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    Capnometry after an inspiratory breath hold, PLATCO2, as a surrogate for PaCO2 in mild to moderate pediatric acute respiratory distress syndrome: A feasibility study
    (Wiley Periodicals, 2023-07-10) Cruces, Pablo; Moreno, Diego; Reveco, Sonia; Améstica, Marjorie; Araneda, Patricio; Ramirez, Yennys; Vásquez-Hoyos, Pablo; Díaz, Franco
    Objective: Accurate and reliable noninvasive methods to estimate gas exchange are necessary to guide clinical decisions to avoid frequent blood samples in children with pediatric acute respiratory distress syndrome (PARDS). We aimed to investigate the correlation and agreement between end‐tidal PCO2 measured immediately after a 3‐s inspiratory‐hold (PLATCO2) by capnometry and PaCO2 measured by arterial blood gases (ABG) in PARDS. Measurements and Main Results: All patients were in volume‐controlled ventilation mode. The regular end‐tidal P P CO ETCO ( ) 2 2 (without the inspiratory hold) was registered immediately after the ABG sample. An inspiratory‐hold of 3 s was performed for lung mechanics measurements, recording PETCO2 in the breath following the inspiratory‐hold. (PLATCO2). End‐tidal alveolar dead space fraction (AVDSf) was calculated as [( – )/ PP P aCO ETCO aCO ] 2 2 2 and its surrogate (S)AVDSf as [( CO – )/ CO PLAT 2 ETCO PLAT 2 P ] 2 . Measurements of PaCO2 were considered the gold standard. We performed concordance correlation coefficient (ρc), Spearman's correlation (rho), and Bland–Altmann's analysis (mean difference ± SD [limits of agreement, LoA]). Eleven patients were included, with a median (interquartile range) age of 5 (2–11) months. Tidal volume was 5.8 (5.7–6.3) mL/kg, PEEP 8 (6–8), driving pressure 10 (8–11), and plateau pressure 17 (17–19) cm H2O. Forty‐one paired measurements were analyzed. PaCO2 was higher than PETCO2 (52 mmHg [48–54] vs. 42 mmHg [38–45], p < 0.01), and there were no significant differences with PLATCO2 (50 mmHg [46–55], p > 0.99). The concordance correlation coefficient and Spearman's correlation between PaCO2 and PLATCO2 were robust (ρc = 0.80 [95% confidence interval [CI]: 0.67–0.90]; and rho = 0.80, p < 0.001.), and for PETCO2 were weak and strong (ρc = 0.27 [95% CI: 0.15–0.38]; and rho = 0.63, p < 0.01). The bias between PLATCO2 and PaCO2 was −0.4 ± 3.5 mmHg (LoA −7.2 to 6.4), and between PETCO2 and PaCO2 was −8.5 ± 4.1 mmHg (LoA −16.6 to −0.5). The correlation between AVDSf and (S)AVDSf was moderate (rho = 0.55, p < 0.01), and the mean difference was −0.5 ± 5.6% (LoA −11.5 to 10.5) Conclusion: This pilot study showed the feasibility of measuring end‐tidal CO2 after a 3‐s end‐inspiratory breath hole in pediatric patients undergoing controlled ventilation for ARDS. Encouraging preliminary results warrant further study of this technique.
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    La extubación durante la noche no se asocia con su fracaso en pacientes pediátricos de Unidad de Cuidados Intensivos: Estudio de cohorte retrospectivo
    (Sociedad Chilena de Pediatría, 2023-04-17) Ibarra V., Maybreet; Andrades E., Francisca; Satta S., María; Díaz, Franco; Donoso F., Alejandro
    Poco es conocido sobre la hora del día y carácter de éste (hábil/no hábil) en que se efectúa la extubación, y si durante la noche esta es segura. Objetivo: describir la frecuencia de extubación nocturna (EN) y en día no hábil (ENH). Adicionalmente determinar la asociación entre éstas y resultados clínicos. Pacientes y Método: Estudio de cohorte retrospectivo de pacientes menores de 18 años quienes recibieron ventilación mecánica (VM) invasiva y se efectuó un intento extubación en una Unidad de Paciente Crítico Pediátrico (UPCP) médico quirúrgica de alta complejidad entre el 01/01/2018 al 31/12/2021. Exposición primaria: EN, la cual fue definida como la realizada entre 20:01 - 8:00 horas. Se evaluó su asociación con fracaso de extubación (FE), duración de VM invasiva y tiempo de esta- día en la UPCP. Resultados: 146 pacientes fueron incluidos (58,9% hombres, edad 1,14 (0,25 - 5,5) años). En el 17,8% se efectuó EN. La extubación nocturna no se asoció con FE como tampoco el día de extubación. El FE fue 3,8% en EN y 5% en la extubación diurna (ED) (p = 0,80). La duración de la VM invasiva fue menor en EN que ED (48 (24-73,5) vs. 72 (48-96) h, p = 0,02). Conclusiones: La EN no se asoció con FE. Los pacientes con EN tuvieron menor duración de VM invasiva, y ésta última se asoció con FE. La retirada de la VM invasiva debe ser considerada en la primera oportunidad y estar determinada por factores clínicos, más que por la hora del día.
