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Clinical Correlates of Cerebellar Injury in Preterm Infants with Surgical Necrotizing Enterocolitis.Research Square Dec 2023Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC).
OBJECTIVE
Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC).
METHODS
Retrospective study compared clinical/pathological information between surgical NEC infants with and those without cerebellar injury.
RESULTS
Infants with cerebellar injury (21/65, 32.3%) had significantly more hemorrhagic and the reparative lesions on the intestinal histopathology, had patent ductus arteriosus (PDA) more often, received red cell transfusion frequently, had blood culture positive sepsis and grew gram positive organisms more often and had cholestasis frequently following NEC than those without cerebellar injury. On multilogistic regression, the positive blood culture sepsis (OR 3.9, CI 1.1-13.7, p = 0.03), PDA (OR 4.5, CI 1.0-19.9, p = 0.04) and severe hemorrhage (grade 3-4)(OR 16.9, CI 2.1-135.5, p = 0.007) were independently associated with higher risk of cerebellar injury.
CONCLUSION
The cerebellar injury was most likely associated with positive blood culture sepsis following NEC, PDA, and severe hemorrhage lesions (grade 3-4) in infants with surgical NEC.
PubMed: 38168331
DOI: 10.21203/rs.3.rs-3720723/v1 -
BMJ Open Jul 2023Severe bronchopulmonary dysplasia (BPD) is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term...
Enteral supplementation with high-dose docosahexaenoic acid on the risk of bronchopulmonary dysplasia in very preterm infants: a collaborative study protocol for an individual participant data meta-analysis.
INTRODUCTION
Severe bronchopulmonary dysplasia (BPD) is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term neurodevelopmental outcomes, the potential adverse effects of high-dose docosahexaenoic acid (DHA) supplementation on this short-term neonatal morbidity need further investigations in infants born very preterm. This study will determine whether high-dose DHA enteral supplementation during the neonatal period is associated with the risk of severe BPD at 36 weeks' postmenstrual age (PMA) compared with control, in contemporary cohorts of preterm infants born at less than 29 weeks of gestation.
METHODS AND ANALYSIS
As part of an Australian-Canadian collaboration, we will conduct an individual participant data (IPD) meta-analysis of randomised controlled trials targeting infants born at less than 29 weeks of gestation and evaluating the effect of high-dose DHA enteral supplementation in the neonatal period compared with a control. Primary outcome will be severe grades of BPD (yes/no) at 36 weeks' PMA harmonised according to a recent definition that predicts early childhood morbidities. Other outcomes will be survival without severe BPD, death, BPD severity grades, serious brain injury, severe retinopathy of prematurity, patent ductus arteriosus and necrotising enterocolitis requiring surgery, sepsis, combined neonatal morbidities and growth. Severe BPD will be compared between groups using a multivariate generalised estimating equations log-binomial regression model. Subgroup analyses are planned for gestational age, sex, small-for-gestational age, presence of maternal chorioamnionitis and mode of delivery.
ETHICS AND DISSEMINATION
The conduct of each trial was approved by institutional research ethics boards and written informed consent was obtained from participating parents. A collaboration and data sharing agreement will be signed between participating authors and institutions. This IPD meta-analysis will document the role of DHA in nutritional management of BPD. Findings will be disseminated through conferences, media interviews and publications to peer-reviewed journals.
PROSPERO REGISTRATION NUMBER
CRD42023431063.
TRIAL REGISTRATION NUMBER
NCT05915806.
Topics: Child, Preschool; Infant; Infant, Newborn; Humans; Infant, Premature; Bronchopulmonary Dysplasia; Docosahexaenoic Acids; Australia; Canada; Infant, Premature, Diseases; Dietary Supplements; Meta-Analysis as Topic
PubMed: 37518076
DOI: 10.1136/bmjopen-2023-076223 -
International Journal of Molecular... Nov 2023Patent ductus arteriosus (PDA) is a common congenital heart disease. CITED2 plays an important role in the development of the heart, and genetic variants in its coding...
