Full Validation and Application to Clinical Research of a High-Performance Liquid Chromatography Method for the Assessment of Urinary 3-Indoxyl Sulfate in Pediatric Patients with Hematopoietic Stem Cell Transplant.

3-indoxyl sulfate (3-IS) results from a hepatic transformation of indole, a tryptophan degradation product produced by commensal gut bacteria. The metabolite has shown promise as a biomarker of dysbiosis and clinical outcomes following hematopoietic stem cell transplant (HSCT) in adults. Nonetheless, there is a paucity of data regarding microbiome health and outcomes in the pediatric HSCT setting. We developed and thoroughly validated an affordable high-performance liquid chromatography/fluorescence detector (HPLC-FLD) method to quantify 3-IS in urine for use in the pediatric setting. Chromatographic separation was achieved on a C18 column (250 × 4.6 mm × 5 µm) with a mobile phase consisting of pH 4.0 acetic acid-triethylamine buffer and acetonitrile (88:12, v/v), eluted isocratically at 1 mL/min. 3-IS fluorescence detection was set at excitation/emission of 280 and 375, respectively. The method was fully validated according to FDA-specified limits including selectivity, linearity (0.10 to 10.00 mg/L, r2 > 0.997), intra- and inter-day accuracy, and precision. 3-IS stability was confirmed after three freeze-thaw cycles, for short- and medium-term on a benchtop and at 4 °C and for long-term up to 60 days at -20 °C. The validated method was used to quantify 3-IS in urine samples from HSCT pediatric patients.

Comparison of SARS-CoV-2 viral load in asymptomatic and symptomatic children attended in a referral public pediatric hospital in Argentina / Comparación de la carga viral de SARS-CoV-2 en niños asintomáticos y sintomáticos atendidos en un hospital pediátrico público de referencia en Argentina

Abstract At present, different reports have shown that children reach similar SARS-CoV-2 viral load (VL) levels compared to adults; however, the impact of VL on children remains ambiguous when asymptomatic versus symptomatic cases are compared. Thus, the aim of this study was to assess VL at the time of diagnosis in asymptomatic and symptomatic SARS-CoV-2 infected children. VL analysis was retrospectively carried out from nasopharyngeal swabs on 82 SARS-CoV-2 infected children, from March to October 2020. Of the 82 children, 31 were asymptomatic. Symptomatic patients had significantly higher VL values compared to asymptomatic ones (median = 7.41 vs4.35 log10 copies/ml, respectively). Notwithstanding, 8 out of 31 asymptomatic children had high VL levels, overlapping levels observed above the first quartile in the symptomatic group. Analysis of different age groups revealed that median VL values were higher in the symptomatic groups, although there was only a significant difference in children younger than 5 years of age. On the other hand, there was no significant difference between the VL values from the 82 SARS-CoV-2 infected children according to age, sex, underlying disease, symptoms or severity of COVID-19 related disease. This study emphasizes the importance of VL analysis in SARS-CoV-2 infected children, who could contribute to viral spread in the community. This concern could be extended to healthcare workers, who are in contact with children.

Resumen Diferentes informes han demostrado que los ninos alcanzan niveles de carga viral (CV) de SARS-CoV-2 similares a los de los adultos, pero el impacto de la CV en los niños continua siendo incierto cuando se compara entre aquellos que son asintomáticos y sintomáticos. El objetivo de este estudio fue evaluar la CV al momento del diagnóstico en ninos asintomáticos y sintomáticos infectados por SARS-CoV-2. El análisis de CV se realizó retrospectivamente a partir de muestras de hisopados nasofaríngeos de 82 niños infectados por SARS-CoV-2 entre marzo y octubre de 2020. De ellos, 31 eran asintomáticos. Encontramos que el grupo sintomático tenía valores de CV significativamente más altos en comparación con el grupo asintomático (mediana = 7,41 vs. 4,35 log10 copias/ml, respectivamente). No obstante, 8 de los 31 ninos asintomáticos presentaron valores de CV elevados, equivalentes a los observados por encima del primer cuartil del grupo sintomático. El análisis por grupos de edad reveló que la mediana de CV fue más alta en los niños sintomáticos, aunque esta diferencia fue significativa solamente en los menores de 5 anos. A su vez, los valores de CV obtenidos a partir de los 82 niños infectados por SARS-CoV-2 no mostraron diferencias significativas según el grupo etario, el sexo, la enfermedad de base, los síntomas y la gravedad de la COVID-19. Este estudio enfatiza la necesidad del análisis de la CV en ninos infectados por SARS-CoV-2, quienes podrían contribuir a la propagación del virus en la comunidad. Esta preocupación podría extenderse a los trabajadores de la salud que están en contacto con los ninños.

COVID-19 in immunocompromised children: comparison of SARS-CoV-2 viral load dynamics between the first and third waves.

SARS-CoV-2 dynamics across different COVID-19 waves has been unclear in immunocompromised children. We aimed to compare the dynamics of SARS-CoV-2 RNA viral load (VL) during the first and third waves of COVID-19 in immunocompromised children. A retrospective and longitudinal cohort study was conducted in a pediatric referral hospital of Argentina. The study included 28 admitted immunocompromised children with laboratory confirmed SARS-CoV-2 infection. Thirteen acquired the infection during COVID-19 first wave (May to August 2020, group 1 (G1)) and fifteen in the third wave (January to March 2022, group 2 (G2)). RNA viral load measure and its dynamic reconstruction were performed in nasopharyngeal swabs by validated quantitative, real time RT-PCR, and linear mixed-effects model, respectively. Of the 28 children included, 54% were girls, most of them had hemato-oncological pathology (57%), and the median age was 8 years (interquartile range (IQR): 3-13). The dynamic of VL was similar in both groups (P = 0.148), starting from a level of 5.34 log10 copies/mL (95% confidence interval (CI): 4.47-6.21) in G1 and 5.79 log10 copies/mL (95% CI: 4.93-6.65) in G2. Then, VL decayed with a rate of 0.059 (95% CI: 0.038-0.080) and 0.088 (95% CI: 0.058-0.118) log10 copies/mL per day since diagnosis and fell below the limit of quantification at days 51 and 39 after diagnosis in G1 and G2, respectively. Our results evidenced a longer viral RNA persistence in immunocompromised pediatric patients and no difference in VL dynamic between COVID-19 first wave-attributed to ancestral infections-and third wave-attributed to Omicron infections.

