Vancomycin population pharmacokinetics analysis in Chinese paediatric patients with varying degrees of renal function and ages: development of new practical dosing recommendations.

OBJECTIVES: To describe the pharmacokinetics of vancomycin in a large Chinese paediatric cohort with varying degrees of renal function and ages and to develop practical dosing guidelines. PATIENTS AND METHODS: We conducted a retrospective population pharmacokinetic study using data from paediatric patients who received vancomycin between June 2013 and June 2022. A non-linear mixed-effect modelling approach with a one-compartment model structure was applied. Monte Carlo simulations were used to stimulate an optimal dosage regimen to achieve the target of AUC24/MIC between 400 and 650. RESULTS: We analysed a total of 673 paediatric patients and 1547 vancomycin serum concentrations. Covariate analysis revealed that physiological maturation, renal function, albumin and cardiothoracic surgery (CTS) significantly affected vancomycin pharmacokinetics. The typical clearance and volume of distribution, standardized to 70 kg, were 7.75 L/h (2.3% relative standard error, RSE) and 36.2 L (1.7% RSE), respectively. Based on the model, we proposed an optimal dosing regimen that considers the patient's age and estimate glomerular filtration rate (eGFR) to achieve a target AUC24/MIC for CTS and non-CTS patients. We also found that a loading dose of 20 mg/kg can help patients with an eGFR of <60 mL/min/1.73 m2 achieve the target AUC on the first day of treatment. CONCLUSIONS: We established vancomycin pharmacokinetic parameters in Chinese paediatric patients and proposed a dosing guideline integrating eGFR, age and CTS status, potentially improving clinical outcomes and reducing nephrotoxicity risk.

Neutrophil CD64 index for diagnosis of infectious disease in the pediatric ICU: a single-center prospective study.

BACKGROUND: Infection is a major cause of death in children, and it is particularly important to identify biological indicators of early infection. Previous studies showed that the neutrophil CD64 (nCD64) index may be a useful biomarker for infection. The purpose of this study was to investigate use of the nCD64 index to identify infection in children from a pediatric ICU (PICU) in China. METHODS: This prospective observational study enrolled 201 children who were admitted to our PICU and were divided into an infection group and a non-infection group. In each patient, C-reactive protein (CRP), nCD64 index, procalcitonin (PCT), and white blood cell count were measured during the first 24 h after admission. Receiver operating characteristic (ROC) analyses were used to determine the sensitivity, specificity, and diagnostic value of the nCD64 index for infection. RESULTS: Among all 201 children, the infection group had greater levels of CRP, nCD64 index, and PCT (all p < 0.05). ROC analysis indicated the nCD64 index had a sensitivity of 68.8%, specificity of 90.7%, accuracy of 80.5%, and an optimal cut-off value of 0.14, which had better diagnostic value than CRP or PCT. For children with postoperative fever, the nCD64 index also distinguished systemic inflammatory response syndrome (SIRS) from infection with accuracy of 79%. CONCLUSIONS: The nCD64 index is a useful biomarker for the diagnosis of early infection in children admitted to the PICU.

Resultados de la ventilación asistida ajustada neuronalmente no invasiva y la presión positiva continua nasal en recién nacidos prematuros: revisión sistemática y metanálisis / Outcomes of noninvasive neurally adjusted ventilatory assist and nasal continuous positive airway pressure in preterm infants: a systematic review and meta-analysis

Introducción: los beneficios de la ventilación asistida ajustada neuronalmente (NAVA) en los recién nacidos prematuros son inciertos. El objetivo de este estudio fue explorar si la NAVA no invasiva (NIV) era más beneficiosa para los recién nacidos prematuros que la presión positiva continua nasal (NCPAP). Diseño del estudio: metanálisis de tres ensayos clínicos: dos ensayos controlados aleatorizados y un estudio de grupos cruzados. Se comparó la NAVA-NIV con la NCPAP y se informó sobre el fracaso del tratamiento, la mortalidad y los eventos adversos como resultados principales. Resultados: tres estudios con 173 pacientes (89 recibieron NAVA-NIV) cumplieron los criterios de inclusión en este metanálisis. No se observaron diferencias en el fracaso del tratamiento entre la NAVA-NIV y la NCPAP (razón de riesgos [RR] = 1,09; intervalo de confianza [IC] del 95 % = 0,65-1,84; diferencia de riesgos = 0,02; IC95% = -0,10-0,14; I2 = 33 %; P = 0,23). De manera similar, no hubo diferencias en la mortalidad (RR = 1,52; IC95% = 0,51-4,52; no aplica heterogeneidad). En comparación con la NCPAP, la NAVA-NIV redujo significativamente el uso de cafeína (RR = 0,85; IC 95% = 0,74-0,98; I2 = 71 %; P = 0,03). Conclusiones: en comparación con la NCPAP, no hay evidencia suficiente para sacar una conclusión sobre los beneficios o daños de la NAVA-NIV en los recién nacidos prematuros. Los hallazgos de esta revisión deben confirmarse en ensayos clínicos con una metodología rigurosa y potencia adecuada

Introduction: The benefits of neurally adjusted ventilatory assist (NAVA) in preterm infants are unclear. This study aimed to explore if noninvasive NAVA is more beneficial for preterm infants than nasal continuous positive airway pressure (NCPAP). Study design: Meta-analysis was performed in three clinical trials comprising two randomized controlled trials and one crossover study. We compared NIV-NAVA and NCPAP and reported treatment failure, mortality, and adverse events as the primary outcomes. Results: Three studies including 173 patients (89 of whom underwent NIV-NAVA) were eligible for this meta-analysis. This review found no difference in treatment failure between NIV-NAVA and NCPAP (RR 1.09, 95% CI 0.65 to 1.84; RD 0.02, 95% CI -0.10-0.14; I2=33%, P=0.23). Similarly, there was no difference in mortality (RR 1.52, 95% CI 0.51-4.52, heterogeneity not applicable). Compared with NCPAP, NIV-NAVA significantly reduced the use of caffeine (RR 0.85, 95% CI 0.74-0.98, I2=71%, P=0.03). Conclusions: Compared with NCPAP, there is insufficient evidence to conclude on the benefits or harm of NIV-NAVA therapy for preterm infants. The findings of this review should be confirmed using methodologically rigorous and adequately powered clinical trials.