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    Plateau pressure and driving pressure in volume- and pressure- controlled ventilation: comparison of frictional and viscoelastic resistive components in pediatric acute respiratory distress syndrome.
    (Society of Critical Care Medicine​ and The World Federation of Pediatric Intensive and Critical Care Societies, 2023-09) Cruces, Pablo; Moreno, Diego; Reveco, Sonia; Ramirez, Yennys; Díaz, Franco
    Objectives: To examine frictional, viscoelastic, and elastic resistive components, as well threshold pressures, during volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) in pediatric patients with acute respiratory distress syndrome (ARDS). Measurements and main results: All patients were in VCV mode during measurement of pulmonary mechanics, including: the first pressure drop (P1) upon reaching zero flow during the inspiratory hold, peak inspiratory pressure (PIP), plateau pressure (P PLAT ), and total positive end-expiratory pressure (tPEEP). We calculated the components of the working pressure, as defined by the following: frictional resistive = PIP-P1; viscoelastic resistive = P1-P PLAT ; purely elastic = driving pressure (ΔP) = P PLAT -tPEEP; and threshold = intrinsic PEEP. The procedures and calculations were repeated on PCV, keeping the same tidal volume and inspiratory time. Measurements in VCV were considered the gold standard. We performed Spearman correlation and Bland-Altman analysis. The median (interquartile range [IQR]) for patient age was 5 months (2-17 mo). Tidal volume was 5.7 mL/kg (5.3-6.1 mL/kg), PIP cm H 2 O 26 (23-27 cm H 2 O), P1 23 cm H 2 O (21-26 cm H 2 O), P PLAT 19 cm H 2 O (17-22 cm H 2 O), tPEEP 9 cm H 2 O (8-9 cm H 2 O), and ΔP 11 cm H 2 O (9-13 cm H 2 O) in VCV mode at baseline. There was a robust correlation (rho > 0.8) and agreement between frictional resistive, elastic, and threshold components of working pressure in both modes but not for the viscoelastic resistive component. The purely frictional resistive component was negligible. Median peak inspiratory flow with decelerating-flow was 21 (IQR, 15-26) and squared-shaped flow was 7 L/min (IQR, 6-10 L/min) ( p < 0.001). Conclusions: P PLAT , ΔP, and tPEEP can guide clinical decisions independent of the ventilatory mode. The modest purely frictional resistive component emphasizes the relevance of maintaining the same safety limits, regardless of the selected ventilatory mode. Therefore, peak inspiratory flow should be studied as a mechanism of ventilator-induced lung injury in pediatric ARDS
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    Factores asociados a ventilación mecánica prolongada en niños con fallo respiratorio de causa pulmonar: estudio de cohortes del registro de LARed Network
    (Elsevier, 2023-06-15) Barajas-Romero, Juan Sebastían; Vásquez-Hoyos, Pablo; Pardo, Rosalba; Jaramillo-Bustamante, Juan Camilo; Grigolli, Regina; Monteverde-Fernández, Nicolas; Gonzalez-Dambrauskas, Sebastián; Jabornisky, Roberto; Cruces, Pablo; Wegner, Adriana; Díaz, Franco; Pietroboni, Pietro
    Objectives: To identify factors associated with prolonged mechanical ventilation (pMV) in pediatric patients in pediatric intensive care units (PICUs). Design: Secondary analysis of a prospective cohort. Setting: PICUs in centers that are part of the LARed Network between April 2017 and January 2022. Participants: Pediatric patients on mechanical ventilation (IMV) due to respiratory causes. We defined IMV time greater than the 75th percentile of the global cohort. Main variables of interest: Demographic data, diagnoses, severity scores, therapies, complications, length of stay, morbidity, and mortality. Results: 1698 children with MV of 8±7 days were included, and pIMV was defined as 9 days. Factors related to admission were age under 6 months (OR 1.61, 95% CI 1.17-2.22), bronchopulmonary dysplasia (OR 3.71, 95% CI 1.87-7.36), and fungal infections (OR 6.66, 95% CI 1.87-23.74), while patients with asthma had a lower risk of pIMV (OR 0.30, 95% CI 0.12-0.78). Regarding evolution and length of stay in the PICU, it was related to ventilation-associated pneumonia (OR 4.27, 95% CI 1.79-10.20), need for tracheostomy (OR 2.91, 95% CI 1.89-4.48), transfusions (OR 2.94, 95% CI 2.18-3.96), neuromuscular blockade (OR 2.08, 95% CI 1.48-2.93), high-frequency ventilation (OR 2.91, 95% CI 1.89-4.48), and longer PICU stay (OR 1.13, 95% CI 1.10-1.16). In addition, mean airway pressure greater than 13cmH2O was associated with pIMV (OR 1.57, 95% CI 1.12-2.21). Conclusions: Factors related to IMV duration greater than 9 days in pediatric patients in PICUs were identified in terms of admission, evolution, and length of stay
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    Reply to Pérez
    (American Thoracic Society, 2023) Cruces, Pablo; Erranz, Benjamín; Díaz, Franco
    Reply to Pérez. Patient self-inflicted and ventilator-induced lung injury: two sides of the same coin?
