Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review

t: Background: Congenital cytomegalovirus (cCMV) infection is the most frequent motherto-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients. Objective: We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels. Methods: A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible. Results: Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established. Conclusions: Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical level

Seminaris pràctics mitjançant l'aprenentatge basat en problemes en l'ensenyament de la pediatria

Podeu consultar la Setena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/43352En 2011, se aplicó la metodología del aprendizaje basado en problemas (ABP) en los seminarios prácticos de Pediatría a los estudiantes de 6º de Medicina. La ABP invierte la organización tradicional de los procesos de aprendizaje: primero se presenta el problema, ya partir de la delimitación de lo que ya se conoce, se establecen los objetivos, se identifican las necesidades de aprendizaje, y se diseña y se sigue un plan de actuación, para que el aprendizaje se acompañe de la reso-lución del problema. Previamente, los profesores realizaron un curso específico so-bre ABP organizado por el IES. Transcurrido el primer curso de aplicación del ABP, se pretende evaluar el grado de satisfacción y de aprendizaje obtenidos de los seminarios prácticos ba-sados en el ABP por parte de los estudiantes

Sociodemographic changes and trends in the rates of new perinatal HIV diagnoses and transmission in Spain from 1997 to 2015

Retrospective study; Spanish Paediatric HIV Network; Rates of perinatal HIVEstudio retrospectivo; Red Española de VIH Pediátrico; Tasas de VIH perinatalEstudi retrospectiu; Xarxa espanyola de VIH Pediàtrica; Taxes de VIH perinatalBackground: There are not enough nationwide studies on perinatal HIV transmission in connection with a combination of antiretroviral treatments in Spain. Our objectives were to study sociodemographic changes and trends in the rates of HIV diagnoses and perinatal transmission in Spain from 1997 to 2015. Methods: A retrospective study using data from Spanish Paediatric HIV Network (CoRISpe) and Spanish Minimum Basic Data Set (MDBS) was performed. HIV- diagnosed children between 1997 and 2015 were selected. Sociodemographic, clinical and immunovirological data of HIV-infected children and their mothers were studied in four calendar periods (P1: 1997-2000; P2: 2001-2005; P3: 2006-2010; P4: 2011-2015). Rates of perinatal HIV diagnoses and transmission from 1997 to 2015 were calculated. Results: A total of 532 HIV-infected children were included in this study. Of these children, 406 were Spanish (76.3%) and 126 immigrants (23.7%). A decrease in the number of HIV diagnoses, 203 (38.2%) children in the first (P1), 149 (28%) in the second (P2), 130 (24.4%) in the third (P3) and 50 (9.4%) in the fourth (P4) calendar periods was studied. The same decrease in the Spanish HIV-infected children (P1, 174 (46.6%), P2, 115 (30.8%), P3, 65 (17.4%) and P4, 19 (5.1%)) was monitored. However, an increase in the number of HIV diagnoses by sexual contact (P1: 0%; P2: 1.3%; P3: 4.6%; P4: 16%) was observed. The rates of new perinatal HIV diagnoses and perinatal transmission in Spanish children decreased from 0.167 to 0.005 per 100,000 inhabitants and 11.4% to 0.4% between 1997 and 2015, respectively. Conclusions: A decline of perinatal HIV diagnoses and transmission was observed. However, an increase of teen-agers HIV diagnoses with sexual infection was studied. Public awareness campaigns directed to teen-agers are advisable to prevent HIV infection by sexual contact.This work has been partially funded by Red Temática de Investigación en SIDA (RED RIS) supported by Instituto de Salud Carlos III (ISCIII) (RD12/0017/0035, RD12/0017/0037 and RD16/0025/0019), project as part of the Plan R+D+I (2008-2011; 2013-2016) and cofinanced by ISCIII Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER), RISEPICLIN-19/2015, Fondo para la Investigación Sanitaria of the Spanish Ministry of Science and Innovation (FIS PI13/00422, PI16/01863), CYTED (214RT0482) and EPIICAL Project. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. COST CA17140 Cancer Nanomedicine-Front The Bench to Bebside. We thank the Spanish HIV HGM BioBank supported by ISC III project RETIC PT13/0010/0028 and PT17/0015/0042. No funding for this work was received from National Institutes of Health (NIH), Wellcome Trust and Howard Hughes Medical Institute (HHMI

A new tool for the paediatric HIV research:general data from the Cohort of the SpanishPaediatric HIV Network (CoRISpe)

