ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection.

Background: Follicular helper T cells (Tfh) are pivotal in B cell responses. Activation of the purinergic receptor P2X7 on Tfh cells regulates their activity. We investigated the ATP-P2X7R axis in circulating Tfh (cTfh) cells during Respiratory Syncytial Virus (RSV) infection. Methods: We analyzed two cohorts: children with RSV infection (moderate, n=30; severe, n=21) and healthy children (n=23). We utilized ELISA to quantify the levels of PreF RSV protein-specific IgG antibodies, IL-21 cytokine, and soluble P2X7R (sP2X7R) in both plasma and nasopharyngeal aspirates (NPA). Additionally, luminometry was employed to determine ATP levels in plasma, NPA and supernatant culture. The frequency of cTfh cells, P2X7R expression, and plasmablasts were assessed by flow cytometry. To evaluate apoptosis, proliferation, and IL-21 production by cTfh cells, we cultured PBMCs in the presence of Bz-ATP and/or P2X7R antagonist (KN-62) and a flow cytometry analysis was performed. Results: In children with severe RSV disease, we observed diminished titers of neutralizing anti-PreF IgG antibodies. Additionally, severe infections, compared to moderate cases, were associated with fewer cTfh cells and reduced plasma levels of IL-21. Our investigation revealed dysregulation in the ATP-P2X7R pathway during RSV infection. This was characterized by elevated ATP levels in both plasma and NPA samples, increased expression of P2X7R on cTfh cells, lower levels of sP2X7R, and heightened ATP release from PBMCs upon stimulation, particularly evident in severe cases. Importantly, ATP exposure decreased cTfh proliferative response and IL-21 production, while promoting their apoptosis. The P2X7R antagonist KN-62 mitigated these effects. Furthermore, disease severity positively correlated with ATP levels in plasma and NPA samples and inversely correlated with cTfh frequency. Conclusion: Our findings indicate that activation of the ATP-P2X7R pathway during RSV infection may contribute to limiting the cTfh cell compartment by promoting cell death and dysfunction, ultimately leading to increased disease severity.

CROCuS, a Phase II Study Evaluating the Antiviral Activity, Clinical Outcomes, and Safety of Rilematovir in Children Aged ≥ 28 Days and ≤ 3 Years with Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children aged ≤ 5 years and adults aged ≥ 60 years worldwide. Despite this, RSV-specific therapeutic options are limited. Rilematovir is an investigational, orally administered inhibitor of RSV fusion protein-mediated viral entry. OBJECTIVE: To establish the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir (low or high dose) in children aged ≥ 28 days and ≤ 3 years with RSV disease. METHODS: CROCuS was a multicenter, international, double-blind, placebo-controlled, randomized, adaptive phase II study, wherein children aged ≥ 28 days and ≤ 3 years with confirmed RSV infection who were either hospitalized (Cohort 1) or treated as outpatients (Cohort 2) were randomized (1:1:1) to receive rilematovir (low or high dose) or placebo. Study treatment was administered daily as an oral suspension from days 1 to 7, with dosing based on weight and age groups. The primary objective was to establish antiviral activity of rilematovir by evaluating the area under the plasma concentration-time curve of RSV viral load in nasal secretions from baseline through day 5. Severity and duration of RSV signs and symptoms and the safety and tolerability of rilematovir were also assessed through day 28 (± 3). RESULTS: In total, 246 patients were randomized, treated, and included in the safety analysis population (Cohort 1: 147; Cohort 2: 99). Of these, 231 were included in the intent-to-treat-infected analysis population (Cohort 1: 138; Cohort 2: 93). In both cohorts, demographics were generally similar across treatment groups. In both cohorts combined, the difference (95% confidence interval) in the mean area under the plasma concentration-time curve of RSV RNA viral load through day 5 was - 1.25 (- 2.672, 0.164) and - 1.23 (- 2.679, 0.227) log10 copies∙days/mL for the rilematovir low-dose group and the rilematovir high-dose group, respectively, when compared with placebo. The estimated Kaplan-Meier median (95% confidence interval) time to resolution of key RSV symptoms in the rilematovir low-dose, rilematovir high-dose, and placebo groups of Cohort 1 was 6.01 (4.24, 7.25), 5.82 (4.03, 8.18), and 7.05 (5.34, 8.97) days, respectively; in Cohort 2, estimates were 6.45 (4.81, 9.70), 6.26 (5.41, 7.84), and 5.85 (3.90, 8.27) days, respectively. A similar incidence of adverse events was reported in patients treated with rilematovir and placebo in Cohort 1 (rilematovir: 61.9%; placebo: 58.0%) and Cohort 2 (rilematovir: 50.8%; placebo: 47.1%), with most reported as grade 1 or 2 and none leading to study discontinuation. The study was terminated prematurely, as the sponsor made a non-safety-related strategic decision to discontinue rilematovir development prior to full recruitment of Cohort 2. CONCLUSIONS: Data from the combined cohort suggest that rilematovir has a small but favorable antiviral effect of indeterminate clinical relevance compared with placebo, as well as a favorable safety profile. Safe and effective therapeutic options for RSV in infants and young children remain an unmet need. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2016-003642-93; ClinicalTrials.gov Identifier: NCT03656510. First posted date: 4 September, 2018.