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    Results of prophylactic simple fasciocutaneous advancement in the initial management of acute ankle fractures with high risk of operative wound complication
    (Elsevier, 2023-09-04) Becerra, Eduardo; Castro, Magdalena; Ruiz Riquelme, Pablo
    Ankle fracture is the third most prevalent fracture in older adults. Wound dehiscence is the most frequent complication. Our objective is to determine the operative wound complication rate in patients with unstable ankle fracture in whom a prophylactic simple fasciocutaneous advancement was used. Prophylactic fasciocutaneous advancement at the beginning of traumatological surgery is technically simple, reproducible, cheap and with low complications.
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    Incidence and clinical implications of anatomical variations in the pancreas and Its ductal system: A systematic review and meta-analysis
    (MDPI, 2023-08-09) Orellana-Donoso, Mathias; Milos Brandenberg, Daniel; Benavente-Urtubia, Andoni; Guerra-Loyola, Javier; Bruna-Mejías, Alejandro; Nova-Baeza, Pablo; Becerra-Farfan, Álvaro; Sepúlveda-Loyola, Walter; Luque-Bernal, Ricardo Miguel; Valenzuela-Fuenzalida, Juan José
    Objetivo: Esta revisión sistemática analiza las variantes anatómicas en el páncreas y su sistema ductal para informar sobre su asociación con patologías pancreáticas. Métodos: Realizamos una búsqueda en las bases de datos MEDLINE, Scopus, Web of Science, Google Scholar, CINAHL y LILACS desde su inicio hasta julio de 2023. La calidad metodológica se evaluó con la herramienta Anatomical Quality Assessment (AQUA). Finalmente, la prevalencia agrupada se estimó mediante un modelo de efectos aleatorios. Resultados: Se encontraron 55 estudios que cumplieron con los criterios de elegibilidad. La prevalencia general de páncreas divisum (PD) fue del 18% (IC del 95% = 15-21%). La prevalencia de EP asociada con pancreatitis fue del 30% (IC 95% = 1-61%). Conclusiones: Una variante anatómica del páncreas como la EP puede ser la causa de la obstrucción de la vía biliar, dando lugar a diversas complicaciones clínicas, como la pancreatitis. De ahí que conocer esta variante sea de suma importancia para los cirujanos, especialmente para quienes tratan la región gastroduodenal.
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    Anatomical variations and abnormalities of the maxillary region and clinical implications: A systematic review and metaanalysis
    (Wolters Kluwer Health, 2023-07-05) Valenzuela-Fuenzalida, Juan José; Baez-Flores, Belén; Ávila-Sepúlveda, Roberto; Moya-Medina, Claudia; Pérez-Jiménez, Rubén; López, Esteban; Sánchis, Juan; Orellana-Donoso, Mathias; Leyton-Silva, Javiera; Rodríguez, Macarena-Cecilia; Iwanaga, Joe
    Objetivo: El objetivo de esta revisión es investigar y analizar las variaciones anatómicas presentes en el seno maxilar (SM), a través de la examinación de la prevalencia de estas variaciones, así como la correspondiente prevalencia de patologías clínicamente significativas y complicaciones asociadas a ellas. Métodos: El proceso de búsqueda se realizó en las siguientes bases de datos; MEDLINE, SCIELO, WOS, CINHAL, SCOPUS y GOOGLE SCHOLAR, utilizando como términos de búsqueda; “Hueso maxilar”, “Seno maxilar”, “Seno paranasal”, “Variaciones anatómicas”, “Sinusitis” y “Anatomía clínica”. Resultados: Se incluyeron un total de 26 artículos y 12969 muestras, de las cuales se registró el sexo de 12,594 sujetos, dando un total de 5802 hombres y 6792 mujeres. Las variantes reportadas por los incluidos fueron células de Haller, Concha Bullosa, Número de septos, Seno hipoplásico, Agger Nasi, Engrosamiento de la mucosa MS, Desviación del tabique nasal, Ostium accesorio y Células de Onodi. Entre los mencionados, los que presentaron mayor número de estudios (entre 8 y 10 estudios incluidos) fueron: las Células de Haller, la Concha Bullosa y el Número de septos, donde la prevalencia fue de 0,30, 0,36, 0,39 respectivamente. Estas variaciones pueden provocar sinusitis, provocar algunos tipos de tumores o afectar estructuras vecinas que podrían verse comprometidas por esta variación. Conclusión: Como resultado, es ciertamente complejo distinguir la presencia de variaciones anatómicas de anomalías patológicas. Por tanto, el conocimiento de las diferentes variaciones y sus relaciones clínicas podría ser un activo útil para los médicos dedicados a esta región.
