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Non-invasive respiratory support delivered through a face mask has become a cornerstone treatment for adults and children with acute or chronic respiratory failure. However, an imperfect mask fit using commercially available interfaces is frequently encountered, which may result in patient discomfort and treatment inefficiency or failure. To overcome this challenge, over the last decade increasing attention has been given to the development of personalized face masks, which are custom made to address the specific facial dimensions of an individual patient. With this scoping review we aim to provide a comprehensive overview of the current advances and gaps in knowledge regarding the personalization of ventilation masks. We performed a systematic search of the literature, and identified and summarized a total of 23 studies. Most studies included were involved in the development of nasal masks. Studies targeting adult respiratory care mainly focused on chronic (home) ventilation and included some clinical testing in a relevant subject population. In contrast, pediatric studies focused mostly on respiratory support in the acute setting, while testing was limited to bench or case studies only. Most studies were positive regarding the performance (i.e. comfort, level of air leak and mask pressure applied to the skin) of personalized masks in bench testing or in human, healthy or patient, subjects. Advances in the field of 3D scanning and soft material printing were identified, but important gaps in knowledge remain. In particular, more insight into cushion materials, headgear design, clinical feasibility and cost-effectiveness is needed, before definite recommendations can be made regarding implementation of large scale clinical programs that personalize non-invasive respiratory support masks for adults and children.
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BACKGROUND: Lung volume optimization maneuvers (LVOM) are necessary to make physiologic use of high-frequency oscillatory ventilation (HFOV), but lung behavior during such maneuvers has not been studied to determine lung volume changes after initiation of HFOV, to quantify recruitment versus derecruitment during the LVOM and to calculate the time to stabilization after a pressure change. METHODS: We performed a secondary analysis of prospectively collected data in subjects < 18 years on HFOV. Uncalibrated respiratory inductance plethysmography (RIP) tracings were used to quantify lung recruitment and derecruitment during the LVOM inflation and deflation. The time constant was calculated according to the Niemann model. RESULTS: RIP data of 51 subjects (median age 3.5 [1.7-13.3] months) with moderate-to-severe pediatric acute respiratory distress syndrome (PARDS) in 85.4% were analyzed. Lung recruitment and derecruitment occurred during the LVOM inflation phase upon start of HFOV and between and within pressure changes. At 90% of maximum inflation pressure, lung derecruitment already started during the deflation phase. Time to stable lung volume (time constant) could only be calculated in 26.2% of all pressure changes during the inflation and in 21.4% during the deflation phase, independent of continuous distending pressure (CDP). Inability to calculate the time constant was due to lack of stabilization of the RIP signal or no change in any direction. CONCLUSIONS: Significant heterogeneity in lung behavior during a staircase incremental-decremental LVOM occurred, underscoring the need for higher initial inflation pressures when transitioning from conventional mechanical ventilation (CMV) and a longer time between pressure changes to allow for equilibration.
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BACKGROUND: Obtaining a properly fitting non-invasive ventilation (NIV) mask to treat acute respiratory failure is a major challenge, especially in young children and patients with craniofacial abnormalities. Personalization of NIV masks holds promise to improve pediatric NIV efficiency. As current customization methods are relatively time consuming, this study aimed to test the air leak and surface pressure performance of personalized oronasal face masks using 3D printed soft materials. Personalized masks of three different biocompatible materials (silicone and photopolymer resin) were developed and tested on three head models of young children with abnormal facial features during preclinical bench simulation of pediatric NIV. Air leak percentages and facial surface pressures were measured and compared for each mask. RESULTS: Personalized NIV masks could be successfully produced in under 12 h in a semi-automated 3D production process. During NIV simulation, overall air leak performance and applied surface pressures were acceptable, with leak percentages under 30% and average surface pressure values mostly remaining under normal capillary pressure. There was a small advantage of the masks produced with soft photopolymer resin material. CONCLUSION: This first, proof-of-concept bench study simulating NIV in children with abnormal facial features, showed that it is possible to obtain biocompatible, personalized oronasal masks with acceptable air leak and facial surface pressure performance using a relatively short, and semi-automated production process. Further research into the clinical value and possibilities for application of personalized NIV masks in critically ill children is needed.
