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.

Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19.

Severe COVID-19 in children is rare, but the reasons underlying are unclear. Profound alterations in T cell responses have been well characterized in the course of adult severe COVID-19, but little is known about the T cell function in children with COVID-19. Here, we made three major observations in a cohort of symptomatic children with acute COVID-19: 1) a reduced frequency of circulating FoxP3+ regulatory T cells, 2) the prevalence of a TH17 polarizing microenvironment characterized by high plasma levels of IL-6, IL-23, and IL17A, and an increased frequency of CD4+ T cells expressing ROR-γt, the master regulator of TH17 development, and 3) high plasma levels of ATP together with an increased expression of the P2X7 receptor. Moreover, that plasma levels of ATP displayed an inverse correlation with the frequency of regulatory T cells but a positive correlation with the frequency of CD4+ T cells positive for the expression of ROR-γt. Collectively, our data indicate an imbalance in CD4+ T cell profiles during pediatric COVID-19 that might favor the course of inflammatory processes. This finding also suggests a possible role for the extracellular ATP in the acquisition of an inflammatory signature by the T cell compartment offering a novel understanding of the involved mechanisms.

[What is the best method for estimating final height in patients with precocious puberty?] / ¿Cuál es el mejor método de estimación de talla final en pacientes con pubertad precoz?

Central precocious puberty is the premature activation of the hypothalamic-pituitary-gonadal axis, leading to an early epiphyseal fusion and, in many cases, heights below the genetic target. Therefore, a proper adult stature prediction is essential for the treatment decision. OBJECTIVE: To compare the concordance of final height using height prediction made by two validated methods versus the ge netic target height in girls who consulted due to central precocious puberty. PATIENTS AND METHOD: Retrospective, non-concurrent cohort study including 93 girls with central precocious puberty, who were not treated with LHRH analogs and had reached their final adult height. The data was obtained from the clinical records. To predict height, the Bayley-Pinneau method and the Roche-Wainer- Thissen method were applied, and the results were compared with the genetic target height. The concordance between the estimated final height and the final height obtained was evaluated using the Bland-Altman method. RESULTS: When comparing the final height obtained with that predicted by the Bayley-Pinneau method, there was a mean difference of 1.01 cm, and using the Rocke-Wainer- Thissen method, there was a difference of +0.96 cm. The calculation of the genetic target height showed a difference of +0.05 cm with respect to the final height. CONCLUSION: The prediction of height made by the Bayley-Pinneau and Roche-Wainer-Thissen methods was adequate and, contrary to expectations, it was similar to the calculation of the genetic target height that does not use the age of bone maturation. This also presented better concordance and less dispersion of the results with respect to the final height obtained.

Insulin resistance parameters in children born very preterm and adequate for gestational age.

BACKGROUND: Preterm neonates are at risk for metabolic syndrome later in life. Whether prematurity constitutes an independent risk factor for the development of cardiovascular disease and metabolic syndrome remains controversial. OBJECTIVE: To compare anthropometric measures, cardiometabolic risk factors and insulin resistance variables between children who were born very preterm (VPT, <32 gestational weeks) and at term (Term, >37 gestational weeks) and adequate for gestational age (AGA). METHODS: We designed a cross-sectional cohort study, recruiting 120 children (5.0-8.5 years old) from the preterm clinic at Red de Salud UC-Christus and Complejo Asistencial Dr. Sótero del Río, and term children from the community. We excluded children born small for gestational age, based on INTERGROWTH21. Anthropometrics data were classified using WHO reference standards. The homeostasis model assessment insulin resistance (HOMA-IR) index, quantitative insulin sensitivity check index (QUICKI), triglyceride-to-HDL-C ratio (TG/HDL-C) and Pediatric Score Index for Metabolic Syndrome (PsiMS) were calculated. RESULTS: VPT children born AGA had lower HDL cholesterol levels (p = .019) and a higher PsiMS score than those born at term (p = .043). We observed a higher percentage of children with HDL cholesterol ≤40 mg/dl (13.0% vs. 2.3%, p = .026) and BP ≥90th percentile among the VPT children than among the Term children (26.0% vs. 11.6%, p = .031). CONCLUSIONS: At school age, blood pressure was higher, and HDL-C was lower among VPT children born AGA, suggesting a potential metabolic risk; therefore, it is essential to follow this group throughout their lives.