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    Systematic review and meta-snalysis: recurrent laryngeal nerve variants and their implication in surgery and neck pathologies, using the Anatomical Quality Assurance (AQUA) checklist
    (MDPI, 2023-04-24) Valenzuela-Fuenzalida, Juan José; Baeza-Garrido, Vicente; Navia-Ramírez, María Fernanda; Cariseo-Ávila, Carolina; Bruna-Mejías, Alejandro; Becerra-Farfan, Álvaro; Lopez, Esteban; Orellana-Donoso, Mathias; Loyola-Sepulveda, Walter
    Introduction: The recurrent laryngeal nerve (RLN) is the structure responsible for sensory and motor innervation of the larynx, and it has been shown that its lesion due to a lack of surgical rigor led to alterations such as respiratory obstruction due to vocal cords paralysis and permanent phonation impairment. The objectives of this review were to know the variants of the RLN and its clinical relevance in the neck region. Methods: This review considered specific scientific articles that were written in Spanish or English and published between 1960 and 2022. A systematic search was carried out in the electronic databases MEDLINE, WOS, CINAHL, SCOPUS, SCIELO, and Latin American and Caribbean Center for Information on Health Sciences to compile the available literature on the subject to be treated and was enrolled in PROSPERO. The included articles were studies that had a sample of RLN dissections or imaging, intervention group to look for RLN variants, or the comparison of the non-recurrent laryngeal nerve (NRLN) variants, and finally, its clinical correlations. Review articles and letters to the editor were excluded. All included articles were evaluated through quality assessment and risk of bias analysis using the methodological quality assurance tool for anatomical studies (AQUA). The extracted data in the meta-analysis were interpreted to calculate the prevalence of the RLN variants and their comparison and the relationship between the RLN and NRLN. The heterogeneity degree between included studies was assessed. Results: The included studies that showed variants of the RLN included in this review were 41, a total of 29,218. For the statistical analysis of the prevalence of the RLN variant, a forest plot was performed with 15 studies that met the condition of having a prevalence of less than 100%. As a result, the prevalence was shown to be 12% (95% CI, SD 0.11 to 0.14). Limitations that were present in this review were the publication bias of the included studies, the probability of not having carried out the most sensitive and specific search, and finally, the authors’ personal inclinations in selecting the articles. Discussion: This meta-analysis can be considered based on an update of the prevalence of RLN variants, in addition to considering that the results show some clinical correlations such as intra-surgical complications and with some pathologies and aspects function of the vocal cords, which could be a guideline in management prior to surgery or of interest for the diagnostic.
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    Trastornos de conducta alimentaria grave en adolescentes durante la pandemia COVID-19: un llamado a la acción
    (Sociedad Chilena de Pediatría, 2022-06) Díaz, Franco; Pilicita, Lorena; Godoy, Luisana; Donoso, Alejandro
    Las investigaciones sobre las repercusiones de la pandemia COVID-19 en los adolescentes con TCA es escasa, no obstante, estos son uno de los desórdenes psiquiátricos de más difícil tratamiento, aún en condiciones de normalidad. Durante el primer año de la pandemia hubo un reporte de un incremento hasta en un 30%, de las admisiones hospitalarias por AN, con un predominio en adolescentes mujeres. Estos datos incipientes muestran solo la punta del iceberg, siendo los problemas de salud mental una de las principales secuelas de la pandemia COVID-19.
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    Relationship between national changes in mobility due to non-pharmaceutical interventions and emergency department visits due to pediatric acute respiratory infections during the COVID-19 pandemic
    (medRxiv (Distribuidor de documentos electrónicos inéditos sobre ciencias de la salud), 2022-01) Díaz, Franco; Carvajal, Cristóbal; Gatica, Sebastián; Vásquez-Hoyos, Pablo; Jabornisky, Roberto; Von Moltke, Richard; Jaramillo-Bustamante, Juan Camilo; Pizarro, Federico; Cruces, Pablo
    Background Strong social distancing measures were quickly implemented in Chile during the SARS-CoV-2 outbreak. One of the aims of non-pharmaceutical interventions (NPI) mandates was to decrease overcrowding, thus is usually measured as mobility changes. Methods we gather data from national health statistics for pediatric emergency (PED) visits for acute respiratory infection (ARI) in children younger than 15. We defined a historical cohort, including data from 2016 to 2019, and compared them with 2020 and 2021 pandemic years. Also, Chile’s national mobility reports from the online google database were downloaded. We tested the correlation between changes in mobility and relative reduction in PED-ARI by Spearman’s Rank Test. Results Historical data showed a mean of 46863 ± 3071 PED-ARI weekly visits with a high seasonal variation, with two peaks in weeks 20 and 28 and weeks 32 to 36. This transient drop was temporally associated with the mid-winter 2-week holiday of schools. The usual PED visits peaks did not occur in 2020 and 2021. Mobility declined from week 9, reaching lower than historical data from week 12 and a minimum of 43% in week 15 of 2020 . The correlation between mobility and PED-ARI visits showed a strong monotonic relationship (quadratic) with a Spearman’s rho of 0.80 (95% CI 0.75 to 0.86) . Conclusion NPI resulting in a decrease in mobility should be considered a robust public health measure to relieve the winter’s collapse of the national health system, decreasing morbimortality in children due to PED-ARI.