Results of training with a low-cost simulation model for endoscope-assisted scaphocephaly repair.

OBJECTIVE: Endoscope-assisted repair of sagittal craniosynostosis is an effective technique that requires a learning curve. Surgical simulation models can be applied to acquire the necessary skills for this procedure. Several models with a wide range of costs have been described for training in this technique. The aim of this work was to present the results of training with a low-cost simulation model for endoscope-assisted sagittal craniosynostosis repair. METHODS: A simulation model for sagittal craniosynostosis was developed using low-cost materials. The model is easily assembled and allows successive uses. Three neurosurgery residents, 3 fellows, and 2 neurosurgeons performed a 4-session training program in sagittal craniosynostosis repair. The Global Rating Scale (GRS) score, number of errors, and the time required to perform the task were reported by 2 independent evaluators using a checklist. Measurements were compared between the first and last training using the Wilcoxon signed-rank test. All participants completed a questionnaire (5-point Likert scale) regarding the realism of the simulation model. RESULTS: A model was developed to recreate the steps required to perform an endoscope-assisted scaphocephaly repair with the patient in a simulated sphinx position. All participants improved their GRS performance between the first and final training. The median time needed to perform the initial training was 47.5 minutes (interquartile range [IQR] 44.5-48 minutes, interrater difference [IRD] p = 0.77), and for the last training was 40.5 minutes (IQR 35.5-43 minutes, IRD p > 0.99). The median number of errors reported in the initial training was 5.5 (IQR 3-7.75 errors, IRD p = 0.8), and in the last training was 1 (IQR 0.75-2.25 errors, IRD p = 0.35). There was a statistically significant difference regarding the time and number of errors between the initial and final training (p < 0.001). More than 85% of the participants found that the surface anatomy, skull and anterior fontanel, fused sagittal suture, and epidural space of the model were realistic and had appropriate detail required to perform the surgery. All respondents agreed or strongly agreed that the endoscope handling was realistic, and that the steps and skills required to complete the task were representative of those required for the real procedure. CONCLUSIONS: A low-cost sagittal craniosynostosis simulation model was developed, allowing successive uses. The acquisition of skills within the simulation was demonstrated for all participants regarding the GRS score and the number of errors and time needed to perform the task. In addition, the model was found to be realistic in terms of anatomical references and the procedural steps required for this minimally invasive technique.

Ultrasound attenuation imaging: a reproducible alternative for the noninvasive quantitative assessment of hepatic steatosis in children.

BACKGROUND: Pediatric hepatic steatosis is a global public health concern, as an increasing number of children are affected by this condition. Liver biopsy is the gold standard diagnostic method; however, this procedure is invasive. Magnetic resonance imaging (MRI)-derived proton density fat fraction has been accepted as an alternative to biopsy. However, this method is limited by cost and availability. Ultrasound (US) attenuation imaging is an upcoming tool for noninvasive quantitative assessment of hepatic steatosis in children. A limited number of publications have focused on US attenuation imaging and the stages of hepatic steatosis in children. OBJECTIVE: To analyze the usefulness of ultrasound attenuation imaging for the diagnosis and quantification of hepatic steatosis in children. MATERIAL AND METHODS: Between July and November 2021, 174 patients were included and divided into two groups: group 1, patients with risk factors for steatosis (n = 147), and group 2, patients without risk factors for steatosis (n = 27). In all cases, age, sex, weight, body mass index (BMI), and BMI percentile were determined. B-mode US (two observers) and US attenuation imaging with attenuation coefficient acquisition (two independent sessions, two different observers) were performed in both groups. Steatosis was classified into four grades (0: absent, 1: mild, 2: moderate and 3: severe) using B-mode US. Attenuation coefficient acquisition was correlated with steatosis score according to Spearman's correlation. Attenuation coefficient acquisition measurements' interobserver agreement was assessed using intraclass correlation coefficients (ICC). RESULTS: All attenuation coefficient acquisition measurements were satisfactory without technical failures. The median values for group 1 for the first session were 0.64 (0.57-0.69) dB/cm/MHz and 0.64 (0.60-0.70) dB/cm/MHz for the second session. The median values for group 2 for the first session were 0.54 (0.51-0.56) dB/cm/MHz and 0.54 (0.51-0.56) dB/cm/MHz for the second. The average attenuation coefficient acquisition was 0.65 (0.59-0.69) dB/cm/MHz for group 1 and 0.54 (0.52-0.56) dB/cm/MHz for group 2. There was excellent interobserver agreement at 0.94 (95% CI 0.92-0.96). There was substantial agreement between both observers (κ = 0.77, with a P < 0.001). There was a positive correlation between ultrasound attenuation imaging and B-mode scores for both observers (r = 0.87, P < 0.001 for observer 1; r = 0.86, P < 0.001 for observer 2). Attenuation coefficient acquisition median values were significantly different for each steatosis grade (P < 0.001). In the assessment of steatosis by B-mode US, the agreement between the two observers was moderate (κ = 0.49 and κ = 0.55, respectively, with a P < 0.001 in both cases). CONCLUSION: US attenuation imaging is a promising tool for the diagnosis and follow-up of pediatric steatosis, which provides a more repeatable form of classification, especially at low levels of steatosis detectable in B-mode US.

