BACKGROUND Pulmonary hypertension(PH)is a severe complication of bronchopulmonary dysplasia(BPD)in premature neonates and is closely related to prognosis.However,there is no effective and safe treatment for PH due to ...BACKGROUND Pulmonary hypertension(PH)is a severe complication of bronchopulmonary dysplasia(BPD)in premature neonates and is closely related to prognosis.However,there is no effective and safe treatment for PH due to BPD in infants.Successful treatment for cases of BPD-associated PH with Tadalafil combined with bosentan is rare.This case may make a significant contribution to the literature because PH is difficult to manage as a serious complication of BPD in preterm infants.Mortality is high,especially when it is complicated by heart failure.CASE SUMMARY An extremely premature neonate with a gestational age of 26+5 wk and birth weight of 0.83 kg was diagnosed with BPD associated with PH;oral sildenafil did not improve the PH.The infant experienced sudden cardiac arrest and serious heart failure with severe PH.After a series of treatments,including cardiopulmonary resuscitation,mechanical ventilation,and inhaled nitric oxide(iNO),the respiratory and circulatory status improved but the pulmonary artery pressure remained high.Then oral sildenafil was replaced with oral tadalafil and bosentan;pulmonary artery pressure improved,and the infant recovered at our hospital.After 2 years of follow-up,she is in good condition,without any cardiovascular complications.CONCLUSION INO can effectively improve the respiratory and circulatory status of infants with PH associated with premature BPD.B-type natriuretic peptide should be routinely measured during hospitalization to evaluate the risk and prognosis of BPD-associated PH in preterm infants.Tadalafil combined with bosentan for the treatment of PH associated with premature BPD was better than sildenafil in this case.Further studies are needed to explore the efficacy and safety of different vasodilators in the treatment of PH associated with premature BPD.展开更多
Background: Bronchopulmonary Dysplasia (BPD) is a chronic lung condition that primarily affects preterm infants. Genetic predispositions, environmental factors, prenatal, and postnatal risk factors have been associate...Background: Bronchopulmonary Dysplasia (BPD) is a chronic lung condition that primarily affects preterm infants. Genetic predispositions, environmental factors, prenatal, and postnatal risk factors have been associated with bronchopulmonary dysplasia. However, there is a lack of consensus regarding these factors. Purpose: To examine the available information on pathogenesis and summarize the points of agreement to generate concise information that can guide patient management and spur further research. Method: PubMed, Embase and Web of Science were used to search for studies that analyzed the risk factors associated with bronchopulmonary dysplasia between 2006 and 2022 with the key search terms “bronchopulmonary dysplasia, etiology, preterm birth, mechanical ventilation”. Results: This study found that the pathogenesis of bronchopulmonary dysplasia is multifactorial, involving close interactions among these major etiological factors and other minor risk factors. A combination of mechanical ventilation, intrauterine factors, inflammation, genetic predispositions, insufficient surfactants, docosahexaenoic acid, and nutrition, among other minor risk factors, was all required in one way or another to influence BPD development. Therefore, studies should continuously update and incorporate the emerging information to assist frontline healthcare workers and generate qualitative data for clinical trial design and further research. Conclusion: Bronchopulmonary Dysplasia is different from other respiratory illnesses, and the pathogenesis of bronchopulmonary is multifactorial.展开更多
To investigate bronchopulmonary dysplasia (BPD) and its treatment with dexamethasone (DEX) in premature infants with birth weight (BW) < 1500 g. We retrospectively reviewed the records of preterm infants admitted t...To investigate bronchopulmonary dysplasia (BPD) and its treatment with dexamethasone (DEX) in premature infants with birth weight (BW) < 1500 g. We retrospectively reviewed the records of preterm infants admitted to the Division of Neonatology, the Second Xiangya Hospital, Central South University between September 2011 and December 2014. Patients were excluded if they needed oxygen therapy but were lost to follow-up at ≤36 weeks post-menstrual age (PMA) or <56 days after birth, or they had severe congenital anomalies. The incidence of BPD was 18% (37/212). Gestational age (GA) was <32 weeks in all BPD patients. GA, BW, and Apgar scores were lower and hospitalization duration and pulmonary surfactant (PS) use were higher in the BPD group than in the non-BPD group (P < 0.05). Risk factors for BPD included neonatal respiratory distress syndrome, neonatal pneumonia, positive sputum culture, pulmonary hemorrhage, respiratory failure. Multivariate logistic regression revealed that GA (odds ratio [OR]: 0.479, P = 0.004) and neonatal respiratory distress syndrome (OR: 6.146, P = 0.043) were independent risk factors for BPD. DEX was administered to 26 patients after the diagnosis of BPD. After one and two weeks of DEX treatment, the oxygen requirement had significantly reduced compared to the week prior to treatment (P < 0.05), while during treatment, the weight gain rate and weight gain efficiency slower significantly than that during either of the two preceding weeks (P < 0.001). These results suggest that low GA was the most important risk factor for BPD, DEX reduced oxygen dependency but decreased weight gain.展开更多
Objectives We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia(BPD)and focus on discussing its relationship with the duration of initial invasive mechanical ventilation(IMV)in very ...Objectives We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia(BPD)and focus on discussing its relationship with the duration of initial invasive mechanical ventilation(IMV)in very preterm neonates less than 32 weeks of gestational age(GA).Methods We performed a prospective cohort study involving infants born at 23–31 weeks of GA who were admitted to 47 different neonatal intensive care unit(NICU)hospitals in China from January 2018 to December 2021.Patient data were obtained from the Sina-northern Neonatal Network(SNN)Database.Results We identified 6538 very preterm infants,of whom 49.5%(3236/6538)received initial IMV support,and 12.6%(823/6538)were diagnosed with moderate-to-severe BPD symptoms.The median duration of initial IMV in the moderateto-severe BPD group was 26(17–41)days,while in the no or mild BPD group,it was 6(3–10)days.The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs.Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV[adjusted odds ratio(AOR):1.97;95%confidence interval(CI):1.10–2.67],late-onset neonatal sepsis(LONS),and patent ductus arteriosus(PDA).Conclusion In this multicenter cohort study,the duration of initial IMV was still relatively long in very premature infants,and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.展开更多
