Impact of Prolonged Mechanical Ventilation in Very Low Birth Weight Infants: Results From a National Cohort Study

Choi, Young-Bin; Lee, Ju Young; Park, Jisun; Jun, Yong Hoon

doi:10.1016/j.jpeds.2017.10.042

Cited by 61 publications

(54 citation statements)

References 18 publications

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“…; Choi et al . ). We discovered that systemic LPS mediated ERK‐dependent increase in angiogenic sprouting and new vessel formation in association with increased DLL4.…”

Section: Discussionmentioning

confidence: 97%

Endothelial immune activation programmes cell‐fate decisions and angiogenesis by inducing angiogenesis regulator DLL4 through TLR4‐ERK‐FOXC2 signalling

Sheng

Menden

Korfhagen

et al. 2018

The Journal of Physiology

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Endothelial cells (ECs) mediate a specific and robust immune response to bacteria in sepsis through the activation of toll-like receptor (TLR) signalling. The mechanisms by which bacterial ligands released during sepsis programme EC specification and altered angiogenesis remain unclear. We postulated that the forkhead box protein C2 (FOXC2) transcriptional factor directs EC cell-fate decisions and angiogenesis during TLR signalling. In human lung ECs, lipopolysaccharide (LPS) induced ERK phosphorylation, FOXC2, and delta-like 4 (DLL4, the master regulator of sprouting angiogenesis expression) in a TLR4-dependent manner. LPS-mediated ERK phosphorylation resulted in FOXC2-ERK protein ligation, ERK-dependent FOXC2 serine and threonine phosphorylation, and subsequent activation of DLL4 gene expression. Chemical inhibition of ERK or ERK-2 dominant negative transfection disrupted LPS-mediated FOXC2 phosphorylation and transcriptional activation of FOXC2. FOXC2-siRNA or ERK-inhibition attenuated LPS-induced DLL4 expression and angiogenic sprouting in vitro. In vivo, intraperitoneal LPS induced ERK and FOXC2 phosphorylation, FOXC2 binding to DLL4 promoter, and FOXC2/DLL4 expression in the lung. ERK-inhibition suppressed LPS-induced FOXC2 phosphorylation, FOXC2-DLL4 promoter binding, and induction of FOXC2 and DLL4 in mouse lung ECs. LPS induced aberrant retinal angiogenesis and DLL4 expression in neonatal mice, which was attenuated with ERK inhibition. FOXC2 mice treated with LPS showed a mitigated increase in FOXC2 and DLL4 compared to FOXC2 mice. These data reveal a new mechanism (TLR4-ERK-FOXC2-DLL4) by which sepsis-induced EC TLR signalling programmes EC specification and altered angiogenesis.

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“…; Choi et al . ). We discovered that systemic LPS mediated ERK‐dependent increase in angiogenic sprouting and new vessel formation in association with increased DLL4.…”

Section: Discussionmentioning

confidence: 97%

Endothelial immune activation programmes cell‐fate decisions and angiogenesis by inducing angiogenesis regulator DLL4 through TLR4‐ERK‐FOXC2 signalling

Sheng

Menden

Korfhagen

et al. 2018

The Journal of Physiology

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“…[7][8][9][10] The aetiology of neonatal CLD, also known as bronchopulmonary dysplasia (BPD), is multifactorial and includes ventilator associated lung injury, inflammation and infection. [11][12][13][14][15][16] Infants who are mechanically ventilated for prolonged periods are at higher risk of developing CLD. 13 Bacterial colonisation has been linked to the development of CLD, due to the inflammatory response to colonisation.…”

Section: What This Paper Addsmentioning

confidence: 99%

Bacterial colonisation of the endotracheal tube in ventilated very preterm neonates: A retrospective cohort study