Impacto de la pandemia por SARS-CoV-2 en el índice de masa corporal de niños asistidos en la Ciudad Autónoma de Buenos Aires / Impact of the SARS-CoV-2 pandemic on the body mass index of children seen in the City of Buenos Aires

Introducción. El sobrepeso y la obesidad infantil constituyen un problema de salud pública. El inicio de la pandemia por COVID-19 pudo haber favorecido esta patología. El puntaje Z del índice de masa corporal (Z-IMC) es un indicador aceptado para su diagnóstico y seguimiento. Objetivo. Evaluar si la prevalencia de sobrepeso y obesidad, y el Z-IMC en niños de 2 a 5 años aumentó durante la pandemia. Población y métodos. Estudio de cohorte retrospectiva. Se incluyeron pacientes asistidos en efectores públicos de salud del Gobierno de la Ciudad Autónoma de Buenos Aires (GCABA), de 2 a 5 años de edad, con registro de peso y talla en dos consultas, antes y después de haber comenzado el aislamiento social preventivo y obligatorio (ASPO). Se registró estado nutricional (Z-IMC) y variación del Z-IMC entre ambas consultas. Resultados. Se evaluaron 3866 sujetos, edad promedio 3,4 ± 0,8 años; el 48,1 % fueron mujeres. El intervalo promedio entre consultas fue 14,3 ± 2,5 meses. La prevalencia de sobrepeso/obesidad aumentó del 12,6 % (IC95% 11,6-13,6) al 20,9 % (IC95% 19,6-22-2); p <0,001, al igual que el Z-IMC (0,4 ± 1,1 vs. 0,8 ± 1,3; p <0,001). Conclusión. La prevalencia de sobrepeso y obesidad, y el Z-IMC en niños de 2 a 5 años aumentó significativamente durante la pandemia.

Introduction. Childhood overweight and obesity are a public health problem. The onset of the COVID-19 pandemic may have contributed to this condition. The body mass index (BMI) Z-score has been accepted as an indicator for overweight and obesity diagnosis and follow-up. Objective. To assess whether the prevalence of overweight and obesity and the BMI Z-score in children aged 2 to 5 years increased during the pandemic. Population and methods. Retrospective, cohort study. Patients included were those seen at public health care facilities in the City of Buenos Aires (CABA), who were aged 2 to 5 years, had weight and height values recorded at 2 different visits, before and after the establishment of the preventive and mandatory social isolation policy. Patients' nutritional status (BMI Z-score) and the variation in this indicator between both visits were recorded. Results. A total of 3866 subjects were assessed; their average age was 3.4 ± 0.8 years; 48.1% were girls. The average interval between both visits was 14.3 ± 2.5 months. The prevalence of overweight/ obesity increased from 12.6% (95% CI: 11.6­13.6) to 20.9% (95% CI: 19.6­22.2), p < 0.001, and so did the BMI Z-score (0.4 ± 1.1 versus 0.8 ± 1.3, p < 0.001). Conclusion. The prevalence of overweight and obesity and the BMI Z-score in children aged 2 to 5 years increased significantly during the pandemic.

Thirty-day readmissions in children with complex chronic conditions.

INTRODUCTION: The rate of hospital readmission within 30 days of discharge is a quality indicator in health care. Paediatric patients with complex chronic conditions have high readmission rates. Failure in the transition between hospital and home care could explain this phenomenon. OBJECTIVES: To estimate the incidence rate of 30-day hospital readmission in paediatric patients with complex chronic conditions, estimate how many are potentially preventable and explore factors associated with readmission. MATERIALS AND METHOD: Cohort study including hospitalised patients with complex chronic conditions aged 1 month to 18 years. Patients with cancer or with congenital heart disease requiring surgical correction were excluded. The outcomes assessed were 30-day readmission rate and potentially preventable readmissions. We analysed sociodemographic, geographic, clinical and transition to home care characteristics as factors potentially associated with readmission. RESULTS: The study included 171 hospitalizations, and 28 patients were readmitted within 30 days (16.4%; 95% CI, 11.6%-22.7%). Of the 28 readmissions, 23 were potentially preventable (82.1%; 95% CI, 64.4%-92.1%). Respiratory disease was associated with a higher probability of readmission. There was no association between 30-day readmission and the characteristics of the transition to home care. CONCLUSIONS: The 30-day readmission rate in patients with complex chronic disease was 16.4%, and 82.1% of readmissions were potentially preventable. Respiratory disease was the only identified risk factor for 30-day readmission.