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CONTEXT: The negative effects of socioeconomic, environmental and ethnic inequalities on childhood respiratory diseases are known in the development of persistent asthma and can result in adverse outcomes. However, little is known about the effects of these disparities on pediatric intensive care unit (PICU) outcomes in respiratory diseases. OBJECTIVE: The purpose of this systematic review is to evaluate the literature on disparities in socioeconomic, environmental and ethnic determinants and PICU outcomes. We hypothesize that these disparities negatively influence the outcomes of children's respiratory diseases at the PICU. METHODS: A literature search (in PubMed, Embase.com and Web of Science Core Collection) was performed up to September 30, 2022. Two authors extracted the data and independently evaluated the risk of bias with appropriate assessment methods. Articles were included if the patients were below 18 years of age (excluding neonatal intensive care unit admissions), they concerned respiratory diseases and incorporated socioeconomic, ethnic or environmental disparities. RESULTS: Eight thousand seven hundred fourty-six references were reviewed, and 15 articles were included; seven articles on the effect of socioeconomic status, five articles on ethnicity, one on the effect of sex and lastly two on environmental factors. All articles but one showed an unfavorable outcome at the PICU. CONCLUSION: Disparities in socioeconomic (such as a low-income household, public health insurance), ethnic and environmental factors (such as exposure to tobacco smoke and diet) have been assessed as risk factors for the severity of children's respiratory diseases and can negatively influence the outcomes of these children admitted and treated at the PICU.
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Complex acoustic systems typically present three-dimensional distributions of noise sources. Conventional acoustic imaging methods with planar microphone arrays are unsuitable for three-dimensional acoustic imaging, given the computational demands and the incapability to explicitly account for the presence of multiple sources. This paper proposes the use of global optimization methods to solve these shortcomings. An experiment with three incoherent speakers proved that this method can accurately determine the three-dimensional location and the respective sound level of each individual source. In addition, super-resolution is achieved beyond half the Rayleigh resolution limit.
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Acústica , Modelos Teóricos , RuidoRESUMEN
Koala retrovirus (KoRV) is unique amongst endogenous (inherited) retroviruses in that its incorporation to the host genome is still active, providing an opportunity to study what drives this fundamental process in vertebrate genome evolution. Animals in the southern part of the natural range of koalas were previously thought to be either virus-free or to have only exogenous variants of KoRV with low rates of KoRV-induced disease. In contrast, animals in the northern part of their range universally have both endogenous and exogenous KoRV with very high rates of KoRV-induced disease such as lymphoma. In this study we use a combination of sequencing technologies, Illumina RNA sequencing of 'southern' (south Australian) and 'northern' (SE QLD) koalas and CRISPR enrichment and nanopore sequencing of DNA of 'southern' (South Australian and Victorian animals) to retrieve full-length loci and intregration sites of KoRV variants. We demonstrate that koalas that tested negative to the KoRV pol gene qPCR, used to detect replication-competent KoRV, are not in fact KoRV-free but harbour defective, presumably endogenous, 'RecKoRV' variants that are not fixed between animals. This indicates that these populations have historically been exposed to KoRV and raises questions as to whether these variants have arisen by chance or whether they provide a protective effect from the infectious forms of KoRV. This latter explanation would offer the intriguing prospect of being able to monitor and selectively breed for disease resistance to protect the wild koala population from KoRV-induced disease.
