El uso de fármacos antrirretrovirales no aprobados en niños en la cohorte pediátrica con infección VIH de la Comunidad de Madrid

La infección por el VIH en niños tiene una progresión más rápida que en adultos y el arsenal terapéutico disponible es escaso, haciendo que haya que tratar fuera de las indicaciones de la ficha técnica (off-label) Estudiamos uso de fármacos off-label en la Cohorte de niños menores de 18 años, infectados por el VIH en la Comunidad de Madrid. Estudio retrospectivo de cohortes multicéntrico de Marzo 1988-Diciembre 2011. Se excluyeron pacientes fallecidos y aquellos infectados por vía no vertical. Comparamos los pacientes tratados off-label con los tratados acorde a ficha técnica, encontramos significativo; menor edad al diagnóstico (1.7 vs 3.5 años), etnia blanco-caucasiana (79% vs 67%), nacidos en España (89% vs 75%), tasa de coinfección por el virus de la hepatitis C (8.6% vs 1.1%), peor situación clínica según la clasificación CDC (estadio C 35% vs 13%) y menor media del porcentaje de los CD4 nadir (14 vs 17%). Un 70% de los pacientes recibió fármacos off-label, un 23% de todas las prescripciones. Los motivos de prescripción off-label fueron inicio o fallo de tratamiento, durante los primeros años de la epidemia, tras 2001 también para simplificar el mismo. Los efectos secundarios tras uso off-label fueron frecuentes (34%), de predominio gastrointestinal (52%). Llevaron a la suspensión en el 12% de los casos. Un 10% de los niños tratados off-label fueron sobredosificados y un 10% infradosificados. Se encontró fallo en el tratamiento en el 50% de los infradosificados vs, 26% en los que recibieron la dosis correcta (p<0.05). Problemas con la ingesta del fármaco llevó a su suspensión en un 3%, generalmente cuando la formulación no era apropiada para la edad (p<0.05). Se necesita disponer de más datos de farmacocinética para evitar el riesgo de sobredosificación e infradosificación y evitar exponer a los niños a selección de resistencias y fallo de tratamiento

Does opening a milk bank in a neonatal unit change infant feeding practices? A before and after study

<p>Abstract</p> <p>Background</p> <p>Donor human milk banks are much more than simple centers for collection, storage, processing, and distribution of donor human milk, as they cover other aspects and represent a real opportunity to promote and support breastfeeding. The aim of our study is to assess the impact that opening a human milk bank has had on the proportion of infants receiving exclusive breast milk at discharge and other aspects related to feeding children with birth weight < or = 1500 g or < 32 weeks gestation admitted to the neonatal unit.</p> <p>Methods</p> <p>The study included babies of < or = 1500 g or < 32 weeks gestation. Fifty infants born from February to July in 2006, before the opening of the human milk bank, and 54 born from February to July in 2008, after its opening, met inclusive criteria. We collected data about days of hospital stay, hours of life when feeding was started, hours of life when full enteral feeding was attained, the type of milk received during admission, and the type of feeding on discharge.</p> <p>Results</p> <p>Children born in 2008 commenced feeding 16 hours earlier than those born in 2006 (p = 0.00). The proportion of infants receiving exclusive breast milk at discharge was 54% in 2006 and 56% in 2008 (p = 0.87). The number of days they received their mother's own milk during the first 28 days of life was 24.2 days in 2006, compared to 23.7 days in 2008 (p = 0.70). In 2006, 60% of infants received infant formula at least once in the first 28 days of life, compared to 37% in 2008 (p = 0.01).</p> <p>Conclusions</p> <p>The opening of a donor human milk bank in a neonatal unit did not reduce the proportion of infants exclusively fed with breast milk at discharge, but did reduce the proportion of infants that received infant formula during the first four weeks of life. Also, having donor human milk available enables commencement of enteral feeding earlier.</p

Finding immunological differences to help diagnosis and early treatment of Kawasaki Disease and MIS-C (Multisystem Inflammatory Syndrome in Children)

Resumen del trabajo presentado en el 43 Congreso De La Sociedad Española de Inmunología, celebrado en León (España) del 22 al 24 de septiembre de 2022.The recent COVID-19 pandemic was first thought to spare children from health deprivation caused by infection with SARS-CoV-2. However, soon a new syndrome resembling Kawasaki Disease (KD) was reported: Multisystem Inflammatory Syndrome in Children (MIS-C). The aim of this study is to provide new biomarkers for both diseases in order to facilitate diagnosis and reduce the time-lapse until treatment is provided – which will reduce the risk of developing severe cardiovascular complications. An extensive immune system characterization by flow cytometry and serum protein characterization by a multiplex technology (Olink) was performed from fresh blood samples of patients with acute MIS-C (n=19) and KD (n=10). For protein characterization we also analysed recovery samples for these groups (n=19 and n=8, respectively). Besides the already described lymphopenia in MIS-C, we found additional significant immune differences in both groups. Although lymphocyte numbers (cells/ml) were lower in MIS-C, percentages of activated T-CD4+ and T-CD8+ cells were higher compared to KD. Moreover, when comparing activated T cells in MIS-C and KD individually, regulatory T cells (Treg) showed the highest levels. These data suggest a stronger response of T cells in MIS-C, and higher Treg activity in both groups, which could reflect the response to the excessive inflammation. Ratios previously described in other inflammatory conditions were evaluated: MIS-C showed higher neutrophil/lymphocyte and Th17/Treg ratios than KD, suggesting higher inflammatory conditions in this group. In addition, monocyte and dendritic cells (DCs) numbers were decreased in MIS-C relative to KD. Parallel to these inflammatory cellular profiles, we identified increased levels of inflammatory cytokines in plasma of patients during the acute phase of the disease compared to recovery samples. Moreover, IL-6, which is one of the main cytokines involved in cytokine storm in adult COVID-19, was higher in MIS-C suggesting, again, stronger inflammatory conditions in this pathology compared to KD

