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European Journal of Human Genetics :... Oct 2023Nuclear receptor subfamily 2 group F member 2 (NR2F2 or COUP-TF2) encodes a transcription factor which is expressed at high levels during mammalian development. Rare...
Nuclear receptor subfamily 2 group F member 2 (NR2F2 or COUP-TF2) encodes a transcription factor which is expressed at high levels during mammalian development. Rare heterozygous Mendelian variants in NR2F2 were initially identified in individuals with congenital heart disease (CHD), then subsequently in cohorts of congenital diaphragmatic hernia (CDH) and 46,XX ovotesticular disorders/differences of sexual development (DSD); however, the phenotypic spectrum associated with pathogenic variants in NR2F2 remains poorly characterized. Currently, less than 40 individuals with heterozygous pathogenic variants in NR2F2 have been reported. Here, we review the clinical and molecular details of 17 previously unreported individuals with rare heterozygous NR2F2 variants, the majority of which were de novo. Clinical features were variable, including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations, thus expanding the phenotypic spectrum associated with NR2F2 variants. The variants seen were predicted loss of function, including a nonsense variant inherited from a mildly affected mosaic mother, missense and a large deletion including the NR2F2 gene. Our study presents evidence for rare, heterozygous NR2F2 variants causing a highly variable syndrome of congenital anomalies, commonly associated with heart defects, developmental delays/intellectual disability, dysmorphic features, feeding difficulties, hypotonia, and genital anomalies. Based on the new and previous cases, we provide clinical recommendations for evaluating individuals diagnosed with an NR2F2-associated disorder.
Topics: Animals; Humans; Abnormalities, Multiple; COUP Transcription Factor II; Heart Defects, Congenital; Hernias, Diaphragmatic, Congenital; Intellectual Disability; Muscle Hypotonia; Syndrome
PubMed: 37500725
DOI: 10.1038/s41431-023-01434-5 -
Revista Colombiana de Obstetricia Y... Sep 2023To report a case of prenatal diagnosis of ectopic intrathoracic kidney with diaphragmatic hernia managed surgically after birth, and to conduct a review of the...
OBJECTIVES
To report a case of prenatal diagnosis of ectopic intrathoracic kidney with diaphragmatic hernia managed surgically after birth, and to conduct a review of the literature on prenatal diagnosis of ectopic intrathoracic kidney and perinatal prognosis.
MATERIAL AND METHODS
We report the case of a 28-week fetus in which, on ultrasound imaging, a mass was observed displacing the heart and lung in the right hemithorax, which was was confirmed by magnetic resonance (MR) to be an ectopic intrathoracic kidney (ITEK). After birth, the neonate was approached by laparoscopy to place a mesh in continuity with the diaphragm, leaving the kidney in the abdomen, with good evolution. A search was conducted in the PubMed, Embase and Cochrane databases for cohorts, case reports and case series of prenatal diagnosis of intrathoracic kidney in the fetus. Information was retrieved regarding design, population, imaging diagnosis, treatment and prognosis.
RESULTS
The search identified 8 studies that met the inclusion criteria, reporting a total of 8 cases. Ultrasound diagnosis showed ectopic intrathoracic kidney associated with diaphragmatic hernia in all the subjects. Fetal magnetic resonance imaging (MRI) was also used in 5 cases.
CONCLUSIONS
Ectopic intrathoracic kidney is a congenital abnormality amenable to prenatal diagnosis. Survival after corrective surgery performed in the neonatal period is common. There is a paucity of publications, limited to case reports, regarding the prenatal diagnosis of this condition.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Prenatal Diagnosis; Hernia, Diaphragmatic; Hernia; Kidney
PubMed: 37937910
DOI: 10.18597/rcog.4020 -
Seminars in Perinatology Mar 2024Optimal respiratory support can only be achieved if the ventilator strategy utilized for each individual patient at any given point in the evolution of their disease... (Review)
Review
Optimal respiratory support can only be achieved if the ventilator strategy utilized for each individual patient at any given point in the evolution of their disease process is tailored to the underlying pathophysiology. The critically ill newborn infant requires individualized patient care when it comes to mechanical ventilation. This can only occur if the clinician has a good understanding of the different pathophysiologies of a variety of conditions that can lead to respiratory failure. In this chapter we describe the key pathophysiological features of bronchopulmonary dysplasia, meconium aspiration syndrome and lung hypoplasia syndromes with emphasis on congenital diaphragmatic hernia. We review available evidence to guide management an provide specific recommendations for pathophysiologically-based mechanical ventilation support.
Topics: Infant; Female; Humans; Infant, Newborn; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Meconium Aspiration Syndrome; Lung; Hernias, Diaphragmatic, Congenital
PubMed: 38555219
DOI: 10.1016/j.semperi.2024.151888 -
The American Surgeon Nov 2023Giovanni Morgagni remains an eminent figure in the field of pathological anatomy. Born in Forli, Italy, he excelled as a child. He entered medical school at the age of...
Giovanni Morgagni remains an eminent figure in the field of pathological anatomy. Born in Forli, Italy, he excelled as a child. He entered medical school at the age of 16 years old in Bologna. By the age of 31 he held the chair position at the University of Padua. During his tenure, he discovered many anatomical and pathological findings, with the most widely known discovery being the Morgagni Hernia. Morgagni first described this eponymic hernia in an adult stonecutter during an autopsy. In addition to his many discoveries, his most esteemed written contribution to the field of medicine came in the form of a five-volume book titled , in which he correlated cadaveric anatomy and symptomatology revealed upon autopsy. He remained on faculty at the University of Padua for over five decades until his death in 1771.
