.

HIV infection continues to be a worldwide public health problem. After the introduction of effective preventive measures, perinatal transmission dramatically decreased. Our aim was to assess the sociodemographic changes in pregnant women living with HIV infection and trends in perinatal transmission rates over time.The Madrid cohort of HIV-infected mother-infant pairs is a multicenter, prospective, observational, and cohort study that collects information on HIV-infected pregnant women and their children.Information on clinical-epidemiological characteristics of HIV-infected pregnant women until delivery and their children from 9 public hospitals was included. Data were collected from a standardized questionnaire from medical records. The results were classified in 3 periods: period 1 (P1) 2000-2006, period 2 (P2) 2007-2013, and period 3 (P3) 2014-2020.A total of 1521 women living with HIV and 1548 newborns were included. In P1, most mothers (75.8%) were Spanish, whereas in P2 and P3 there was a predominance of foreign origin [62.8% and 70.5% respectively ( P0.01)]. The percentage of women with antiretroviral treatment before pregnancy increased significantly in P3 ( P0.01). The proportion of Caesarean sections decreased over time ( P0.01): 66.2% (n = 472) in P1, 54.9% (n = 245) in P2, and 46.7% (n = 141) in P3. The percentage of preterm and low birth weight newborns showed a statistically significant decrease. Even though there were no statistically significant differences ( P = 0.154), a decrease in cases of perinatal infection was observed (1.6% in P1, 1.3% in P2 and 0.3% in P3).The epidemiologic characteristics of pregnant women with HIV infection have changed over time in our setting, with an increase of non-Caucasian, heterosexual, and perinatally infected mothers. Although there are still perinatal infections, especially in vulnerable populations such as immigrant women, transmission rate has markedly decreased in recent years and is still of major concern. Prevention measures should be reinforced in the most socially disadvantaged groups.

This study provides practical recommendations on infection screening in pediatric patients with immune-mediated rheumatic diseases and immunosuppressive therapies. For this reason, a qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using Mesh and free texts to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases and immunosuppressive therapies. The results were presented and discussed in a nominal group meeting, comprising a committee of 12 pediatric rheumatologists from the infections prevention and treatment working group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants to the process produced a score ranging from 0 = totally disagree to 10 = totally agree. Agreement was considered if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (21 on infection screening) voted by 59 pediatric rheumatologists and other pediatric specialists, all of them achieving the pre-established agreement level. The recommendations on screening cover all the procedures (serology, assessment of risk factors, and other clinical activities) connected with the screening for infections including tuberculosis; hepatitis A, B, and C viruses; measles; mumps; rubella; diphtheria; and other infections. Conclusion: Screening for infections is an essential part of risk management in pediatric patients with immune-mediated rheumatic diseases and immunosuppressive therapies. What is Known: • Infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. • At present, practical information on infectious prophylaxis in children with rheumatic diseases is limited, and often extrapolated from children with cancer. What is New: • In the absence of evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that would be useful in clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists.

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

Perinatal transmission of HIV has dramatically decreased in high-income countries in the last few years with current rates below 1%, but it still occurs in high-risk situations, mainly pregnant women with late diagnosis of infection, poor antiretroviral adherence and a high viral load (VL). In these high-risk situations, many providers recommend combined neonatal prophylaxis (CNP). Our aim was to evaluate the safety and toxicity of CNP in infants deemed at high-risk of HIV infection among mother-infant pairs in the Madrid Cohort.Prospective, multicenter, observational cohort study between years 2000 and 2019. The subgroup of newborns on CNP and their mothers were retrospectively selected (cohort A) and compared with those who received monotherapy with zidovudine (cohort B). Infants with monotherapy were classified according to treatment regimes in long (6 weeks) and short (4 weeks) course.We identified 227 newborns (33.3% preterm and 7 sets of twins) with CNP. A maternal diagnosis of HIV-1 infection was established during the current pregnancy in 72 cases (36.4%) and intrapartum or postpartum in 31 cases (15.7%). Most infants received triple combination antiretroviral therapy (65.6%; n = 149). The perinatal transmission rate in cohort A was 3.5% (95% confidence interval: 1.13%-5.92%). Infants from cohort A developed anemia (26.1% vs. 19.4%, P = 0.14) and neutropenia more frequently at 50-120 days (21.4% vs. 10.9%, P0.01), without significant differences in grade 3 and 4 anemia or neutropenia between the two cohorts. There were no differences in increased alanine aminotransferase. Neutropenia was more common in the long zidovudine regimes.Our findings provide further evidence of the safety of CNP in infants with high-risk of HIV-1 perinatal transmission.

An increasing number of women living with perinatally acquired HIV are reaching adulthood and becoming pregnant. Achieving viral suppression is challenging in this population frequently exposed to numerous antiretroviral regimens. This study describes the long-term outcomes of pregnant women living with perinatally acquired HIV in Spain.Descriptive, retrospective, multicenter study of the women living with perinatally acquired HIV who gave birth between January 2000 and December 2019 in Madrid. Epidemiological, clinical, and HIV-related data were collected from the first delivery to the end of the study period, including antiretroviral therapy, prevention strategies, and outcomes.Sixty-three live births in 33 women were included. The mean number of pregnancies per women was 1.9 (range: 1-6). At first delivery, women's median age was 20 years (interquartile range: 18-23), 11 (33.3%) had been previously diagnosed with AIDS and 6 (18%) with mental health disorders. Forty percent became pregnant unsuppressed, whereas 81% achieved viral suppression at delivery. Treatment interruptions were common after delivery, as were losses to follow-up, with no positive effect of pregnancy on retention to care or the immune virological situation. Five women (15%) experienced a new AIDS event, and there were 2 deaths (6%) during follow-up. There was 1 case of mother-to-child transmission in a nonadherent woman in whom preventive measures could not be implemented.Pregnancy in this unique population of women living with perinatally acquired HIV poses particular challenges. Specific strategies, including a multidisciplinary approach, are needed to minimize perinatal transmission risks and improve outcomes during the postpartum period.

Data regarding humoral and cellular response against SARS-CoV-2 in children are scarce. We analysed seroconversion rate, decrease of anti-RBD IgG antibodies over time and T-cell response in paediatric patients who suffered COVID-19.Longitudinal study of paediatric patients COVID-19 diagnosed by positive molecular assay in nasopharyngeal swabs. Blood samples were drawn 1-2 months and 6-7 months after acute infection. Anti-RBD IgG were determined using the Alinity® SARS-CoV-2 IgG II Quant assay (Abbott). Cellular immune response was analysed by T-SPOT® SARS-CoV-2 assay kit (Oxford Immunotec Ltd.).27/39 (69,2%) patients seroconverted. Despite a significant decrease in antibody levels over time (p 0,01), no children seroreverted between first and second visits. Only 6/16 (37,2%) children under 6 years-old were seropositive compared to 21/23 (91,3%) over 6 years-old (p 0,01). Highest antibody levels were found in seropositive younger children (p = 0,036). Thirteen (33,3%) children showed T-cell response. Among participants showing humoral response, no cellular response was detected in 14 (51,9%).Anti-RBD IgG antibodies persistence at 6-7-months after SARS-CoV-2 infection was observed. A different IgG response was found depending on age. As measured by T-SPOT, most patients did not display cellular response 6-7 months after infection.