Impact of the SARS-CoV-2 pandemic on the body mass index of children seen in the City of Buenos Aires. / Impacto de la pandemia por SARS-CoV-2 en el índice de masa corporal de niños asistidos en la Ciudad Autónoma de Buenos Aires.

Introduction. Childhood overweight and obesity are a public health problem. The onset of the COVID-19 pandemic may have contributed to this condition. The body mass index (BMI) Z-score has been accepted as an indicator for overweight and obesity diagnosis and follow-up. Objective. To assess whether the prevalence of overweight and obesity and the BMI Z-score in children aged 2 to 5 years increased during the pandemic. Population and methods. Retrospective, cohort study. Patients included were those seen at public health care facilities in the City of Buenos Aires (CABA), who were aged 2 to 5 years, had weight and height values recorded at 2 different visits, before and after the establishment of the preventive and mandatory social isolation policy. Patients' nutritional status (BMI Z-score) and the variation in this indicator between both visits were recorded. Results. A total of 3866 subjects were assessed; their average age was 3.4 ± 0.8 years; 48.1% were girls. The average interval between both visits was 14.3 ± 2.5 months. The prevalence of overweight/ obesity increased from 12.6% (95% CI: 11.6-13.6) to 20.9% (95% CI: 19.6-22.2), p < 0.001, and so did the BMI Z-score (0.4 ± 1.1 versus 0.8 ± 1.3, p < 0.001). Conclusion. The prevalence of overweight and obesity and the BMI Z-score in children aged 2 to 5 years increased significantly during the pandemic.

Introducción. El sobrepeso y la obesidad infantil constituyen un problema de salud pública. El inicio de la pandemia por COVID-19 pudo haber favorecido esta patología. El puntaje Z del índice de masa corporal (Z-IMC) es un indicador aceptado para su diagnóstico y seguimiento. Objetivo. Evaluar si la prevalencia de sobrepeso y obesidad, y el Z-IMC en niños de 2 a 5 años aumentó durante la pandemia. Población y métodos. Estudio de cohorte retrospectiva. Se incluyeron pacientes asistidos en efectores públicos de salud del Gobierno de la Ciudad Autónoma de Buenos Aires (GCABA), de 2 a 5 años de edad, con registro de peso y talla en dos consultas, antes y después de haber comenzado el aislamiento social preventivo y obligatorio (ASPO). Se registró estado nutricional (Z-IMC) y variación del Z-IMC entre ambas consultas. Resultados. Se evaluaron 3866 sujetos, edad promedio 3,4 ± 0,8 años; el 48,1 % fueron mujeres. El intervalo promedio entre consultas fue 14,3 ± 2,5 meses. La prevalencia de sobrepeso/obesidad aumentó del 12,6 % (IC95% 11,6-13,6) al 20,9 % (IC95% 19,6-22-2); p <0,001, al igual que el Z-IMC (0,4 ± 1,1 vs. 0,8 ± 1,3; p <0,001). Conclusión. La prevalencia de sobrepeso y obesidad, y el Z-IMC en niños de 2 a 5 años aumentó significativamente durante la pandemia.

Waiting for the next winter. Outpatient pediatric visits for respiratory infections before, during, and after the COVID-19 pandemic in the city of Buenos Aires.

INTRODUCTION: During the COVID-19 pandemic, pediatric visits due to acute lower respiratory infections (ALRIs) decreased, but most reports are from hospitalized patients. There is little information on this phenomenon in outpatients, who are the majority in ALRI. We evaluated the impact of the COVID-19 pandemic on ALRI-related outpatient visits in the City of Buenos Aires. METHODS: Observational study including all outpatient visits of children under 2 years of age to the public health system of the City of Buenos Aires, between 1 January 2018 and 31 December 2022. We analyzed the total number of visits and the ALRI-related visits, and their distribution throughout the study period. RESULTS: A total of 704,426 visits were registered, 7.38% of them due to ALRI. ALRI-related visits decreased from the implementation of a national lockdown (2020) and increased again as the restriction measures decreased, particularly the return to full school attendance (2021). In general, the proportion of ALRI-related visits was significantly higher in the cold months than in the warm ones (9.8% vs. 5.5%; odds ratio: 1.76, 95% confidence interval: 1.73-1.79; p < .001). This difference was observed before (2018 and 2019) and after the pandemic (2022), but not in 2020-2021. The peak of ALRI-related visits occurred in the cold months in pre-pandemic years (2018-2019), did not appear in 2020, reappeared delayed in 2021, and recovered seasonality in 2022. CONCLUSION: Outpatient ALRI-related visits decreased significantly in the city of Buenos Aires during the COVID-19 pandemic and currently seem to have recovered their magnitude and seasonality.