Antoine

Inglis

Way

et al. 2020

J Paediatrics Child Health

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Aim: To determine the rate, type and timing of bacterial endotracheal tube (ETT) colonisation in neonates born <32 weeks gestational age (GA); and if bacterial colonisation is associated with chronic lung disease (CLD), septicaemia, length-of-stay or mortality. Methods: All intubated newborns born <32 weeks GA were included. Endotracheal aspirates were routinely obtained three times-per-week. Cohort was divided into three colonisation groups: no growth, normal respiratory flora only, significant bacteria. Logistic regression was performed to identify if ETT bacterial colonisation was associated with CLD, septicaemia or mortality. A general linear model was fitted for lengthof-stay. Results: ETT aspirates were sent from 1054 infants: no growth n = 319, only normal respiratory flora n = 357, and significant bacteria n = 378. ETTs became colonised in 70%, most in the first week of life (82%). Most grew normal respiratory flora (642 infants). In those with significant bacteria, 40% grew Gram-negative species; Klebsiella in 34%. Staphylococcus aureus grew in 104 patients. Adjusted odds ratios for CLD (43% of cohort) compared with no growth were, for normal respiratory flora, 0.58 (95% confidence interval (CI) 0.34-0.99) and, for significant bacteria, 0.48 (95% CI 0.24-0.93). With no overall association between colonisation group and CLD in the adjusted model P = 0.07. The odds of septicaemia (10% of cohort) were 4.50 (95% CI 1.98-10.23, P < 0.001) times greater for significant bacteria compared with no growth. No significant associated was found with mortality or length-of-stay. Conclusions: Bacterial colonisation of ETTs is common. It is associated with more septicaemia. There was no significant association with CLD, longer admission or mortality.

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“…The study participants were infants with severe BPD who spent long periods of their initial life in hospital because of respiratory morbidity. Prolonged hospitalization is known to be a marker for poor outcome in the preterm population . As the primary outcomes of this trial were safety related and there was no control group, it is not possible for us to conclude on any long‐term impact of hAEC treatment on these clinical morbidities.…”

Section: Discussionmentioning

confidence: 96%

“…Prolonged hospitalization is known to be a marker for poor outcome in the preterm population. 20,21 As the primary outcomes of this trial were safety related and there was no control group, it is not possible for us to conclude on any long-term impact of hAEC treatment on these clinical morbidities. Such insights will only be afforded by future randomized controlled trials.…”

Section: Discussionmentioning

confidence: 98%

Two-year outcomes of infants enrolled in the first-in-human study of amnion cells for bronchopulmonary dysplasia

Malhotra

Lim

Mockler

et al. 2019

Stem Cells Translational Medicine

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We previously reported on the immediate safety and neonatal outcomes of six premature infants with severe bronchopulmonary dysplasia (BPD) who were administered human amnion epithelial cells (hAECs). One infant died in the neonatal period due to unrelated causes. In this study, we aimed to assess the long‐term safety and follow‐up outcomes of the five surviving infants until 2 years corrected age (CA). hAECs were administered intravenously at a dose of 1 × 106 cells per kilogram after 36 weeks postconceptional age in infants with established BPD. Study follow‐up consisted of assessment of any adverse events, growth, and respiratory, cardiac, and neurodevelopmental outcomes over four time points (6, 12, 18, and 24 months CA). Investigations included chest x‐rays, cranial and abdominal ultrasounds, and echocardiograms at regular intervals as well as a magnetic resonance imaging (MRI) brain at 2 years CA. All five infants were alive at 2 years CA. Median time to wean off oxygen was 24 (10‐36) months. Two infants had pulmonary hypertension, which resolved by 2 years of age. Four infants were rehospitalized briefly for viral or bacterial infections during the 2 years. MRI brain findings included normal (n = 1), and mild to moderate white matter loss (n = 2). Neurodisabilities diagnosed included hemiplegic cerebral palsy (n = 1), global developmental delay (n = 3), and severe hearing loss (n = 3). No evidence of tumor formation was noted on physical examinations or on any imaging. There were no long‐term adverse events observed that could be attributed to hAEC administration. We observed long‐term effects of extreme prematurity and severe BPD in the cohort.

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Impact of Prolonged Mechanical Ventilation in Very Low Birth Weight Infants: Results From a National Cohort Study

Cited by 61 publications

References 18 publications

Endothelial immune activation programmes cell‐fate decisions and angiogenesis by inducing angiogenesis regulator DLL4 through TLR4‐ERK‐FOXC2 signalling

Endothelial immune activation programmes cell‐fate decisions and angiogenesis by inducing angiogenesis regulator DLL4 through TLR4‐ERK‐FOXC2 signalling

Bacterial colonisation of the endotracheal tube in ventilated very preterm neonates: A retrospective cohort study

Two-year outcomes of infants enrolled in the first-in-human study of amnion cells for bronchopulmonary dysplasia

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