La fenilcetonuria y otras hiperfenilalaninemias son enfermedades genéticas cuya detección actualmente es obligatoria en México, tanto en el sector público como en el privado. La detección y el tratamiento oportunos han demostrado prevenir las manifestaciones neurológicas y la discapacidad que caracterizan esta enfermedad. Por ello, es de suma importancia que el pediatra y el personal de salud involucrados en la atención de estos pacientes conozcan, comprendan e implementen el manejo nutricional de manera correcta. Aunque existen varios tratamientos, el más utilizado es la restricción dietética de fenilalanina. El tratamiento nutricio incluye el uso de la llamada «fórmula médica» o «fórmula metabólica sin fenilalanina», la cual fue concebida desde el primer tercio del siglo XX. Posteriormente, se han realizado múltiples estudios y modificaciones con el fin de mejorar el pronóstico de los pacientes. El presente trabajo describe las principales características y diferencias entre las fórmulas libres de fenilalanina de seguimiento disponibles en México, para que el personal de salud cuente con elementos para su correcta prescripción.

Background Chagas disease (CD) has become an emerging global health problem in association with the immigration of individuals from endemic areas (in LatinAmerica) to other countries.Spain is the country in Europe with the highest number of CD cases. Concerning pediatric CD, treatment is not only better tolerated by younger children but also has greater cure possibilities. The aim of this study was to describe clinical and epidemiological aspects of CD in a pediatric population diagnosed of 10 hospitals in the Community of Madrid during the 2004–2018 period, as well as the safety and efficacy of CD treatment on this population. Methodology/Principal findings A multicenter, retrospective, descriptive study was conducted. The studied population included all identified children under the age of 18 with a diagnosis of CD. Diagnosis was performed with a positive parasitological test (with subsequent confirmation) or confirmed persistence of positive serology beyond 9 months, for children younger than one year-old, and with two different positive serological tests, for children older than one. Fifty-one children were included (59% male; 50.9% born in Spain). All mothers were from Latin America. The median age at diagnosis was 0.7 months for those under one year of age, and 11.08 years for those older than one year-old. Only one case presented a symptomatic course (hydrops faetalis, haemodynamic instability at birth, ascites, anaemia). For 94% treatment was completed. Considering patients who received benznidazole (47), AE were recorded in 48,9%. Among the 32 patients older than one year-old treated with benznidazole, 18 (56.25%) had adverse events whereas in the 15 under one year, 5(33,3%) did. Eigtheen (78.2%) of the patients with benznidazole AE were older than one year-old(median age 11.4 years). Of the patients treated with nifurtimox (9), AE were reported in 3 cases (33,3%). Cure was confirmed in 80% of the children under one year-old vs 4.3% in those older (p Conclusions/Significances Screening programs of CD since birth allow early diagnosis and treatment, with a significantly higher cure rate in children treated before one year of age, with lower incidence of adverse events. The high proportion of patients lost to follow-up in this vulnerable population is of concern.

Background Despite a notable decrease in acute rheumatic fever (ARF) incidence in the past few decades, there are still cases in our setting. Sydenham chorea (SC) may be the initial manifestation for this condition in childhood in a significant proportion of children. We report two cases of choreoathetosis in children as the first manifestation of ARF. Case presentation A previously healthy 8-year-old boy presented with right hemichorea with a predominance in the brachial region, orofacial dyskinesias and speech difficulties for the past 2 weeks. The only medical history of interest was a common catarrhal illness 3 weeks before and nonspecific bilateral tenosynovitis in both feet since a year prior. A brain computerized tomography was normal and the echocardiogram showed mild mitral and aortic regurgitation, meeting ARF criteria. He demonstrated clinical improvement with treatment based on prednisone and carbamazepine. The second patient was a 10-year-old girl with choreic movements of the right half of the body and repetitive right eye closure of 1 week duration. She had symptoms of fever and rash the previous week and pharyngitis that resolved without antibiotic 2 months before. Blood tests revealed elevated C reactive protein (12 mg/dl) and erythrocyte sedimentation rate (96 mm/h). Brain magnetic resonance was normal and echocardiogram showed left ventricle dilation and mild mitral regurgitation, leading to the diagnosis of ARF. Due to neurological involvement, she received corticosteroids and intravenous immunoglobulin treatment, with worsening of neurological symptoms that required valproic acid with remission of the hemichorea. In addition skin lessions compatible with erythema marginatum appeared on the upper limbs. Conclusions SC should be the main diagnostic consideration in cases of hemichorea with normal neuroimaging in children. The cases reported highlight the need to maintain a high index of suspicion even in settings where incidende of ARF is low and the need to perform cardiological investigations in all patients with suspected SC, due to the possibility of subclinical valve lesions. Good adherence to secondary prophylaxis is crucial to avoid chorea relapses and worsening valve disease.

Introduction Immune abnormalities have been described among youth with vertically acquired HIV (YWVH) despite antiretroviral treatment (ART). The CD4/CD8 ratio could be a useful prognostic marker. We assess immune activation and senescence in a cohort of YWVH in comparison to youth without vertically acquired HIV. Methods YWVH under suppressive ART were included and compared to a group of HIV‐negative donors (HD) matched by age and sex, from September 2019 to September 2020. Subset distribution and expression of activation, maturation, senescence and exhaustion markers on T and NK cells were studied on peripheral blood mononuclear cells by multiparametric flow cytometry. Results Thirty‐two YWVH (median age: 24.4 years (interquartile range: 22.5 to 28.3 years)) were included. Among YWVH, CD4‐ and CD8‐T cells showed high levels of activation (HLA‐DR/CD38), IL‐7 receptor expression (CD127) and exhaustion (TIM‐3). Regarding NK cells, YWVH showed increased levels of activation and exhaustion markers compared to HD. Strong inverted correlations were observed between T‐cell activation (HLA‐DR/CD38), senescence (CD57) and exhaustion (TIGIT, PD‐1) levels with the CD4/CD8 ratio among YWVH. HLA‐DR, CD69, NKG2D and NKG2A expression levels on NK cells also correlated with the CD4/CD8 ratio. Age at ART initiation was directly associated with higher frequency of CD16high NK‐cell subsets, exhaustion T‐cell levels (CD57, TIM3) and NK cells activation levels. Conclusions Immunological changes associated with vertically acquired HIV, characterized by increased activation and exhaustion levels in innate and adaptive immune components, are only partially restored by ART. The CD4/CD8 ratio can be a useful marker of disease progression for routine clinical practice.

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

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%.

This article belongs to the Special Issue Role of Prebiotics and Probiotics in Health and Disease., [Aims]: The gut microbiota exerts a critical influence in the immune system. The gut microbiota of human virus immunodeficiency (HIV)-infected children remains barely explored. We aimed to characterize the fecal microbiota in vertically HIV-infected children and to explore the effects of its modulation with a symbiotic nutritional intervention., [Methods]: A pilot, double blind, randomized placebo-controlled study including HIV-infected children who were randomized to receive a nutritional supplementation including prebiotics and probiotics or placebo for four weeks. HIV-uninfected siblings were recruited as controls. The V3–V4 region of the 16S rRNA gene was sequenced in fecal samples., [Results]: 22 HIV-infected children on antiretroviral therapy (ART) and with viral load (VL), [Conclusions]: Vertical HIV infection is characterized by changes in gut microbiota structure, distinct at the compositional level from the findings reported in adults. A short nutritional intervention attenuated bacterial dysbiosis, without clear changes at the community level., [Summary]: In a group of 24 vertically HIV-infected children, in comparison to 11 uninfected controls, intestinal dysbiosis was observed despite effective ART. Although not fully effective to restore the microbiota, a short intervention with pre/probiotics attenuated bacterial dysbiosis., This work was funded by the Instituto de Salud Carlos III, Acción Estratégica en Salud (PI13/0422, ICI14/00207, PI17/01283, and PI18/00042) and by an agreement between the Instituto de Salud Carlos III and the Fundación Asociación Española contra el Cáncer within the ERANET TRANSCAN-2 program, grant number AC17/00022. CoRISpe is integrated in the Spanish AIDS Research Network (RIS), supported by the Instituto de Salud Carlos III (Grant nº RD06/0006/0034 and nº RD06/0006/0035). TS was funded by a 2014 Research Fellowship Award from the European Society of Pediatric Infectious Diseases (ESPID) and is now funded by the Spanish Ministry of Science and Innovation- Instituto de Salud Carlos III and Fondos FEDER (Contratos Juan Rodés R16/00021). Nutricion Médica NM, SL, manufactured and packaged the nutritional product under investigation.