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Gammaretrovirus , Phascolarctidae , Infecciones por Retroviridae , Animales , Australia/epidemiología , Gammaretrovirus/genética , Retroviridae/genética , Infecciones por Retroviridae/veterinariaRESUMEN
BACKGROUND: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes. METHODS: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days). RESULTS: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P<0.001 and 236 versus 270 minutes; P<0.001, respectively). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 66%; P<0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07-1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98-1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99-1.30]). Outcomes were consistent in the analysis per chronological quartile. CONCLUSIONS: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Procedimientos Endovasculares/métodos , Humanos , Estudios Longitudinales , Sistema de Registros , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Allowing the ventilated adult patient to breathe spontaneously may improve tidal volume (VT) distribution toward the dependent lung regions, reduce shunt fraction, and decrease dead space. It has not been studied if these effects under various levels of ventilatory support also occur in children. We sought to explore the effect of level of ventilatory support on VT distribution and end-expiratory lung volume (EELV) in spontaneously breathing ventilated children in the recovery phase of their acute respiratory failure. METHODS: This is a secondary analysis of data from a prospective clinical trial comparing 2 different ventilator modes during weaning in mechanically ventilated children < 5 y: CPAP + pressure support ventilation (PSV) and pressure control (PC)/intermittent mandatory ventilation (IMV) + PSV with the mandatory breath rate set at 25% of baseline. Using electrical impedance tomography (EIT), we assessed VT distribution by calculating the center of ventilation. Polynomial functions of the second degree were plotted to evaluate regional lung filling characteristics. Changes in end-expiratory impedance were calculated to assess changes in EELV. Baseline measurements were compared with measurements during CPAP/PSV, PC/IMV + PSV, and during a downward titration of the level of pressure support. RESULTS: Thirty-five subjects with a median age 4.5 (2.1-12.9) months and a median ventilation time of 4.9 (3.3-6.9) d were studied. The overall median coefficient of variation was 50.1% and not different between CPAP/PSV or PC/synchronized IMV + PSV. Regional filling characteristics of the lung identified a homogeneous VT distribution under all study conditions. Downtapering of the level of PSV resulted in a significant shift of the coefficient of variation toward the dependent lung regions. CONCLUSIONS: Our data showed that allowing ventilated children in the recovery phase of respiratory failure to breathe spontaneously in a continuous spontaneous ventilation mode did not negatively affect VT distribution or EELV.
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Respiración con Presión Positiva , Respiración Artificial , Preescolar , Humanos , Lactante , Pulmón , Estudios Prospectivos , Respiración Artificial/métodos , Volumen de Ventilación PulmonarRESUMEN
OBJECTIVES: Driving pressure (ratio of tidal volume over respiratory system compliance) is associated with mortality in acute respiratory distress syndrome. We sought to evaluate if such association could be identified in critically ill children. DESIGN: We studied the association between driving pressure on day 1 of mechanical ventilation and ventilator-free days at day 28 through secondary analyses of prospectively collected physiology data. SETTING: Medical-surgical university hospital PICU. PATIENTS: Children younger than 18 years (stratified by Pediatric Mechanical Ventilation Consensus Conference clinical phenotype definitions) without evidence of spontaneous respiration. INTERVENTIONS: Inspiratory hold maneuvers. MEASUREMENTS AND MAIN RESULTS: Data of 222 patients with median age 11 months (2-51 mo) were analyzed. Sixty-five patients (29.3%) met Pediatric Mechanical Ventilation Consensus Conference criteria for restrictive and 78 patients (35.1%) for mixed lung disease, and 10.4% of all patients had acute respiratory distress syndrome. Driving pressure calculated by the ratio of tidal volume over respiratory system compliance for the whole cohort was 16 cm H2O (12-21 cm H2O) and correlated with the static airway pressure gradient (plateau pressure minus positive end-expiratory pressure) (Spearman correlation coefficient = 0.797; p < 0.001). Bland-Altman analysis showed that the dynamic pressure gradient (peak inspiratory pressure minus positive end-expiratory pressure) overestimated driving pressure (levels of agreement -2.295 to 7.268). Rematching the cohort through a double stratification procedure (obtaining subgroups of patients with matched mean levels for one variable but different mean levels for another ranking variable) showed a reduction in ventilator-free days at day 28 with increasing driving pressure in patients ventilated for a direct pulmonary indication. Competing risk regression analysis showed that increasing driving pressure remained independently associated with increased time to extubation (p < 0.001) after adjusting for Pediatric Risk of Mortality III 24-hour score, presence of direct pulmonary indication jury, and oxygenation index. CONCLUSIONS: Higher driving pressure was independently associated with increased time to extubation in mechanically ventilated children. Dynamic assessments of driving pressure should be cautiously interpreted.