Recomendaciones para el cuidado, prevención de infecciones y quimioprofilaxis en los errores innatos de la inmunidad / Recommendations for care, prevention of infections and chemoprophylaxis in inborn errors of immunity

Los errores innatos de la inmunidad (EII), antes llamados inmunodeficiencias primarias (IDP), son un grupo heterogéneo de trastornos genéticos con defectos en uno o más componentes del sistema inmune. Los pacientes afectados por EII presentan aumentada susceptibilidad a microorganismos únicos o múltiples que se manifestará con infecciones recurrentes de diferente tipo y gravedad dependiendo del tipo de la localización del defecto. La prevención de infecciones es uno de los pilares fundamentales en el abordaje integral de los pacientes con EII. En este trabajo se resumen las conclusiones consensuadas en el Grupo de Trabajo de Inmunología Pediátrica de la Sociedad Argentina de Pediatría, sobre la base de la revisión de la evidencia disponible, respecto a los principios esenciales para el cuidado, la prevención de infecciones y la quimioprofilaxis en los errores innatos de la inmunidad para la orientación del pediatra y especialista dedicados al seguimiento de estas enfermedades.

Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert.

[Recommendations for care, prevention of infections and chemoprophylaxis in inborn errors of immunity]. / Recomendaciones para el cuidado, prevención de infecciones y quimioprofilaxis en los errores innatos de la inmunidad.

Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert..

Los errores innatos de la inmunidad (EII), antes llamados inmunodeficiencias primarias (IDP), son un grupo heterogéneo de trastornos genéticos con defectos en uno o más componentes del sistema inmune. Los pacientes afectados por EII presentan aumentada susceptibilidad a microorganismos únicos o múltiples que se manifestará con infecciones recurrentes de diferente tipo y gravedad dependiendo del tipo de la localización del defecto. La prevención de infecciones es uno de los pilares fundamentales en el abordaje integral de los pacientes con EII. En este trabajo se resumen las conclusiones consensuadas en el Grupo de Trabajo de Inmunología Pediátrica de la Sociedad Argentina de Pediatría, sobre la base de la revisión de la evidencia disponible, respecto a los principios esenciales para el cuidado, la prevención de infecciones y la quimioprofilaxis en los errores innatos de la inmunidad para la orientación del pediatra y especialista dedicados al seguimiento de estas enfermedades.

Comparative effectiveness of telesimulation versus standard simulation for pediatric Minimally Invasive Surgery (MIS) essential skills training.

BACKGROUND: Proctored on site simulation-based surgical education has been integrated in our residents curricula since 2012. Due to COVID-19 pandemic and social distance protocols, we developed a Tele-assisted Essential Skills Training Module (T-ESTM). The aim of this study is to evaluate comparative effectiveness between Telesimulation (T) versus Standard Simulation (S) for minimally invasive surgery (MIS) essential skills training. METHODS: ESTM includes academic lectures, tutorials for ergonomics and 7 hands-on tasks scheduled into 2 sessions of 3 hours. Initial and final assessment scoring (adapted from GOALS) as well as timing for 3 of the tasks were registered. Telesimulation (T) group accessed the content online and completed their Hands-On practice through a digital communication platform. Standard Simulation (S) group attended conferences and Hands-On practice at the simulation center. Both groups were proctored by the same educators with summative and formative feedback and debriefing. Data was analyzed with the R-studio software program. RESULTS: Each group had 20 participants with a mean age of 28 ± 5 years. 67.5% were surgeons in training, 47.5% had performed low complexity procedures and 40% had previous experience with simulation training. We observed a significant improvement in scoring and time reduction for all assessed tasks in S and T groups (p < 0.001), with no statistically significant differences when comparing both groups. Similar performance could be achieved with both strategies. CONCLUSION: Telesimulation is a reproducible and effective educational tool for remote MIS essential skills training, and should be considered as an alternative to on-site simulation programs. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Clinical Research.

Effectiveness of a program for the reduction of central venous catheter-related bacteremias in a Pediatric Cardiovascular Unit / Efectividad de un programa de reducción de bacteriemias relacionadas con catéter venoso central en una unidad cardiovascular pediátrica

INTRODUCTION: Central venous catheter (CVC)- related bacteremias are common in pediatric patients following surgery for complex congenital heart disease admitted to a pediatric cardiac intensive care unit (PCICU) and have a high morbidity and mortality. OBJECTIVE: To analyze the effectiveness of an interdisciplinary program for the prevention of CVC-related bacteremias in the PCICU. MATERIAL AND METHODS: Quasi-experimental, before and after implementation study without a control group. Study period: 01-01-2008 to 12- 31-2018. Population: PCICU staff who care for patients following surgery for complex heart disease at a hospital. Pre-intervention period: 01- 01-2008 to 12-31-2008; intervention period: 01-01- 2009 to 01-01-2018. Intervention: implementation of an ongoing improvement program. The rate of CVC-related bacteremias/1000 days and CVC use/100 days, RACHS score, standardized infection ratio (SIR), relative risk (RR), and 95% confidence interval (CI) were analyzed and a p value < 0.05 was considered statistically significant. The reference rate was estimated as the average for the 2008-2009 period and the annual and reference rates were compared. RESULTS: The bacteremia reference rate for 2008- 2009 was 10.6/1000 days of CVC to analyze the SIR. A RACHS score over 3 was similar across all studied periods. The annual comparison showed a statistically significant reduction (p < 0.05) in the SIR. The comparison between the baseline bacteremia rate/1000 days of CVC (11.9) and the final rate (3.8) showed a significant reduction (RR: 0.16; 95 % CI: 0.07-0.35; p < 0.001). CONCLUSIONS: The program was effective; the rate of CVC-related bacteremias in the PCICU showed a progressive, significant reduction.

