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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.

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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.

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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.

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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.

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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.

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