Background Home oxygen therapy(HOT)is indicated upon discharge in some preterm infants with severe bronchopulmonary dysplasia(BPD).There is a lack of evidence-based consensus on the indication for HOT among these infa...Background Home oxygen therapy(HOT)is indicated upon discharge in some preterm infants with severe bronchopulmonary dysplasia(BPD).There is a lack of evidence-based consensus on the indication for HOT among these infants.Because wide variation in the institutional use of HOT exists,little is known about the role of regional social-economic level in the wide variation of HOT.Methods This was a secondary analysis of Chinese Neonatal Network(CHNN)data from January 1,2019 to December 31,2019.Infants at gestational ages<32 weeks,with a birth weight<1500 g,and with moderate or severe BPD who survived to discharge from tertiary hospitals located in 25 provinces were included in this study.Infants with major congenital anomalies and those who were discharged against medical advice were excluded.Results Of 1768 preterm infants with BPD,474 infants(26.8%)were discharged to home with oxygen.The proportion of HOT use in participating member hospitals varied from 0 to 89%,with five of 52 hospitals’observing proportions of HOT use that were significantly greater than expected,with 14 hospitals with observing proportions significantly less than expected,and with 33 hospitals with appropriate proportions.We noted a negative correlation between different performance groups of HOT and median GDP per capita(P=0.04).Conclusions The use of HOT varied across China and was negatively correlated with the levels of provincial economic levels.A local HOT guideline is needed to address the wide variation in HOT use with respect to different regional economic levels in countries like China.展开更多
Severe bronchopulmonary dysplasia(BPD)is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system;no effective pharmacotherapy for this dise...Severe bronchopulmonary dysplasia(BPD)is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system;no effective pharmacotherapy for this disease exists,and mortality remains high.Based on the evidence from previous preclinical studies and phase I clinical trials,this study aims to test the safety of intravenous application of a single dose of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)in patients with severe BPD.The Mesenchymal Stem cells for Bronchopulmonary Dysplasia Treatment(MSBDT)trial is a single center,open-label,dose-escalation phase I clinical trial.Severe BPD patients were enrolled in Children Hospital of Chongqing Medical University,Chongqing,China.The first six patients were treated with low-dose hUC-MSCs(1×10^(6) cells/kg)and the next seven patients were treated with high-dose hUC-MSCs(5×10^(6) cells/kg).This study is registered with ClinicalTrials.gov,number NCT03558334.No prespecified infusion-associated adverse events,immediate complication,respiratory or cardiovascular compromise were observed during infusion and 24 h after infusion.No significant changes in safety laboratory values were observed.One death event occurred in the low-dose group on study day 10,and one death event occurred in the high-dose group on study day 24,while,after review in detail,the two cases are not believed to be infusion-associated events.In conclusion,intravenous application of a single dose of hUC-MSCs was tolerated in thirteen patients with severe BPD.展开更多
Background This study aimed to systematically review and meta-analyze the available literature on the association between preterm infant bronchopulmonary dysplasia(BPD)and pre-adulthood asthma.Methods Studies examinin...Background This study aimed to systematically review and meta-analyze the available literature on the association between preterm infant bronchopulmonary dysplasia(BPD)and pre-adulthood asthma.Methods Studies examining the association between BPD and asthma in children and adolescents were systematically reviewed,and a meta-analysis was conducted.We searched Scopus,Embase,Web of Science,PubMed,and Cochrane Library from the database inception to March 26,2022.The pooled odds ratio(OR)estimate was used in our meta-analysis to calculate the correlation between BPD and the probability of developing asthma before adulthood.Stata 12.0 was used to conduct the statistical analysis.Results The correlation between asthma and BPD in preterm newborns was examined in nine studies.We used a random effect model to pool the OR estimate.Our results indicated a marked increase in the risk of subsequent asthma in preterm infants with BPD[OR=1.73,95% confidence interval(CI)=1.43-2.09].Moreover,there was no obvious heterogeneity across the studies(P=0.617,I^(2)=0%).The pooled OR remained stable and ranged from 1.65(95%CI=1.35-2.01)to 1.78(95%CI=1.43-2.21).Regarding publication bias,the funnel plot for asthma risk did not reveal any noticeable asymmetry.We further performed Begg’s and Egger’s tests to quantitatively evaluate publication bias.There was no evidence of a publication bias for asthma risk(P>|Z|=0.602 for Begg’s test,and P>|t|=0.991 for Egger’s test).Conclusions Our findings indicate that preterm infants with BPD have a much higher risk of developing asthma in the future(OR=1.73,95%CI=1.43-2.09).Preterm infants with BPD may benefit from long-term follow-up.展开更多
Background Bronchopulmonary dysplasia(BPD)is a common chronic lung disease in extremely preterm neonates.The outcome and clinical burden vary dramatically according to severity.Although some prediction tools for BPD e...Background Bronchopulmonary dysplasia(BPD)is a common chronic lung disease in extremely preterm neonates.The outcome and clinical burden vary dramatically according to severity.Although some prediction tools for BPD exist,they seldom pay attention to disease severity and are based on populations in developed countries.This study aimed to develop machine learning prediction models for BPD severity based on selected clinical factors in a Chinese population.Methods In this retrospective,single-center study,we included patients with a gestational age<32 weeks who were diagnosed with BPD in our neonatal intensive care unit from 2016 to 2020.We collected their clinical information during the maternal,birth and early postnatal periods.Risk factors were selected through univariable and ordinal logistic regression analyses.Prediction models based on logistic regression(LR),gradient boosting decision tree,XGBoost(XGB)and random forest(RF)models were implemented and assessed by the area under the receiver operating characteristic curve(AUC).Results We ultimately included 471 patients(279 mild,147 moderate,and 45 severe cases).On ordinal logistic regression,gestational diabetes mellitus,initial fraction of inspiration O_(2) value,invasive ventilation,acidosis,hypochloremia,C-reactive protein level,patent ductus arteriosus and Gram-negative respiratory culture were independent risk factors for BPD severity.All the XGB,LR and RF models(AUC=0.85,0.86 and 0.84,respectively)all had good performance.Conclusions We found risk factors for BPD severity in our population and developed machine learning models based on them.The models have good performance and can be used to aid in predicting BPD severity in the Chinese population.展开更多