Introducción. Las bacteriemias relacionadas con catéteres venosos centrales (CVC) son frecuentes en pacientes pediátricos posquirúrgicos de cardiopatías congénitas complejas internados en la unidad de cuidados intensivos pediátricos cardiovascular (UCIP-CV) y tienen alta morbimortalidad. OBJETIVO: Analizar la efectividad de un programa interdisciplinario para prevención de bacteriemias relacionadas con CVC en la UCIP-CV. Material y métodos. Estudio de implementación, cuasiexperimental, antes-después, sin grupo control. Período de estudio del 1 de enero de 2008 al 31 de diciembre de 2018. Población: equipo de salud de la UCIP-CV que atiende pacientes posquirúrgicos de cardiopatías complejas de un hospital. Período preintervención del 1 de enero de 2008 al 31 de diciembre de 2008; período de intervención del 1 de enero de 2009 al 1 de enero de 2018. Intervención: implementación de un programa de mejora continua. Se analizaron tasas de bacteriemias CVC/1000 días y de uso de CVC/100 días, puntaje de RACHS, razón estandarizada de infecciones (REI), riesgo relativo (RR), intervalo de confianza del 95 % (IC95%), estimando una p < 0,05 como estadísticamente significativa. La tasa de referencia se estimó como el promedio del período 2008/2009 y se comparó la tasa anual con la tasa de referencia. RESULTADOS: La tasa de referencia de bacteriemia 2008/2009 fue 10,6/1000 días CVC para analizar la REI. El puntaje de RACHS mayor a 3 fue similar en todos los períodos analizados. Se observó una reducción de la REI estadísticamente significativa (p < 0,05) en la comparación anual. Al comparar la tasa de bacteriemia/1000 días de CVC inicial de 11,9 vs. final de 3,8, se observó una reducción significativa (RR: 0,16; IC95%: 0,07-0,35; p < 0,001). CONCLUSIONES: El programa fue efectivo; se observó reducción progresiva y significativa de la tasa de bacteriemias relacionadas con CVC en la UCIP-CV.

Efectividad de un programa de reducción de bacteriemias relacionadas con catéter venoso central en una unidad cardiovascular pediátrica / Effectiveness of a program for the reduction of central venous catheter-related bacteremias in a Pediatric Cardiovascular Unit

Introducción. Las bacteriemias relacionadas con catéteres venosos centrales (CVC) son frecuentes en pacientes pediátricos posquirúrgicos de cardiopatías congénitas complejas internados en la unidad de cuidados intensivos pediátricos cardiovascular (UCIP-CV) y tienen alta morbimortalidad. Objetivo. Analizar la efectividad de un programa interdisciplinario para prevención de bacteriemias relacionadas con CVC en la UCIP-CV. Material y métodos. Estudio de implementación, cuasiexperimental, antes-después, sin grupo control. Período de estudio del 1 de enero de 2008 al 31 de diciembre de 2018. Población: equipo de salud de la UCIP-CV que atiende pacientes posquirúrgicos de cardiopatías complejas de un hospital. Período preintervención del 1 de enero de 2008 al 31 de diciembre de 2008; período de intervención del 1 de enero de 2009 al 1 de enero de 2018. Intervención: implementación de un programa de mejora continua. Se analizaron tasas de bacteriemias CVC/1000 días y de uso de CVC/100 días, puntaje de RACHS, razón estandarizada de infecciones (REI), riesgo relativo (RR), intervalo de confianza del 95 % (IC95%), estimando una p < 0,05 como estadísticamente significativa. La tasa de referencia se estimó como el promedio del período 2008/2009 y se comparó la tasa anual con la tasa de referencia. Resultados. La tasa de referencia de bacteriemia 2008/2009 fue 10,6/1000 días CVC para analizar la REI. El puntaje de RACHS mayor a 3 fue similar en todos los períodos analizados. Se observó una reducción de la REI estadísticamente significativa (p < 0,05) en la comparación anual. Al comparar la tasa de bacteriemia/1000 días de CVC inicial de 11,9 vs. final de 3,8, se observó una reducción significativa (RR: 0,16; IC95%: 0,07-0,35; p < 0,001). Conclusiones. El programa fue efectivo; se observó reducción progresiva y significativa de la tasa de bacteriemias relacionadas con CVC en la UCIP-CV.

Introduction. Central venous catheter (CVC)related bacteremias are common in pediatric patients following surgery for complex congenital heart disease admitted to a pediatric cardiac intensive care unit (PCICU) and have a high morbidity and mortality. Objective.To analyze the effectiveness of an interdisciplinary program for the prevention of CVC-related bacteremias in the PCICU. Material and methods. Quasi-experimental,before and after implementation study without a control group. Study period: 01-01-2008 to 1231-2018. Population: PCICU staff who care for patients following surgery for complex heart disease at a hospital. Pre-intervention period: 0101-2008 to 12-31-2008; intervention period: 01-012009 to 01-01-2018. Intervention: implementation of an ongoing improvement program. The rate of CVC-related bacteremias/1000 days and CVC use/100 days, RACHS score, standardized infection ratio (SIR), relative risk (RR), and 95% confidence interval (CI) were analyzed and a p value < 0.05 was considered statistically significant. The reference rate was estimated as the average for the 2008-2009 period and the annual and reference rates were compared. Results. The bacteremia reference rate for 20082009 was 10.6/1000 days of CVC to analyze the SIR. A RACHS score over 3 was similar across all studied periods. The annual comparison showed a statistically significant reduction (p < 0.05) in the SIR. The comparison between the baseline bacteremia rate/1000 days of CVC (11.9) and the final rate (3.8) showed a significant reduction (RR: 0.16; 95 % CI: 0.07­0.35; p < 0.001). Conclusions. The program was effective; the rate of CVC-related bacteremias in the PCICU showed a progressive, significant reduction.

Carbapenem-resistant Enterobacteriaceae bloodstream infections: A case-control study from a pediatric referral hospital in Argentina.