Background: Propionate inborn errors of metabolism (PIEM), including propionic (PA) and methylmalonic (MMA) acidemias, are inherited metabolic diseases characterized by toxic accumulation of propionic, 3-hydroxypropionic, methylcitric, and methylmalonic organic acids in biological fluids, causing recurrent acute metabolic acidosis events and encephalopathy, which can lead to fatal outcomes if managed inadequately. PIEM patients can develop hematological abnormalities and immunodeficiency, either as part of the initial clinical presentation or as chronic complications. The origin and characteristics of these abnormalities have been studied poorly. Thus, the aim of the present work was to evaluate and describe lymphoid, myeloid, and erythroid cell population profiles in a group of clinically stable PIEM patients. Methods: This was a retrospective study of 11 nonrelated Mexican PIEM patients. Clinical, biochemical, nutritional, hematological, and lymphocyte subsets were analyzed. Results: Despite being considered clinically stable, 91% of patients had hematological or immunological abnormalities. The absolute lymphocyte subset counts were low in all patients but one, with CD4+ T-cell lymphopenia, being the most common one. Furthermore, of the 11 studied subjects, nine presented with a low CD4/CD8 ratio. Among the observed hematological alterations, bicytopenia was the most common (82%) one, followed by anemia (27%). Conclusion: Our results contribute to the landscape of immunological abnormalities observed previously in PIEM patients; these abnormalities can become a life-threatening chronic com-plications because of the increased risk of opportunistic diseases. These findings allow us to propose the inclusion of monitoring immune biomarkers, such as subsets of lymphocytes in the follow up of PIEM patients.

Background Maternal HIV coinfection is a key factor for mother-to-child transmission (MTCT) of HCV. However, data about HCV MTCT in HIV/HCV-coinfected pregnant women on combined antiretroviral treatment (ART) are scarce. This study assessed the HCV MTCT rate in the Madrid Cohort of HIV-infected women. Methods Retrospective study within the Madrid Cohort of HIV-infected pregnant women (2000-2012). Epidemiological, clinical and treatment related variables were analysed for the mother and infant pairs. HCV MTCT rate was determined. Results Three hundred thirty-nine HIV/HCV-coinfected women and their exposed infants were recorded. A total of 227 (67%) paired mother-children had available data of HCV follow-up and were included for the analysis. Sixteen children (rate 7.0%, 95%CI 3.7-10.4%) were HCV infected by 18 months of age, none of them coinfected with HIV. HIV/HCV-coinfected pregnant women were mostly of Spanish origin with a background of previous injection drug use. HCV-genotype 1 was predominant. The characteristics of mothers that transmitted HCV were similar to those that did not transmit HCV with respect to sociodemographic and clinical features. A high rate (50%) of preterm deliveries was observed. Infants infected with HCV were similar at birth in weight, length and head circumference than those uninfected. Conclusion MTCT rates of HCV among HIV/HCV-coinfected women on ART within the Madrid cohort were lower than previously described. However, rates are still significant and strategies to eliminate any HCV transmission from mother to child are needed.

Background Tetrahydrobiopterin (BH4) is the cofactor for 6-pyruvoyl-tetrahydropterin synthase (PTPS); it is involved in BH4 biosynthesis and is encoded by PTS gene. Its deficiency (PTPSD) is characterized by hyperphenylalaninemia (HPA) and deficit in central monoamine neurotransmitters. We describe the clinical and mutational spectrum of five patients with PTPSD, from four unrelated Mexican families. All patients had symptomatic diagnosis and presented severe early neurological manifestations and HPA. Methods Clinical and biochemical data from studied patients were recorded. Responsible PTPSD genotypes was determined by direct and bidirectional Sanger DNA sequencing of the six PTS coding exons and their exon-intron borders, and these were directly searched in the available relatives. The novel PTS missense variant [NM_3000317.2:331G > T, p.(Ala111Ser)] was subjected to in silico, to predict a possible deleterious effect. Results Diminished fetal movements were perceived as a uniform characteristic in the studied group. DNA sequencing showed two known p.(Arg25∗) and p.(Val132TyrFs∗19) and the novel missense p.(Ala111Ser) PTS variants, the latter representing potentially a frequent PTPSD-responsible allele (50%, 4/8) in Mexican patients. In silico protein modeling analysis of the p.(Ala111Ser) variant revealed loss of hydrophobic interactions between the alanine and neighboring valines, suggesting that these changes in polarity may be detrimental for enzyme function, structure and/or stability. Conclusions This work contributes to the knowledge of PTPS molecular spectrum. The delayed diagnosis of these patients emphasizes the importance of considering BH4 metabolism defects in the differential diagnosis of HPA, especially for countries that are beginning their HPA newborn screening programs.

Establishing the genotypes of patients with hyperphenylalaninemia (HPA)/phenylketonuria (PKU, MIM#261600) has been considered a cornerstone for rational medical management. However, knowledge of the phenylalanine hydroxylase gene (PAH) mutational spectrum in Latin American populations is still limited. Herein, we aim to update the mutational PAH spectrum in the largest cohort of HPA/PKU Mexican patients (N = 124) reported to date. The biallelic PAH genotype was investigated by Sanger automated sequencing, and genotypes were correlated with documented biochemical phenotypes and theoretical tetrahydrobiopterin (BH4) responsiveness. Patients were biochemically classified as having classic PKU (50%, 62/124), mild PKU (20.2%, 25/124) and mild HPA (29.8%, 37/124). Furthermore, 78.2% of the included patients (97/124) were identified by newborn screening. A total of 60 different pathogenic variants were identified, including three novel ones (c. 23del, c. 625_626insC and c. 1315 + 5_1315 + 6insGTGTAACAG), the main categories being missense changes (58%, 35/60) and those affecting the catalytic domain (56.6%, 34/60), and c. 60 + 5G &gt, T was the most frequent variant (14.5%, 36/248) mainly restricted (69.2%) to patients from the central and western parts of Mexico. These 60 types of variants constituted 100 different biallelic PAH genotypes, with the predominance of compound-heterozygous ones (96/124, 77%). The expected BH4 responsiveness based on the PAH genotype was estimated in 52% of patients (65/124), mainly due to the p. (Val388Met) (rs62516101) allele. Instead, our study identified 27 null variants with an allelic phenotype value of zero, with a predominance of c. 60 + 5G &gt, T, which predicts the absence of BH4 responsiveness. An identical genotype reported in BIOPKUdb was found in 92/124 (74%) of our patients, leading to a genotype–phenotype concordance in 80/92 (86.9%) of them. The high number of variants found confirms the heterogeneous and complex mutational landscape of HPA/PKU in Mexico.