[Exclusive breastfeeding and disease evolution in hospitalized infants with bronchiolitis]. / Lactancia materna exclusiva y evolución de la enfermedad en lactantes hospitalizados por bronquiolitis.

Bronchiolitis is the main reason for hospitalization in infancy. Breastfeeding is a protective factor aga inst infections, however, although there is evidence that breastfeeding could prevent hospitalizations due to bronchiolitis, its effect in patients already hospitalized because of this disease is less clear. OBJECTIVE: To evaluate if there are differences in the evolution of patients hospitalized due to bronchiolitis fed with exclusive breastfeeding (EBF) vs. breast milk substitutes (BMS). PATIENTS AND METHOD: Prospec tive cohort study. Children hospitalized due to bronchiolitis aged from 1 to 6 months were included. Evolution was compared with respect to days of hospitalization, days of oxygen therapy, requirement of high-flow nasal cannula (HFNC), presence of associated pneumonia, transfer to intensive care, and death. RESULTS: During the study period, 131 infants hospitalized due to bronchiolitis met the selection criteria, 54 were fed with EBF, 29 with BMS, and 48 received mixed feeding. The EBF group required significantly fewer days of oxygen therapy (5.1 ± 2.4 vs. 6.6 ± 3.5; p < 0.02) and hospitalization (7.0 ± 2.4 vs. 8.4 ± 3.6; p < 0.04) than the BMS group. Although males in the BMS group required on average more days of hospitalization and oxygen therapy, this difference was not statistically significant. No deaths were recorded in the groups studied. CONCLUSION: Patients fed with EBF required fewer days of oxygen therapy and hospitalization than those who received BMS.

[Circulation dynamics of respiratory syncytial virus and its relationship with ambient temperature. 25-year series in Buenos Aires] / Dinámica de circulación de virus sincicial respiratorio y su relación con la temperatura ambiental. Serie de 25 años en Buenos Aires.

Objective: To evaluate changes in RSV seasonality in the last 25 years and their correlation with the mean annual temperature. Methods: Cross-sectional study, based on RSV and temperature data from the City of Buenos Aires (1995-2019). For each year, we describe the beginning, end, and duration of the RSV season and the correlation with the mean annual temperature. Results: We identified 10,183 RSV infections. The duration of the RSV season decreased significantly (1995: 29 weeks vs. 2019: 18 weeks; R: 0.6 (p< 0.001)), due to an earlier ending (1995: week 45 vs. 2019: week 34; 0.6 (p<0.001)). No correlation was observed between mean annual temperature and the duration, start, or end of the RSV season. Conclusion: In the last 25 years, the duration of the RSV season has been significantly shortened due to an earlier ending, without correlation with temperature.

Introducción: El cambio climático global podría alterar la circulación del virus sincicial respiratorio (VSR). Objetivo: Evaluar modificaciones en la circulación de VSR en los últimos 25 años y su correlación con la temperatura ambiente. Métodos: Estudio transversal, utilizando registros de VSR y temperatura de la Ciudad de Buenos Aires (1995-2019). Para cada año, describimos inicio, fin y duración de la temporada de VSR y evaluamos su correlación con la temperatura media anual. Resultados: Se identificaron 10183 infecciones por VSR. La duración de la temporada disminuyó significativamente (1995: 29 semanas vs. 2019: 18 semanas; R: 0.6 (p< 0,001)), debido a una finalización más precoz (1995: semana 45 vs. 2019: semana 34; 0,6 (p<0,001)). No se observó correlación entre temperatura media anual y duración, comienzo ni finalización de la temporada de VSR. Conclusión: En los últimos 25 años, la duración de la temporada de VSR se acortó significativamente, sin correlación con la temperatura.