Background: Antibiotic-resistant gram-negative bloodstream infections (BSI) remain a leading cause morbidity and mortality in pediatric patients with a high impact on the public health system. Data in resource-limited countries, including those in Latin America and the Caribbean region, are scarce. The aim of the study was to identify risk factors for acquiring carbapenem-resistant Enterobacteriaceae (CRE) bacteremia in children and to assess the use of resources. Methods: A retrospective case-control study was conducted to analyze demographic, epidemiological, clinical, microbiological, and outcome data as well as the use of resources between 2014 and 2019. Univariate and logistic regression analysis was performed in order to identify risk factors associated with CRE-BSI. The R software version 4.1.2 was used. Results: A total of 46 cases with CRE-BSI and 92 controls with gram-negative non-CRE-BSI were included. No statistical difference was observed regarding: median age (36 months; IQR, 11.2-117 vs. 48 months, IQR 13-119), male sex (50 vs. 60%), and underlying disease (98 vs. 91%) in cases vs. controls, respectively. The most frequent mechanism of CRE bacteremia were: KPC in 74%, OXA in 15%, and NDM in 6.5%. A total of 54.3% of cases vs. 32.6 % (p = 0.016) of controls were admitted to the pediatric intensive care unit (PICU), and 48 vs. 21% (p = 0.001) required mechanical ventilation. Bacteremia secondary to intra-abdominal infection was observed in 56.5% of cases vs. 35% of controls (p = 0.032). Previous colonization with CRE was detected in 76% of cases vs. 8% of controls. Combination antimicrobial treatment was most frequent in cases vs. control (100 vs. 56.5%). No difference was observed in median length of hospital stay (22 days; IQR, 19-31 in cases vs. 17.5 days; IQR, 10-31 in controls; p = 0.8). Overall case fatality ratio was 13 vs. 5.5%, respectively. The most statistically significant risk factors included previous PICU stay (OR, 4; 95%CI, 2-8), invasive procedures/surgery (OR, 3; 95%CI, 1-7), central venous catheter placement (OR, 6.5; 95%CI, 2-19), urinary catheter placement (OR, 9; 95%CI 4-20), mechanical ventilation (OR, 4; 95%CI, 2-10), liver transplantation (OR, 8; 95%CI, 2-26), meropenem treatment (OR, 8.4; 3.5-22.6) in univariate analysis. The logistic regression model used for multivariate analysis yielded significant differences for previous meropenem treatment (OR, 13; 95%CI, 3-77; p = 0.001), liver transplantation (OR, 13; 95%CI, 2.5-100; p = 0.006), and urinary catheter placement (OR, 9; 95%CI, 1.4-94; p = 0.03). Conclusion: CRE-BSI affects hospitalized children with underlying disease, mainly after liver transplantation, with previous urinary catheter use and receiving broad-spectrum antibiotics, leading to high PICU requirement and mortality. These risk factors will have to be taken into account in our region in order to establish adequate health policies and programs to improve antimicrobial stewardship.

Características epidemiológicas en pacientes pediátricos con COVID-19 durante la primera ola pandémica / Experience in pediatric patients with COVID-19 during the first pandemic wave

Resumen La infección por SARS-CoV-2 se ha extendido en todo el mundo. La mayoría de las publicaciones describen un comportamiento diferente entre población adulta y pediátrica, esta última asociada a menor gravedad y morbimortalidad. El objetivo del trabajo fue analizar el proceso de atención, las característi cas clínicas epidemiológicas, la evolución y la utilización de recursos en pacientes pediátricos asistidos durante la primera ola pandémica a principio del 2020. Se realizó un estudio observacional, retrospectivo, descriptivo y analítico de pacientes pediátricos con infección por SARS-CoV-2, desde el 1 de abril al 31 de agosto del 2020, atendidos en un centro de alta complejidad. Se incluyeron 333 pacientes, 175 (53%) residentes del área Metropolitana de Buenos Aires (AMBA). La mediana de edad fue de 5.5 años (RIC 1.1-10.9) y 177 (53%) eran mujeres. Requirieron internación 209 (63%) y 152 (46%) tenían enfermedad de base. El 89% (n 295) cursó una enfermedad leve/asintomática y el síntoma predominante fue fiebre (n 169, 65%). En el análisis univariado, la enfermedad neurológica (OR 4.5, IC95% 1.9-11, p 0.002), pulmonar crónica (OR 3.9, IC95%1.5-10.3, p 0.002) y genética (OR 11, IC95%3.4-34.4, p< 0.001), así como los síntomas neurológicos (OR 2.8, IC95%1.1-6.6, p 0.035) y respiratorios (OR 20.2, IC95%8.5-48.2, p 0.001) se asociaron a mayor gravedad. Se deberá continuar con la vigilancia activa de aquellos con enfermedad compleja a fin de determinar los efectos de la pandemia en esta población.

Abstract Coronavirus 2 infection has spread rapidly throughout the world. Most of the current publications describe differ ent behavior between an adult and pediatric population, this last one is associated with less clinical severity. The purpose of this study was to analyze the process of care, the epidemiological and clinical features, the evolution and the use of resources in pediatric patients with SARS-Cov-2 infection, treated during the first pandemic wave, at the beginning of 2020. An observational and retrospective study was carried out in the pediatric population with SARS-CoV-2 infection, treated in a highly complex pediatric hospital from April 1 to August 31, 2020. A total of 333 patients were included, 175 (53%) residents of the Metropolitan area of Buenos Aires (AMBA). The median age was 5.47 years (IQR 1.1-10.9) and 177 (53%) were women. A total of 209 (63%) patients required hospi talization and 152 (46%) had an underlying disease. Most of the patients (n 295, 89%) had mild/asymptomatic disease and the main symptom was fever (N169, 65%). In the univariate analysis, neurological disease (OR 4.5, IC95% 1.9-11, p 0.002), chronic respiratory disease (OR 3.9, IC95%1.5-10.3, p 0.002) and genetics (OR 11, IC95%3.4-34.4, p < 0.001), as well as neurological symptoms (OR 2.8, IC95%1.1-6.6, p 0.035) and respiratory (OR 20.2, IC95%8.5-48.2, p 0.001) were associated with more severe disease. Active surveillance of pediatric patients with underlying diseases should continue to define the pandemic's impact on this specific population.