Warthin-like and classic papillary thyroid cancer have similar clinical presentation and prognosis.

OBJECTIVE: Warthin-like papillary thyroid cancer (WL-PTC) is an uncommon variant of PTC, usually associated with lymphocytic thyroiditis. Scarce evidence suggests that WL-PTC has similar clinical presentation to classic PTC (C-PTC), with no studies comparing risks of recurrence and response to treatment between both variants. Our objective was to describe the clinical presentation and prognosis of WL-PTC and compare it to C-PTC. METHODS: Retrospective analysis of a prospective cohort, including 370 (96%) patients with C-PTC and 17 (4%) with WL-PTC, consecutively treated with total thyroidectomy with or without RAI, followed for at least 6 months. We compared clinical presentation, risk of mortality and recurrence, as well as response to treatment between both variants. RESULTS: Of the total cohort: 317 (82%) female, 38 ± 13.5 years, median follow-up 4 years (0.5-28.5); most of them stage I and low/intermediate risk of recurrence. We found no differences regarding clinical-pathological data and risk of recurrence. WL-PTC was associated with a higher rate of anti-thyroglobulin antibodies (TgAb) (65% vs. 36%, p = 0.016) and lymphocytic thyroiditis (59% vs. 34%, p = 0.03). The rates of biochemical and structural incomplete responses were similar in both variants. WL-PTC had a lower rate of excellent response (23% vs. 54%, p = 0.01), which became non-significant when performing analysis by TgAb presence (50% vs. 67%, p = NS). CONCLUSION: WL-CPT and C-CPT have similar clinical presentation and rate of recurrence. The lower rate of excellent response to treatment in WL-PTC is due to a higher frequency of TgAb. WL-PCT should not be considered an aggressive variant of PTC.

Frailty and reduced gait speed are independently related to mortality of cirrhotic patients in long-term follow-up.

INTRODUCTION AND OBJECTIVES: Frailty is characterized by a poor restoration of homeostasis after a stressor event. Although it is not usually diagnosed, it has been associated with decreased survival in cirrhotic patients. We aimed to evaluate the impact of frailty and decreased gait speed over survival in cirrhotic patients at long-term follow-up. MATERIALS AND METHODS: We included stable cirrhotic patients Child-Pugh B-C or MELD ≥12, ≥50 years old. We performed a clinical evaluation, anthropometry, and laboratory tests. Frailty was diagnosed using Fried Frailty Index. We evaluated survival at a 4-year follow-up. RESULTS: We included 126 patients; mean age 64±8.3 years, median MELD-Na 15[12-17], median follow-up was 881 [349-1277] days. The main etiology was MAFLD (31.4%). Frailty was diagnosed in 65.1% of patients. There were no significant differences in baseline characteristics per frailty condition. Mortality was higher in frail patients than non-frail patients (68.2% versus 20.6% at 48 months, respectively; p-value <0.001). The mean gait speed in frail and non-frail patients was 0.86±0.3m/s and 1.16±0.2m/s, respectively (p-value <0.001). Interestingly, 26.9% of patients presented a reduced gait speed (≤0.8m/s). Patients with decreased gait speed also had higher mortality than patients with normal gait speed (79.9% versus 40.8%, respectively; p-value <0.001). A multivariate-adjusted model showed that decreased gait speed (HR=3.27, 95%CI:1.74-6.14; p<0.001) and frailty (HR=4.24, 95%CI:1.89-9.51; p<0.001) were associated with mortality. CONCLUSIONS: Frailty is independently associated with decreased survival at long-term follow-up. Reduced gait speed is strongly associated with mortality and could be a surrogate marker of frailty in clinical practice.