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Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Niño , Humanos , Respiración con Presión Positiva/métodos , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/terapia , Insuficiencia Respiratoria/terapia , Volumen de Ventilación PulmonarRESUMEN
Many studies show the sensitivity of our environment to manmade changes, especially the anthropogenic impact on atmospheric and hydrological processes. The effect on Solid Earth processes such as subsidence is less straightforward. Subsidence is usually slow and relates to the interplay of complex hydro-mechanical processes, thus making relations to atmospheric changes difficult to observe. In the Dead Sea (DS) region, however, climatic forcing is strong and over-use of fresh water is massive. An observation period of 3 years was thus sufficient to link the high evaporation (97 cm/year) and the subsequent drop of the Dead Sea lake level (- 110 cm/year), with high subsidence rates of the Earth's surface (- 15 cm/year). Applying innovative Global Navigation Satellite System (GNSS) techniques, we are able to resolve this subsidence of the "Solid Earth" even on a monthly basis and show that it behaves synchronous to atmospheric and hydrological changes with a time lag of two months. We show that the amplitude and fluctuation period of ground deformation is related to poro-elastic hydro-mechanical soil response to lake level changes. This provides, to our knowledge, a first direct link between shore subsidence, lake-level drop and evaporation.
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OBJECTIVES: To explore the level and time course of patient-ventilator asynchrony in mechanically ventilated children and the effects on duration of mechanical ventilation, PICU stay, and Comfort Behavior Score as indicator for patient comfort. DESIGN: Secondary analysis of physiology data from mechanically ventilated children. SETTING: Mixed medical-surgical tertiary PICU in a university hospital. PATIENTS: Mechanically ventilated children 0-18 years old were eligible for inclusion. Excluded were patients who were unable to initiate and maintain spontaneous breathing from any cause. MEASUREMENTS AND MAIN RESULTS: Twenty-nine patients were studied with a total duration of 109 days. Twenty-two study days (20%) were excluded because patients were on neuromuscular blockade or high-frequency oscillatory ventilation, yielding 87 days (80%) for analysis. Patient-ventilator asynchrony was detected through analysis of daily recorded ventilator airway pressure, flow, and volume versus time scalars. Approximately one of every three breaths was asynchronous. The percentage of asynchronous breaths significantly increased over time, with the highest prevalence on the day of extubation. There was no correlation with the Comfort Behavior score. The percentage of asynchronous breaths during the first 24 hours was inversely correlated with the duration of mechanical ventilation. Patients with severe patient-ventilator asynchrony (asynchrony index > 10% or > 75th percentile of the calculated asynchrony index) did not have a prolonged duration of ventilation. CONCLUSIONS: The level of patient-ventilator asynchrony increased over time was not related to patient discomfort and inversely related to the duration of mechanical ventilation.
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Respiración Artificial , Ventiladores Mecánicos , Adolescente , Extubación Traqueal , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Ventilación con Presión Positiva Intermitente , Estudios ProspectivosRESUMEN
Despite representing 30% to 40% of newly diagnosed cases of adult non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL) rarely presents (1) in the leukemic phase (2) with dysregulation of the TP53 tumor suppressor gene and (3) an elevated serum lactic acid level. In this case report and literature review, we highlight this unfortunate triad of poor prognostic features associated with an aggressive and fatal clinical course in a 53-year-old man with recrudescent DLBCL. A leukemic presentation of de novo or relapsed DLBCL is rare and may be related to differential expressions of adhesion molecules on cell surfaces. In addition, TP53 gene mutations are present in approximately 20% to 25% of DLBCL cases and foreshadow worse clinical outcomes. Finally, an elevated serum lactic acid level in DLBCL that is not clearly associated with sepsis syndrome is a poor prognostic factor for survival and manifests as type B lactic acidosis through the Warburg effect.
