Renal Function Impairment in Children With Congenital Cytomegalovirus Infection: A Cross-sectional Study

Albuminuria; Congenital cytomegalovirus infection; Renal tubuleAlbuminuria; Infección congénita por citomegalovirus; Túbulo renalAlbuminúria; Infecció congènita per citomegalovirus; Túbul renalBackground: We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment. Methods: This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients 0.4) proteinuria. Signs and symptoms of cCMV at birth, the use of antivirals and cCMV-associated sequelae at last available follow-up were obtained from Spanish Registry of Congenital Cytomegalovirus Infection. Results: Seventy-seven patients (37 females, 48.1%; median [interquartile range] age: 14.0 [4.4-36.2] months) were included. Symptom-free elevated urinary protein/creatinine and albumin/creatinine ratios were observed in 37.5% and 41.9% of patients, respectively, with tubular proteinuria prevailing (88.3%) over glomerular proteinuria (11.6%). Proteinuria in the nephrotic range was not observed in any patients. In multivariate analysis, female gender was the only risk factor for tubular proteinuria (adjusted odds ratio = 3.339, 95% confidence interval: 1.086-10.268; P = 0.035). cCMV disease at birth, long-term sequelae, viruria or the use of antivirals were not associated with urinalysis findings. Conclusions: Mild nonsymptomatic tubular proteinuria affects approximately 40% of infants and toddlers with mostly symptomatic cCMV in the first 5 years of life.This study has been funded by Instituto de Salud Carlos III through the projects PI19/00095, PI19/01333, PI22/01540, and grant INT20/00086 (cofunded by European Regional Development Fund. ERDF, a way to build Europe). M.R.-B. was supported by a predoctoral contract for training in health research (PFIS) by Instituto de Salud Carlos III, ref. FI20/00237. The other authors have no conflicts of interest to disclos

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST-/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36-0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20-440) per 100,000 person-years), both probable de novo infections. Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective

Recomanacions per a la prevenció de la transmissió vertical del VIH

Transmissió vertical; Transmissió mare-fill; VIHTransmisión vertical; Transmisión madre-hijo; VIHVertical transmission; Mother-son transmission; HIVLa transmissió vertical o mare-fill del virus de la immunodeficiència humana (VIH) és la principal via d’infecció en l’edat pediàtrica. Es pot produir durant la gestació, el part i durant el postpart a través de l’alletament matern. En aquest document s’exposen les recomanacions per a la prevenció de la transmissió vertical del VIH a Catalunya. Parteix de la necessitat d’establir l’estat serològic de la futura mare, tant si ja està embarassada i el desconeix, com si es tracta d’una dona infectada pel VIH que es planteja tenir un fill. Analitza en primer lloc el procediment que cal seguir perquè la gestant conegui el seu estat serològic i també què han de tenir en compte les dones infectades pel VIH abans d’iniciar un embaràs. A continuació s’exposen els controls i tractaments que ha de seguir la gestant infectada, en quines condicions s’ha de desenvolupar el part i a quins controls i procediments s’ha de sotmetre el nadó per protegir-lo de la infecció. Aquest material té l’objectiu de millorar i facilitar la informació necessària en el moment del part, als professionals sanitaris de la xarxa de centres hospitalaris de Catalunya, especialment els pediatres, ginecòlegs, obstetres, infermeres i llevadores, que habitualment estan treballant a la sala de parts i facilitar la presa de decisions en el dia a dia.La transmisión vertical o madre-hijo del virus de la inmunodeficiencia humana (VIH) es la principal vía de infección en la edad pediátrica. Se puede producir durante la gestación, el parto y durante el posparto a través de la lactancia materna. En este documento se exponen las recomendaciones para la prevención de la transmisión vertical del VIH en Cataluña. Parte de la necesidad de establecer el estado serológico de la futura madre, tanto si ya está embarazada y desconoce, como si se trata de una mujer infectada por el VIH que se plantea tener un hijo. Analiza en primer lugar el procedimiento a seguir para que la gestante conozca su estado serológico y también que deben tener en cuenta las mujeres infectadas por el VIH antes de iniciar un embarazo. A continuación se exponen los controles y tratamientos que debe seguir la gestante infectada, en qué condiciones se debe desarrollar el parto y en qué controles y procedimientos se someterá al bebé para protegerlo de la infección. Este material tiene el objetivo de mejorar y facilitar la información necesaria en el momento del parto, a los profesionales sanitarios de la red de centros hospitalarios de Cataluña, especialmente los pediatras, ginecólogos, obstetras, enfermeras y matronas, que habitualmente están trabajando en la sala de partes y facilitar la toma de decisiones en el día a día