Pulmonary hypertension is a rare and potentially fatal disease in children if left untreated. Emerging therapies, including Bosentan, a dual endothelin receptor antagonist, have shown significant benefits in the adult...Pulmonary hypertension is a rare and potentially fatal disease in children if left untreated. Emerging therapies, including Bosentan, a dual endothelin receptor antagonist, have shown significant benefits in the adult pulmonary hypertension population;however, few studies have assessed the efficacy and safety of endothelin receptor antagonists in infants and young children. Our study was a single-center retrospective analysis of patients less than two years of age with a confirmed diagnosis of pulmonary hypertension and initiated on Bosentan therapy between 2017 and 2020. Twelve cases met eligibility criteria. Demographic data, laboratory data, echocardiographic, and cardiac catheterization data were analyzed. With treatment, there was a statistically significant decrease in mean right ventricular systolic pressure estimated by the tricuspid regurgitation jet (79 ± 23 mmHg reduced to 52 ± 25 mmHg;p < 0.001) N-terminal pro-hormone B-type natriuretic peptide levels (21,071 reduced to 2,037;p < 0.001). Additionally, improvement and eventual normalization of right ventricular function and septal geometry was seen within the first four months of therapy. Patients who underwent cardiac catheterization after therapy initiation (n = 4) demonstrated hemodynamic improvements;however, only the decrease in diastolic pulmonary artery pressure was statistically significant (p = 0.018). No significant differences in hemoglobin, platelet count, or liver function tests were observed between groups. In conclusion, these data suggest that Bosentan may be an effective and relatively safe treatment option for children less than two years of age with pulmonary hypertension. Further long-term randomized control studies are necessary to validate the potential clinical benefit of utilizing this drug therapy in young children.展开更多
The present study aimed to examine the effectiveness of bi-level positive airway pressure(BiPAP)versus continuous positive airway pressure(CPAP)in preterm infants with birth weight less than 1500 g and respiratory dis...The present study aimed to examine the effectiveness of bi-level positive airway pressure(BiPAP)versus continuous positive airway pressure(CPAP)in preterm infants with birth weight less than 1500 g and respiratory distress syndrome(RDS)following intubation-surfactant-extubation(INSURE)treatment.A two-center randomized control trial was performed.The primary outcome was the reintubation rate of infants within 72 h of age after INSURE.Secondary outcomes included bronchopulmonary dysplasia(BPD),necrotizing enterocolitis(NEC),retinopathy of prematurity(ROP)and incidences of adverse events.Lung function at one year of corrected age was also compared between the two groups.There were 140 cases in the CPAP group and 144 in the BiPAP group.After INSURE,the reintubation rates of infants within 72 h of age were 15%and 11.1%in the CPAP group and the BiPAP group,respectively(P>0.05).Neonates in the BiPAP group was on positive airway pressure(PAP)therapy three days less than in the CPAP group(12.6 d and 15.3 d,respectively,P<0.05),and on oxygen six days less than in the CPAP group(20.6 d and 26.9 d,respectively,P<0.05).Other outcomes such as BPD,NEC,ROP and feeding intolerance were not significantly different between the two groups(P>0.05).There was no difference in lung function at one year of age between the two groups(P>0.05).In conclusion,after INSURE,the reintubation rate of infants within 72 h of age was comparable between the BiPAP group and the CPAP group.BiPAP was superior to CPAP in terms of shorter durations(days)on PAP support and oxygen supplementation.There were no differences in the incidences of BPD and ROP,and lung function at one year of age between the two ventilation methods.展开更多
BACKGROUND Bronchopulmonary dysplasia(BPD)is not merely a chronic lung disease,but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure.Despite advances in current ma...BACKGROUND Bronchopulmonary dysplasia(BPD)is not merely a chronic lung disease,but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure.Despite advances in current management strategies,limited progress has been made in reducing the BPD-related systemic damage.Meanwhile,although the protective effects of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)or their exosomes on hyperoxia-induced lung injury have been explored by many researchers,the underlying mechanism has not been addressed in detail,and few studies have focused on the therapeutic effect on systemic multiple organ injury.AIM To investigate whether hUC-MSC intratracheal administration could attenuate hyperoxia-induced lung,heart,and kidney injuries and the underlying regulatory mechanisms.METHODS Neonatal rats were exposed to hyperoxia(80%O_(2)),treated with hUC-MSCs intratracheal(iT)or intraperitoneal(iP)on postnatal day 7,and harvested on postnatal day 21.The tissue sections of the lung,heart,and kidney were analyzed morphometrically.Protein contents of the bronchoalveolar lavage fluid(BALF),myeloper oxidase(MPO)expression,and malondialdehyde(MDA)levels were examined.Pulmonary inflammatory cytokines were measured via enzyme-linked immunosorbent assay.A comparative transcriptomic analysis of differentially expressed genes(DEGs)in lung tissue was conducted via RNA-sequencing.Subsequently,we performed reverse transcription-quantitative polymerase chain reaction and western blot analysis to explore the expression of target mRNA and proteins related to inflammatory and oxidative responses.RESULTS iT hUC-MSCs administration improved pulmonary alveolarization and angiogenesis(P<0.01,P<0.01,P<0.001,and P<0.05 for mean linear intercept,septal counts,vascular medial thickness index,and microvessel density respectively).Meanwhile,treatment with hUC-MSCs iT ameliorated right ventricular hypertrophy(for Fulton’s index,P<0.01),and relieved reduced nephrogenic zone width(P<0.01)and glomerular diameter(P<0.001)in kidneys.Among the beneficial effects,a reduction of BALF protein,MPO,and MDA was observed in hUC-MSCs groups(P<0.01,P<0.001,and P<0.05 respectively).Increased pro-inflammatory cytokines tumor necrosis factor-alpha,interleukin(IL)-1β,and IL-6 expression observed in the hyperoxia group were significantly attenuated by hUC-MSCs administration(P<0.01,P<0.001,and P<0.05 respectively).In addition,we observed an increase in anti-inflammatory cytokine IL-10 expression in rats that received hUC-MSCs iT compared with rats reared in hyperoxia(P<0.05).Transcriptomic analysis showed that the DEGs in lung tissues induced by hyperoxia were enriched in pathways related to inflammatory responses,epithelial cell proliferation,and vasculature development.hUC-MSCs administration blunted these hyperoxia-induced dysregulated genes and resulted in a shift in the gene expression pattern toward the normoxia group.hUC-MSCs increased heme oxygenase-1(HO-1),JAK2,and STAT3 expression,and their phosphorylation in the lung,heart,and kidney(P<0.05).Remarkably,no significant difference was observed between the iT and iP administration.CONCLUSION iT hUC-MSCs administration ameliorates hyperoxia-induced lung,heart,and kidney injuries by activating HO-1 expression and JAK/STAT signaling.The therapeutic benefits of local iT and iP administration are equivalent.展开更多
Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature s...Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature search including EMBASE,MEDLINE,and CINAHL databases to identify all relevant papers published in the English and German literature on influenza and respiratory syncytial virus infection associated with preterm infant,prematurity,and BPD between 1980 and 2014.Results:Recurrent respiratory symptoms remain common at preschool age,school age and even into young adulthood.Acute viral respiratory tract infections due to different pathogens cause significant morbidity and necessitate rehospitalizations during the fi rst years of life.Infl uenza virus infection plays a minor role compared to respiratory syncytial virus(RSV)associated respiratory tract infection during infancy and early childhood.Nevertheless,particular morbidity to both viruses is high.Conclusions:The particular burden of both viral diseases in preterm infants is dominated by RSV and its associated rehospitalizations during the fi rst two years of life.Prophylactic measures include vaccination against influenza virus of family members and caregivers and active immunization starting at the age of 6 months,and monthly injections of palivizumab during the cold season to avoid severe RSV disease and its sequelae.展开更多
Background:To determine the characteristics and outcomes of pulmonary arterial hypertension(PAH)in extremely low birth weight(ELBW)infants.Methods:A retrospective case-control study of all ELBW infants admitted to a l...Background:To determine the characteristics and outcomes of pulmonary arterial hypertension(PAH)in extremely low birth weight(ELBW)infants.Methods:A retrospective case-control study of all ELBW infants admitted to a level III neonatal intensive care unit(NICU)between January 1,2003 and December 31,2010.Results:During the study period,450 ELBW infants were admitted.6.4%(29/450)were diagnosed with PAH and were matched to 26 controls.The mean gestational age of infants with PAH and their controls were similar[24.5±1.3 vs.24.9±1.8 weeks(P=0.26)];however the cases were smaller at birth than were controls[640.7±119.5 vs.727.0±184.5 g(P=0.04)].The diagnosis of PAH was made at a mean postnatal age of 131.8±53.7 days.Infants with PAH had a higher rate of intrauterine exposure to illicit maternal drug use[12/29(41%)vs.1/25(4%);P=0.001],a longer duration of initial mechanical ventilation[74.9±28.3 vs.59.1±27.8 days;(P=0.04)],a higher incidence of severe BPD[23/29(79%)vs.13/26(50%);P=0.02],and a greater NICU mortality rate[12/29(41%)vs.4/26(15%);P=0.04].Conclusion:PAH in ELBW infants is associated with maternal illicit drug use in pregnancy,longer exposure to mechanical ventilation,severe bronchopulmonary dysplasia and a significant increase in early mortality.展开更多
Background:To investigate strategies used for the management of respiratory distress syndrome(RDS)and bronchopulmonary dysplasia(BPD)in extremely low birth weight(ELBW)infants.Methods:A survey of neonatal specialists ...Background:To investigate strategies used for the management of respiratory distress syndrome(RDS)and bronchopulmonary dysplasia(BPD)in extremely low birth weight(ELBW)infants.Methods:A survey of neonatal specialists working in US academic institutions with fellowship training programs.Results:Eighty percent(72/89)of the identifi ed academic institutions had at least one physician who responded to the survey.Among respondents,85%(171/201)agreed or strongly agreed to use continuous positive airway pressure(CPAP)initially for the management of RDS,and the majority agreed or strongly agreed to use a fraction of inspired oxygen(FiO2)≥0.4 and a mean airway pressure(MAP)≥10 cm H2O as a criteria for surfactant therapy;and 73%(146/200)sometimes or always used caffeine to prevent BPD.Only 25%(50/202)sometimes or almost always used steroids to prevent or treat BPD.Identified indications to use steroids were 3 or more extubation failures or inability to extubate beyond 8 weeks of age.Conclusions:Variability in treatment strategies of ELBW is common among neonatal specialists.However,the majority of the respondents agreed or strongly agreed to use early CPAP for the management of RDS,consider a FiO2≥0.4 and a MAP≥10 cm H2O as criteria for surfactant therapy,and sometimes or almost always used caffeine to prevent BPD.Steroids continue to have a role in the management of BPD in infants who are diffi cult to extubate.展开更多
Background To compare short and long outcomes between early(≤28 days)(EL)and late ligation(LL)groups.To explore factors predicting early extubation(≤7 days)after patent ductus arteriosus(PDA)ligation.Methods We cond...Background To compare short and long outcomes between early(≤28 days)(EL)and late ligation(LL)groups.To explore factors predicting early extubation(≤7 days)after patent ductus arteriosus(PDA)ligation.Methods We conducted a single center,retrospective cohort study of preterm infants<32 weeks who underwent surgical ligation over a 10-year period(2009-2019).Results A total of 133 infants underwent PDA ligation,in the study period.Both groups had similar short-term outcome such as bronchopulmonary dysplasia(BPD)or death(96%vs.98%,P=0.64)and long-term clinical outcomes including Bayley's assessment at 2 years corrected age.Fewer infants in the EL group developed severe BPD(63%vs.81%,P=0.02).Age at ligation had adjusted odds ratio of 1.04 with over lapping confidence interval(95%CI 1.0-1.1,P=0.02)for severe BPD/death.There was no difference in day of extubation between the EL and LL group(8 days vs.7 days,P=0.85).Left atrium/aortic root ratio of ≥1.75 would give sensitivity of 41% and 80% specificity for early extubation(area under the curve of 0.61).There was marginal reduction of hospital stay in the EL group[113(105-121)days vs.115(107-123)days;log rank P=0.026].Conclusion EL can be delivered safely with a clinically important lower incidenee of severe BPD and shorter duration of hospital stay compared to LL.展开更多
Cellular senescence is a status of irreversible growth arrest,which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external factors.Senescent cells are typically enlarged and flattened,a...Cellular senescence is a status of irreversible growth arrest,which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external factors.Senescent cells are typically enlarged and flattened,and characterized by numerous molecular features.The latter consists of increased surfaceome,increased resid-ual lysosomal activity at pH 6.0(manifested by increased activity of senescence-associated beta-galactosidase[SA-𝛽-gal]),senescence-associated mitochondrial dysfunction,cytoplasmic chromatin fragment,nuclear lamin b1 exclusion,telomere-associated foci,and the senescence-associated secretory phenotype.These features vary depending on the stressor leading to senescence and the type of senescence.Cellular senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related diseases.Interestingly,senescence can also both promote and inhibit wound healing processes.We recently report that senescence as a programmed pro-cess contributes to normal lung development.Lung senescence is also observed in Down Syndrome,as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this disease.Furthermore,this senescence results in neonatal lung injury.In this review,we briefly discuss the molecular features of senescence.We then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving senescence.Finally,we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.展开更多
基金Supported by The Clinical Research Fund of West China Second University Hospital,Sichuan University,No.KL109(to Li J),No.KL014(to Yang XY),and No.KL075(to Shi J).