Background Assessing the role of HIV and non-HIV related factors is essential for a better understanding of the neurocognitive outcomes in perinatally HIV-infected (PHIV+) young people. The aim of our study was to assess cognition and quality of life (QoL) of a PHIV+ cohort of young people and to compare it with a control group. Methods Thirty PHIV+ and 30 HIV(−) healthy young adults matched by age, sex and socioeconomic status completed a protocol that included neurocognitive tests, a psychosocial semi-structured interview and a QoL questionnaire (PedsQL). Neurocognitive domain-specific and domain-general (NPZ-5) Z-scores were calculated. CDC AIDS-defining category C or not C (PHIV+/C, PHIV+/noC) was considered to evaluate differences within the PHIV+ group. Univariate and multivariate analysis were performed. Results Sixty patients were included; 67% were female; median age (IQR) 19 years (18–21). Regarding PHIV+ young people, 27% showed CDC C category (none encephalopathy), 93% were on ART and 77% had undetectable viral load. No differences regarding occupation were found, although the HIV(−) group repeated less grades (p = 0.028) and had a higher education level (p = 0.021). No differences were found between PHIV+/noC and HIV(−) participants. However, the PHIV+/C group showed poorer performance than PHIV+/noC (NPZ-5, p = 0.037) and HIV(−) subjects (crystallised intelligence, p = 0.025; intelligence quotient, p = 0.016). Higher nadir CD4+ T-cell count was related to better Z-score in memory (p = 0.007) and NPZ-5 (p = 0.025). Earlier and longer exposure to ART resulted in better performance in memory (p = 0.004) and executive functions (p = 0.015), respectively. Conclusions No significant differences were found in the neurocognitive profile nor QoL between PHIV+/noC and HIV(−) adolescents; however, PHIV+/C participants obtained lower scores. The use of longer and earlier ART seems to have a beneficial effect.

Introduction Tuberculosis (TB) continues to be a serious public health problem and establishing a definitive diagnosis among children is extremely challenging. Pulmonary tuberculosis is the most prevalent form, with children under the age of 2 years being at greatest risk of severe and disseminated forms. The aim of this study was to describe TB among children in Spain in recent years. Patients and methods A retrospective study of paediatric patients diagnosed with TB in two hospitals of the Community of Madrid over a 26-year period (1991-2017). Epidemiological and clinical variables, additional tests and treatments received were analysed. Results 170 children were included. The two most-affected age groups were infancy and adolescence. 42.9% of patients were immigrant children (South-America or Morocco). The main reasons for consultation were TB contact (20.6%) and fever (15.3%). At diagnosis, 61.8% of cases referred an epidemic environment, and 30.6% were asymptomatic. The Mantoux tuberculin skin test was positive in 92.2% of patients and IGRA was positive in 70.6%. Pulmonary TB was identified in 91.8% of children vs. 8.2% with extrapulmonary forms. Gastric juice culture was positive in 36.9% of cases and three strains resistant to isoniazid were isolated. All patients were cured without complications except one who died. Conclusions Pulmonary TB continues to be the most prevalent form among children and presumptive diagnosis (symptoms consistent with positive Mantoux test or suggestive X-ray) is the most common form of diagnosis. It is important to conduct a contact investigation in order to control the spread of TB.

Background Tyrosinemia type 1 (HT1, MIM#276700) is caused by a deficiency in fumarylacetoacetate hydrolase (FAH) and it is associated with severe liver and renal disfunction. At present, the mutational FAH (15q25.1, MIM*613871) spectrum underlying HT1 in the Mexican population is unknown. The objective of this study was to determine the FAH genotypes in eight nonrelated Mexican patients with HT1, who were diagnosed clinically. Methods Sequencing of FAH and their exon–intron boundaries and in silico protein modeling based on the crystallographic structure of mouse FAH. Results We identified pathogenic variants in 15/16 studied alleles (93.8%). Nine different variants were found. The most commonly detected HT1‐causing allele was NM_000137.2(FAH):c.3G > A or p.(?) [rs766882348] (25%, n = 4/16). We also identified a novel missense variant NM_000137.2(FAH):c.36C > A or p.(Phe12Leu) in a homozygous patient with an early and fatal acute form. The latter was classified as a likely pathogenic variant and in silico protein modeling showed that Phe‐12 residue substitution for Leu, produces a repulsion in all possible Leu rotamers, which in turn would lead to a destabilization of the protein structure and possible loss‐of‐function. Conclusion HT1 patients had a heterogeneous mutational and clinical spectrum and no genotype–phenotype correlation could be established., A heterogeneous clinical and mutational spectrum of FAH was found in Mexican patients with tyrosinemia type 1 and a novel missense variant c.36C > A or p.(Phe12Leu) associated with the fatal acute form of the disease was described. This variant based on protein modeling, would cause a destabilization of FAH structure.

Studies investigating health-related quality of life (HRQoL) in youth with perinatally acquired HIV (PHIV+) are scarce. This study aimed to compare HRQoL of PHIV+ to sociodemographic-matched youth not living with HIV (HIV−), Spanish general youth population, and to explore associations between sociodemographic variables, drug consumption, and HRQoL. PHIV+ youth were randomly selected from CoRISpe database (Cohort of the Spanish Pediatric HIV Network). HRQoL was evaluated by SF-12v2. Thirty-nine PHIV+ youth (mean age: 23.36 years, SD = 3.83) and thirty-nine HIV− youth (mean age: 22.97 years, SD = 3.80) participated in this study. PHIV+ obtained lower scores in SF-12 physical health subscale (PCS) than HIV− (P = 0.001) and Spanish general youth population (P = 0.006). PHIV+ had lower scores on the mental health subscale (MCS) than the Spanish general youth population (P

Maple syrup urine disease (MSUD) is a metabolic disorder caused by mutations in three of the branched-chain α-keto acid dehydrogenase complex (BCKDC) genes. Classical MSUD symptom can be observed immediately after birth and include ketoacidosis, irritability, lethargy, and coma, which can lead to death or irreversible neurodevelopmental delay in survivors. The molecular diagnosis of MSUD can be time-consuming and difficult to establish using conventional Sanger sequencing because it could be due to pathogenic variants of any of the BCKDC genes. Next-generation sequencing-based methodologies have revolutionized the molecular diagnosis of inborn errors in metabolism and offer a superior approach for genotyping these patients. Here, we report an MSUD case whose molecular diagnosis was performed by clinical exome sequencing (CES), and the possible structural pathogenic effect of a novel E1α subunit pathogenic variant was analyzed using in silico analysis of α and β subunit crystallographic structure. Molecular analysis revealed a new homozygous non-sense c.1267C>T or p.Gln423Ter variant of BCKDHA. The novel BCKDHA variant is considered pathogenic because it caused a premature stop codon that probably led to the loss of the last 22 amino acid residues of the E1α subunit C-terminal end. In silico analysis of this region showed that it is in contact with several residues of the E1β subunit mainly through polar contacts, hydrogen bonds, and hydrophobic interactions. CES strategy could benefit the patients and families by offering precise and prompt diagnosis and better genetic counseling.

Background Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; pInterpretation Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients.

