Cellular consequences of small supernumerary marker chromosome derived from chromosome 12: mosaicism in daughter and father

Constitutional genomic imbalances are known to cause malformations, disabilities, neurodevelopmental delay, and dysmorphia and can lead to dysfunctions in the cell cycle. In extremely rare genetic conditions such as small supernumerary marker chromosomes (sSMC), it is important to understand the cellular consequences of this extra marker, as well the factors that contribute to their maintenance or elimination through successive cell cycles and phenotypic impact. The study of chromosomal mosaicism provides a natural model to characterize the effect of aneuploidy on genome stability and compare cells with the same genetic background and environment exposure, but differing in the presence of sSMC. Here, we report the functional characterization of different cell lines from two familial patients with mosaic sSMC derived from chromosome 12. We performed studies of proliferation dynamics, stability, and variability of these cells using fluorescent in situ hybridization (FISH), sister chromatid exchanges (SCE), and conventional staining. We also quantified the telomere-related genomic instability of sSMC cells using 3D telomeric profile analysis by quantitative-FISH. sSMC cells exhibited differences in the cell cycle dynamics compared to normal cells. First, the sSMC cells exhibited lower proliferation index and higher frequency of SCE than normal cells, associated with a higher level of chromosomal instability. Second, sSMC cells exhibited more telomeric-related genomic instability. Lastly, the differences of sSMC cells distribution among tissues could explain different phenotypic repercussions observed in patients. These results will help in our understanding of the sSMC stability, maintenance during cell cycle, and the cell cycle variables involved in the different phenotypic manifestations.

Evolución de pacientes con bronquiolitis tratados con cánulas de alto flujo de oxígeno que ingresan a la unidad de cuidados intensivos / Outcome of patients with bronchiolitis treated with high-flow oxygen nasal cannulas admitted to the intensive care unit

Objetivo: Describir la evolución en la Unidad de Cuidados Intensivos Pediátricos (UCIP) de los pacientes con bronquiolitis, tratados inicialmente con cánula nasal de alto flujo de oxígeno (CAFO) en la Unidad Emergencias. Determinar factores predisponentes de ingreso a ventilación no invasiva (VNI) o invasiva con intubación orotraqueal (TET). Métodos: Trabajo descriptivo retrospectivo por revisión de historias clínicas. Se incluyeron todos los pacientes menores de 2 años de edad con diagnóstico de bronquiolitis, sin comorbilidades, que ingresaron a UCIP polivalente luego de haber sido previamente tratados con CAFO en la Unidad de Emergencias entre los meses de Agosto 2017 y Agosto 2019. Resultados: Se evaluaron 145 pacientes. La mediana de edad fue de 4,4 meses (RIC 2-6 meses), con una mediana de tiempo desde el inicio de los síntomas hasta la consulta de 45,4 hs (RIC 24-72). La mediana del score de TAL modificado al ingreso a UCIP 8,4 (RIC 8-9). El 98,6% requirió asistencia respiratoria mecánica (ARM), en el grupo VNI 52,4% (75) y en el grupo TET 47,5% (68). El rescate de germen fue en 60% de los casos virus sincicial respiratorio (VSR). El 5,5% fueron co-infecciones. De los pacientes con rescate positivo para VSR, el 52,9% (46) requirieron VNI y 47,1% (41) TET. Los pacientes estudiados permanecieron en CAFO una mediana de 20 hs previo al ingreso a UCIP (RIC: 6-24). Aquellos que estuvieron en VNI con una mediana de 23,3 hs (RIC 6-24) y los que requirieron TET 17 hs (RIC 6-21). La mortalidad evidenciada en el grupo TET fue de 1,38% correspondiente a 2 pacientes, donde también se encontró un 7,5% de complicaciones. La mediana de días de internación en UCIP fue de 8,6 (5-11) para la totalidad de la población estudiada siendo 5,2 (4-6) para los pacientes en VNI y 12 días (9-14) para los pacientes en TET. Conclusiones: Casi la totalidad de pacientes tratados con CAFO en la Unidad Emergencias que requirieron pasar a UCI necesitaron ARM. Ni el score de TAL ni la cantidad de horas de CAFO previo al ingreso en UCI nos permitieron diferenciar los pacientes del grupo VNI de aquellos del grupo TET (AU)