Neuroimaging in infants with congenital cytomegalovirus infection and its correlation with outcome: emphasis on white matter abnormalities

Objective: To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs). Methods: Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at ≤3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at ≥6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability. Results: Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89±0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia. Conclusions: Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis

Guia sobre la infecció pel VIH i la sida a l’atenció primària

Sida; Transmissió; Atenció socialAIDS; Transmission; Social careSida; Transmisión; Atención socialAquesta nova Guia sobre la infecció pel VIH i la sida a l’atenció primària vol ser una eina útil i facilitadora per als professionals del primer nivell assistencial a l’hora d’establir estratègies preventives i actuacions clíniques relacionades amb la infecció pel VIH amb la finalitat de contribuir a la millora de l’atenció a les persones afectades

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

A Mitocentric View of the Main Bacterial and Parasitic Infectious Diseases in the Pediatric Population

Infectious diseases occur worldwide with great frequency in both adults and children. Both infections and their treatments trigger mitochondrial interactions at multiple levels: (i) incorporation of damaged or mutated proteins to the complexes of the electron transport chain, (ii) mitochondrial genome (depletion, deletions, and point mutations) and mitochondrial dynamics (fusion and fission), (iii) membrane potential, (iv) apoptotic regulation, (v) generation of reactive oxygen species, among others. Such alterations may result in serious adverse clinical events with great impact on children’s quality of life, even resulting in death. As such, bacterial agents are frequently associated with loss of mitochondrial membrane potential and cytochrome c release, ultimately leading to mitochondrial apoptosis by activation of caspases-3 and -9. Using Rayyan QCRI software for systematic reviews, we explore the association between mitochondrial alterations and pediatric infections including (i) bacterial: M. tuberculosis, E. cloacae, P. mirabilis, E. coli, S. enterica, S. aureus, S. pneumoniae, N. meningitidis and (ii) parasitic: P. falciparum. We analyze how these pediatric infections and their treatments may lead to mitochondrial deterioration in this especially vulnerable population, with the intention of improving both the understanding of these diseases and their management in clinical practice

Clàssics d'ahir i d'avui en la gramàtica del català

Textos: Jesús Jiménez, Ricard Herrero, sílvia Llach Carles, Joan Mascaró, Clàudia Pns-Moll, Andrew Nevins, Isabel Oltra-Massuet, jaume Mateu, jordi Fortuny, Mercè Lorente Casafont i Teresa Vallès / Edició: Maria-Rosa Lloret, Clàudia Pons-Moll i Eva Bosch-RouraHi ha qüestions gramaticals del català que actualment són objecte d’anàlisi des de perspectives teòriques renovadores. Aquest volum aplega les aportacions d’un dels col·loquis de referència, el Col·loqui Lingüístic de la Universitat de Barcelona, del qual s’ha arribat a celebrar la 21a edició. En l’àmbit de la fonètica, Jesús Jiménez (UV), Ricard Herrero (UCV) i Sílvia Llach Carles (UdG) exploren l’harmonia vocàlica i el canvi lingüístic; en l’àmbit de la fonologia, Joan Mascaró (UAB) i Clàudia Pons-Moll (UB), la regularitat i les excepcions en la fonologia del català; en l’àmbit de la morfologia, Andrew Nevins (UCL) i Isabel Oltra-Massuet (URV) s’ocupen de les manifestacions de l’al·lomorfia en els sufixos preaccentuats; en l’àmbit de la sintaxi, Jaume Mateu (UAB) i Jordi Fortuny (UB), de la inacusativitat i de la selecció de l’auxiliar en català antic, i, en l’àmbit de la lexicologia, Mercè Lorente Casafont (UPF) i Teresa Vallès (UIC), de la formació de compostos nominals