Advances in care and antiretroviral treatment, improved life expectancy and quality of life in children with perinatally-acquired human immunodeficiency virus (HIV) infection. There is increasing interest in the chronic effects of growing up with HIV. The aim of this study was to assess the psychosocial, emotional and behavioural functioning in a cohort of perinatally-acquired HIV-infected adolescents. Data were obtained through semi-structured interviews and the Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural disorders screening.A total of 95 patients (58% women) were assessed with a median age of 15 years (11-19.1) and a median age at diagnosis of 1.7 years (0-12.2). The median CD4 count, at the inclusion, was 626 cells/mm(3) (132-998), with 34% (10-52%). Viral load was50 copies/ml in 72% of patients. Eighty-one per cent knew their diagnosis and optimal adherence was achieved in 53%. Passive coping was reported in 58.4% of the adolescents. Only 7.7% of teenagers had a complete and adequate knowledge of their disease and only 18.2% had shared it with their friends. Six unwanted pregnancies occurred (11% of women). Most of them (90%) attended school but 60% had been held back one or more school years. Overall, SDQ scored a risk of behavioural and emotional problems in 24.5%. The report of behaviours associated with hyperactivity was high in 14.9% of the population and borderline in 18.1%. Adolescents with encephalopathy accounted for 44% of those whose total scores fell in either the abnormal and borderline ranges for emotional difficulties (p = .038).Perinatally-acquired HIV-infected adolescents showed significant psychosocial and behavioural health risks that should bring attention to prevention and health care programmes. An earlier disclosure to children could favour a better psychological adjustment and a better treatment adherence. Future studies are needed to assess the relationship between vertically acquired HIV-infection and hyperactivity.

Background The influenza antiviral oseltamivir is not licensed for infants aged Methods In this prospective, observational, non-randomized study, infants aged Results A total of 65 patients were enrolled: 40, 20 and 5 in cohorts 1, 2 and 3, respectively. Systemic exposure to oseltamivir carboxylate (active metabolite) reached therapeutic levels in all patients, with an adequate safety margin. On-treatment adverse events ( n=48) were reported by 32 patients (49%). At least one adverse event was reported by 43%, 65% and 40% of infants in cohorts 1, 2 and 3, respectively; most frequently vomiting and diarrhoea. Eight serious adverse events were reported, all of which were considered unrelated to treatment by the investigator. No deaths occurred and no patient had treatment withdrawn. Oseltamivir resistance mutations were detected in eight patients. Conclusions Oseltamivir dosages of 2–3 mg/kg were well tolerated in infants aged

Hepatorenal tyrosinemia is a treatable metabolic disease characterized by progressive liver failure, renal damage and pronounced coagulopathy. Its clinical diagnosis is difficult because of its low prevalence and heterogeneous symptoms. In developed countries, expanded newborn screening, based on succinylacetone quantification by tandem mass spectrometry, has been very valuable in the early detection of hepatorenal tyrosinemia, providing the opportunity for rapid treatment of affected patients. In developing countries without systematic expanded newborn screening, however, diagnosis and treatment of this disease remain major challenges, as genetic diseases in these countries are not a health priority and there are few referral centers for infants with inherited errors of metabolism. This chapter describes the diagnosis, follow-up and outcome of 20 Mexican patients with hepatorenal tyrosinemia. This chapter also constitutes a call to action to pediatricians, gastroenterologists, geneticists and other health professionals, and to academic organizations, health authorities and patient advocacy groups, to promote early patient detection and treatment, reducing the unacceptably high mortality rate (75%) in Mexican infants with this potentially deadly but eminently treatable condition.

The mutational spectrum of the phenylalanine hydroxylase gene (PAH) in Mexico is unknown, although it has been suggested that PKU variants could have a differential geographical distribution. Genotype-phenotype correlations and genotype-based predictions of responsiveness to tetrahydrobiopterin (BH4 ) have never been performed. We sequenced the PAH gene and determined the geographic origin of each allele, mini-haplotype associated, genotype-phenotype correlations and genotype-based prediction of BH4 responsiveness in 48 Mexican patients. The mutational spectrum included 34 variants with c.60+5G>T being the most frequent (20.8%) and linked to haplotype 4.3 possibly because of a founder effect and/or genetic drift. Two new variants were found c.1A>T and c.969+6T>C. The genotype-phenotype correlation was concordant in 70.8%. The genotype-based prediction to BH4 -responsiveness was 41.7%, this information could be useful for the rational selection of candidates for BH4 testing and therapy.

Aim: To determine whether the treatment with oseltamivir improves the outcome of children with confirmed influenza infection and no other underlying disease. Methods: Multicentric, retrospective study performed in 10 hospitals of Madrid between September 2010 and June 2012. All children admitted to the hospitals with confirmed influenza infections were eligible. Children with risk factors for serious disease and nosocomial influenza infections were excluded. Asthma was not considered an exclusion factor. The study compared patients treated and untreated with oseltamivir. Fever duration, oxygen support, antibiotics administration, length of hospital stay, intensive care admission and bacterial complications were analyzed. To compare variables, χ2 test, Fisher exact test, ANOVA or Mann-Whitney U test were used. Results: Two hundred eighty-seven children were included and 93 of them were treated with oseltamivir (32%). There were no significant differences between treated and untreated patients in days of fever after admission (1.7 ± 2; 2.1 ± 2.9, P > 0.05), length of stay (5.2 ± 3.6; 5.5 ± 3.4, P > 0.05), days of hypoxia (1.6 ± 2.3; 2.1 ± 2.9, P > 0.05), diagnosis of bacterial pneumonia (10%; 17%, P > 0.05), intensive care admission (6.5%; 1.5%,P > 0.05) or antibiotic prescription (44%; 51%, P > 0.05). There were no differences when the population was stratified by age (below or over 1 year) or by the presence or absence of asthma. Conclusions: There were no proven benefits of treatment with oseltamivir in hospitalized pediatric patients without the underlying diseases or risk factors for developing a serious illness, including those with asthma.

Polymerase chain reaction (PCR) assays have shown to be useful and quick for the diagnosis of enterovirus in aseptic meningitis. The aim of our study was to analyse the changes in clinical practice after the introduction of a real-time polymerase chain reaction (RT-PCR) technique using the Xpert EV (CepheidA retrospective study was performed in children older than 1year, diagnosed with enterovirus meningitis in a third level hospital from November 2006 to February 2013. The first period, before the availability of Xpert EV (CepheidForty-one patients (60.9% male) were included, with a median age of 64 months (interquartile range 28-96). Twenty-six patients (63.4%) were included in Group2. There were non-statistically significant differences in the epidemiological, disease severity, and laboratory characteristics between both periods of study. A significant difference was observed in the mean length of stay, with it being shorter in Group2 (48hours vs 40.5hours, P=.039), and a significant lower inpatient cost per case (€779.77 vs €656.05, P.05).Xpert EV (Cepheid

