Examinando por Autor "Diaz, Franco"

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    Comparison of Interleukin-6 Plasma Concentration in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Pediatric Sepsis
    (Frontiers Media S.A., 2021-11) Diaz, Franco; Bustos B., Raúl; Yagnam, Felipe; Karsies, Todd J.; Vásquez-Hoyos, Pablo; Jaramillo-Bustamante, Juan-Camilo; Gonzalez-Dambrauskas, Sebastián; Drago, Michelle; Cruces, Pablo
    Importance: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection is thought to be driven by a post-viral dysregulated immune response, where interleukin 6 (IL-6) might have a central role. In this setting, IL-6 inhibitors are prescribed as immunomodulation in cases refractory to standard therapy. Objective: To compare plasma IL-6 concentration between critically ill children with MIS-C and sepsis. Design: A retrospective cohort study from previously collected data. Setting: Individual patient data were gathered from three different international datasets. Participants: Critically ill children between 1 month-old and 18 years old, with an IL-6 level measured within 48 h of admission to intensive care. Septic patients were diagnosed according to Surviving Sepsis Campaign definition and MIS-C cases by CDC criteria. We excluded children with immunodeficiency or immunosuppressive therapy. Exposure: None. Main Outcome(s) and Measure(s): The primary outcome was IL-6 plasma concentration in MIS-C and sepsis group at admission to the intensive care unit. We described demographics, inflammatory biomarkers, and clinical outcomes for both groups. A subgroup analysis for shock in each group was done. Results: We analyzed 66 patients with MIS-C and 44 patients with sepsis. MIS-C cases were older [96 (48, 144) vs. 20 (5, 132) months old, p < 0.01], but no differences in sex (41 vs. 43% female, p = 0.8) compared to septic group. Mechanical ventilation use was 48.5 vs. 93% (p < 0.001), vasoactive drug use 79 vs. 66% (p = 0.13), and mortality 4.6 vs. 34.1% (p < 0.01) in MIS-C group compared to sepsis. IL-6 was 156 (36, 579) ng/dl in MIS-C and 1,432 (122, 6,886) ng/dl in sepsis (p < 0.01), while no significant differences were observed in procalcitonin (PCT) and c-reactive protein (CRP). 52/66 (78.8%) patients had shock in MIS-C group, and 29/44 (65.9%) had septic shock in sepsis group. Septic shock had a significantly higher plasma IL-6 concentration than the three other sub-groups. Differences in IL-6, CRP, and PCT were not statistically different between MIS-C with and without shock. Conclusions and Relevance: IL-6 plasma concentration was elevated in critically ill MIS-C patients but at levels much lower than those of sepsis. Furthermore, IL-6 levels don't discriminate between MIS-C cases with and without shock. These results lead us to question the role of IL-6 in the pathobiology of MIS-C, its diagnosis, clinical outcomes, and, more importantly, the off-label use of IL-6 inhibitors for these cases. Copyright © 2021 Diaz, Bustos B, Yagnam, Karsies, Vásquez-Hoyos, Jaramillo-Bustamante, Gonzalez-Dambrauskas, Drago and Cruces.
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    Mapping regional strain in anesthetised healthy subjects during spontaneous ventilation
    (BMJ Open Respiratory Research, 2019) Cruces, Pablo; Erranz, Benjamin; Lillo, Felipe; Sarabia-Vallejos, Mauricio A.; Iturrieta, Pablo; Morales, Felipe; Blaha, Katherine; Medina, Tania; Diaz, Franco; Hurtado, Daniel E.