Objective: To describe outcome of patients who were admitted to the pediatric intensive care unit (PICU) with bronchiolitis initially treated with high-flow oxygen through a nasal cannula (HFNC) at the emergency department and to determine predisposing factors for the need for non-invasive ventilation (NIV) or invasive endotracheal intubation (ETI). Methods: A retrospective descriptive study with a review of the clinical records was conducted. All patients less than 2 years of age with bronchiolitis without comorbidities that were admitted to the general PICU following treatment with HFNC at the emergency department between August 2017 and August 2019 were included in the study. Results: 145 patients were evaluated. Median age was 4.4 months (IQR 2-6 months). Median time from symptom onset to first consultation was 45.4 hours (IQR 24-72). Median modified TAL score on PICU admission was 8.4 (IQR 8-9). Overall 98,6% required mechanical ventilation (MV), 52.4% (75) in the NIV and 47.5% (68) in the ETI group. In 60% of the cases respiratory syncytial virus (RSV) was isolated. Co-infections were found in 5.5%. Of the patients with an RSV-positive isolate, 52.9% (46) required NIV and 47.1% (41) ETI. Patients had remained on HFNC for a median of 20 hours prior to PICU admission (IQR 6-24). Patients were on NIV for a median time of 23.3 hours (IQR 6-24) and on ETI for a median time of 17 hours (IQR 6-21). In the ETI group, mortality rate was 1.38%, corresponding to two patients, while the complication rate was 7.5%. Median length of PICU stay was 8.6 days (5-11) for the entire study population, 5.2 days (4-6) for patients on NIV, and 12 days (9-14) for those on ETI. Conclusions: Almost all patients treated with HFNC at the emergency department who required admission to the PICU needed MV. Neither TAL score nor time on HFNC allowed us to differentiate patients requiring NIV from those who needed ETI (AU)

Impacto de la cateterización venosa central percutánea bajo guía ecográfica en una terapia intensiva pediátrica polivalente / Impact of ultrasound-guided percutaneous central venous catheterization at a general pediatric intensive care unit

Introducción: La cateterización venosa central es un procedimiento usual en Unidades de Cuidados Intensivos (UCI). El ultrasonido (US) para guiar la cateterización, ofrece ventajas, permitiendo tener una imagen topográfica precisa del vaso, reduciendo las complicaciones, el tiempo y el número de punciones. Objetivo: determinar, si la US en la colocación de catéteres venosos centrales (CVC), podría disminuir el número de punciones y lograr la cateterización exitosa. Población y métodos: Estudio descriptivo, prospectivo de los CVC colocados mediante punción guiada por US, en una UCI polivalente del Hospital de Pediatría Juan P. Garrahan, entre el año 2018 al 2019. Población: pacientes de 1 mes a 18 años que requirieron colocación de un CVS por US. Se consideró significativo un valor de p< 0.05. Resultados: VYI en 66 pacientes (43,5%), VF fue en 86 pacientes (56,5%). 86 (56,5%) CVC, fueron insertados en el primer intento y 66 (43,5%), requirieron más de un intento. Las inserciones en VYI fueron exitosas en el primer intento en 46 pac. (53,5%) 20 pac. requirieron más de un intento (30,3%) p 0,004 OR 0,37 (IC 95% 0,18-0,78. En <6 meses los CVC colocados en VYI tuvieron menos riesgo de requerir más de un intento, con respecto a aquellos en los cuales se eligió la VF, p 0,0026 OR 0,31 (IC 95% 0,12 -0,75). 5,2% presentaron complicaciones, no hubo mortalidad relacionada al procedimiento. Conclusiones: La inserción de CVC guiados por US fue segura y significativamente exitosa en el primer intento cuando el vaso de elección fue la VYI, especialmente en < 6 meses (AU)

IIntroduction: Central venous catheterization is a common procedure in intensive care units (ICU). The use of ultrasound (US) to guide catheterization offers advantages, allowing for an accurate topographic image of the vessel, reducing complications as well as time and number of punctures. Objective: To determine whether the use of US for the placement of central venous catheters (CVCs) may decrease the number of punctures and achieve successful catheterization. Patients and methods: A descriptive, prospective study was conducted of CVCs placed by US-guided puncture at a general ICU of Hospital de Pediatría Juan P. Garrahan between 2018 and 2019. Patients from 1 month to 18 years of age who required US-guided placement of a CVC were included. A p< 0.05 was considered significant. Results: The internal jugular vein (IJV) was used in 66 (43.5%) and the femoral vein (FV) in 86 patients (56.5%). Overall, in 86 (56.5%) CVC were inserted on the first attempt and 66 (43.5%) required more than one attempt. Insertions into the VYI were successful on the first attempt in 46 (53.5%) patients and 20 (30.3%) patients required more than one attempt, p 0.004; OR 0.37 (95% CI 0.18-0.78). In patients <6 months CVCs placed in the IJV had a lower risk of requiring more than one attempt compared to those in which the FV was chosen, p 0.0026 OR 0.31 (95% CI 0.12 -0.75). Complications occurred in 5.2%; no procedure-related mortality was observed. Conclusions: US-guided insertion of CVC was safe and significantly successful on the first attempt when the vessel of choice was the IJV, especially in patients < 6 months (AU)