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BACKGROUND: Titration of the continuous distending pressure during a staircase incremental-decremental pressure lung volume optimization maneuver in children on high-frequency oscillatory ventilation is traditionally driven by oxygenation and hemodynamic responses, although validity of these metrics has not been confirmed. METHODS: Respiratory inductance plethysmography values were used construct pressure-volume loops during the lung volume optimization maneuver. The maneuver outcome was evaluated by three independent investigators and labeled positive if there was an increase in respiratory inductance plethysmography values at the end of the incremental phase. Metrics for oxygenation (SpO2, FiO2), proximal pressure amplitude, tidal volume and transcutaneous measured pCO2 (ptcCO2) obtained during the incremental phase were compared between outcome maneuvers labeled positive and negative to calculate sensitivity, specificity, and the area under the receiver operating characteristic curve. Ventilation efficacy was assessed during and after the maneuver by measuring arterial pH and PaCO2. Hemodynamic responses during and after the maneuver were quantified by analyzing heart rate, mean arterial blood pressure and arterial lactate. RESULTS: 41/54 patients (75.9%) had a positive maneuver albeit that changes in respiratory inductance plethysmography values were very heterogeneous. During the incremental phase of the maneuver, metrics for oxygenation and tidal volume showed good sensitivity (> 80%) but poor sensitivity. The sensitivity of the SpO2/FiO2 ratio increased to 92.7% one hour after the maneuver. The proximal pressure amplitude showed poor sensitivity during the maneuver, whereas tidal volume showed good sensitivity but poor specificity. PaCO2 decreased and pH increased in patients with a positive and negative maneuver outcome. No new barotrauma or hemodynamic instability (increase in age-adjusted heart rate, decrease in age-adjusted mean arterial blood pressure or lactate > 2.0 mmol/L) occurred as a result of the maneuver. CONCLUSIONS: Absence of improvements in oxygenation during a lung volume optimization maneuver did not indicate that there were no increases in lung volume quantified using respiratory inductance plethysmography. Increases in SpO2/FiO2 one hour after the maneuver may suggest ongoing lung volume recruitment. Ventilation was not impaired and there was no new barotrauma or hemodynamic instability. The heterogeneous responses in lung volume changes underscore the need for monitoring tools during high-frequency oscillatory ventilation.
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BACKGROUND: Recurrent delivery of tidal mechanical energy (ME) inflicts ventilator-induced lung injury (VILI) when stress and strain exceed the limits of tissue tolerance. Mechanical power (MP) is the mathematical description of the ME delivered to the respiratory system over time. It is unknown how ME relates to underlying lung pathology and outcome in mechanically ventilated children. We therefore tested the hypothesis that ME per breath with tidal volume (Vt) normalized to bodyweight correlates with underlying lung pathology and to study the effect of resistance on the ME dissipated to the lung. METHODS: We analyzed routinely collected demographic, physiological, and laboratory data from deeply sedated and/or paralyzed children < 18 years with and without lung injury. Patients were stratified into respiratory system mechanic subgroups according to the Pediatric Mechanical Ventilation Consensus Conference (PEMVECC) definition. The association between MP, ME, lung pathology, and duration of mechanical ventilation as a primary outcome measure was analyzed adjusting for confounding variables and effect modifiers. The effect of endotracheal tube diameter (ETT) and airway resistance on energy dissipation to the lung was analyzed in a bench model with different lung compliance settings. RESULTS: Data of 312 patients with a median age of 7.8 (1.7-44.2) months was analyzed. Age (p < 0.001), RR p < 0.001), and Vt < 0.001) were independently associated with MPrs. ME but not MP correlated significantly (p < 0.001) better with lung pathology. Competing risk regression analysis adjusting for PRISM III 24 h score and PEMVECC stratification showed that ME on day 1 or day 2 of MV but not MP was independently associated with the duration of mechanical ventilation. About 33% of all energy generated by the ventilator was transferred to the lung and highly dependent on lung compliance and airway resistance but not on endotracheal tube size (ETT) during pressure control (PC) ventilation. CONCLUSIONS: ME better related to underlying lung pathology and patient outcome than MP. The delivery of generated energy to the lung was not dependent on ETT size during PC ventilation. Further studies are needed to identify injurious MErs thresholds in ventilated children.