infantile nephropathic cystinosis (INC) is an autosomal recessive disorder that causes defects in cystine transport with subsequent accumulation in almost all body tissues, especially kidneys. There are few studies regarding the nutritional status assessment of patients with INC. It has been reported that patients with INC showed increased urinary losses of carnitine, resulting in plasma and muscle carnitine deficiency also increased metabolic requirements of carnitine in this patients have also been proposed, but to date carnitine supplementation is controversial.the aim of this study was to compare carnitine blood concentrations with nutritional status assessed by three anthropometric parameters: body mass index, mid-upper arm circumference and tricipital skin fold in patients with INC.anthropometric assessment of 10 patients with INC which included measurement of weight, height, mid-upper arm circumference and tricipital skin fold thickness. Free carnitine (C0) was measured by tandem mass spectrometry in fasting blood samples.a total of 10 patients with INC were analyzed, 5 with and 5 without renal graft. According to the body mass index, 3/10 presented malnutrition. Muscular mass was found low in 8/10 patients (3 without renal graft and all the transplanted) the mid-upper arm circumference showed correlation with C0 blood concentrations (r2 = 0.353); non transplanted patients had C0 levels significantly lower than the transplanted ones (Chi2 = 0.0027).in this study we found that 70% of patients had low C0 blood levels that had a correlation with depleted lean body mass. It is recommendable to evaluate the nutritional status of these patients as part of their routine medical evaluation.Introducción: la cistinosis nefropática infantil (CNI) es una enfermedad genética debida a un defecto del transporte de la cistina, con la subsecuente acumulación de este aminoácido predominantemente en el riñón. Existen pocos estudios sobre la evaluación del estado nutricional en pacientes con esta patología, pero se sabe que tienen una excreción de carnitina urinaria aumentada, lo que puede dar como resultado una deficiencia plasmática y muscular de este compuesto; sin embargo, la suplementación de carnitina en CNI es controversial. Objetivo: comparar la concentración sanguínea de carnitina libre (C0) con el estado nutricional de una cohorte de pacientes con CNI. Material y métodos: evaluación antropométrica mediante la medición de peso, talla, perímetro braquial (PB) y pliegue cutáneo tricipital (PCT). La C0 se cuantificó mediante espectrometría de masas en tándem en muestras de sangre en ayuno. Resultados: se analizaron 10 pacientes con CNI, 5 con y 5 sin trasplante renal. De acuerdo con el IMC, 3/10 presentaron desnutrición. La reserva de masa magra se encontró baja en 8/10 pacientes (3 no trasplantados y todos los trasplantados). El PB mostró correlación con las concentraciones sanguíneas de C0 (r2 = 0,353); Los pacientes no trasplantados tuvieron niveles de C0 significativamente más bajos que los trasplantados (Chi2 = 0,0027). Conclusión: en esta población de pacientes con CNI se encontró un 70% de sujetos con C0 baja, que se correlaciona con la masa magra disminuida. Es recomendable hacer una evaluación nutricional de rutina que incluya los tres parámetros antropométricos como parte del seguimiento médico-nutricional integral de estos pacientes.

ObjectiveTo expose causes leading to the delayed arrival of phenylketonuria (PKU) patients at a governmental reference centre (RC), and to describe their clinical characteristics.Material and methodsPKU files registered during the past 18 years at the National Institute of Pediatrics in Mexico City were evaluated. Patients were classified into two groups according to their age at arrival: Group I (early reference), patients arriving during the first month of life; and Group II (late reference), those who arrived after thirty days of age. Time and causes of delay were documented.ResultsOf 57 recorded files, 10 were classified in Group I and 47 in Group II. Causes leading to the late arrival of Group II patients were absence of routine newborn screening (NBS), PKU not included in the routine NBS, sampling after the recommended age, false negative result, results without interpretation and/or instructions to follow, delayed notification of results, poor medical criteria of attending physician, difficulties in obtaining confirmatory tests, and administrative failures.ConclusionThe main cause of late referral of PKU patients was the absence of PKU testing. As a developing country, Mexico still faces challenges in the proper functioning and expansion of the NBS programme. Most PKU patients arrived at the RC late, presenting with varying degrees of the clinical spectrum. Incorporating PKU testing into the already established Mexican NBS system and adding quality indicators to guarantee proper operation in all NBS phases is necessary to achieve the goal of identifying, referring, diagnosing, and treating patients promptly.

OBJECTIVE To evaluate any possible association between indicators of social inequalities and the geographical distribution of HIV-1 mother-to-child transmission (MTCT) cases in Madrid. METHODS We carried out an observational survey of 224 HIV-1 vertically infected children born in 1980-2006 living in Madrid. We elaborated maps representing the prevalence of HIV-1 MTCT cases. We assessed the association between indicators of social inequalities and the spatial distribution of MTCT cases. Poisson univariate and multivariate analysis of risk factors for MTCT were performed. RESULTS We identified core areas of transmission mainly in southern Madrid until 2006. The prevalence of MTCT cases was significantly correlated to the percentage of immigrants, illiterates, unemployed women and the income in 1996 and 2000/2001. The risk of MTCT increased in the periods up to 1996 compared with the calendar period 1980-1989, whereas the risk decreased in 1999-2006 [relative risk, 0.08; 95% confidence interval (CI), 0.03-0.18; P < 0.001]. The risk was especially high in the districts of Usera (absolute relative risk, 11.4; 95% CI, 2.6-49.5; P = 0.001), Puente de Vallecas (absolute relative risk, 14.0; 95% CI, 3.4-57.9; P < 0.001) and San Blas (absolute relative risk, 12.5; 95% CI, 2.9-53.6; P = 0.001). The percentage of illiterates was the indicator that explained the risk of MTCT (absolute relative risk, 1.07; 95% CI, 1.05-1.10; P = 0.001). CONCLUSION We observed a geographic heterogeneity of the HIV-1 vertical transmission with the highest prevalence in disadvantaged districts. What is described in the present review is the HIV-1 vertical transmission within a social context; this approach could be relevant in analysing the pattern of HIV-1 transmission in other Western cities or highlighting the distribution of other infectious diseases.

Background: Staphylococcus aureus remains the most common etiologic agent of acute osteomyelitis in children. Recently, methicillin-resistant S. aureus (MRSA) has emerged as a major pathogen. Methods: Records of all children admitted with acute osteomyelitis from January 1999 to December 2003 were reviewed. For the comparative analysis, the study population was evenly distributed in 2 periods: period A, January 1999 to June 2001; n= 113; and period B, July 2001 to December 2003; n = 177. In addition, clinical findings of MRSA osteomyelitis were compared with non-MRSA osteomyelitis, including methicillin-sensitive S. aureus infections. Results: Two hundred ninety children (60% male subjects) with acute osteomyelitis were identified. Median (25th-75th percentile) age at diagnosis was 6 years (range, 2-11 years). Significant clinical findings included the following: localized pain (84%), fever (67%), and swelling (62%). Affected bones included the following: foot (23%), femur (20%), tibia (16%), and pelvis (7%). Thirty-seven percent of blood cultures were positive, and a bacterial isolate was obtained in 55% of cases. Bacteria most frequently isolated included the following: methicillin-sensitive S. aureus (45%) (57% in period A vs 40% in period B), MRSA (23%) (6% in A vs 31% in B; P < 0.001), Streptococcus pyogenes (6%), and Pseudomonas aeruginosa (5%). Children with MRSA compared with those with non-MRSA osteomyelitis had significantly greater erythrocyte sedimentation rate and C-reactive protein values on admission and increased length of hospital stay, antibiotic therapy, and overall rate of complications. We observed significant changes in antibiotic therapy related to increased use of agents with activity against MRSA. Conclusions: Methicillin-resistant S. aureus was isolated more frequently in the second study period and was associated with worse clinical outcomes.