Case Report: Hyperinflammatory Status in an Immunocompromised Child With a Highly Sustained Viral Load of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is spreading throughout the world. Limited data are available for the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL) in immunocompromised pediatric patients. Here, we report the clinical characteristics and the dynamics of SARS-CoV-2 VL of a pediatric patient with acute myeloid leukemia who developed a hyperinflammatory status mimicked MIS-C. The clinical course was characterized by the late onset of fever, GI symptoms, rash, and respiratory distress, including oxygen requirement with sustained VL of SARS-CoV-2 around 7 log10 RNA copies/mL for 6 weeks. It is important to note that the hyperinflammatory status developed early at the third week of hospitalization-in a context of high VL and immunocompromised status. All these characteristics make this clinical case unique. On the other hand, while many reports have characterized the dynamics of SARS-CoV-2 VL in adults and immunocompetent hosts, it remains unreported in pediatrics-even less in immunosuppressed children.

Factors Related to Extralaryngeal Spread in Juvenile Recurrent Respiratory Papillomatosis.

OBJECTIVES/HYPOTHESIS: To identify factors associated to increased risk of extra-laryngeal spread in pediatric patients with recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Retrospective chart review. METHODS: A retrospective study was conducted evaluating the clinical charts of patients younger than 16 years with histopathologically confirmed RRP treated between January 2014 and December 2018. Characteristics of patients with and without extra-laryngeal disease dissemination were compared. Odds ratios were calculated and multivariate logistic regression analysis was performed. RESULTS: Data from 82 patients were analyzed. Mean age at symptom onset was 42 months. Fifteen (18.29%) patients had extra-laryngeal spread (ELS) at time of diagnosis and in four, the disease continued to spread to other sites. Of 67 patients with disease restricted to the larynx, 17 (25.37%) developed ELS during the disease course. Human papilloma virus (HPV) typing was performed in 49 (59.8%) patients; in 28 (57.1%) HPV subtype 6 was identified and in 21 (42.9%) HPV subtype 11. ELS was found in 11 patients with serotype 11 (52.38%) and in seven patients with serotype 6 (25%) (P = .048). Statistically significant differences for ELS were also found for age at diagnosis younger than 5 years (P = .045), presence of tracheostomy (P = .031), and need for adjuvant therapy (P = .010). CONCLUSIONS: Age at diagnosis of RRP younger than 5 years and presence of tracheostomy were factors related to ELS. A statistically significant association between infection with HPV subtype 11 and ELS were also observed. Adjuvant medication might be considered a protective factor against ELS. Laryngoscope, 131:1652-1656, 2021.

Experiencia con el uso de daptomicina en un hospital pediátrico de alta complejidad / Experience with daptomycin in a tertiary pediatric hospital

Resumen Introducción: Vancomicina ha sido considerada como el tratamiento de elección en especial para Staphylococcus aureus resistente a meticilina (SARM); pero su escasa penetración tisular, su toxicidad renal y el requerir monitoreo de su dosis, plantean la necesidad de nuevas alternativas de tratamiento, como daptomicina. Objetivos: Analizar la seguridad y efectividad de daptomicina en niños. Pacientes y Métodos: Se incluyeron, retrospectivamente, niños con infecciones microbiológicamente documentadas, tratados con daptomicina. Resultados: Las infecciones más frecuentes fueron endocarditis en 9 (32%), sepsis de la comunidad en 4 (14%), bacteriemia en 7 (asociada a catéter en 3) (25%), osteomielitis en 3 (10%), peritonitis asociada a diálisis en 3 (10%) y tromboflebitis supurativa en 2 pacientes (7%). Staphylococcus aureus resistente a meticilina fue el patógeno más común en 18 pacientes (64%), Daptomicina fue indicada por el fracaso del tratamiento convencional en 17 (61%), y la toxicidad o intolerancia a vancomicina en 11 pacientes (39%). La duración media de tratamiento fue de 19 días (RIC 95% 7-42 días). Cuatro pacientes (14%) completaron tratamiento ambulatorio. Tuvieron respuesta favorable 22 pacientes (79%) Se reportaron eventos adversos en tres pacientes: dos elevaciones de creatina-fosfocinasa) y una erupción cutánea grave. Conclusiones: Daptomicina demostró una eficacia y seguridad favorables en esta población pediátrica.

Abstract Background: Vancomycin has been considered the treatment of choice especially for methicillin-resistant Staphylococcus aureus (MRSA) infections; but its poor tissue penetration, renal toxicity, and requiring of dosages monitoring, raises the need for new treatment alternatives such as daptomycin. Aims: To analyze the safety and effectiveness of daptomycin in children. Methods: Children with microbiologically documented infections treated with daptomycin were retrospectively included. Results: The most frequent infections were endocarditis in 9 (32%), sepsis in 4 (14%), bacteremia in 7 (associated with catheter in 3) (25%), osteomyelitis in 3 (10%), peritonitis associated with dialysis in 3 (10%) and suppurative thrombophlebitis in 2 patients (p) (7%). Methicillin-resistant Staphylococcus aureus was the most common pathogen in 18 patients (64%). The indications for daptomycin were due to the failure of conventional treatment in 17 (61%), and the toxicity or intolerance to vancomycin in 11 patients (39%). The average duration of treatment was 19 days (95% ICR 7-42 days). Four patients (14%) completed outpatient treatment, 22 patients had a favorable response (79%). Adverse events were reported in 3 patients (2 creatinine-phosfo-kinase increase) and in one severe skin rash. Conclusions: Daptomycin demonstrated a favorable efficacy and safety in this pediatric population.

