New Imaging Tools Allow Bronchopulmonary Dysplasia to Enter the Age of Precision Medicine.
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ABSTRACT:
SUBMITTER: Shepherd EG
PROVIDER: S-EPMC7528804 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
New Imaging Tools Allow Bronchopulmonary Dysplasia to Enter the Age of Precision Medicine.
Shepherd Edward G EG De Luca Daniele D
American journal of respiratory and critical care medicine 20201001 7
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Project description:Aberrant remodelling of the extracellular matrix in the developing lung may underlie arrested alveolarisation associated with bronchopulmonary dysplasia (BPD). Transglutaminases are regulators of extracellular matrix remodelling. Therefore, the expression and activity of transglutaminases were assessed in lungs from human neonates with BPD and in a rodent model of BPD. Transglutaminase expression and localisation were assessed by RT-PCR, immunoblotting, activity assay and immunohistochemical analyses of human and mouse lung tissues. Transglutaminase regulation by transforming growth factor (TGF)-β was investigated in lung cells by luciferase-based reporter assay and RT-PCR. TGF-β signalling was neutralised in vivo in an animal model of BPD, to determine whether TGF-β mediated the hyperoxia-induced changes in transglutaminase expression. Transglutaminase 2 expression was upregulated in the lungs of preterm infants with BPD and in the lungs of hyperoxia-exposed mouse pups, where lung development was arrested. Transglutaminase 2 localised to the developing alveolar septa. TGF-β was identified as a regulator of transglutaminase 2 expression in human and mouse lung epithelial cells. In vivo neutralisation of TGF-β signalling partially restored normal lung structure and normalised lung transglutaminase 2 mRNA expression. Our data point to a role for perturbed transglutaminase 2 activity in the arrested alveolarisation associated with BPD.
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Project description:ObjectiveTo quantify and compare levels of potential biomarkers in neonates with (i) Bronchopulmonary dysplasia (BPD); (ii) BPD-associated pulmonary hypertension (BPD-PH); (iii) PH without BPD; and (iv) neonates without lung disease at ~36 weeks postmenstrual age.Study designMultiple potential biomarkers were measured in plasma samples of 90 patients using a multi-spot enzyme-linked immunosorbent assay. Statistical tests done included one-way ANOVA to compare levels of biomarkers between different groups.ResultsHigher levels of ICAM-1 were present in infants with BPD and correlated with its severity. Infants with BPD have significantly higher levels of ANG-2 and lower levels of ANG-1. Infants with PH have higher levels of: IL-6, IL-8, IL-10, and TNF-α. Infants with BPD-PH have significantly lower levels of MCP-1 and higher levels of IL-1β than infants with PH without BPD.ConclusionICAM-1 may be used as a specific biomarker for diagnosis of BPD and its severity.
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Project description:BackgroundHepatocellular carcinoma (HCC) is a serious threat to public health due to its poor prognosis. The current study aimed to develop and validate a prognostic nomogram to predict the overall survival of HCC patients.MethodsThe model cohort consisted of 24,991 mRNA expression data points from 348 HCC patients. The least absolute shrinkage and selection operator method (LASSO) Cox regression model was used to evaluate the prognostic mRNA biomarkers for the overall survival of HCC patients.ResultsUsing multivariate Cox proportional regression analyses, a prognostic nomogram (named Eight-mRNA prognostic nomogram) was constructed based on the expression data of N4BP3, -ADRA2B, E2F8, MAPT, PZP, HOXD9, COL15A1, and -NDST3. The C-index of the Eight-mRNA prognostic nomogram was 0.765 (95% CI 0.724-0.806) for the overall survival in the model cohort. The Harrell's concordance-index of the Eight-mRNA prognostic nomogram was 0.715 (95% CI 0.658-0.772) in the validation cohort. The survival curves demonstrated that the HCC patients in the high risk group had a significantly poorer overall survival than the patients in the low risk group.ConclusionIn the current study, we have developed two convenient and efficient predictive precision medicine tools for hepatocellular carcinoma. These two predictive precision medicine tools are helpful for predicting the individual mortality risk probability and improving the personalized comprehensive treatments for HCC patients. The Smart Cancer Predictive System can be used by clicking the following URL: https://zhangzhiqiao2.shinyapps.io/Smart_cancer_predictive_system_HCC_2/. The Gene Survival Analysis Screen System is available at the following URL: https://zhangzhiqiao5.shinyapps.io/Gene_Survival_Analysis_A1001/.