Background There are few data on long-term effects of highly active antiretroviral therapy (HAART) on weight and height in HIV-infected children. Objectives Our objective was to assess the effect of HAART on the weight and height of HIV-infected children over time in the Madrid cohort, and analyze possible factors associated with the effect. Patients and methods This was a retrospective study of HIV-infected children starting HAART in 1997 or later. Serial measurements of weight, height and body mass index (BMI) were performed and converted to z-scores using the Spanish revised reference data. Changes from baseline in weight, height and BMI at 12, 24, 36, 48 and 60 months were determined. Associations of z-scores at the last visit with immunologic (CD4% above 25%) and virologic responses (more than 50% of samples below 400 copies/mL), CDC (Centers for Disease Control) clinical category, and the presence and type of lipodystrophy (lipoatrophy or lipohypertrophy) were evaluated. Results Twelve hundred and twelve children, 97% of them vertically-infected, received HAART starting in 1997 for a median of 71 months (4-102 months). Median age at initiation of HAART was 6 years (1 month-18 years). Thirty-nine percentage were antiretroviral naive and 61% had received NRTI therapy previously. Thirty-two percentage and 53% had CDC class C and immunologic class 3, respectively. At the final evaluation, 24% of children remained on their first combination therapy, 39% on the second and 37% had received at least 3 different HAART regimens. Fifty-one percentage were classified as virologic responders. Thirty-nine percentage of children in this study were diagnosed with lipodystrophy. At baseline, median z-score for weight, height and BMI were -0.45, -0.60 and -0.33, respectively. HAART was associated with significant increases in z-scores of weight and height but not BMI at the different time-points analyzed. Virologic nonresponders had significantly lower z-scores for weight and height but not for BMI. CDC class C was associated with lower z-scores for height. No differences in final measurements were observed for baseline CD4, immunologic response or lipoatrophy. Children with lipohypertophy had a significantly higher BMI at the last visit. Conclusions HIV-infected children experienced a continued catch-up in weight and height 5 years after starting HAART. Virologic control is related to sustained growth.

Great efforts have been made in the last few years in order to implement the prevention of mother-to-child transmission (PMTCT) program in Equatorial Guinea (GQ). The aim of this study was to evaluate the rates of mother-to-child HIV transmission based on an HIV early infant diagnosis (EID) program.A prospective observational study was performed in the Regional Hospital of Bata and Primary Health Care Centre Maria Rafols, Bata, GQ. Epidemiological, clinical, and microbiological characteristics of HIV-1-infected mothers and their exposed infants were recorded. Dried blood spots (DBS) for HIV-1 EID were collected from November 2012 to December 2013. HIV-1 genome was detected using Siemens VERSANT HIV-1 RNA 1.0 kPCR assay.Sixty nine pairs of women and infants were included. Sixty women (88.2%) had WHO clinical stage 1. Forty seven women (69.2%) were on antiretroviral treatment during pregnancy. Forty five infants (66.1%) received postnatal antiretroviral prophylaxis. Age at first DBS analysis was 2.4 months (IQR 1.2-4.9). One infant died before a HIV-1 diagnosis could be ruled out. Two infants were HIV-1 infected and started HAART before any symptoms were observed. The rate of HIV-1 transmission observed was 2.9% (95%CI 0.2-10.5).The PMTCT rate was evaluated for the first time in GQ based on EID. EID is the key for early initiation of antiretroviral therapy and to reduce the mortality associated with HIV infection.

the nutrition management of patients with inborn errors of metabolism (IEM) requires the permanent use of elemental medical formulas whose organoleptic characteristics sometimes impede oral acceptance. In addition, these patients may have gastrointestinal disorders and require constant use of drugs, that often complicate treatment adherence, thereby committing their nutritional status and disease control. Gastrostomy is an alternative to facilitate feeding and treatment, but its use is controversial.to compare nutrition status and length of hospitalizations before and after gastrostomy surgery in a group of IEM patients.retrospective analysis of anthropometric data, number of hospitalizations due to metabolic decompensation and length in pediatric patients with IEM before and after gastrostomy.16 children were analyzed, 40% with propionate disorders, 25% with abnormal urea cycle and 35% other IEM. After gastrostomy, the number of eutrophic patients increased from 6-56%, and malnutrition decreased from 94 to 44%. After gastrostomy inpatient hospital days significantly decrease from 425 to 131 (p = 0.011), admission numbers pre-gastrostomy decreased from 33 to 17, however this difference was not statistically significant.in this sample, gastrostomy improved nutritional status in 56% of EIM patients and significantly reduced hospital days caused by metabolic decompensation.Introducción: el tratamiento nutricional de los pacientes con errores innatos del metabolismo (EIM) implica el uso permanente de fórmulas modificadas en aminoácidos cuyas características organolépticas pueden dificultar su aceptación por vía oral. Estos pacientes pueden tener alteraciones gastrointestinales y requieren el uso constante de medicamentos, lo cual complica la adherencia al tratamiento, comprometiéndose con ello su estado nutricional y el control de la enfermedad. La gastrostomía es una alternativa para facilitar la alimentación y el tratamiento, pero existen controversias sobre su uso. Objetivo: comparar el estado nutricional y la duración de las hospitalizaciones antes y después de la realización de la gastrostomía en un grupo de pacientes con EIM. Métodos: análisis retrospectivo de datos antropométricos, número de internamientos por descompensación metabólica y su duración en pacientes pediátricos con EIM antes y después de la gastrostomía. Resultados: se analizaron 16 niños; 40% con defectos del propionato, 25% con alteraciones del ciclo de la urea y 35% con otros EIM. Después de la gastrostomía, la proporción de pacientes eutróficos aumentó del 6 al 56% y la desnutrición disminuyó del 94 al 44%. Después de la gastrostomía, la duración de los periodos hospitalarios disminuyó significativamente de 425 a 131 días (p = 0.011); el número de internamientos disminuyó de 33 antes de la intervención a 17, sin embargo, esta diferencia no tuvo significación estadística. Conclusión: en esta muestra, la gastrostomía mejoró el estado nutricional en 56% de los pacientes con EIM, y redujo significativamente los días de hospitalización por descompensación metabólica.

Objective To compare the incidence and epidemiology of bacteremic community-acquired pneumonia (CAP) in the setting of changes in 13-valent pneumococcal conjugate vaccine (PCV13) coverage. Study design In the region of Madrid, universal immunization with the PCV13 started in May 2010. In July 2012, public funding ceased. Vaccination coverage decreased from >95% to 82% in 2013 and to 67% in 2014. We performed a multicenter surveillance and case-control study from 2009-2014. Cases were hospitalized children with bacteremic CAP. Controls were children selected 1:1 from next-admitted with negative blood cultures and typical, presumed bacterial CAP. Results Annual incidence of bacteremic CAP declined from 7.9/100 000 children (95% CI 5.1-11.1) in 2009 to 2.1/100 000 children (95% CI 1.1-4.1) in 2012. In 2014, 2 years after PCV13 was withdrawn from the universal vaccination program, the incidence of bacteremic CAP increased to 5.4/100 000 children (95% CI 3.5-8.4). We enrolled 113 cases and 113 controls. Streptococcus pneumoniae caused most of bloodstream infections (78%). Empyema was associated with bacteremia ( P = .003, OR 3.6; 95% CI 1.4-8.9). Simple parapneumonic effusion was not associated with bacteremia. Incomplete PCV immunization was not a risk factor for bacteremic pneumonia. Conclusions High rate of PCV13 immunization was associated with decreased incidence of bacteremic CAP; this incidence increased when rate of immunization fell. Empyema (but not parapneumonic pleural effusion) was associated with bacteremia.