Series de Pediatría Garrahan. El niño y las infecciones / Garrahan Pediatrics Series. The child and the infections

Las consultas pediátricas por temas infectológicos son frecuentes y relevantes durante toda la infancia, desde la etapa neonatal hasta la adolescencia. En este nuevo volumen de las Series Garrahan: El ñino y las infecciones, se han seleccionado temas específicos, sobre la base de la actualización del conocimiento, los cambios epidemiológicos y de las conductas clínicas ocurridos en los últimos años y la necesidad del manejo adecuado de estas afecciones, ya sea ambulatorio o durante la internación. Entre sus aspectos sobresalientes se incluyen: El estudio de temas destacados como el abordaje del niño febril; las infecciones de piel y partes blandas, incluidas las asociadas con mordeduras; las infecciones en el recién nacido; las infecciones respiratorias bajas, incluida la tuberculosis; y las infecciones osteoarticulares, del sistema nervioso central e intraabdominales. La inclusión de un capítulo especial sobre la prevención de infecciones para ayudar a reducir su incidencia. El enfoque práctico, con discusión de casos clínicos y definición de conductas, y ubicando al pediatra en un papel central como coordinador de la atención interdisciplinaria. Aspectos clave y lecturas recomendadas en el cierre de cada capítulo. Una obra actualizada que aporta información científica y la experiencia de los profesionales del Hospital Garrahan, dedicada a todos los miembros del equipo de salud que atienden y cuidan niños dondequiera que trabajen al servicio de la salud infantil

Experiencias, barreras y facilitadores en la implementación de intervenciones de control del Aedes aegypti en América Latina y Caribe: estudio cualitativo / Experiences, barriers and facilitators to the implementation of interventions for controlling Aedes aegypti in Latin America and the Caribbean: a qualitative study / Experiências, barreiras e facilitadores na implementação de intervenções de controle do Aedes aegypti na América Latina e no Caribe: estudo qualitativo

El objetivo fue describir experiencias, barreras y facilitadores en la implementación de intervenciones de control del Aedes aegypti en América Latina y Caribe. Fue realizado un abordaje cualitativo con entrevistas en profundidad semiestructuradas a expertos en implementación de programas (19 participantes de nueve países). Se utilizó un software para la codificar los datos y se confeccionaron matrices para su comparación. En base a los hallazgos desarrollamos una representación gráfica de dimensiones teóricas que agrupan las barreras y facilitadores para la implementación de intervenciones. A nivel global, el ambiente natural y construido contribuye a la reproducción del mosquito. En el sistema de salud, la falta de priorización del problema y la escasez de recursos materiales y humanos representan los obstáculos más importantes. Se necesita que otros sectores diferentes al de salud se responsabilicen de las acciones para mejorar los determinantes sociales de la salud. Existen barreras transversales relacionadas con la gobernanza, como la descoordinación entre los niveles centrales y locales, falta de continuidad de las intervenciones y de los grupos técnicos. La comunidad enfrenta problemas como la falta de información, pobreza o resistencias a recomendaciones. La opinión pública puede tener un impacto positivo o negativo, influyendo indirectamente en las decisiones políticas. Este estudio propone un marco de dimensiones de análisis construido desde los hallazgos; describe factores influyentes en la implementación de políticas que pueden orientar las acciones futuras desde un enfoque integrado.

This study sought to describe experiences, barriers and facilitators to the implementation of interventions for controlling Aedes aegypti in Latin America and the Caribbean. A qualitative approach with semi-structured in-depth interviews with program implementation experts (19 participants in nine countries) was carried out. We used a software to codify the data and created matrices to compare them. Based on our findings, we developed a graphic representation of the theoretical dimensions that encompass the barriers and facilitators to the implementation of interventions. At the global level, the natural and built environment contributed to the mosquito's reproduction. In the health system, the lack of priority given to the problem and the scarcity of material and human resources are the most important obstacles. Sectors other than health must take responsibility for actions directed at improving social determinants of health. There are transversal barriers related to governance, lack of coordination between central and local levels, lack of continuity in terms of interventions and technical groups. The community faces problems such as lack of information, poverty or resistance to recommendations. Public opinion can have a positive or negative impact, indirectly influencing political decisions. This study proposes a framework of analytical dimensions based on our findings; describes factors that influence policy implementation, which can guide future actions from an integrated perspective.

O objetivo foi descrever experiências, barreiras e facilitadores na implementação de intervenções de controle do Aedes aegypti na América Latina e no Caribe. Uma abordagem qualitativa foi realizada com entrevistas semiestruturadas em profundidade com especialistas na implementação do programa (19 participantes de nove países). Foi usado um software para codificar os dados e foram feitas matrizes para comparação. Com base nos resultados, desenvolvemos uma representação gráfica das dimensões teóricas que agruparam as barreiras e facilitadores para a implementação das intervenções. Em nível global, o ambiente natural e construído contribui para a reprodução do mosquito. No sistema de saúde, a falta de priorização do problema e a escassez de recursos materiais e humanos representam os obstáculos mais importantes. É necessário que outros setores, além do setor saúde, assumam ações de melhoria dos determinantes sociais da saúde. Existem barreiras transversais relacionadas à governança, como a falta de coordenação entre os níveis central e local e a falta de continuidade das intervenções e dos grupos técnicos. A comunidade enfrenta problemas como falta de informação, pobreza ou resistência a recomendações. A opinião pública pode ter um impacto positivo ou negativo, influenciando indiretamente as decisões políticas. Este estudo propõe um quadro de dimensões de análise construído a partir dos resultados; descreve fatores influentes na implementação de políticas que podem orientar ações futuras a partir de uma abordagem integrada.

Workshop for priority-setting in Aedes aegypti control interventions in Latin America and the Caribbean: a policy dialogue / Workshop de priorização de intervenções para o controle do mosquito Aedes aegypti na América Latina e no Caribe: diálogo de políticas / Taller de priorización de intervenciones para el control del mosquito Aedes aegypti en Latinoamérica y el Caribe: diálogo de políticas

This article presents the results of a dialogue between decision-makers and experts in Latin America and the Caribbean on priority-setting for interventions and studies on Aedes aegypti control. The article is part of a project that included a systematic review of mosquito control strategies and a qualitative study with key informants from the region. Using a collective deliberative process assisted by the results of the above-mentioned projects, a list of priorities was developed by consensus for the implementation of vector control strategies and the development of key regional research lines. It was agreed that the best strategy is integrated vector management, divided into: (a) chemical control; (b) biological control; (c) environmental management; (d) community participation; and (e) integrated surveillance. The workshop highlighted the crucial role of government leadership and inter-sector coordination between government agencies and civil society stakeholders. The proposed priorities for research lines were: Ae. aegypti vector competence and associated factors; community components of interventions; incorporation of technology into vector control and monitoring; most efficient modalities of integrated surveillance; entomological indicators with the best predictive capacity; and resistance to insecticides. The policy dialogue methodology allowed validating and enriching the results of other levels of research, besides establishing priorities for regional research and control strategies.