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    Nueva morbilidad tras enfermedad crítica en niños latinoamericanos menores de 18 años con infección severa del tracto respiratorio inferior
    (Sociedad Chilena de Pediatría, 2023-01) Caporal, Paula; Vásquez-Hoyos, Pablo; Díaz, Franco; Monteverde-Fernández, Nicolás; Pedrozo, Luis; Carvajal, Cristóbal; Tellechea Rotta, Alexandre; González-Dambrauskas, Sebastián
    Objetivo: analizar el desarrollo de nuevas morbilidades adquiridas tras hospitalización por Infección del Tracto Respiratorio Inferior (ITRI) en unidades de cuidados intensivos pediátricos (UCIP). Pacientes y Método: Se incluyeron pacientes de 35 UCIP de 8 países, edades 0 a 18 años con diagnóstico de ITRI, dados de alta vivos, registrados entre abril 2018 y septiembre 2019, y que hayan requerido algún tipo de soporte ventilatorio (sistema de alto flujo, ventilación no invasiva o ventilación invasiva), incluidos en el registro de LARed Network, que incluye la Escala de Estado Funcional (FSS en inglés) validada en población pediátrica, que evalúa el estado funcional en seis dominios: estado mental, sensorial, comunicación, motor, alimentación y estado respiratorio. NM consideró ITRI posterior a su hospitalización y se definió como un incremento≥ 3 puntos en la FSS. Resultados: De 3280 niños con ITRI, 85 (2, 6%) desarrollaron NM, asociada a diagnósticos de sepsis y síndrome de dificultad respiratoria aguda (SDRA), infección por neumococo o por adenovirus, infecciones asociadas a la atención en salud y ventilación mecánica invasiva. La infección por adenovirus, el SDRA y las IAH se asociaron de forma independiente con NM. Conclusiones: Observamos que el desarrollo de NM al egreso de UCIP es infrecuente, pero está asociada a factores de riesgo modificables. Estos datos definen ciertos grupos de riesgo para realizar futuras intervenciones e iniciativas en la mejora de la calidad de atención.
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    Boron Schiff bases derived from a-amino acids as nucleoli/cytoplasm cell-staining fluorescent probes in vitro
    (The Royal Society of Chemistry, 2020-08-26) Lara-Cerón, Jesús A; Jiménez Pérez, Víctor M; Xochicale-Santana, Leonardo; Ochoa, María E; Chávez-Reyes, Arturo; Muñoz-Flores, Blanca M; Blanca M. Muñoz-Flores; Arturo Chavez-Reyes
    The size, shape, and number of nucleoli in a cell's nucleus might help to distinguish a malignant from a benign tumor. Cellular biology and histopathology often require better visualization to understand nucleoli-related processes, thus organelle-specific fluorescent markers are needed. Here, we report the design, synthesis, and fully chemo-photophysical characterization of fluorescent boron Schiff bases (BOSCHIBAs), derived from a-amino acids (i.e., phenylalanine, tyrosine and tryptophan), with nucleoli- and cytoplasm-specific staining in cells. It is the first time that Boron Schiff bases derived from a-amino acids act as notorious dual (nucleoli and cytoplasm) cell-staining fluorescent probes. The boron derivatives not only showed good photostability and acceptable quantum yields ($5%) in solution, but also exhibited low cytotoxicity (>90% cell viability at 0.1 and 1 mg mL 1), which make them good candidates to be used in medical diagnosis.