Evaluación de residentes de pediatría con una modalidad virtual durante la pandemia COVID 19: presentación de una experiencia / Using a virtual mode for the pediatric residents evaluation during the COVID 19 pandemic: report of an experience

El examen clínico objetivo estructurado (ECOE) es una herramienta válida para medir competencias clínicas. En el contexto de la pandemia por COVID-19 se debieron adaptar las evaluaciones, habitualmente presenciales, a un formato virtual. El objetivo de este artículo es comunicar la experiencia de utilizar una modalidad virtual del ECOE para residentes de primer año de pediatría durante la pandemia por COVID-19. El ECOE comprendió 12 estaciones utilizando casos simulados en línea y consultas virtuales a distancia. Participaron del ECOE 115 residentes, aprobaron 110 (95,7%) y solo 17 participantes aprobaron el 100% de las estaciones. Las estaciones con mejor rendimiento fueron las referidas a alimentación complementaria, abordaje del traumatismo encéfalo craneano, interpretación de resultados de laboratorio y de imágenes radiológicas. El menor rendimiento se observó en uso de equipo de protección personal y vacunas. La encuesta de satisfacción fue respondida por 80/115 participantes (69,5%). El 91% de los participantes encontró fácil de utilizar la plataforma virtual. La mayoría (73/80) consideró que los temas fueron acordes al nivel de formación. La estación de pautas madurativas fue identificada como la más difícil. El 57% refirió que el ECOE les resultó útil para identificar puntos débiles en su formación. La implementación de una modalidad virtual del ECOE fue posible y presentó buena aceptación de los participantes.

The objective structured clinical examination (OSCE) is a helpful tool for assessing clinical competencies. During the COVID-19 pandemic, assessments usually carried out in person had to be adapted to a virtual format. We aim to report our experience using a virtual OSCE administered to first-year pediatric residents during the COVID-19 pandemic. The OSCE included 12 stations, including online simulated cases and virtual remote consultations. In total 115 residents participated in the OSCE; 110 (95.7%) passed the test, but only 17 participants passed all stations. The stations with the highest performance were related to complementary feeding, management of traumatic head injury, interpretation of lab test results and imaging. The lowest performance was observed using personal protective equipment and checking vaccine schedules. The user satisfaction survey was completed by 80 out of 115 participants (69.5%); 91 % of the participants found the virtual platform easy to use. Most of the residents (73/80) considered the topics to be appropriate for their training level. The station related to child development guidelines was identified as the most challenging. 57% reported that the OSCE was helpful for identifying weaknesses in their training. Conclusion: the implementation of a virtual OSCE was feasible and it was well accepted by the participants.

Impacto de la contaminación ambiental en las consultas por enfermedad respiratoria en niños menores de 2 años.

Introducción: La contaminación del aire incrementaría el riesgo de infección respiratoria aguda (IRA) en pediatría. Objetivo: evaluar el impacto de la contaminación del aire en las consultas por IRA realizadas en efectores del Gobierno de la Ciudad de Buenos Aires. Método: estudio ecológico, de series temporales. Fuentes de información: Agencia de Protección Ambiental, Servicio Meteorológico Nacional e Historia de Salud Integral del Sistema de Gestión Hospitalaria. Población: Pacientes menores de 2 años que consultaron por IRA a un efector del GCBA y que residían en una comuna con monitoreo ambiental continuo, durante el 2018. Variables de predicción: Niveles diarios de CO, NO2, PM10 de las estaciones de monitoreo ambiental continuo de la Ciudad Autónoma de Buenos Aires. Variables de resultado: número de consultas totales y por IRA. Variables a controlar: efector, sexo y temperatura media. Se construyó una definición operativa para seleccionar en la base de datos a las consultas objeto de estudio. Resultados: Se registraron 80.287 consultas, 24.847 por IRA (30%). Las consultas por IRA tuvieron correlación positiva en la estación "Córdoba" con el N2O (RR: 1,13 [1,00-1,28]). El número de consultas por IRA en los meses fríos fue mayor que en los cálidos (19,9% vs 11,9%; RR:1,67 [1,61-1,72]). Conclusión: Los valores promedios de PM10 y N2O muestran correlación con el número de las consultas totales y por infección respiratoria aguda, respectivamente. Las consultas se incrementaron durante el invierno.

Ética en investigación: desafíos durante la pandemia / Research ethics: challenges during the pandemic

Durante la pandemia de Covid-19 los hospitales pediatricos se vieron menos afectados, debido a la menor infección en niños, y sus recursos fueron reasignados en distintas tareas.. El Comité de Ética en Investigación del Hospital General de Niños Pedro de Elizalde presenta los distintos procedimientos implementados en esta emergencia, para sostener diferentes investigaciones, y que les permitió una rápida respuesta a esta situación.