Este trabalho apresenta os resultados de um diálogo entre tomadores de decisão e expertos da América Latina e do Caribe sobre a priorização de intervenções e pesquisas para o controle do mosquito Aedes aegypti. Faz parte de um projeto que compreendeu uma revisão sistemática sobre estratégias e controle do mosquito e um estudo qualitativo com informantes chave da região. Através de um processo deliberativo em instâncias coletivas, assistido pelos resultados dos mencionados projetos, foi elaborada uma listagem consensuada de prioridades de implementação de estratégias de controle vetorial e de desenvolvimento regional de linhas essenciais de pesquisa. Foi acordado que a melhor estratégia é a gestão integrada de vetores ou Estratégia de Gestão Integrada, desagregada em: (a) controle químico; (b) controle biológico; (c) gestão ambiental; (d) participação comunitária; (e) vigilância integrada. Foi destacado o rol fundamental e indelegável da direção do estado e a coordenação intersetorial entre agências estaduais com atores da sociedade civil. Foi proposto priorizar como linhas de pesquisa: a capacidade vetorial do Ae. aegypti e fatores associados; componentes comunitários das intervenções; a incorporação de tecnologia para o controle vetorial e para o monitoramento; modos mais eficientes de vigilância integrada; indicadores entomológicos com melhor capacidade preditiva e resistência a pesticidas. A metodologia do diálogo de políticas permitiu validar e enriquecer os resultados de outras áreas de pesquisa, possibilitou estabelecer prioridades a propósito da pesquisa, além de estratégias para o controle regional.

Este trabajo presenta los resultados de un diálogo entre tomadores de decisión y expertos de América Latina y el Caribe sobre la priorización de intervenciones e investigaciones para el control del mosquito Aedes aegypti. Forma parte de un proyecto que comprendió una revisión sistemática sobre estrategias control del mosquito y un estudio cualitativo con informantes clave de la región. Mediante un proceso deliberativo en instancias colectivas, asistido por los resultados de los mencionados proyectos, se elaboró un listado consensuado de prioridades de implementación de estrategias de control vectorial y de desarrollo regional de líneas clave de investigación. Se convino en que la mejor estrategia es el manejo integrado de vectores o Estrategia de Gestión Integrada, desagregada en: (a) control químico; (b) control biológico; (c) manejo ambiental; (d) participación comunitaria; y (e) vigilancia integrada. Se destacó el fundamental e indelegable rol de rectoría del estado y la coordinación intersectorial entre agencias estatales y con actores de la sociedad civil. Se propuso priorizar como líneas de investigación: la capacidad vectorial del Ae. aegypti y factores asociados; componentes comunitarios de las intervenciones; la incorporación de tecnología al control vectorial y al monitoreo; los modos más eficientes de vigilancia integrada; indicadores entomológicos con mejor capacidad predictiva y resistencia a insecticidas. La metodología del diálogo de políticas permitió validar y enriquecer los resultados de otras instancias de investigación, y permitió establecer prioridades sobre investigación y estrategias para el control regional.

Embolismo arterial agudo como forma de presentación clínica inicial de una hidatidosis diseminada: reporte de un caso / Acute arterial embolism as the clinical presentation of a disseminated hydatidosis: case report

La hidatidosis es una zoonosis producida por el parásito Echinococcus granulosus. En el ciclo zoonótico del parásito, el hombre es un huésped intermediario y sufre la enfermedad tras la ingesta de alimentos y agua contaminados por la materia fecal de animales infectados. En Argentina, la enfermedad constituye un problema importante de salud pública. Suele manifestarse con compromiso hepático y pulmonar. La afectación de otros órganos, que incluyen el corazón, es infrecuente.

Hydatidosis is a parasitic infection caused by the Echinococcus granulosus larvae, transmitted by the ingestion of infected food, characterized by the formation of cysts in vital organs. In Argentina, the disease is spread throughout the territory, constituting an important public health issue. The disease usually affects the liver and lungs. The affection of other organs is rare, and even more uncommon the affection of the heart. We present the case of a disseminated hydatidosis in a pediatric patient, whose initial clinical manifestation was an acute arterial embolism of the right limb caused by the rupture of a hydatidic cardiac cyst.

Acute arterial embolism as the clinical presentation of a disseminated hydatidosis: case report. / Embolismo arterial agudo como forma de presentación clínica inicial de una hidatidosis diseminada: reporte de un caso.

Hydatidosis is a parasitic infection caused by the Echinococcus granulosus larvae, transmitted by the ingestion of infected food, characterized by the formation of cysts in vital organs. In Argentina, the disease is spread throughout the territory, constituting an important public health issue. The disease usually affects the liver and lungs. The affection of other organs is rare, and even more uncommon the affection of the heart. We present the case of a disseminated hydatidosis in a pediatric patient, whose initial clinical manifestation was an acute arterial embolism of the right limb caused by the rupture of a hydatidic cardiac cyst.

La hidatidosis es una zoonosis producida por el parásito Echinococcus granulosus. En el ciclo zoonótico del parásito, el hombre es un huésped intermediario y sufre la enfermedad tras la ingesta de alimentos y agua contaminados por la materia fecal de animales infectados. En Argentina, la enfermedad constituye un problema importante de salud pública. Suele manifestarse con compromiso hepático y pulmonar. La afectación de otros órganos, que incluyen el corazón, es infrecuente. Se presenta un caso de embolia arterial aguda como manifestación clínica inicial de una hidatidosis diseminada en un paciente pediátrico, a partir de la ruptura de un quiste hidatídico cardíaco.