Estudien la relació entre els antiretrovirals i la hiperlactacidèmia en fills de mares VIH

La hiperlactacidèmia és una alta concentració de lactat al sèrum deguda a trastorns metabòlics, i pot suposar una greu alteració en la vida normal del pacient. Aquest desordre pot ser provocat, entre altres causes, per l'ús de fàrmacs i alguns estudis relacionen la seva aparició en nadons amb l'ús d'antiretrovirals per al VIH a les seves mares. La següent tesi doctoral ha demostrat, però, que no es pot establir una relació entre el tractament amb antiretrovirals i l'aparició d'hiperlactacidèmia, sinò que hi ha altres factors, com la prematuritat, que poden tenir especial importància per a la seva incidència.La hiperlactacidemia es una alta concentración de lactato en suero debida a trastornos metabólicos, y puede suponer una grave alteración en la vida normal del paciente. Este desorden puede ser provocado, entre otras causas, por el uso de fármacos y algunos estudios relacionan su aparición en bebés con el uso de antirretrovirales para el VIH en sus madres. La siguiente tesis doctoral ha demostrado, sin embargo, que no se puede establecer una relación entre el tratamiento con antirretrovirales y la aparición de hiperlactacidemia, sino que hay otros factores, como la prematuridad, que pueden tener especial importancia en su incidencia.Hyperlactatemia is a high serum lactate concentration due to metabolic disorders, and may result in serious deterioration of the patient's normal life. This disorder can be caused, among other factors, by the use of drugs and in some studies its appearance in infants is related to the use of antiretroviral drugs for HIV by their mothers. This thesis shows however that is not possible to establish a relationship between antiretroviral treatment and the occurrence of hyperlactatemia, since there are other factors such as prematurity that may have particular importance in its incidence

Primer estudi del sud d'Europa sobre la qualitat de vida d'infants i joves afectats per immunodeficiències primàries

Les Immunodeficiències Primàries (IDP) són malalties rares que afecten 1 de cada 2.000 nascuts vius. En aquest estudi s'ha avaluat com afecten les múltiples dimensions relacionadas amb la qualitat de vida d'infants i joves. Les principals afectacions corresponen a l'àmbit de les relacions i el benestar psíquic. Els resultats obtinguts permetran millorar les intervencions mèdiques actuals i millorar el programa "Tinc IDP. No estic sol", que l'Hospital Universitari Vall d'Hebron té en marxa des del 2016 per atendre les persones afectades.La Inmunodeficiencias Primarias (IDP) son enfermedades raras que afectan a 1 de cada 2.000 nacidos vivos. En este estudio se ha evaluado cómo afectan a múltiples dimensiones relacionadas con la calidad de vida de niños y jóvenes. Las principales afectaciones corresponden al ámbito de las relaciones sociales y el bienestar psíquico. Los resultados obtenidos permitirán mejorar las intervenciones médicas actuales y mejorar el programa «Tengo IDP. No estoy solo», que el Hospital Universitario Vall d'Hebron tiene en marcha desde el 2016 para atender a las personas afectadas.Primary Immunodeficiencies (PIDs) are rare diseases affecting 1 in every 2,000 live births. This study evaluates how they affect multiple dimensions related to the quality of life of children and young people. The main effects correspond to the field of social relations and mental wellbeing. The results obtained will make it possible to improve current medical interventions and the Vall d'Hebron's Universitary Hospital programme "Tinc IDP: no estic sol", which was founded in 2016 to offer support to those suffering from PIDs

Impacte a nivell hospitalari de les infeccions respiratòries virals de vies baixes en la població infantil