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    The human-specific duplicated α7 gene inhibits the ancestral α7, negatively regulating nicotinic acetylcholine receptor-mediated transmitter release
    (American Society for Biochemistry and Molecular Biology, 2020-10-22) Martín-Sánchez, Carolina; Alés, Eva; Balseiro-Gómez, Santiago; Atienza, Gema; Arnalich, Francisco; Bordas, Anna; Cedillo, José L; Extremera, María; Chávez-Reyes, Arturo; Montiel, Carmen; Carmen Montiel; Arturo Chavez-Reyes
    Gene duplication generates new functions and traits, enabling evolution. Human-specific duplicated genes in particular are primary sources of innovation during our evo- lution although they have very few known functions. Here we examine the brain function of one of these genes (CHRFAM7A) and its product (dupα7 subunit). This gene results from a partial duplication of the ancestral CHRNA7 gene encoding the α7 subunit that forms the homopentameric α7 nicotinic acetylcholine receptor (α7-nAChR). The functions of α7- nAChR in the brain are well defined, including the modula- tion of synaptic transmission and plasticity underlying normal attention, cognition, learning, and memory processes. Howev- er, the role of the dupα7 subunit remains unexplored at the neuronal level. Here, we characterize that role by combining immunoblotting, quantitative RT-PCR and FRET techniques with functional assays of α7-nAChR activity using human neuroblastoma SH-SY5Y cell variants with different dupα7 expression levels. Our findings reveal a physical interaction between dupα7 and α7 subunits in fluorescent protein-tagged dupα7/α7 transfected cells that negatively affects normal α7-nAChR activity. Specifically, in both single cells and cell populations, the [Ca2+]i signal and the exocytotic response induced by selective stimulation of α7-nAChR were either significantly inhibited by stable dupα7 overexpression or augmented after silencing dupα7 gene expression with specific siRNAs. These findings identify a new role for the dupα7 subunit as a negative regulator of α7-nAChR-mediated control of exocytotic neurotransmitter release. If this effect is exces- sive, it would result in an impaired synaptic transmission that could underlie the neurocognitive and neuropsychiatric dis- orders associated with α7-nAChR dysfunction.
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    Therapeutic effects of WT1 silencing via respiratory administration of neutral DOPC Liposomal-siRNA in a lung metastasis melanoma murine model.
    (MDPI, 2023-03-22) Ramos-Gonzalez, Martin R; Vazquez-Garza, Eduardo; Garcia-Rivas, Gerardo; Rodriguez-Aguayo, Cristian; Chavez-Reyes, Arturo
    The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 protein by siRNA in both in vitro in the B16F10 melanoma cell line and in vivo in a murine model of lung metastatic melanoma. We did this by implementing a novel respiratory delivery strategy of a neutral DOPC liposomal-siRNA system (L-siRNA). In vitro studies showed an effective silencing of the WT1 protein in the siRNAs’ WT1-treated cells when compared with controls, resulting in a loss of the cell’s viability and proliferation by inducing G1 arrest, the inhibition of the migration and invasion capacities of the cells, as well as the induction of apoptosis. In vivo, the respiratory administration of L-WT1 siRNA showed an efficient biodistribution on the lungs. After two weeks of treatment, the silencing of the WT1 protein resulted in an important antitumor activity that reduced the tumor weight. In the survival study, L-WT1 treatment could significantly delay the death of the animals. This work demonstrates the efficacy of the L-siRNA respiratory administration as a novel therapy to reduce pulmonary tumors and to increase survivability by silencing specific cancer oncogenes as WT1.
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    Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study
    (Elsevier, 2023-02-14) Channon-Wells, Samuel; Vito, Ortensia; McArdle, Andrew J; Díaz, Franco
    Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries.
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    Mecánica pulmonar en el síndrome de distrés respiratorio agudo pediátrico asociado a COVID-19 aguda y MIS-C: implicaciones para las terapias y los resultados
    (Sociedad Chilena de Pediatría, 2023) Díaz, Franco; Domínguez-Rojas, Jesús; Coronado Muñoz, Álvaro; Luna-Delgado, Yesica; Alvarado-Gamarra, Giancarlo; Quispe Flores, Gaudi; Caqui-Vilca, Patrick; Atamari-Anahui, Noé; Muñoz Ramírez, Cleotilde Mireya; Tello-Pezo, Mariela; Cruces, Pablo; Vásquez-Hoyos, Pablo
    Objetivo: describir la mecánica pulmonar en el síndrome de distrés respiratorio agudo pediátrico (SDRAP) asociado a COVID-19 aguda y MIS-C con insuficiencia respiratoria. Métodos: se realizó un estudio observacional multicéntrico concurrente, analizando variables clínicas y mecánica pulmonar del SDRAP asociado a COVID-19 en 4 unidades de cuidados intensivos pediátricos (UCIP) del Perú. El análisis de subgrupos incluyó el SDRAP asociado a síndrome inflamatorio multisistémico en niños (MIS-C), MIS-PARDS, y el SDRAP con infección respiratoria primaria por COVID-19, C-PARDS. Además, se realizó un análisis de curva operador receptor (ROC) para mortalidad y mecánica pulmonar. Resultados: Se incluyeron 30 pacientes. La edad fue de 7,5(4-11) años, 60% varones y la mortalidad del 23%. El 47% correspondió al grupo MIS-PARDS y el 53% al grupo C-PARDS. C-PARDS tuvo RT-PCR positiva en el 67% y MIS-PARDS ninguna (p<0,001). El grupo C-PARDS presentaba una hipoxemia más profunda (relación P/F <100, 86% frente a 38%, p<0,01) y una presión de conducción más alta [14(10-22) frente a 10(10-12) cmH2O], así como una menor distensibilidad del sistema respiratorio (CRS) [0,5 (0,3-0,6) frente a 0,7(0,6-0,8) ml/kg/cmH2O] en comparación con MIS-PARDS (todos p<0,05). El análisis ROC para la mortalidad mostró que la presión de conducción tenía el mejor rendimiento [AUC 0,91(IC95%0,81-1,00), con el mejor punto de corte de 15 cmH2O (100% de sensibilidad y 87% de especificidad). La mortalidad en los C-PARDS fue del 38% y del 7% en los MIS-PARDS (p=0,09). Los días sin VM fueron 12(0-23) en la C-PARDS y 23(21-25) en la MIS-PARDS (p=0,02). Conclusiones: Los pacientes con C-PARDS, presentan características de mecánica pulmonar similares al SDRAP clásico de moderado a grave. Esto no se observó en los pacientes con MIS-C. Como se ha visto en otros estudios, una presión de conducción ≥ 15 cmH2O fue el mejor discriminador de mortalidad. Estos hallazgos pueden ayudar a guiar las estrategias de manejo ventilatorio para estas dos presentaciones diferentes.