    Introduction Breathing produces a phenomenon of cyclic deformation throughout life. Biomechanically, deformation of the lung is measured as strain. Regional strain recently started to be recognised as a tool in the study of lung pathophysiology, but regional lung strain has not been studied in healthy subjects breathing spontaneously without voluntary or pharmacological control of ventilation. Our aim is to generate three-dimensional (3D) regional strain and heterogeneity maps of healthy rat lungs and describe their changes over time. Methods Micro-CT and image-based biomechanical analysis by finite element approach were carried out in six anaesthetised rats under spontaneous breathing in two different states, at the beginning of the experiment and after 3 hours of observation. 3D regional strain maps were constructed and divided into 10 isovolumetric region-of-interest (ROI) in three directions (apex to base, dorsal to ventral and costal to mediastinal), allowing to regionally analyse the volumetric strain, the strain progression and the strain heterogeneity. To describe in depth these parameters, and systematise their report, we defined regional strain heterogeneity index [1+strain SD ROI(x)]/[1+strain mean ROI(x)] and regional strain progression index [ROI(x)-mean of final strain/ROI(x)-mean of initial strain]. Results We were able to generate 3D regional strain maps of the lung in subjects without respiratory support, showing significant differences among the three analysed axes. We observed a significantly lower regional volumetric strain in the apex sector compared with the base, with no significant anatomical systematic differences in the other directions. This heterogeneity could not be identified with physiological or standard CT methods. There was no progression of the analysed regional volumetric strain when the two time-points were compared. Discussion It is possible to map the regional volumetric strain in the lung for healthy subjects during spontaneous breathing. Regional strain heterogeneity and changes over time can be measured using a CT image-based numerical analysis applying a finite element approach. These results support that healthy lung might have significant regional strain and its spatial distribution is highly heterogeneous. This protocol for CT image acquisition and analysis could be a useful tool for helping to understand the mechanobiology of the lung in many diseases.
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    Mechanical power in pediatric acute respiratory distress syndrome: a PARDIE study
    (BioMed Central Ltd, 2022-12) Bhalla, Anoopindar K.; Klein, Margaret J.; Modesto I Alapont, Vicent; Emeriaud, Guillaume; Kneyber, Martin C. J.; Medina, Alberto; Cruces, Pablo; Diaz, Franco; Takeuchi, Muneyuki; Maddux, Aline B.; Mourani, Peter M.; Camilo, Cristina; White, Benjamin R.; Yehya, Nadir; Pappachan, John; Di Nardo, Matteo; Shein, Steven; Newth, Christopher; Khemani, Robinder; Poterala, Rossana; Fernandez, Analia; Vera, Antonio Ávila; Vidal, Nilda Agueda; Rosemary, Deheza; Turon, Gonzalo; Monjes, Cecilia; Serrate, Alejandro Siaba; Iolster, Thomas; Torres, Silvio; Castellani, Pablo; Giampieri, Martin; Pedraza, Claudia; Landry, Luis Martin; Althabe, Maria; Fortini, Yanina Vanesa; Erickson, Simon; Barr, Samantha; Shea, Sara; Butt, Warwick; Delzoppo, Carmel; Pintimalla, Alyssa; León, Alejandro Fabio Martínez; Rivera, Gustavo Alfredo Guzmán; Jouvet, Philippe; Dumitrascu, Mariana; French, Mary Ellen; Caro I, Daniel; Acuna, Carlos; Núnez, María José; Chen, Yang; Alarcón, Yurika Paola López; Izquierdo, Ledys María; Piñeres Olave, Byron Enrique; Hoyos, Pablo Vásquez; Bourgoin, Pierre; Baudin, Florent; Briassoulis, George; Ilia, Stavroula; Chiusolo, Fabrizio; Shime, Nobuaki
    Mechanical power is a composite variable for energy transmitted to the respiratory system over time that may better capture risk for ventilator-induced lung injury than individual ventilator management components. We sought to evaluate if mechanical ventilation management with a high mechanical power is associated with fewer ventilator-free days (VFD) in children with pediatric acute respiratory distress syndrome (PARDS). Methods: Retrospective analysis of a prospective observational international cohort study. Results: There were 306 children from 55 pediatric intensive care units included. High mechanical power was associated with younger age, higher oxygenation index, a comorbid condition of bronchopulmonary