There are approximately from 1,100 to 1,200 HIV-infected children in a follow-up in Spain. In 2008 an open, multicentral, retrospective and prospective Cohort of the Spanish Paediatric HIV Network (CoRISpe) was founded. The CoRISpe is divided into the node 1 and node 2 representing geographically almost the whole territory of Spain. Since 2008 seventy-five hospitals have been participating in the CoRISpe. All the retrospective data of the HIV-infected children have been kept in the CoRISpe since 1995 and prospective data since 2008. In this article we are going to present the notion of CoRISpe, its role, the structure, how the CoRISpe works and the process how a child is transferred from Paediatric to Adults Units. The main objective of the CoRISpe is to contribute to furthering scientific knowledge on paediatric HIV infection by providing demographic, sociopsychological, clinical and laboratory data from HIV-infected paediatric patients. Its aim is to enable high-quality research studies on HIV-infected children

safety and efficacy of fidaxomicin and vancomycin in children and adolescents with clostridioides clostridium difficile infection a phase 3 multicenter randomized single blind clinical trial sunshine

Abstract Background Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children. Methods Patients aged <18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, 4 times daily). Safety assessments included treatment-emergent adverse events. The primary efficacy end point was confirmed clinical response (CCR), 2 days after the end of treatment (EOT). Secondary end points included global cure (GC; CCR without CDI recurrence) 30 days after EOT (end of study; EOS). Plasma and stool concentrations of fidaxomicin and its active metabolite OP-1118 were measured. Results Of 148 patients randomized, 142 were treated (30 <2 years old). The proportion of participants with treatment-emergent adverse events was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of 3 deaths in the fidaxomicin arm during the study, none were CDI or treatment related. The rate of CCR at 2 days after EOT was 77.6% (76 of 98 patients) with fidaxomicin and 70.5% (31 of 44) with vancomycin, whereas the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% vs 50.0%; adjusted treatment difference, 18.8%; 95% confidence interval, 1.5%–35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal, and stool concentrations were high. Conclusions Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI. ClinicalTrials.gov identifier NCT0221837

Pediatric antimicrobial stewardship in the COVID-19 outbreak

Growing evidence supports the positive impact of antimicrobial stewardship programs (ASPs) on antimicrobial use, including pediatrics.1 Although short of the level of acceptance these have reached in the United States, the implementation of pediatric ASPs in European hospitals has increased over the last few years.1 It has been suggested that the ASP should be helpful in the preparation for and response to the SARS-CoV-2/COVID-19 outbreak, 2 but no formal recommendations have been published. Whether pediatric ASP remains an essential activity or not during the COVID-19 pandemic has yet to be clarified. Here, we describe how the COVID-19 pandemic has impacted antimicrobial use in a referral pediatric hospital, and we propose a supporting role for ASP teams in the local management of the outbreak. The first COVID-19 case in Catalonia, Spain, was reported on February 25, 2020. By mid-March, most pediatric and obstetrics departments in the region were shut to increase the capacity for adult COVID-19 patients. Hospital Sant Joan de Déu Barcelona (SJD) remained the largest pediatric and maternal referral center in the region. COVID-19 and non-COVID-19 pediatric and young adult patients were transferred to our wards and pediatric ICU (PICU), and the number of daily deliveries tripled, whereas all nonemergency clinical, teaching, and research activities were postponed. Compared to the same months in 2019, in March 2020, total hospital stays decreased by 0.8% in the PICU and 15.2% in non-PICU areas, and in April 2020, total hospital stays decreased by 23.7% in the PICU and 22.2% in non-PICU areas

Deletion of Wt1 during early gonadogenesis leads to differences of sex development in male and female adult mice

Assessing the role of the WT1 transcription factor (WT1) during early gonad differentiation and its impact on adult sex development has been difficult due to the complete gonadal agenesis and embryonic lethality exhibited by Wt1KO mouse models. Here, we generated Wt1LoxP/GFP;Wt1Cre mice, the first Wt1KO mouse model that reaches adulthood with a dramatically reduced Wt1 expression during early gonadogenesis. Wt1LoxP/GFP;Wt1Cre mice lacked mature gonads and displayed genital tracts containing both male and female genital structures and ambiguous genitalia. We found that WT1 is necessary for the activation of both male and female sex-determining pathways, as embryonic mutant gonads failed to upregulate the expression of the genes specific for each genetic programme. The gonads of Wt1LoxP/GFP;Wt1Cre mice showed a lack of production of Sertoli and pre-granulosa cells and a reduced number of germ cells. NR5A1 and the steroidogenic genes expression was modulated differently in XY and XX Wt1LoxP/GFP;Wt1Cre gonads, explaining the mutant phenotypes. Further studies of the XX Wt1LoxP/GFP;Wt1Cre gonads revealed that deletion of WT1 at an early stage impaired the differentiation of several cell types including somatic cells and the ovarian epithelium. Through the characterisation of this Wt1KO mouse model, we show that the deletion of Wt1 during early gonadogenesis produces dramatic defects in adult sex development