Epidemiological and clinical features of Kawasaki disease in Spain over 5 years and risk factors for aneurysm development. (2011-2016): KAWA-RACE study group

Background: Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology affecting mainly children less than 5 years of age. Risk factors for cardiac involvement and resistance to treatment are insufficiently studied in non-Japanese children. Objective: This study aimed to investigate the epidemiology, clinical features and risk factors for resistance to treatment and coronary artery lesions (CAL) in KD in Spain. Methods: Retrospective study (May 2011-June 2016) of all patients less than 16 years of age diagnosed with KD included in KAWA-RACE network (84 Spanish hospitals). Results: A total of 625 cases were analyzed, 63% were males, 79% under 5 year-olds and 16.8% younger than 12 months. On echocardiographic examination CAL were the most frequent findings (23%) being ectasia the most common (12%). Coronary aneurysms were diagnosed in 9.6%, reaching 20% in infants under 12 months (p 900,000 cells/mm3, maximum temperature 10 days and fever before treatment ≥ 8 days as independent risk factors for developing coronary aneurysms. Conclusions: In our population, children under 12 months develop coronary aneurysms more frequently and children with KD with anemia and leukocytosis have high risk of cardiac involvement. Adding steroids early should be considered in those patients, especially if the treatment is not started before 8 days of fever. A score applicable to non-Japanese children able to predict the risk of aneurysm development and IVIG resistance is necessary

Prevalence and Clinical Characteristics of SARS-CoV-2 Confirmed and Negative Kawasaki Disease Patients During the Pandemic in Spain

Introduction: COVID-19 has a less severe course in children. In April 2020, some children presented with signs of multisystem inflammation with clinical signs overlapping with Kawasaki disease (KD), most of them requiring admission to the pediatric intensive care unit (PICU). This study aimed to describe the prevalence and clinical characteristics of KD SARS-CoV-2 confirmed and negative patients during the pandemic in Spain. Material and Methods: Medical data of KD patients from January 1, 2018 until May 30, 2020 was collected from the KAWA-RACE study group. We compared the KD cases diagnosed during the COVID-19 period (March 1-May 30, 2020) that were either SARS-CoV-2 confirmed (CoV+) or negative (CoV-) to those from the same period during 2018 and 2019 (PreCoV). Results: One hundred and twenty-four cases were collected. There was a significant increase in cases and PICU admissions in 2020 (P-trend = 0.001 and 0.0004, respectively). CoV+ patients were significantly older (7.5 vs. 2.5 yr) and mainly non-Caucasian (64 vs. 29%), had incomplete KD presentation (73 vs. 32%), lower leucocyte (9.5 vs. 15.5 × 109) and platelet count (174 vs. 423 × 109/L), higher inflammatory markers (C-Reactive Protein 18.5vs. 10.9 mg/dl) and terminal segment of the natriuretic atrial peptide (4,766 vs. 505 pg/ml), less aneurysm development (3.8 vs. 11.1%), and more myocardial dysfunction (30.8 vs. 1.6%) than PreCoV patients. Respiratory symptoms were not increased during the COVID-19 period. Conclusion: The KD CoV+ patients mostly meet pediatric inflammatory multisystem syndrome temporally associated with COVID-19/multisystem inflammatory syndrome in children criteria. Whether this is a novel entity or the same disease on different ends of the spectrum is yet to be clarified

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

Observation of tW production in the single-lepton channel in pp collisions at root s=13 TeV

A measurement of the cross section of the associated production of a single top quark and a W boson in final states with a muon or electron and jets in proton-proton collisions at root s = 13 TeV is presented. The data correspond to an integrated luminosity of 36 fb(-1) collected with the CMS detector at the CERN LHC in 2016. A boosted decision tree is used to separate the tW signal from the dominant t (t) over bar background, whilst the subleading W+jets and multijet backgrounds are constrained using data-based estimates. This result is the first observation of the tW process in final states containing a muon or electron and jets, with a significance exceeding 5 standard deviations. The cross section is determined to be 89 +/- 4 (stat) +/- 12 (syst) pb, consistent with the standard model.Peer reviewe

Measurements of the Electroweak Diboson Production Cross Sections in Proton-Proton Collisions at root s=5.02 TeV Using Leptonic Decays

The first measurements of diboson production cross sections in proton-proton interactions at a center-of-mass energy of 5.02 TeV are reported. They are based on data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 302 pb(-1). Events with two, three, or four charged light leptons (electrons or muons) in the final state are analyzed. The WW, WZ, and ZZ total cross sections are measured as sigma(WW) = 37:0(-5.2)(+5.5) (stat)(-2.6)(+2.7) (syst) pb, sigma(WZ) = 6.4(-2.1)(+2.5) (stat)(-0.3)(+0.5)(syst) pb, and sigma(ZZ) = 5.3(-2.1)(+2.5)(stat)(-0.4)(+0.5) (syst) pb. All measurements are in good agreement with theoretical calculations at combined next-to-next-to-leading order quantum chromodynamics and next-to-leading order electroweak accuracy