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    Pediatric ARDS phenotypes in critical COVID-19: implications for therapies and outcomes
    (medRxiv (Distribuidor de documentos electrónicos inéditos sobre ciencias de la salud), 2022-06) Díaz, Franco; Domínguez-Rojas, Jesús; Luna-Delgado, Yesica; Caqui-Vilca, Patrick; Martel-Ramírez, Carlos; Quispe-Chipana, Miguel; Cruz-Arpi, Mario; Atamari-Anahui, Noé; Muñoz Ramírez, Cleotilde Mireya; Quispe Flores, Gaudi; Tello-Pezo, Mariela; Cruces, Pablo; Vásquez-Hoyos, Pablo
    Purpose to describe lung mechanics in Pediatric Acute Respiratory Disease Syndrome (PARDS) associated with COVID-19. We hypothesize two phenotypes according to respiratory system mechanics and clinical diagnosis. Methods a concurrent multicenter observational study was performed, analyzing clinical variables and pulmonary mechanics of PARDS associated with COVID-19 in 4 Pediatric intensive care units (PICUs) of Perú. Subgroup analysis included PARDS associated with multisystem inflammatory syndrome in children (MIS-C), MIS-PARDS, and PARDS with COVID-19 primary respiratory infection, C-PARDS. In addition, receiver operator curve analysis (ROC) for mortality was performed. Results 30 patients were included. Age was 7.5(4-11) years, 60% male, and mortality 23%. 47% corresponded to MIS-PARDS and 53% to C-PARDS phenotypes. C-PARDS had positive RT-PCR in 67% and MIS-PARDS none (p<0.001). C-PARDS group had more profound hypoxemia (P/Fratio<100, 86%vs38%,p<0.01) and higher driving-pressure (DP) [14(10-22)vs10(10-12)cmH2O], and lower compliance of the respiratory system (CRS)[0.5(0.3-0.6)vs 0.7(0.6-0.8)ml/kg/cmH2O] compared to MIS-PARDS (all p<0.05). ROC-analysis for mortality showed that DP had the best performance [AUC 0.91(95%CI0.81-1.00), with the best cut-point of 15 cmH2O (100% sensitivity and 87% of specificity). Mortality in C-PARDS was 38% and 7% in MIS-PARDS(p=0.09). MV free-days were 12(0-23) in C-PARDS and 23(21-25) in MIS-PARDS(p=0.02) Conclusion critical pediatric COVID-19 is heterogeneous in children. COVID-19 PARDS had two phenotypes with distinctive pulmonary mechanics features. Characteristics of C-PARDS are like a classic primary PARDS, while a decoupling between compliance and hypoxemia was more frequent in MIS-PARDS. In addition, C-PARDS had fewer MV free-days. DP ≥ 15 cmH2O had the best performance of the quasi-static calculations to discriminate for mortality. Standardized pulmonary mechanics measurements in PARDS might reveal essential information to tailor the ventilatory strategy in pediatric critical COVID-19.