Patent ductus arteriosus (PDA) is a common congenital heart disease. CITED2 plays an important role in the development of the heart, and genetic variants in its coding region are significantly associated with cardiac malformations. However, the role of variants in the promoter region of CITED2 in the development of PDA remains unclear. We extracted the peripheral blood of 646 subjects (including 353 PDA patients and 293 unrelated healthy controls) for sequencing. We identified 13 promoter variants of the CITED2 gene (including 2 novel heterozygous variants). Of the 13 variants, 10 were found only in PDA patients. In mouse cardiomyocytes (HL-1) and rat cardiac myocytes (RCM), the transcriptional activity of the CITED2 gene promoter was significantly changed by the variants ( < 0.05). The results of the experiments of electrophoretic mobility indicated that these variants may affect the transcription of the CITED2 gene by influencing the binding ability of transcription factors. These results, combined with the JASPAR database analysis, showed that the destruction/production of transcription factor binding sites due to the variants in the promoter region of the CITED2 gene may directly or indirectly affect the binding ability of transcription factors. Our results suggest for the first time that variants at the CITED2 promoter region may cause low expression of CITED2 protein related to the formation of PDA.
Topics: Humans; Animals; Mice; Rats; Ductus Arteriosus, Patent; Heart Defects, Congenital; Transcription Factors; Myocytes, Cardiac; Promoter Regions, Genetic; Repressor Proteins; Trans-Activators
PubMed: 38003393
DOI: 10.3390/ijms242216204 -
Annals of Cardiac Anaesthesia Jan 2024The quadricuspid aortic valve is a rare congenital anomaly, usually associated with aortic regurgitation requiring surgical intervention. It may be associated with other...
The quadricuspid aortic valve is a rare congenital anomaly, usually associated with aortic regurgitation requiring surgical intervention. It may be associated with other congenital anomalies such as coronary anomalies, patent ductus arteriosus, ventricular septal defect, pulmonary stenosis, and subaortic stenosis. The diagnosis is generally established by either transthoracic or transesophageal echocardiography. Herein, we report a case of a 52-year-old woman who was diagnosed to have quadricuspid aortic valve by intraoperative transesophageal echocardiography.
Topics: Humans; Female; Aortic Valve; Middle Aged; Echocardiography, Transesophageal; Aortic Valve Insufficiency; Heart Defects, Congenital
PubMed: 38722121
DOI: 10.4103/aca.aca_110_23 -
Molecular Pharmacology Feb 2024Vascular smooth muscle K channels critically regulate blood flow and blood pressure by modulating vascular tone and therefore represent attractive drug targets for...
Vascular smooth muscle K channels critically regulate blood flow and blood pressure by modulating vascular tone and therefore represent attractive drug targets for treating several cardiovascular disorders. However, the lack of potent inhibitors that can selectively inhibit Kir6.1/SUR2B (vascular K) over Kir6.2/SUR1 (pancreatic K) has eluded discovery despite decades of intensive research. We therefore screened 47,872 chemically diverse compounds for novel inhibitors of heterologously expressed Kir6.1/SUR2B channels. The most potent inhibitor identified in the screen was an -aryl-'-benzyl urea compound termed VU0542270. VU0542270 inhibits Kir6.1/SUR2B with an IC of approximately 100 nM but has no apparent activity toward Kir6.2/SUR1 or several other members of the Kir channel family at doses up to 30 µM (>300-fold selectivity). By expressing different combinations of Kir6.1 or Kir6.2 with SUR1, SUR2A, or SUR2B, the VU0542270 binding site was localized to SUR2. Initial structure-activity relationship exploration around VU0542270 revealed basic texture related to structural elements that are required for Kir6.1/SUR2B inhibition. Analysis of the pharmacokinetic properties of VU0542270 showed that it has a short in vivo half-life due to extensive metabolism. In pressure myography experiments on isolated mouse ductus arteriosus vessels, VU0542270 induced ductus arteriosus constriction in a dose-dependent manner similar to that of the nonspecific K channel inhibitor glibenclamide. The discovery of VU0542270 provides conceptual proof that SUR2-specific K channel inhibitors can be developed using a molecular target-based approach and offers hope for developing cardiovascular therapeutics targeting Kir6.1/SUR2B. SIGNIFICANCE STATEMENT: Small-molecule inhibitors of vascular smooth muscle K channels might represent novel therapeutics for patent ductus arteriosus, migraine headache, and sepsis; however, the lack of selective channel inhibitors has slowed progress in these therapeutic areas. Here, this study describes the discovery and characterization of the first vascular-specific K channel inhibitor, VU0542270.