文摘BACKGROUND Pulmonary hypertension(PH)is a severe complication of bronchopulmonary dysplasia(BPD)in premature neonates and is closely related to prognosis.However,there is no effective and safe treatment for PH due to BPD in infants.Successful treatment for cases of BPD-associated PH with Tadalafil combined with bosentan is rare.This case may make a significant contribution to the literature because PH is difficult to manage as a serious complication of BPD in preterm infants.Mortality is high,especially when it is complicated by heart failure.CASE SUMMARY An extremely premature neonate with a gestational age of 26+5 wk and birth weight of 0.83 kg was diagnosed with BPD associated with PH;oral sildenafil did not improve the PH.The infant experienced sudden cardiac arrest and serious heart failure with severe PH.After a series of treatments,including cardiopulmonary resuscitation,mechanical ventilation,and inhaled nitric oxide(iNO),the respiratory and circulatory status improved but the pulmonary artery pressure remained high.Then oral sildenafil was replaced with oral tadalafil and bosentan;pulmonary artery pressure improved,and the infant recovered at our hospital.After 2 years of follow-up,she is in good condition,without any cardiovascular complications.CONCLUSION INO can effectively improve the respiratory and circulatory status of infants with PH associated with premature BPD.B-type natriuretic peptide should be routinely measured during hospitalization to evaluate the risk and prognosis of BPD-associated PH in preterm infants.Tadalafil combined with bosentan for the treatment of PH associated with premature BPD was better than sildenafil in this case.Further studies are needed to explore the efficacy and safety of different vasodilators in the treatment of PH associated with premature BPD.
文摘Background: Bronchopulmonary Dysplasia (BPD) is a chronic lung condition that primarily affects preterm infants. Genetic predispositions, environmental factors, prenatal, and postnatal risk factors have been associated with bronchopulmonary dysplasia. However, there is a lack of consensus regarding these factors. Purpose: To examine the available information on pathogenesis and summarize the points of agreement to generate concise information that can guide patient management and spur further research. Method: PubMed, Embase and Web of Science were used to search for studies that analyzed the risk factors associated with bronchopulmonary dysplasia between 2006 and 2022 with the key search terms “bronchopulmonary dysplasia, etiology, preterm birth, mechanical ventilation”. Results: This study found that the pathogenesis of bronchopulmonary dysplasia is multifactorial, involving close interactions among these major etiological factors and other minor risk factors. A combination of mechanical ventilation, intrauterine factors, inflammation, genetic predispositions, insufficient surfactants, docosahexaenoic acid, and nutrition, among other minor risk factors, was all required in one way or another to influence BPD development. Therefore, studies should continuously update and incorporate the emerging information to assist frontline healthcare workers and generate qualitative data for clinical trial design and further research. Conclusion: Bronchopulmonary Dysplasia is different from other respiratory illnesses, and the pathogenesis of bronchopulmonary is multifactorial.
文摘To investigate bronchopulmonary dysplasia (BPD) and its treatment with dexamethasone (DEX) in premature infants with birth weight (BW) < 1500 g. We retrospectively reviewed the records of preterm infants admitted to the Division of Neonatology, the Second Xiangya Hospital, Central South University between September 2011 and December 2014. Patients were excluded if they needed oxygen therapy but were lost to follow-up at ≤36 weeks post-menstrual age (PMA) or <56 days after birth, or they had severe congenital anomalies. The incidence of BPD was 18% (37/212). Gestational age (GA) was <32 weeks in all BPD patients. GA, BW, and Apgar scores were lower and hospitalization duration and pulmonary surfactant (PS) use were higher in the BPD group than in the non-BPD group (P < 0.05). Risk factors for BPD included neonatal respiratory distress syndrome, neonatal pneumonia, positive sputum culture, pulmonary hemorrhage, respiratory failure. Multivariate logistic regression revealed that GA (odds ratio [OR]: 0.479, P = 0.004) and neonatal respiratory distress syndrome (OR: 6.146, P = 0.043) were independent risk factors for BPD. DEX was administered to 26 patients after the diagnosis of BPD. After one and two weeks of DEX treatment, the oxygen requirement had significantly reduced compared to the week prior to treatment (P < 0.05), while during treatment, the weight gain rate and weight gain efficiency slower significantly than that during either of the two preceding weeks (P < 0.001). These results suggest that low GA was the most important risk factor for BPD, DEX reduced oxygen dependency but decreased weight gain.
基金supported by the Project of“2021 Shandong Medical Association Clinical Research Fund”(Qilu Special Project,YXH2022DZX0200X)Shandong Key Research and Development Project(2018GSF118163).
文摘Objectives We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia(BPD)and focus on discussing its relationship with the duration of initial invasive mechanical ventilation(IMV)in very preterm neonates less than 32 weeks of gestational age(GA).Methods We performed a prospective cohort study involving infants born at 23–31 weeks of GA who were admitted to 47 different neonatal intensive care unit(NICU)hospitals in China from January 2018 to December 2021.Patient data were obtained from the Sina-northern Neonatal Network(SNN)Database.Results We identified 6538 very preterm infants,of whom 49.5%(3236/6538)received initial IMV support,and 12.6%(823/6538)were diagnosed with moderate-to-severe BPD symptoms.The median duration of initial IMV in the moderateto-severe BPD group was 26(17–41)days,while in the no or mild BPD group,it was 6(3–10)days.The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs.Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV[adjusted odds ratio(AOR):1.97;95%confidence interval(CI):1.10–2.67],late-onset neonatal sepsis(LONS),and patent ductus arteriosus(PDA).Conclusion In this multicenter cohort study,the duration of initial IMV was still relatively long in very premature infants,and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.