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Fenómenos Mecánicos , Respiración Artificial/clasificación , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pediatría/métodos , Pediatría/tendencias , Respiración Artificial/instrumentación , Respiración Artificial/estadística & datos numéricos , Fenómenos Fisiológicos Respiratorios , Lesión Pulmonar Inducida por Ventilación Mecánica/prevención & controlRESUMEN
OBJECTIVES: We sought to investigate factors that affect the difference between the peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions (resistive pressure) during pressure controlled ventilation across a range of endotracheal tube sizes, respiratory mechanics, and ventilator settings. DESIGN: In vitro study. SETTING: Research laboratory. PATIENTS: None. INTERVENTIONS: An in vitro bench model of the intubated respiratory system during pressure controlled ventilation was used to obtain the difference between peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions across a range of endotracheal tubes sizes (3.0-8.0 mm). Measurements were taken at combinations of pressure above positive end-expiratory pressure (10, 15, and 20 cm H2O), airway resistance (no, low, high), respiratory system compliance (ranging from normal to extremely severe), and inspiratory time at constant positive end-expiratory pressure (5 cm H2O). Multiple regression analysis was used to construct models predicting resistive pressure stratified by endotracheal tube size. MEASUREMENTS AND MAIN RESULTS: On univariate regression analysis, respiratory system compliance (ß -1.5; 95% CI, -1.7 to -1.4; p < 0.001), respiratory system resistance (ß 1.7; 95% CI, 1.5-2.0; p < 0.001), pressure above positive end-expiratory pressure (ß 1.7; 95% CI, 1.4-2.0; p < 0.001), and inspiratory time (ß -0.7; 95% CI, -1.0 to -0.4; p < 0.001) were associated with resistive pressure. Multiple linear regression analysis showed the independent association between increasing respiratory system compliance, increasing airway resistance, increasing pressure above positive end-expiratory pressure, and decreasing inspiratory time and resistive pressure across all endotracheal tube sizes. Inspiratory time was the strongest variable associated with a proportional increase in resistive pressure. The contribution of airway resistance became more prominent with increasing endotracheal tube size. CONCLUSIONS: Peak inspiratory pressures measured during pressure controlled ventilation overestimated plateau pressure irrespective of endotracheal tube size, especially with decreased inspiratory time or increased airway resistance.
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Intubación Intratraqueal/instrumentación , Respiración con Presión Positiva/estadística & datos numéricos , Respiración Artificial/métodos , Mecánica Respiratoria , Resistencia de las Vías Respiratorias , Diseño de Equipo/estadística & datos numéricos , Humanos , Modelos Lineales , Presiones Respiratorias Máximas/estadística & datos numéricos , Modelos Teóricos , Respiración Artificial/estadística & datos numéricos , Sistema Respiratorio , Ventiladores Mecánicos/estadística & datos numéricosRESUMEN
BACKGROUND: The advent of the immunomodulatory imide drugs (IMiDs) lenalidomide and thalidomide for the treatment of patients with plasma cell myeloma (PCM), has contributed to more than a doubling of the overall survival of these individuals. As a result, PCM patients join survivors of other malignancies such as breast and prostate cancer with a relatively new clinical problem - second primary malignancies (SPMs) - many of which are a result of the treatment of the initial cancer. PCM patients have a statistically significant increased risk for acute myeloid leukemia (AML) and Kaposi sarcoma. IMiD treatment has also been associated with an increased risk of myelodysplastic syndrome (MDS), AML, and squamous cell carcinoma of the skin. However, within these overlapping groups, acute lymphoblastic leukemia (ALL) is much less common. CASE PRESENTATION: Herein, we describe an elderly man with PCM and a 14-year cumulative history of IMiD therapy who developed persistent pancytopenia and was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). He joins a group of 17 other patients documented in the literature who have followed a similar sequence of events starting with worsening cytopenias while on IMiD maintenance for PCM. These PCM patients were diagnosed with B-ALL after a median time of 36 months after starting IMiD therapy and at a median age of 61.5 years old. CONCLUSIONS: PCM patients with subsequent B-ALL have a poorer prognosis than their de novo B-ALL counterparts, however, the very low prevalence rate of subsequent B-ALL and high efficacy of IMiD maintenance therapy in PCM should not alter physicians' current practice. Instead, there should be a low threshold for bone marrow biopsy for unexplained cytopenias.