Warthin-like and classic papillary thyroid cancer have similar clinical presentation and prognosis

ABSTRACT Objective Warthin-like papillary thyroid cancer (WL-PTC) is an uncommon variant of PTC, usually associated with lymphocytic thyroiditis. Scarce evidence suggests that WL-PTC has similar clinical presentation to classic PTC (C-PTC), with no studies comparing risks of recurrence and response to treatment between both variants. Our objective was to describe the clinical presentation and prognosis of WL-PTC and compare it to C-PTC. Subjects and methods Retrospective analysis of a prospective cohort, including 370 (96%) patients with C-PTC and 17 (4%) with WL-PTC, consecutively treated with total thyroidectomy with or without RAI, followed for at least 6 months. We compared clinical presentation, risk of mortality and recurrence, as well as response to treatment between both variants. Results Of the total cohort: 317 (82%) female, 38 ± 13.5 years, median follow-up 4 years (0.5-28.5); most of them stage I and low/intermediate risk of recurrence. We found no differences regarding clinical-pathological data and risk of recurrence. WL-PTC was associated with a higher rate of anti-thyroglobulin antibodies (TgAb) (65% vs. 36%, p = 0.016) and lymphocytic thyroiditis (59% vs. 34%, p = 0.03). The rates of biochemical and structural incomplete responses were similar in both variants. WL-PTC had a lower rate of excellent response (23% vs. 54%, p = 0.01), which became non-significant when performing analysis by TgAb presence (50% vs. 67%, p = NS). Conclusions WL-CPT and C-CPT have similar clinical presentation and rate of recurrence. The lower rate of excellent response to treatment in WL-PTC is due to a higher frequency of TgAb. WL-PCT should not be considered an aggressive variant of PTC.

Detección de errores y eventos adversos en UCIPS públicas argentinas / Detection of errors and adverse events in Argentine public ICUs

Los errores y/o eventos adversos relacionados con la atención de la salud deben traducirse en información útil para prevenirlos y garantizar los procesos asistenciales seguros. OBJETIVOS Determinar la frecuencia de errores y eventos adversos relacionados al cuidado de la salud en las Unidades de Cuidados Intensivos Pediátricos (UCIPs) del ámbito público de Argentina y la calidad de la atención. Diseño; Estudio multicéntrico descriptivo observacional con cuatro cohortes transversales. Población; Pacientes entre 1 y 217 meses internados entre el 1 de junio de 2016 y el 31 de marzo 2017 en 6 UCIP. MÉTODOS Se completaron cuestionarios con escala estructurada diseñada por los investigadores para registrar los errores o eventos encontrados durante 24 horas por corte, a pie de cama, por médico, kinesiólogo, enfermero y farmacéutico de cada centro. Para cinco categorías elegidas (ventilación mecánica (VM), accesos permanentes, falla de equipos, alarmas y medicación. Además, se consideró factores de cada UCIPs, de gravedad de los pacientes, factores humanos como sobrecarga de trabajo del equipo, escala NEMS y del sistema. RESULTADOS Se detectaron 1753 errores en los 262 pacientes en los 4 cortes/seis UCIPs en la población de 291 pacientes. Prevalencia de errores 0,90. Los errores más frecuentes fueron las alarmas 71,36%, de accesos 2,45%, de VM 10,38% y de medicación 15,80%. Todos los errores se presentaron en mayor proporción en horario matutino. En la regresión logística múltiple se tomó una de las 3 variables significativas del univariado, el NEMS que mostró asociación estadísticamente significativa con presentar un evento. OR=1,07 (IC95%: 1,03 a 1,11). P valor= 0,01. DISCUSIÓN La sobrecarga de trabajo de enfermería fue lo más significativo y el registro de ello permite evaluar, medir la situación. La falta de atención de alarmas, prescripciones y ruidos de comunicación lo más vulnerables. Se debe gestionar estrategias y prioridades en la atención