Early and Highly Suppressive ART are Main Factors Associated with Low Viral Reservoir in European Perinatally HIV Infected Children

Abstract BACKGROUND: Future strategies aiming to achieve HIV-1 remission are likely to target individuals with small reservoir size. SETTING: We retrospectively investigated factors associated with HIV-1 DNA levels in European, perinatally HIV-infected children starting ART <6 months of age. METHODS: Total HIV-1 DNA was measured from 51 long-term suppressed children 6.3 years (median) after initial viral suppression. Factors associated with log10 total HIV-1 DNA were analyzed using linear regression. RESULTS: At ART initiation, children were aged median [IQR] 2.3 [1.2,4.1] months, CD4% 37 [24,45] %, CD8% 28 [18,36] %, log10 plasma viral load (VL) 5.4 [4.4,5.9] copies/ml. Time to viral suppression was 7.98 [4.6,19.3] months. Following suppression, 13 (25%) children had suboptimal response [ 652 consecutive VL50-400 followed by VL<50] and/or experienced periods of virological failure [ 652 consecutive VL 65400 followed by VL<50]. Median total HIV-1 DNA was 43 [6,195] copies/10 PBMC.Younger age at therapy initiation was associated with lower total HIV-1 DNA (adjusted coefficient [AC] 0.12 per month older, p=0.0091), with a month increase in age at ART start being associated with a 13% increase in HIV DNA. Similarly, a higher proportion of time spent virally suppressed (AC 0.10 per 10% higher, p=0.0022) and absence of viral failure/suboptimal response (AC 0.34 for those with fail/ suboptimal response, p=0.0483) were associated with lower total HIV-1 DNA. CONCLUSION: Early ART initiation and a higher proportion of time suppressed are linked with lower total HIV-1 DNA. Early ART start and improving adherence in perinatally HIV-1 infected children minimize the size of viral reservoir.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal

Premature aging and immune senescence in HIV-infected children.

Objective: Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV. Design: Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0-5 years, were studied for biological aging and immune senescence. Methods: Telomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4+ and CD8+ cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry. Results: Telomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8+ recent thymic emigrant cells (CD45RA+CD31+) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28−CD57+), activated (CD38+HLA-DR+), and exhausted (PD1+) CD8+ cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4+ cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former. Conclusions: HIV-infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8+ cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatment. Keywords: immune activation, immune senescence, microbial translocation, pediatric HIV/AIDS, premature aging, telomere length, T-cell receptor rearrangement excision circl

New diagnoses of human immunodeficiency virus infection in the Spanish pediatric HIV Cohort (CoRISpe) from 2004 to 2013

Vertical human immunodeficiency virus (HIV) infection has decreased in industrialized countries in recent decades, but there are no studies on the mechanisms of HIV transmission among infected children in Spain. Our aim was to study the characteristics and trends of diagnoses of vertically HIV-infected children in Spain from 2004 to 2013. Vertically HIV-infected children were selected if they were diagnosed from 2004 to 2013, were aged 0 to 18 years old, and were included in the Cohort of the Spanish Pediatric HIV Network (CoRISpe). Demographic, clinical, immunological, and virological data at diagnosis were obtained. The rate of diagnoses of vertically HIV-infected children was calculated as the number of cases per 100,000 inhabitants. Obstetric data of mothers of Spanish children and prophylaxis at childbirth and postpartum were obtained. A total of 218 HIV-infected children were included in the study. Of this sample, 182 children (83.5%) were perinatally HIV infected, and 125 out of those 182 children (68.7%) were born in Spain. The vertically HIV-infected Spanish children were diagnosed earlier and were in better clinical and immunological condition at diagnosis than were foreign children. The rate of vertically HIV-infected children declined from 0.09 in 2004 to 0.03 in 2013 due to the decrease in the rate of children born in Spain (0.08 in 2004 vs 0.01 in 2013). A total of 60 out of 107 mothers (56.1%) of Spanish children were diagnosed at or after childbirth. However, this number declined between 2004 and 2013. The rate of new HIV diagnoses of vertically HIV-infected children decreased significantly between 2004 and 2013 from 0.09 to 0.03 per 100,000 inhabitants