Topics: Animals; Mice; Glyburide; KATP Channels; Muscle, Smooth, Vascular; Sulfonylurea Receptors
PubMed: 38302135
DOI: 10.1124/molpharm.123.000783 -
Archivos de Cardiologia de Mexico Feb 2024To communicate the experience in an Andean country with the OcclutechTM Duct Occluder device for the closure of patent ductus arteriosus.
BACKGROUND AND OBJECTIVE
To communicate the experience in an Andean country with the OcclutechTM Duct Occluder device for the closure of patent ductus arteriosus.
METHOD
observational, retrospective, cross-sectional study with basic statistical analysis. Period: December/2014 to December/2022. Data: medical chart, reports of catheterization.
RESULTS
Forty-six patients, female 71.3%, male 28.7%; age: 0.6-38 years-old (median [Me]: 5.2); weight: 6.3-60 kg (Me: 16.5). Origin: Andean 91.3%, coast 8.7%. Types of patent ductus arteriosus: E 54.4%, A 32.6%, D 13%. Minimum ductal diameter: 1.8-11.8 mm (Me: 3.5). Mean pulmonary artery pressure prior to occlusion: 14-67 mmHg (Me: 27). Pulmonary vascular resistance index prior to occlusion: 0.28-4.9 WU/m2 (Me: 1.3). Six of them were classified as hypertensive patent ductus arteriosus. Occlusion rate: 47.8% immediate, 81% at 24 hours, 100% after six months. Fluoroscopy time: 2-13.8 minutes (Me: 4). Complications: a migrated device. Follow-up: 1-6.5 years.
CONCLUSIONS
Occlutech Duct Occluder device was effective and safe for the closure of patent ductus arteriosus type E, A and D in low-altitude and high-altitude dwellers, whether they were children or adults, even when these ductus arteriosus were hypertensive.
PubMed: 38359430
DOI: 10.24875/ACM.23000126 -
BMC Pediatrics Jul 2023Neonatal necrotizing enterocolitis (NEC) is a common critical illness of the gastrointestinal system in neonatal intensive care units with complex causes. We want to... (Observational Study)
Observational Study
Patent ductus arterious and increased conjugated bilirubin in the second week after birth are independent risk factors for necrotizing enterocolitis in preterm infants: an observational study.
BACKGROUND
Neonatal necrotizing enterocolitis (NEC) is a common critical illness of the gastrointestinal system in neonatal intensive care units with complex causes. We want to explore effects of serum-conjugated bilirubin on the occurrence of NEC in preterm infants.
METHODS
A retrospective study of clinical case data of premature infants from 2017 to 2020 in the Department of pediatrics of the First Affiliated Hospital of Nanjing Medical University was conducted. Among these, 41 were diagnosed with NEC. After screening, 2 cases were excluded because of incomplete data. Propensity-matching score (PSM) was performed according to the ratio of 1:2(2 preterm infants in the NEC group were not matched), and finally, 37 cases were in the NEC group (average time to diagnosis was 18.9 days), and 74 cases in the non-NEC group. We compared the difference between the NEC and non-NEC groups in early serum-conjugated bilirubin and total bilirubin levels (time points: the first day of birth, 1 week after birth, 2 weeks after birth).
RESULTS
(1) The changing trend of conjugated bilirubin was different between the two groups(F = 4.085, P = 0.019). The NEC group's serum-conjugated bilirubin levels gradually increased ([Formula: see text] ± s:12.64±2.68; 17.11±4.48; 19.25±11.63), while the non-NEC group did not show a continuous upward trend ([Formula: see text] ± s:13.39±2.87; 15.63±3.75; 15.47±4.12). (2) Multiple analyses showed that patent ductus arteriosus(PDA) (odds ratio[OR] = 5.958, 95%confidence interval[CI] = 2.102 ~ 16.882) and increased conjugated bilirubin in the 2nd week (OR = 1.105, 95%CI = 1.013 ~ 1.206) after birth were independent risk factors for NEC.
CONCLUSIONS
The body had already experienced an elevation of conjugated bilirubin before the occurrence of NEC. The change of early conjugated bilirubin may be an important factor in the occurrence of NEC.