dysplasia, higher tidal volume, higher delta pressure (peak inspiratory pressure—positive end-expiratory pressure), and higher respiratory rate. Higher mechanical power was associated with fewer 28-day VFD after controlling for confounding variables (per 0.1 J·min−1·Kg−1 Subdistribution Hazard Ratio (SHR) 0.93 (0.87, 0.98), p = 0.013). Higher mechanical power was not associated with higher intensive care unit mortality in multivariable analysis in the entire cohort (per 0.1 J·min−1·Kg−1 OR 1.12 [0.94, 1.32], p = 0.20). But was associated with higher mortality when excluding children who died due to neurologic reasons (per 0.1 J·min−1·Kg−1 OR 1.22 [1.01, 1.46], p = 0.036). In subgroup analyses by age, the association between higher mechanical power and fewer 28-day VFD remained only in children < 2-years-old (per 0.1 J·min−1·Kg−1 SHR 0.89 (0.82, 0.96), p = 0.005). Younger children were managed with lower tidal volume, higher delta pressure, higher respiratory rate, lower positive end-expiratory pressure, and higher PCO2 than older children. No individual ventilator management component mediated the effect of mechanical power on 28-day VFD. Conclusions: Higher mechanical power is associated with fewer 28-day VFDs in children with PARDS. This association is strongest in children < 2-years-old in whom there are notable differences in mechanical ventilation management. While further validation is needed, these data highlight that ventilator management is associated with outcome in children with PARDS, and there may be subgroups of children with higher potential benefit from strategies to improve lung-protective ventilation. Take Home Message: Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome. This association is strongest in children <2-years-old in whom there are notable differences in mechanical ventilation management. © 2021, The Author(s).
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    Morphological Differences between Patient Self-inflicted and Ventilator-induced Lung Injury: An Experimental Study
    (2023-03) Cruces, Pablo; Erranz, Benjamín; Carlos, González,; Diaz, Franco
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    Progression of regional lung strain and heterogeneity in lung injury: assessing the evolution under spontaneous breathing and mechanical ventilation
    (Springer, 2020-12) Hurtado, Daniel E.; Erranz, Benjamín; Lillo, Felipe; Sarabia-Vallejos, Mauricio; Iturrieta, Pablo; Morales, Felipe; Blaha, Katherine; Medina, Tania; Diaz, Franco; Cruces, Pablo
    Background: Protective mechanical ventilation (MV) aims at limiting global lung deformation and has been associ‑ ated with better clinical outcomes in acute respiratory distress syndrome (ARDS) patients. In ARDS lungs without MV support, the mechanisms and evolution of lung tissue deformation remain understudied. In this work, we quantify the progression and heterogeneity of regional strain in injured lungs under spontaneous breathing and under MV. Methods: Lung injury was induced by lung lavage in murine subjects, followed by 3 h of spontaneous breathing (SB-group) or 3 h of low Vt mechanical ventilation (MV-group). Micro-CT images were acquired in all subjects at the beginning and at the end of the ventilation stage following induction of lung injury. Regional strain, strain progres‑ sion and strain heterogeneity were computed from image-based biomechanical analysis. Three-dimensional regional strain maps were constructed, from which a region-of-interest (ROI) analysis was performed for the regional strain, the strain progression, and the strain heterogeneity. Results: After 3 h of ventilation, regional strain levels were signifcantly higher in 43.7% of the ROIs in the SB-group. Signifcant increase in regional strain was found in 1.2% of the ROIs in the MV-group. Progression of regional strain was found in 100% of the ROIs in the SB-group, whereas the MV-group displayed strain progression in 1.2% of the ROIs. Progression in regional strain heterogeneity was found in 23.4% of the ROIs in the SB-group, while the MV-group resulted in 4.7% of the ROIs showing signifcant changes. Deformation progression is concurrent with an increase of non-aerated compartment in SB-group (from 13.3%±1.6% to 37.5%±3.1%), being higher in ventral regions of the lung. Conclusions: Spontaneous breathing in lung injury promotes regional strain and strain heterogeneity progression. In contrast, low Vt MV prevents regional strain and heterogeneity progression in injured lungs.