基金funded by the Canadian Institutes of Health Research(CTP87518 to Shoo Lee).
文摘Background Home oxygen therapy(HOT)is indicated upon discharge in some preterm infants with severe bronchopulmonary dysplasia(BPD).There is a lack of evidence-based consensus on the indication for HOT among these infants.Because wide variation in the institutional use of HOT exists,little is known about the role of regional social-economic level in the wide variation of HOT.Methods This was a secondary analysis of Chinese Neonatal Network(CHNN)data from January 1,2019 to December 31,2019.Infants at gestational ages<32 weeks,with a birth weight<1500 g,and with moderate or severe BPD who survived to discharge from tertiary hospitals located in 25 provinces were included in this study.Infants with major congenital anomalies and those who were discharged against medical advice were excluded.Results Of 1768 preterm infants with BPD,474 infants(26.8%)were discharged to home with oxygen.The proportion of HOT use in participating member hospitals varied from 0 to 89%,with five of 52 hospitals’observing proportions of HOT use that were significantly greater than expected,with 14 hospitals with observing proportions significantly less than expected,and with 33 hospitals with appropriate proportions.We noted a negative correlation between different performance groups of HOT and median GDP per capita(P=0.04).Conclusions The use of HOT varied across China and was negatively correlated with the levels of provincial economic levels.A local HOT guideline is needed to address the wide variation in HOT use with respect to different regional economic levels in countries like China.
基金partially supported by the Science and Technology Research Program of Chongqing Municipality Education Commision(No.KJQN201800407).
文摘Severe bronchopulmonary dysplasia(BPD)is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system;no effective pharmacotherapy for this disease exists,and mortality remains high.Based on the evidence from previous preclinical studies and phase I clinical trials,this study aims to test the safety of intravenous application of a single dose of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)in patients with severe BPD.The Mesenchymal Stem cells for Bronchopulmonary Dysplasia Treatment(MSBDT)trial is a single center,open-label,dose-escalation phase I clinical trial.Severe BPD patients were enrolled in Children Hospital of Chongqing Medical University,Chongqing,China.The first six patients were treated with low-dose hUC-MSCs(1×10^(6) cells/kg)and the next seven patients were treated with high-dose hUC-MSCs(5×10^(6) cells/kg).This study is registered with ClinicalTrials.gov,number NCT03558334.No prespecified infusion-associated adverse events,immediate complication,respiratory or cardiovascular compromise were observed during infusion and 24 h after infusion.No significant changes in safety laboratory values were observed.One death event occurred in the low-dose group on study day 10,and one death event occurred in the high-dose group on study day 24,while,after review in detail,the two cases are not believed to be infusion-associated events.In conclusion,intravenous application of a single dose of hUC-MSCs was tolerated in thirteen patients with severe BPD.
基金the funding of Key R&D Guidance Plan Projects in Liaoning Province(2020JH1/10300001).
文摘Background This study aimed to systematically review and meta-analyze the available literature on the association between preterm infant bronchopulmonary dysplasia(BPD)and pre-adulthood asthma.Methods Studies examining the association between BPD and asthma in children and adolescents were systematically reviewed,and a meta-analysis was conducted.We searched Scopus,Embase,Web of Science,PubMed,and Cochrane Library from the database inception to March 26,2022.The pooled odds ratio(OR)estimate was used in our meta-analysis to calculate the correlation between BPD and the probability of developing asthma before adulthood.Stata 12.0 was used to conduct the statistical analysis.Results The correlation between asthma and BPD in preterm newborns was examined in nine studies.We used a random effect model to pool the OR estimate.Our results indicated a marked increase in the risk of subsequent asthma in preterm infants with BPD[OR=1.73,95% confidence interval(CI)=1.43-2.09].Moreover,there was no obvious heterogeneity across the studies(P=0.617,I^(2)=0%).The pooled OR remained stable and ranged from 1.65(95%CI=1.35-2.01)to 1.78(95%CI=1.43-2.21).Regarding publication bias,the funnel plot for asthma risk did not reveal any noticeable asymmetry.We further performed Begg’s and Egger’s tests to quantitatively evaluate publication bias.There was no evidence of a publication bias for asthma risk(P>|Z|=0.602 for Begg’s test,and P>|t|=0.991 for Egger’s test).Conclusions Our findings indicate that preterm infants with BPD have a much higher risk of developing asthma in the future(OR=1.73,95%CI=1.43-2.09).Preterm infants with BPD may benefit from long-term follow-up.
基金funded by the Science and Technology Commission of Shanghai Municipality(No.21511104502)the National Key Research and Development Program of China(No.2021ZD0113501).
文摘Background Bronchopulmonary dysplasia(BPD)is a common chronic lung disease in extremely preterm neonates.The outcome and clinical burden vary dramatically according to severity.Although some prediction tools for BPD exist,they seldom pay attention to disease severity and are based on populations in developed countries.This study aimed to develop machine learning prediction models for BPD severity based on selected clinical factors in a Chinese population.Methods In this retrospective,single-center study,we included patients with a gestational age<32 weeks who were diagnosed with BPD in our neonatal intensive care unit from 2016 to 2020.We collected their clinical information during the maternal,birth and early postnatal periods.Risk factors were selected through univariable and ordinal logistic regression analyses.Prediction models based on logistic regression(LR),gradient boosting decision tree,XGBoost(XGB)and random forest(RF)models were implemented and assessed by the area under the receiver operating characteristic curve(AUC).Results We ultimately included 471 patients(279 mild,147 moderate,and 45 severe cases).On ordinal logistic regression,gestational diabetes mellitus,initial fraction of inspiration O_(2) value,invasive ventilation,acidosis,hypochloremia,C-reactive protein level,patent ductus arteriosus and Gram-negative respiratory culture were independent risk factors for BPD severity.All the XGB,LR and RF models(AUC=0.85,0.86 and 0.84,respectively)all had good performance.Conclusions We found risk factors for BPD severity in our population and developed machine learning models based on them.The models have good performance and can be used to aid in predicting BPD severity in the Chinese population.