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Project description:RationaleBenefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment.ObjectivesTo identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death.MethodsWe assessed infants of 23-30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000-2004.Measurements and main resultsBronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and Fi(O(2)), and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org.ConclusionsThe probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.
| S-EPMC3136997 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-10-01 | GSE151345 | GEO
Project description:AimTo test the hypothesis that plasma lipid metabolite levels in premature infants are associated with the development of bronchopulmonary dysplasia (BPD). The studies also tested a secondary hypothesis that plasma lipid metabolite levels were correlated with gestational age.MethodsInfants born <32 weeks' gestation were enrolled during the first 72 h of life. Plasma samples were obtained and lipid levels were measured by LC-MS/MS. Clinical data were collected to determine infant outcomes and BPD diagnosis.ResultsFollowing adjustment for confounders, lipid levels were not associated with BPD; however, levels of specific lipid metabolites were correlated with gestational age.ConclusionImmature lipid metabolism pathways in premature infants may contribute to the pathogenesis of BPD and other diseases.
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Project description:The development of clustered regularly interspaced short palindromic repeats (CRISPR) has spurred a successive wave of genome-engineering following zinc finger nucleases and transcription activator-like effector nucleases, and made gene-editing a promising strategy in the prevention and treatment of genetic diseases. However, gene-editing is not widely adopted in clinics due to some technical issues that challenge its safety and efficacy, and the lack of appropriate clinical regulations allowing them to advance toward improved human health without impinging on human ethics. By systematically examining the oncological applications of gene-editing tools and critical factors challenging their medical translation, genome-editing has substantial contributions to cancer driver gene discovery, tumor cell epigenome normalization, targeted delivery, cancer animal model establishment, and cancer immunotherapy and prevention in clinics. Gene-editing tools, epitomized by CRISPR, are predicted to represent a promising strategy toward the precise control of cancer initiation and development. However, some technical problems and ethical concerns are serious issues that need to be appropriately addressed before CRISPR can be incorporated into the next generation of molecular precision medicine. In this light, new technical developments to limit off-target effects are discussed herein, and the use of gene-editing approaches for treating otherwise incurable cancers is brought into focus.
| S-EPMC7312441 | biostudies-literature
Project description:ObjectiveLong-term respiratory consequences of bronchopulmonary dysplasia (BPD) in preterm infants born in the post-surfactant era ("new" BPD) remain partially unknown. The present study aimed to evaluate the respiratory outcomes of "new" BPD in adolescents who were born preterm.MethodsThis multicenter, cross-sectional study included 286 adolescents born between 2003 and 2005 (mean age: 14.2 years); among them, 184 and 102 were born extremely preterm (EP; <28 weeks' gestation) and moderate-late preterm (32 to <37 weeks' gestation), respectively. Among EP adolescents, 92 had BPD, and 92 did not. All participants underwent lung function tests, skin prick testing, and questionnaires on asthma symptoms and quality of life.ResultsEP adolescents with BPD had significantly lower forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC), FEV1 /FVC ratio, and forced expiratory flow between 25% and 75% of FVC than other included adolescents. FEV1 /FVC ratios were below the lower limit of normal (z-score <-1.645) in 30.4% of EP adolescents with BPD, 13.0% of EP adolescents without BPD, and 11.8% of adolescents who were born moderate-late preterm. Bronchodilator response and air-trapping were significantly higher in BPD adolescents than in other adolescents. Diffusion capacity was significantly lower in EP adolescents than in moderate-late preterm adolescents. Asthma symptoms and quality-of-life scores were similar among groups.ConclusionEP adolescents with "new" BPD had poorer pulmonary function than EP adolescents without BPD or moderate-late preterm adolescents. Further studies are needed to determine whether "new" BPD is associated with early-onset chronic obstructive pulmonary disease in adulthood.
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Project description:Rationale: Patients with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) have increased morbidity and mortality. Noninvasive assessment relies on echocardiograms (echos), which are technically challenging in this population. Improved assessment could augment decisions regarding PH therapies.Objectives: We hypothesized that neonatal cardiac magnetic resonance imaging (MRI) will correlate with BPD severity and predict short-term clinical outcomes, including need for PH therapies for infants with BPD.Methods: A total of 52 infants (31 severe BPD, 9 moderate BPD, and 12 with either mild or no BPD) were imaged between 39 and 47 weeks postmenstrual age on a neonatal-sized, neonatal ICU-sited 1.5-T magnetic resonance (MR) scanner. MR left ventricular eccentricity index (EI), main pulmonary artery-to-aorta (PA/AO) diameter ratio, and pulmonary arterial blood flow were determined. Echos obtained for clinical indications were reviewed. MRI and echo indices were compared with BPD severity and clinical outcomes, including length of stay (LOS), duration of respiratory support, respiratory support at discharge, and PH therapy.Measurements and Main Results: PA/AO ratio increased with BPD severity. Increased PA/AO ratio, MR-EI, and echo-EIs were associated with increased LOS and duration of respiratory support. No correlation was seen between pulmonary arterial blood flow and BPD outcomes. Controlling for gestational age, birth weight, and BPD severity, MR-EI was associated with LOS and duration of respiratory support. Increased PA/AO ratio and MR-EI were associated with PH therapy during hospitalization and at discharge.Conclusions: MRI can provide important image-based measures of cardiac morphology that relate to disease severity and clinical outcomes in neonates with BPD.
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