A Catalunya hi ha poca informació sobre el consum de recursos sanitaris que impliquen les infeccions respiratòries virals de vies baixes (bronquiolitis, bronquitis, agudització asmàtica i pneumònia) en la població infantil. Un nou estudi ha analitzat l'epidemiologia, els símptomes, la gravetat i el consum de recursos sanitaris d'aquestes infeccions entre 2012 i 2020 a l'Hospital Infantil Vall d'Hebron.En Cataluña existe poca información sobre el consumo de recursos sanitarios que implican las infecciones respiratorias virales de vías bajas (bronquiolitis, bronquitis, agudización asmática y neumonía) en la población infantil. Un nuevo estudio ha analizado la epidemiología, los síntomas, la gravedad y el consumo de recursos sanitarios de estas infecciones entre 2012 y 2020 en el Hospital Infantil Vall d'Hebron.In Catalonia, information is scarce about the in-hospital burden of diseases involving viral lower respiratory tract infections (bronchiolitis, bronchitis, asthma exacerbation and pneumonia) in paediatric population. A new study has analyzed the epidemiology, the symptoms, the severity and the economical features of these infections between 2012 and 2020 at the Children's Hospital in Vall d'Hebron Barcelona Hospital Campus

The lung in primary immunodeficiencies: new concepts in infection and inflammation

Immunoglobulin replacement therapy (IGRT) has contributed critically to the management of primary antibody deficiencies (PAD) and the decrease in pneumonia rate. However, despite adequate IGRT and improved prognosis, patients with PAD continue to experience recurrent respiratory tract infections, leading to bronchiectasis and continuing decline in lung function with a severe impact on their quality of life. Moreover, non-infectious inflammatory and interstitial lung complications, such as granulomatous-lymphocytic interstitial lung disease, contribute substantially to the overall morbidity of PAD. These conditions develop much more often than appreciated and represent a major therapeutic challenge. Therefore, a regular assessment of the structural and functional condition of the lung and the upper airways with appropriate treatment is required to minimize the deterioration of lung function. This work summarizes the knowledge on lung complications in PAD and discusses the currently available diagnostic tools and treatment options

BT595, a 10% Human Normal Immunoglobulin, for Replacement Therapy of Primary Immunodeficiency Disease: Results of a Subcohort Analysis in Children

Children; Pharmacokinetics; Serious bacterial infectionsNiños; Farmacocinética; Infecciones bacterianas gravesNens; Farmacocinètica; Infeccions bacterianes greusPurpose To assess the efficacy, pharmacokinetics, and safety of a new, highly purified 10% IVIg (BT595, Yimmugo®) administered in children with PID. Methods This was an open-label, prospective, uncontrolled, multicenter Phase III pivotal trial. Among the 67 subjects in the trial were 18 pediatric patients aged 2 to 17 years with diagnosis of PID included in this analysis. They received doses between 0.2 and 0.8 g/kg body weight for approximately 12 months at intervals of either 3 or 4 weeks. Dosage and dosing interval were based on each patient’s pre-trial infusion schedule. The rates of acute serious bacterial infections (SBI), secondary efficacy, safety, and pharmacokinetic outcomes were evaluated. Results No SBI occurred in the pediatric population. Two hundred sixty infusions were administered to the 18 pediatric patients. The mean (SD) IgG trough level was 8.55 (1.67) g/L at baseline and 8.84 (2.17) g/L at the follow-up visit after the last BT595 infusion. At the single infusions respectively, the average mean IgG trough levels ranged between 8.52 and 10.58 g/L. More than 85% of all infusions administered were not associated with any infusional AE (start during or within 72 h post-infusion). None of the severe or serious AEs were related to the investigational medicinal product (IMP). No premedication was used. Thirteen children reached a maximum infusion rate between > 2.0 and 8 mL/kg/h; no AE with an onset during the infusion occurred at these infusion rates. Conclusion BT595 is effective, convenient, well tolerated, and safe for the treatment of children with PID.This trial was funded by Biotest AG, Dreieich, Germany

Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia

Immunodeficiency; Immunoglobulins; MortalityInmunodeficiencia; Inmunoglobulinas; MortalidadImmunodeficiència; Immunoglobulines; MortalitatPatients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978)Open Access funding enabled and organized by Projekt DEAL. The ESID Registry was supported by the German Federal Ministry of Education and Research (BMBF 01GM0896, 01GM1111B, 01GM1517C, 01EO1303 and 01ZZ1801B) EU grant no. HEALTH-F2-2008–201549 (EURO-PADnet), the pharmaceutical companies Novartis, GlaxoSmithKline, LFB, and UCB UK, the Plasma Protein Therapeutics Association (PPTA), the Care-for-Rare Foundation, PROimmune e.V, LFB, and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC 2155 RESIST—Project ID 39087428. EGD is supported by the UK National Institute of Health Research and the Great Ormond Street Hospital Biomedical Research Centre

Primary and Secondary Immunodeficiency Diseases in Oncohaematology: Warning Signs, Diagnosis, and Management

Antibodies deficiency; Autoimmunity; Hematologic neoplasmsDeficiència d'anticossos; Autoimmunitat; Neoplàsies hematològiquesDeficiencia de anticuerpos; Autoimmunidad; Neoplasias hematológicasBackground: Immunodeficiencies (ID), in particular primary immunodeficiencies (PID), are often associated with haematological manifestations, such as peripheral cytopenias or lymphoproliferative syndromes. Early diagnosis and management have significant prognostic implications. Secondary immunodeficiencies (SID) may also be induced by oncohaematological diseases and their treatments. Haematologists and oncologists must therefore be aware of the association between blood disorders and cancer and ID, and be prepared to offer their patients appropriate treatment without delay. Our aim was to define the warning signs of primary and secondary IDs in paediatric and adult patients with oncohaematological manifestations. Methods: A multidisciplinary group of six experts (2 haematologists, 2 immunologists, and 2 paediatricians specializing in ID) conducted a literature review and prepared a document based on agreements reached an in-person meeting. An external group of 44 IDs specialists from all over Spain assessed the document and were consulted regarding their level of agreement. Results: This document identifies the haematological and extra-haematological diseases that should prompt a suspicion of PIDs in adults and children, in both primary care and haematology and oncology departments. Cytopenia and certain lymphoproliferative disorders are key diagnostic pointers. The diagnosis must be based on a detailed clinical history, physical exploration, complete blood count and standard laboratory tests. The immunological and haematological tests included in the diagnostic process will depend on the care level. Patients who are candidates for immunoglobulin replacement therapy must be carefully selected, and treatment should be offered as soon as possible to avoid the development of complications. Finally, this document recommends procedures for monitoring these patients. Conclusions: This document combines scientific evidence with the opinion of a broad panel of experts, and emphasizes the importance of an early diagnosis and treatment to avoid complications. The resulting document is a useful tool for primary care physicians and specialists who see both adult and paediatric patients with oncohaematological diseases

Current Transition Practice for Primary Immunodeficiencies and Autoinflammatory Diseases in Europe: a RITA-ERN Survey

Autoinflammatory diseases; Primary immunodeficiencies; TransitionEnfermedades autoinflamatorias; Inmunodeficiencias primarias; TransiciónMalalties autoinflamatòries; Immunodeficiències primàries; TransicióBackground Due to the absence of curative treatments for inborn errors of immunity (IEI), children born with IEI require long-term follow-up for disease manifestations and related complications that occur over the lifespan. Effective transition from pediatric to adult services is known to significantly improve adherence to treatment and long-term outcomes. It is currently not known what transition services are available for young people with IEI in Europe. Objective To understand the prevalence and practice of transition services in Europe for young people with IEI, encompassing both primary immunodeficiencies (PID) and systemic autoinflammatory disorders (AID). Methods A survey was generated by the European Reference Network on immunodeficiency, autoinflammatory, and autoimmune diseases Transition Working Group and electronically circulated, through professional networks, to pediatric centers across Europe looking after children with IEI. Results Seventy-six responses were received from 52 centers, in 45 cities across 17 different countries. All services transitioned patients to adult services, mainly to specialist PID or AID centers, typically transferring up to ten patients to adult care each year. The transition process started at a median age of 16–18 years with transfer to the adult center occurring at a median age of 18–20 years. 75% of PID and 68% of AID centers held at least one joint appointment with pediatric and adult services prior to the transfer of care. Approximately 75% of PID and AID services reported having a defined transition process, but few centers reported national disease-specific transition guidelines to refer to. Conclusions Transition services for children with IEI in Europe are available in many countries but lack standardized guidelines to promote best practice.This study was supported by the ERN-RITA