文摘Pulmonary hypertension is a rare and potentially fatal disease in children if left untreated. Emerging therapies, including Bosentan, a dual endothelin receptor antagonist, have shown significant benefits in the adult pulmonary hypertension population;however, few studies have assessed the efficacy and safety of endothelin receptor antagonists in infants and young children. Our study was a single-center retrospective analysis of patients less than two years of age with a confirmed diagnosis of pulmonary hypertension and initiated on Bosentan therapy between 2017 and 2020. Twelve cases met eligibility criteria. Demographic data, laboratory data, echocardiographic, and cardiac catheterization data were analyzed. With treatment, there was a statistically significant decrease in mean right ventricular systolic pressure estimated by the tricuspid regurgitation jet (79 ± 23 mmHg reduced to 52 ± 25 mmHg;p < 0.001) N-terminal pro-hormone B-type natriuretic peptide levels (21,071 reduced to 2,037;p < 0.001). Additionally, improvement and eventual normalization of right ventricular function and septal geometry was seen within the first four months of therapy. Patients who underwent cardiac catheterization after therapy initiation (n = 4) demonstrated hemodynamic improvements;however, only the decrease in diastolic pulmonary artery pressure was statistically significant (p = 0.018). No significant differences in hemoglobin, platelet count, or liver function tests were observed between groups. In conclusion, these data suggest that Bosentan may be an effective and relatively safe treatment option for children less than two years of age with pulmonary hypertension. Further long-term randomized control studies are necessary to validate the potential clinical benefit of utilizing this drug therapy in young children.
文摘The present study aimed to examine the effectiveness of bi-level positive airway pressure(BiPAP)versus continuous positive airway pressure(CPAP)in preterm infants with birth weight less than 1500 g and respiratory distress syndrome(RDS)following intubation-surfactant-extubation(INSURE)treatment.A two-center randomized control trial was performed.The primary outcome was the reintubation rate of infants within 72 h of age after INSURE.Secondary outcomes included bronchopulmonary dysplasia(BPD),necrotizing enterocolitis(NEC),retinopathy of prematurity(ROP)and incidences of adverse events.Lung function at one year of corrected age was also compared between the two groups.There were 140 cases in the CPAP group and 144 in the BiPAP group.After INSURE,the reintubation rates of infants within 72 h of age were 15%and 11.1%in the CPAP group and the BiPAP group,respectively(P>0.05).Neonates in the BiPAP group was on positive airway pressure(PAP)therapy three days less than in the CPAP group(12.6 d and 15.3 d,respectively,P<0.05),and on oxygen six days less than in the CPAP group(20.6 d and 26.9 d,respectively,P<0.05).Other outcomes such as BPD,NEC,ROP and feeding intolerance were not significantly different between the two groups(P>0.05).There was no difference in lung function at one year of age between the two groups(P>0.05).In conclusion,after INSURE,the reintubation rate of infants within 72 h of age was comparable between the BiPAP group and the CPAP group.BiPAP was superior to CPAP in terms of shorter durations(days)on PAP support and oxygen supplementation.There were no differences in the incidences of BPD and ROP,and lung function at one year of age between the two ventilation methods.
基金Supported by Rongxiang Regenerative Medicine Foundation of Shandong University, No. 2019SDRX-18Clinical Practical New Technology Development Found of Qilu Hospital of Shandong University, No. KYC 2019-0057+1 种基金Clinical Research Center of Shandong University, No. 2020SDUCRCA010Natural Science Foundation of Shandong Province, No. ZR2020MH063
文摘BACKGROUND Bronchopulmonary dysplasia(BPD)is not merely a chronic lung disease,but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure.Despite advances in current management strategies,limited progress has been made in reducing the BPD-related systemic damage.Meanwhile,although the protective effects of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)or their exosomes on hyperoxia-induced lung injury have been explored by many researchers,the underlying mechanism has not been addressed in detail,and few studies have focused on the therapeutic effect on systemic multiple organ injury.AIM To investigate whether hUC-MSC intratracheal administration could attenuate hyperoxia-induced lung,heart,and kidney injuries and the underlying regulatory mechanisms.METHODS Neonatal rats were exposed to hyperoxia(80%O_(2)),treated with hUC-MSCs intratracheal(iT)or intraperitoneal(iP)on postnatal day 7,and harvested on postnatal day 21.The tissue sections of the lung,heart,and kidney were analyzed morphometrically.Protein contents of the bronchoalveolar lavage fluid(BALF),myeloper oxidase(MPO)expression,and malondialdehyde(MDA)levels were examined.Pulmonary inflammatory cytokines were measured via enzyme-linked immunosorbent assay.A comparative transcriptomic analysis of differentially expressed genes(DEGs)in lung tissue was conducted via RNA-sequencing.Subsequently,we performed reverse transcription-quantitative polymerase chain reaction and western blot analysis to explore the expression of target mRNA and proteins related to inflammatory and oxidative responses.RESULTS iT hUC-MSCs administration improved pulmonary alveolarization and angiogenesis(P<0.01,P<0.01,P<0.001,and P<0.05 for mean linear intercept,septal counts,vascular medial thickness index,and microvessel density respectively).Meanwhile,treatment with hUC-MSCs iT ameliorated right ventricular hypertrophy(for Fulton’s index,P<0.01),and relieved reduced nephrogenic zone width(P<0.01)and glomerular diameter(P<0.001)in kidneys.Among the beneficial effects,a reduction of BALF protein,MPO,and MDA was observed in hUC-MSCs groups(P<0.01,P<0.001,and P<0.05 respectively).Increased pro-inflammatory cytokines tumor necrosis factor-alpha,interleukin(IL)-1β,and IL-6 expression observed in the hyperoxia group were significantly attenuated by hUC-MSCs administration(P<0.01,P<0.001,and P<0.05 respectively).In addition,we observed an increase in anti-inflammatory cytokine IL-10 expression in rats that received hUC-MSCs iT compared with rats reared in hyperoxia(P<0.05).Transcriptomic analysis showed that the DEGs in lung tissues induced by hyperoxia were enriched in pathways related to inflammatory responses,epithelial cell proliferation,and vasculature development.hUC-MSCs administration blunted these hyperoxia-induced dysregulated genes and resulted in a shift in the gene expression pattern toward the normoxia group.hUC-MSCs increased heme oxygenase-1(HO-1),JAK2,and STAT3 expression,and their phosphorylation in the lung,heart,and kidney(P<0.05).Remarkably,no significant difference was observed between the iT and iP administration.CONCLUSION iT hUC-MSCs administration ameliorates hyperoxia-induced lung,heart,and kidney injuries by activating HO-1 expression and JAK/STAT signaling.The therapeutic benefits of local iT and iP administration are equivalent.