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    XIV Congreso Panamericano e Ibérico de Medicina Crítica y Terapia Intensiva. XVII Congreso Internacional de Medicina Intensiva. I Congreso Panamericano e Ibérico de Medicina Crítica Pediátrica
    (Elsevier, 2022) Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias; Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva
    01.- Influencia respiratoria por COVID-19: ¿Cuándo decidimos parar? / Morales Vargas G. y otros.. 02.- La gravedad del síndrome de dificultad respiratoria aguda interfiere con el valor clínico de la potencia mecánica / Pistillo N. y otros.. 03.- La presencia de injuria relacionada a la ventilación mecánica (VILI) vortex estuvo asociada con alta mortalidad por hipoxemia refractaria / Pistillo N. y otros.. 04.- Efecto de la edad y la comorbilidad en la supervivencia de los pacientes ventilados mecánicamente por SARS-COV2 durante el primer trimestre de la pandemia en Cataluña, España / Yebenes JC, Vela y otros.. 05.- Diferencias morfológicas entre lesión pulmonar autoinfligida por el paciente y lesión pulmonar inducida por ventilador / Díaz Franco y otros.. 06.- Relevancia Clínica del vasoespasmo cerebral prolongado en hemorragia subaracnoidea / Amundarain ED, y otros.. 07.- Eficacia del protocolo de neumonía cero en la incidencia de neumonía intrahospitalaria Cajamarca-Perú / Torrel Villanueva B A. 08.- Tendencia de la mortalidad en sepsis según los diferentes fracasos de órganos durante 15 años / Lorencio Cárdenas y otros.. 09.- Análisis de Embarazo e infección por COVID-19 en Servicio de UPC de Clínica Indisa durante la segunda ola de Pandemia año 2021 / Maurena E. y otros.. 10.- Morbilidad materna extrema en cuidados intensivos en un hospital de segundo nivel 2018- 2022 / Hidalgo M, Saraguro. 11.- Estudio descriptivo de la rotura hepática en el Instituto nacional materno perinatal 2005 a 2022 / Meza Salcedo. 12.- Encuesta de percepción de los intensivistas Colombianos sobre el cuidado intensivo obstétrico / Olaya Garay S. y otros.. 13.- Evaluación de la hemodinamia cerebral en pacientes bajo asistencia circulatoria mecánica / Gutiérrez Gutiérrez J. y otros. 14.- Oxigenación por membrana extracorpórea veno-venosa en insuficiencia respiratoria por neumonía grave SARS-CoV-2: experiencia local Unidad de cuidados intensivos Hospital Guillermo Grant Benavente / Fernández Andrade P. y otros.. 15.- Analgesia multimodal post operatoria con la aplicación de bloqueo del plano erector de la espina en pacientes de trasplante renal / Delgado Márquez J. y otros.. 16.- Caracterización clínica y microbiológica de pacientes con neutropenia febril en las Unidades de cuidados críticos pediátricos de tres hospitales de alta complejidad en la ciudad de Medellín, Colombia / Fernández Laverde M., y otros.. 17.- Trauma craneoencefálico grave en pediatría, estudio en una cohorte en Medellín, Colombia, periodo 2015 -2020 / Fernández Laverde M., y otros.. 18.- Epidemiologia del gran quemado experiencia de 10 años de una unidad especializada junio2013 / Marin R. 19.- Desarrollo e implementación de un protocolo de cirugía cardíaca fast-track en pacientes de alta complejidad, una iniciativa para favorecer la recuperación intensificada de los pacientes y mejorar la calidad asistencial / Gutierrez Gutierrez J., y otros.. 20.- Experiencia del personal clínico y no clínico en cuidados intensivos con la simulación inSitu / Ferre Contreras A A, y otros..
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    Prevalence and clinical consideration of anatomical variants of the splenic artery: a systematic review and meta-analysis
    (MDPI AG, 2023-03-09) Valenzuela-Fuenzalida, Juan José; Martínez-Hernández, Daniela; Pérez-Jiménez, Daniela; Nova Baeza, Pablo; Becerra-Farfan, Álvaro; Orellana-Donoso, Mathias; Bruna Mejias, Alejandro; Rodriguez Luengo, Macarena; Iwanaga, Joe
    Background: The spleen is the largest secondary immune organ in the body. Knowledge regarding the normal splenic vascular anatomy and its anatomical variants is crucial in the medical practice of surgeons and radiologists and is useful for diagnostic evaluations and the guidance of various surgical procedures. Hence, in this research, we aim to characterize the behavior of the lineal or splenic artery in humans from an anatomoclinical point of view. Methods: A systematic search was carried out in electronic databases to compile the available literature on the research subject. Searches were undertaken in the following databases: Medline, Scielo, Wos, Cinahl, Scopus, and Google Scholar. The search terms were “Splenic artery”, “Splenic vascularization”, “Anatomical variations’’, “Splenic organ”, and “Clinical anatomy”. Results: From the 35 studies included in this review, clinical correlations of anatomical variations in the splenic artery with surgical procedures in the abdominal region were reported in 8 studies. These correlations are mainly associated with surgical procedures for the pancreas, liver, stomach, and bile ducts through imaging of the spleen. To verify our conclusions, the risk of bias of the anatomical studies was measured using the AQUA checklist. Conclusions: Recognition of the usual anatomy and anatomical variants of the splenic artery is crucial for both morphology professionals and clinicians addressing the abdominal region and its vascular components. In this review, we determined that the splenic artery could present a variation in its origin or entry into the splenic hilum, which could mean that in any abdominal intervention there may be complications if the splenic artery variation is overlooked. More anatomic clinical studies considering this variation in both diagnostic and surgical processes are suggested for further investigations.