Topics: Female; Infant, Newborn; Humans; Child; Infant, Premature; Enterocolitis, Necrotizing; Indomethacin; Retrospective Studies; Ductus Arteriosus, Patent; Fetal Diseases; Risk Factors; Infant, Newborn, Diseases; Bilirubin
PubMed: 37442980
DOI: 10.1186/s12887-023-04173-0 -
Journal of Cardiothoracic Surgery Jun 2024As the pediatric patient with right pulmonary artery agenesis (PAA) matured, she progressively presented symptoms of pulmonary hypertension and hemoptysis. There is... (Review)
Review
Embolization treatment of right pulmonary artery agenisis with patent ductus arteriosus causing pulmonary hypertension and hemoptysis: a case report and literature review.
As the pediatric patient with right pulmonary artery agenesis (PAA) matured, she progressively presented symptoms of pulmonary hypertension and hemoptysis. There is limited clinical literature on this condition, and currently, there is no consensus regarding its diagnosis and treatment. This article presents a case study of a 16-year-old female patient with right pulmonary artery hypoplasia, providing a comprehensive summary and analysis of her developmental progression, pathology, diagnosis, and treatment.
Topics: Humans; Female; Hemoptysis; Pulmonary Artery; Adolescent; Embolization, Therapeutic; Hypertension, Pulmonary; Ductus Arteriosus, Patent
PubMed: 38926785
DOI: 10.1186/s13019-024-02883-9 -
Veterinary Sciences Nov 2023This retrospective cohort study included one hundred fifty-seven medium and large-size dogs with the aim of evaluating the effect of signalment and echocardiographic...
A Retrospective Cohort Evaluation of Left Ventricular Remodeling, Perioperative Complications and Outcome in Medium and Large Size Dogs with Patent Ductus Arteriosus after Percutaneous Closure.
This retrospective cohort study included one hundred fifty-seven medium and large-size dogs with the aim of evaluating the effect of signalment and echocardiographic features on complications, outcomes and left ventricular modifications before and after patent ductus arteriosus (PDA) closure. The patients were divided in two groups based on the heart remodeling after closure: Group A included dogs that had a reduction in the end-systolic volume index (ESVI) after closure compared to the ESVI measured before; Group B included dogs without a reduction in ESVI after closure. Body weight, minimal ductal diameter (MDD) of PDA, end-diastolic volume index and presence of arrhythmias at presentation were significantly higher in Group B compared to Group A. The shortening fraction and ejection fraction after closure were reduced in both groups, but in Group B there was a major reduction, and the mean values indicated a possible systolic dysfunction. Complications during the procedure and death due to cardiac reasons were greater in Group B compared to Group A. In conclusion, a higher body weight, a larger MDD, a more severe heart enlargement or arrhythmias at presentation increased the risk of developing a worsening structural and functional condition after ductal closure, and this can be associated with perioperative complications and cardiac death.
PubMed: 38133219
DOI: 10.3390/vetsci10120669 -
Cureus Dec 2023Preterm birth causes constant challenges, with bronchopulmonary dysplasia (BPD) being a major concern. Immediately after birth, it takes time to establish feeding... (Review)
Review
Preterm birth causes constant challenges, with bronchopulmonary dysplasia (BPD) being a major concern. Immediately after birth, it takes time to establish feeding between the mother and the premature baby. During this time, the telological shifting of fluid from extracellular space to intracellular space will help the baby; this transition should be smooth. Both normal physiologic changes and pathophysiologic events are capable of disrupting this delicate fluid shifting that occurs in very low-birth-weight infants during the first week of life. The immaturity of the renal system and evaporative losses complicate this process. This lack of fluid displacement can be associated with an increased amount of water in the lungs and reduced lung compliance. This can lead to the need for more ventilatory support and a higher oxygen requirement, which, in turn, leads to lung damage. The fluid restriction is also associated with complications such as severe dehydration, intracranial hemorrhage, and bilirubin toxicity. However, the administration of large amounts of fluid and salt is associated with an increased incidence of patent ductus arteriosus, BPD, necrotizing enterocolitis, and intraventricular hemorrhage. There were studies conducted in both the pre-surfactant and surfactant eras that were inconclusive regarding fluid restriction in BPD. We only included very recent studies. This systematic review attempts to summarize the current evidence, focusing on the efficacy and safety of early fluid management in preterm infants. This reduces the risk of BPD and improves outcomes for premature infants. As we know, intact survival is very important. Our review supported the early fluid restriction.
PubMed: 38249238
DOI: 10.7759/cureus.50805