Symptom-Based Predictive Model of COVID-19 Disease in Children

COVID-19; Microbiology; PaediatricsCOVID-19; Microbiología; PediatríaCOVID-19; Microbiologia; PediatriaBackground: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is neither always accessible nor easy to perform in children. We aimed to propose a machine learning model to assess the need for a SARS-CoV-2 test in children (<16 years old), depending on their clinical symptoms. Methods: Epidemiological and clinical data were obtained from the REDCap® registry. Overall, 4434 SARS-CoV-2 tests were performed in symptomatic children between 1 November 2020 and 31 March 2021, 784 were positive (17.68%). We pre-processed the data to be suitable for a machine learning (ML) algorithm, balancing the positive-negative rate and preparing subsets of data by age. We trained several models and chose those with the best performance for each subset. Results: The use of ML demonstrated an AUROC of 0.65 to predict a COVID-19 diagnosis in children. The absence of high-grade fever was the major predictor of COVID-19 in younger children, whereas loss of taste or smell was the most determinant symptom in older children. Conclusions: Although the accuracy of the models was lower than expected, they can be used to provide a diagnosis when epidemiological data on the risk of exposure to COVID-19 is unknown.This research has received external funding from the Fundació la Marató tv3 after being awarded in the COVID-19 research call with the expedient number 202134-30-31

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome

Immunodeficiència primària; Limfoproliferació; Inhibidor de mTORInmunodeficiencia primaria; Linfoproliferación; Inhibidor de mTORPrimary immunodeficiency; Lymphoproliferation; MTOR inhibitorBackground Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT). Objectives This study sought to characterize HCT outcomes in APDS. Methods Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT. Results Pre-HCT comorbidities such as lung, gastrointestinal, and liver pathology were common, with hematologic malignancy in 26%. With median follow-up of 2.3 years, 2-year overall and graft failure–free survival probabilities were 86% and 68%, respectively, and did not differ significantly by APDS1 versus APDS2, donor type, or conditioning intensity. The 2-year cumulative incidence of graft failure following first HCT was 17% overall but 42% if mammalian target of rapamycin inhibitor(s) (mTORi) were used in the first year post-HCT, compared with 9% without mTORi. Similarly, 2-year cumulative incidence of unplanned donor cell infusion was overall 28%, but 65% in the context of mTORi receipt and 23% without. Phenotype reversal occurred in 96% of evaluable patients, of whom 17% had mixed chimerism. Vulnerability to renal complications continued post-HCT, adding new insights into potential nonimmunologic roles of phosphoinositide 3-kinase not correctable through HCT. Conclusions Graft failure, graft instability, and poor graft function requiring unplanned donor cell infusion were major barriers to successful HCT. Post-HCT mTORi use may confer an advantage to residual host cells, promoting graft instability. Longer-term post-HCT follow-up of more patients is needed to elucidate the kinetics of immune reconstitution and donor chimerism, establish approaches that reduce graft instability, and assess the completeness of phenotype reversal over time.This research was funded in part from the Intramural Program of the National Cancer Institute, National Institutes of Health. The funding source had no involvement in study design; collection, analysis, and interpretation of data; writing of the report; or in the decision to submit the article for publication