Objective To assess whether dexamethasone (DXM) decreases the time to recovery in patients with parapneumonic pleural effusion. Study design This was a multicenter, randomized, double blind, parallel-group, placebo-controlled clinical trial of 60 children, ranging in age from 1 month to 14 years, with community-acquired pneumonia (CAP) and pleural effusion. Patients received either intravenous DXM (0.25 mg/kg/dose) or placebo every 6 hours over a period of 48 hours, along with antibiotics. The primary endpoint was the time to recovery in hours, defined objectively. We also evaluated complications and adverse events. Results Among the 60 randomized patients (mean age, 4.7 years; 58% female), 57 (95%) completed the study. Compared with placebo recipients, the patients receiving DXM had a shorter time to recovery, after adjustment by severity group and stratification by center (hazard ratio, 1.95; 95% CI, 1.10-3.45; P = .021). The median time to recovery for patients receiving DXM was 68 hours (2.8 days) shorter than patients receiving placebo (109 hours vs 177 hours; P = .037). In exploratory subgroup analysis, the median time to recovery for patients with simple effusion receiving DXM was 76 hours (3.1 days) shorter than for patients with simple effusion receiving placebo ( P = .017). The median time to recovery for patients with complicated effusion receiving DXM was 14 hours (0.5 days) shorter than for patients with complicated effusion receiving placebo ( P = .66). The difference in the effect of DXM in the 2 severity groups was not statistically significant ( P = .138 for interaction). There were no significant differences in complications or adverse events attributable to the study drugs, except for hyperglycemia. Conclusion In this trial, DXM seemed to be a safe and effective adjunctive therapy for parapneumonic pleural effusion. Trial registration ClinicalTrials.gov : NCT01261546 .

«PFAPA syndrome» is an autoinflammatory entity consisting of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis. Its etiology is unknown although a dysregulation in the control of the autoinflammatory response seems to play a role. Although a genetic origin is suspected, no specific mutation has been determined yet. Corticosteroids are the mainstay of the treatment during the acute attacks. However, in long-term follow-up the role of tonsillectomy is controversial.A retrospective study of the pediatric cases diagnosed with the PFAPA syndrome was performed in our center during the last 4 years.Ten patients were diagnosed with the syndrome who received corticosteroids as the only treatment with improvement and favourable prognosis.PFAPA syndrome is the most common periodic fever disorder described in childhood whose genetic background has not been yet clarified. Our contribution with 10 patients further supports the common existence of this entity and the need to keep it in mind when having recurrent fevers.

Micafungin is an echinocandin approved by the European Medicines Evaluation Agency for the treatment of invasive candidiasis in children, including premature infants born before 29 weeks of pregnancy, and as prophylaxis in children undergoing hematopoietic stem-cell transplantation or patients at risk of prolonged neutropenia. This drug has good activity in several Candida spp., including those resistant to fluconazole. Although micafungin is active against Aspergillus spp., it has been used mainly in combination therapy for invasive aspergillosis. There is ample information on the use of micafungin in children, including neonates, and this drug is the only echinocandin approved for use in infants aged less than 3 months. The efficacy, pharmacokinetics and safety of micafungin have been evaluated in phase II and III clinical trials in children, in which its efficacy and safety were demonstrated in comparison with liposomal amphotericin B and fluconazole. The pharmacokinetic profile of micafungin in children allows once daily intravenous administration, with greater clearance than in adults, and consequently pediatric doses are relatively higher. The most appropriate dose in children weighing less than 40 kg is 2 mg/kg/day in the treatment of invasive candidiasis and 1 mg/kg/day as prophylaxis in children undergoing hematopoietic stem-cell transplantation. Doses in neonates should be higher. In premature infants, the most appropriate doses to achieve levels in the brain parenchyma are 7 mg/kg/day and 10 mg/kg/day in those weighing more and less than 1,000 g, respectively. Micafungin has few drug-drug interactions and an acceptable safety profile. Withdrawal of this drug due to adverse effects is rare, although transaminase monitoring is recommended during treatment, as well as evaluation of the risk-benefit balance in patients with liver disease or concomitant administration of hepatotoxic drugs.

Background: Effective therapies have increased life expectancy of human immunodeficiency virus (HIV)-infected pediatric patients. We investigated the underlying causes of death, mortality, and acquired immune deficiency syndrome (AIDS) rates in HIV-infected pediatric patients in Madrid, Spain. Methods: We studied a multicenter cohort of 478 HIV-infected pediatric patients in Madrid. Mortality and AIDS incidence rates, causes of death, CD4 + T-cell, and HIV RNA were analyzed during calendar periods (CPs): pre-HAART (highly active antiretroviral therapy) (CP1: 1982-1996) and post-HAART era (CP2: 1997-2009). Results: During 5690 person-years of follow-up 157 (32.8%) deaths occurred. Median age at death increased (CP1: 3.2 years [1.0-6.3] vs. CP2: 7.7 years [3.1-11.4]; P < 0.01). Mortality and AIDS rates decreased 10.6-fold (95% confidence intervals [CI]: 6.9-16.7) and 6.9-fold (95% CI: 5.0-9.6), respectively, between CPs. Nevertheless, mortality was 10.4-fold (95% CI: 5.8-18.8; P < 0.001) higher than in age-similar general population in late-CP2. In all, 169 causes of death were reported. Multiple causes were reported in 16 of 151 (10.6%) patients. In 81.1% (137/169), the causes were AIDS-defining, 11.8% (20/169) HIV-related, and 7.1% (12/169) non-HIV-related. Infections were the leading causes (60.8%, 101/166); from 1999 to 2007 the risk of death from infections was 115.9 times (95% CI: 42.0-265.8; P < 0.001) higher than in the age-similar general population. Comorbidity was reported in 66.9% (101/151) of patients. Median HIV-1 RNA at death decreased (CP1: 5.9 [5.0-6.3]; CP2: 5.3 [4.2-5.8]; P < 0.01). Conclusions: Despite decline in mortality and AIDS rates, it is important to monitor all causes of death as prolonged survival might allow underlying comorbidity to become more clinically relevant.

PFAPA syndrome" is an autoinflammatory entity composed of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. There have been many reports of children with the disease, but only occasionally have been described in siblings, and no specific genetic mutation has been determined yet. Corticosteroids are the mainstay in the treatment of the acute attacks. The role of surgery in long-term follow-up (tonsillectomy with or without adenoidectomy) is controversial. We report two brothers affected with the syndrome, in whom cortico- steroids as the only treatment led to an improvement. A genetic work-up was performed, making very unlikely other possible syndromes of recurrent fever. Conclusion: PFAPA syndrome is the most common recurrent periodic fever disorder described in childhood. Its genetic back- ground has not been elucidated yet. Our contribution with two siblings affected with PFAPA syndrome further support the genetic basis for the entity.

The number of children of immigrant origin in the last few years has increased the cohort of HIV-infected children in the Community of Madrid. The objectives of the study were to evaluate the epidemiological and clinical characteristics of the new diagnosed children and describe the different subtypes of HIV-1.The new diagnosed children were analysed from the year 1997, divided into 3 periods: P1 (1997-2000), P2 (2001-2004), P3 (2005-2009). The regions and countries of origin, the clinical, immune and viral characteristics, as well as the response to treatment were analysed. The subtypes of HIV-1 were evaluated by phylogenetic analysis of protease genes and reverse transcriptase.We identified 141 new diagnoses of HIV infection, the percentage of immigrant origin in P1 was (22.5%), P2 (50%) and P3 (68%). The origin had changed from Latin America in P1 to sub-Saharan Africa in P3. There were no differences between Spanish and immigrant children in the age at diagnosis, the CDC clinical stage A/B/C, viral load, percentage of CD4 at diagnosis and actual. Better viral response was more likely in immigrants after the first regimen of HAART (Highly active antiretroviral treatment) independently of the treatment received. A total of 66 subtypes were obtained, 24% were subtypes non-B (56% recombinants forms). All subtypes of Spanish children (43) and Latin American (5) were subtypes B, and all the children from sub-Saharan Africa (14) were subtypes non-B.There were no differences between immigrants and Spanish children infected by HIV, except the different subtypes of HIV-1.