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Lenalidomida/efectos adversos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/etiología , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiología , Talidomida/efectos adversos , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Médula Ósea , Humanos , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Lenalidomida/uso terapéutico , Masculino , Talidomida/uso terapéuticoRESUMEN
Engine noise shielding is an important measure towards low-noise aircraft configurations. Such designs are supported by prediction tools that indicate high values for shielding of engine noise. Most prediction models approximate the complex nature of engine noise to simple noise sources such as monopoles or dipoles. This work compares predictions of noise shielding with experiments using different noise sources and shielding body geometries. The experiments considered in this work concern a monopole source shielded by a flat plate and a NACA 64-008 A wing, and a propeller shielded by the same wing. Comparisons between models and measurements are made by analysis of noise levels at individual microphones and using conventional beamforming. Results show that for the monopole cases the model predictions are in agreement with the experimental data, with an average deviation of 2-3 dB. The curvature of the leading edge of the wing influences the noise shielding results. The measured values of noise shielding of propeller noise are lower than those measured for the omni-directional source. Different types of source directivity are used to approximate the propeller in the predictions: monopole, dipole and a multi-source. The dipole approximation shows the best agreement with the experiments for the case of the propeller.
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BACKGROUND: High-frequency oscillatory ventilation (HFOV) is a common but unproven management strategy in paediatric critical care. Oscillator settings have been traditionally guided by patient age and/or weight rather than by lung mechanics, thereby potentially negating any beneficial effects. We have adopted an open-lung HFOV strategy based on a corner frequency approach using an initial incremental-decremental mean airway pressure titration manoeuvre, a high frequency (8-15 Hz), and high power to initially target a proximal pressure amplitude (∆Pproximal) of 70-90 cm H2O, irrespective of age or weight. METHODS: We reviewed prospectively collected data on patients < 18 years of age who were managed with HFOV for acute respiratory failure. We measured metrics for oxygenation, ventilation, and haemodynamics as well as the use of sedative-analgesic medications and neuromuscular blocking agents. RESULTS: Data from 115 non-cardiac patients were analysed, of whom 53 had moderate-to-severe paediatric acute respiratory distress syndrome (PARDS). Sixteen patients (13.9%) died. Frequencies≥ 8 Hz and high ∆Pproximal were achieved in all patients irrespective of age or PARDS severity. Patients with severe PARDS showed the greatest improvement in oxygenation. pH and PaCO2 normalized in all patients. Haemodynamic parameters, cumulative amount of fluid challenges, and daily fluid balance did not deteriorate after transitioning to HFOV in any age or PARDS severity group. We observed a transient increase neuromuscular blocking agent use after switching to HFOV, but there was no increase in the daily cumulative amount of continuous midazolam or morphine in any age or PARDS severity group. No patients experienced clinically apparent barotrauma. CONCLUSIONS: This is the first study reporting the feasibility of an alternative, individualized, physiology-based open-lung HFOV strategy targeting high F and high ∆Pproximal. No adverse effects were observed with this strategy. Our findings warrant further systematic evaluation.