Outcomes of noninvasive neurally adjusted ventilatory assist and nasal continuous positive airway pressure in preterm infants: a systematic review and meta-analysis. / Resultados de la ventilación asistida ajustada neuronalmente no invasiva y la presión positiva continua nasal en recién nacidos prematuros: revisión sistemática y metanálisis.

INTRODUCTION: The benefits of neurally adjusted ventilatory assist (NAVA) in preterm infants are unclear. This study aimed to explore if noninvasive NAVA is more beneficial for preterm infants than nasal continuous positive airway pressure (NCPAP). STUDY DESIGN: Meta-analysis was performed in three clinical trials comprising two randomized controlled trials and one crossover study. We compared NIV-NAVA and NCPAP and reported treatment failure, mortality, and adverse events as the primary outcomes. RESULTS: Three studies including 173 patients (89 of whom underwent NIV-NAVA) were eligible for this meta-analysis. This review found no difference in treatment failure between NIVNAVA and NCPAP (RR 1.09, 95% CI 0.65 to 1.84; RD 0.02, 95% CI -0.10-0.14; I2=33%, P=0.23). Similarly, there was no difference in mortality (RR 1.52, 95% CI 0.51-4.52, heterogeneity not applicable). Compared with NCPAP, NIVNAVA significantly reduced the use of caffeine (RR 0.85, 95% CI 0.74-0.98, I2=71%, P=0.03). CONCLUSIONS: Compared with NCPAP, there is insufficient evidence to conclude on the benefits or harm of NIV-NAVA therapy for preterm infants. The findings of this review should be confirmed using methodologically rigorous and adequately powered clinical trials.

Introducción: los beneficios de la ventilación asistida ajustada neuronalmente (NAVA) en los recién nacidos prematuros son inciertos. El objetivo de este estudio fue explorar si la NAVA no invasiva (NIV) era más beneficiosa para los recién nacidos prematuros que la presión positiva continua nasal (NCPAP). Diseño del estudio: metanálisis de tres ensayos clínicos: dos ensayos controlados aleatorizados y un estudio de grupos cruzados. Se comparó la NAVA-NIV con la NCPAP y se informó sobre el fracaso del tratamiento, la mortalidad y los eventos adversos como resultados principales. Resultados: tres estudios con 173 pacientes (89 recibieron NAVA-NIV) cumplieron los criterios de inclusión en este metanálisis. No se observaron diferencias en el fracaso del tratamiento entre la NAVA-NIV y la NCPAP (razón de riesgos [RR] = 1,09; intervalo de confianza [IC] del 95 % = 0,65-1,84; diferencia de riesgos = 0,02; IC95% = -0,10-0,14; I2 = 33 %; P = 0,23). De manera similar, no hubo diferencias en la mortalidad (RR = 1,52; IC95% = 0,51-4,52; no aplica heterogeneidad). En comparación con la NCPAP, la NAVA-NIV redujo significativamente el uso de cafeína (RR = 0,85; IC 95% = 0,74-0,98; I2 = 71 %; P = 0,03). Conclusiones: en comparación con la NCPAP, no hay evidencia suficiente para sacar una conclusión sobre los beneficios o daños de la NAVA-NIV en los recién nacidos prematuros. Los hallazgos de esta revisión deben confirmarse en ensayos clínicos con una metodología rigurosa y potencia adecuada.

Activin A inhibits activities of lipopolysaccharide-activated macrophages via TLR4, not of TLR2.

Activin A, a member of TGF-ß superfamily, is involved in either pro-inflammatory or anti-inflammatory responses. Our previous studies have reported that lipopolysaccharide (LPS) can simulate activin A secretion from macrophage, and activin A can induce rest macrophage activation in mice, but inhibit the activities of the activated macrophages. However, the relationship of activin and LPS actions and their mechanism are not well characterized. In the present study, the results showed that both activin A and LPS promoted the phagocytic activities of mouse peritoneal macrophages in vivo and in vitro, but activin A inhibited the phagocytosis of LPS-activated macrophages. Simultaneously, the results revealed that activin A inhibited the Toll-like receptor 4 (TLR4) expression on LPS-activated mouse peritoneal macrophages in vivo and in vitro, whereas there was no obvious change of TLR2 expression. Moreover, the results showed that activin A obviously reduced the TLR4 mRNA and protein expressions in LPS-activated macrophage cell line RAW264.7 cells, and the inhibitory effect of activin A on the TLR4 expression was significantly attenuated in Smad3 knock-down RAW264.7 cells. Interestingly, LPS promoted the expression of activin type IIA receptor (ActRIIA) on mouse peritoneal macrophages in vivo, and also up-regulated ActRIIA and activin signal molecules Smad2, 3 mRNA expressions. These data suggest that activin A inhibits LPS action on macrophages in vivo via suppressing TLR4 expression, and LPS further augments the negative feedback action of activin A via up-regulating activin signaling transduction.