文摘Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature search including EMBASE,MEDLINE,and CINAHL databases to identify all relevant papers published in the English and German literature on influenza and respiratory syncytial virus infection associated with preterm infant,prematurity,and BPD between 1980 and 2014.Results:Recurrent respiratory symptoms remain common at preschool age,school age and even into young adulthood.Acute viral respiratory tract infections due to different pathogens cause significant morbidity and necessitate rehospitalizations during the fi rst years of life.Infl uenza virus infection plays a minor role compared to respiratory syncytial virus(RSV)associated respiratory tract infection during infancy and early childhood.Nevertheless,particular morbidity to both viruses is high.Conclusions:The particular burden of both viral diseases in preterm infants is dominated by RSV and its associated rehospitalizations during the fi rst two years of life.Prophylactic measures include vaccination against influenza virus of family members and caregivers and active immunization starting at the age of 6 months,and monthly injections of palivizumab during the cold season to avoid severe RSV disease and its sequelae.
文摘Background:To determine the characteristics and outcomes of pulmonary arterial hypertension(PAH)in extremely low birth weight(ELBW)infants.Methods:A retrospective case-control study of all ELBW infants admitted to a level III neonatal intensive care unit(NICU)between January 1,2003 and December 31,2010.Results:During the study period,450 ELBW infants were admitted.6.4%(29/450)were diagnosed with PAH and were matched to 26 controls.The mean gestational age of infants with PAH and their controls were similar[24.5±1.3 vs.24.9±1.8 weeks(P=0.26)];however the cases were smaller at birth than were controls[640.7±119.5 vs.727.0±184.5 g(P=0.04)].The diagnosis of PAH was made at a mean postnatal age of 131.8±53.7 days.Infants with PAH had a higher rate of intrauterine exposure to illicit maternal drug use[12/29(41%)vs.1/25(4%);P=0.001],a longer duration of initial mechanical ventilation[74.9±28.3 vs.59.1±27.8 days;(P=0.04)],a higher incidence of severe BPD[23/29(79%)vs.13/26(50%);P=0.02],and a greater NICU mortality rate[12/29(41%)vs.4/26(15%);P=0.04].Conclusion:PAH in ELBW infants is associated with maternal illicit drug use in pregnancy,longer exposure to mechanical ventilation,severe bronchopulmonary dysplasia and a significant increase in early mortality.
文摘Background:To investigate strategies used for the management of respiratory distress syndrome(RDS)and bronchopulmonary dysplasia(BPD)in extremely low birth weight(ELBW)infants.Methods:A survey of neonatal specialists working in US academic institutions with fellowship training programs.Results:Eighty percent(72/89)of the identifi ed academic institutions had at least one physician who responded to the survey.Among respondents,85%(171/201)agreed or strongly agreed to use continuous positive airway pressure(CPAP)initially for the management of RDS,and the majority agreed or strongly agreed to use a fraction of inspired oxygen(FiO2)≥0.4 and a mean airway pressure(MAP)≥10 cm H2O as a criteria for surfactant therapy;and 73%(146/200)sometimes or always used caffeine to prevent BPD.Only 25%(50/202)sometimes or almost always used steroids to prevent or treat BPD.Identified indications to use steroids were 3 or more extubation failures or inability to extubate beyond 8 weeks of age.Conclusions:Variability in treatment strategies of ELBW is common among neonatal specialists.However,the majority of the respondents agreed or strongly agreed to use early CPAP for the management of RDS,consider a FiO2≥0.4 and a MAP≥10 cm H2O as criteria for surfactant therapy,and sometimes or almost always used caffeine to prevent BPD.Steroids continue to have a role in the management of BPD in infants who are diffi cult to extubate.
文摘Background To compare short and long outcomes between early(≤28 days)(EL)and late ligation(LL)groups.To explore factors predicting early extubation(≤7 days)after patent ductus arteriosus(PDA)ligation.Methods We conducted a single center,retrospective cohort study of preterm infants<32 weeks who underwent surgical ligation over a 10-year period(2009-2019).Results A total of 133 infants underwent PDA ligation,in the study period.Both groups had similar short-term outcome such as bronchopulmonary dysplasia(BPD)or death(96%vs.98%,P=0.64)and long-term clinical outcomes including Bayley's assessment at 2 years corrected age.Fewer infants in the EL group developed severe BPD(63%vs.81%,P=0.02).Age at ligation had adjusted odds ratio of 1.04 with over lapping confidence interval(95%CI 1.0-1.1,P=0.02)for severe BPD/death.There was no difference in day of extubation between the EL and LL group(8 days vs.7 days,P=0.85).Left atrium/aortic root ratio of ≥1.75 would give sensitivity of 41% and 80% specificity for early extubation(area under the curve of 0.61).There was marginal reduction of hospital stay in the EL group[113(105-121)days vs.115(107-123)days;log rank P=0.026].Conclusion EL can be delivered safely with a clinically important lower incidenee of severe BPD and shorter duration of hospital stay compared to LL.
基金supported by an NIH R01 R01HL166327Institutional Development Award(IDeA)from the NIGMS of NIH un-der grant No.P20GM103652the Rhode Island Foundation grant No.14699_20231340(HY),and the Warren Alpert Foundation of Brown University(PAD).
文摘Cellular senescence is a status of irreversible growth arrest,which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external factors.Senescent cells are typically enlarged and flattened,and characterized by numerous molecular features.The latter consists of increased surfaceome,increased resid-ual lysosomal activity at pH 6.0(manifested by increased activity of senescence-associated beta-galactosidase[SA-𝛽-gal]),senescence-associated mitochondrial dysfunction,cytoplasmic chromatin fragment,nuclear lamin b1 exclusion,telomere-associated foci,and the senescence-associated secretory phenotype.These features vary depending on the stressor leading to senescence and the type of senescence.Cellular senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related diseases.Interestingly,senescence can also both promote and inhibit wound healing processes.We recently report that senescence as a programmed pro-cess contributes to normal lung development.Lung senescence is also observed in Down Syndrome,as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this disease.Furthermore,this senescence results in neonatal lung injury.In this review,we briefly discuss the molecular features of senescence.We then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving senescence.Finally,we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.