Topics: Italy; History, 18th Century; Humans; Anatomy; Hernia, Diaphragmatic
PubMed: 33886389
DOI: 10.1177/00031348211011108 -
American Journal of Respiratory Cell... Nov 2023Abnormal lung development is the main cause of morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH), a common birth defect (1:2,500) of largely...
Abnormal lung development is the main cause of morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH), a common birth defect (1:2,500) of largely unknown pathobiology. Recent studies discovered that inflammatory processes, and specifically NF-κB-associated pathways, are enriched in human and experimental CDH. However, the molecular signaling of NF-κB in abnormal CDH lung development and its potential as a therapeutic target require further investigation. Using sections and hypoplastic lung explant cultures from the nitrofen rat model of CDH and human fetal CDH lungs, we demonstrate that NF-κB and its downstream transcriptional targets are hyperactive during abnormal lung formation in CDH. NF-κB activity was especially elevated in the airway epithelium of nitrofen and human CDH lungs at different developmental stages. Fetal rat lung explants had impaired pseudoglandular airway branching after exposure to nitrofen, together with increased phosphorylation and transcriptional activity of NF-κB. Dexamethasone, the broad and clinically applicable antiinflammatory NF-κB antagonist, rescued lung branching and normalized NF-κB signaling in hypoplastic lung explants. Moreover, specific NF-κB inhibition with curcumenol similarly rescued lung hypoplasia and restored NF-κB signaling. Last, we showed that prenatal intraperitoneal dexamethasone administration to pregnant rat dams carrying fetuses with hypoplastic lungs significantly improves lung branching and normalizes NF-κB . Our results indicate that NF-κB is aberrantly activated in human and nitrofen CDH lungs. Antiinflammatory treatment with dexamethasone and/or specific NF-κB inhibition should be investigated further as a therapeutic avenue to target lung hypoplasia in CDH.
Topics: Pregnancy; Female; Humans; Rats; Animals; Hernias, Diaphragmatic, Congenital; NF-kappa B; Rats, Sprague-Dawley; Lung; Lung Diseases; Dexamethasone; Disease Models, Animal
PubMed: 37552822
DOI: 10.1165/rcmb.2023-0138OC -
Journal of Clinical Medicine Mar 2024Pleural effusion and chylothorax are common complications in the treatment of congenital diaphragmatic hernia (CDH). We set out to identify risk factors for chylothorax...
Pleural effusion and chylothorax are common complications in the treatment of congenital diaphragmatic hernia (CDH). We set out to identify risk factors for chylothorax development in patients with CDH and to investigate the association of pleural effusion and chylothorax with neonatal morbidity and mortality. In this retrospective cohort study, we included 396 neonates with CDH treated at our institution between January 2013 and June 2019. Preoperative and postoperative chest radiographs and clinical data were evaluated and correlated with morbidity, complications and mortality. Laboratory-confirmed chylothorax occurred in 58 (18.6%) of all CDH cases. Pleural effusion was frequently observed as a postoperative complication but also occurred as a pre-existing condition. Neonates with large defects of size C and D, patch repair, the need for presurgical and/or postsurgical ECMO support, pulmonary hypertension, liver-up phenomenon and lower relative fetal lung volume were associated with higher occurrences of chylothorax. After stepwise logistic regression, larger CDH defects ( < 0.0001) and the need for postsurgical ECMO ( = 0.0158) remained significant risk factors for CTX to occur (AUC 0.71). The same potential risk factors were used to assess their association with both presurgical and postsurgical pleural effusion. After stepwise logistic regression, only the need for presurgical ECMO remained significantly associated with presurgical PE ( < 0.01, AUC 0.65) and patch repair as the therapeutic intervention remained significantly associated with the occurrence of postsurgical PE ( < 0.0001, AUC 0.80). Patients with CTX had longer durations of both MV ( < 0.0001) and subsequent ventilatory assistance with spontaneous breathing ( = 0.0004), increased total lengths of hospitalization ( < 0.0001), increased durations of ECMO ( < 0.01) and increased incidences of CLD ( < 0.0001) compared to patients without CTX. No significant difference could be found for survival in both groups ( = 0.12). Our data suggest that the incidence of chylothorax is associated with large diaphragmatic defects, the need for postsurgical ECMO and the development of chronic lung disease, but not with survival.
PubMed: 38541987
DOI: 10.3390/jcm13061764 -
Surfactant Therapy in Congenital Diaphragmatic Hernia and Fetoscopic Endoluminal Tracheal Occlusion.The Journal of Surgical Research Apr 2024Congenital diaphragmatic hernia (CDH) is a complex pathology with severe pulmonary morbidity. Administration of surfactant in CDH is controversial, and the advent of...
INTRODUCTION
Congenital diaphragmatic hernia (CDH) is a complex pathology with severe pulmonary morbidity. Administration of surfactant in CDH is controversial, and the advent of fetoscopic endoluminal tracheal occlusion (FETO) has added further complexity. While FETO has been shown to improve survival outcomes, there are risks of prematurity and potential surfactant deficiency. We aim to evaluate the characteristics and outcomes of surfactant administration for CDH infants and elucidate potential benefits or risks in this unique population.
METHODS
A single-center retrospective cohort review of patients with unilateral CDH from September 2015 to July 2022 was performed. Demographics, prognostic perinatal imaging features, and outcomes were collected. Patients were stratified by surfactant administration and history of FETO. Data were analyzed with descriptive statistics, two-sample t-tests, chi-squared analyses, and logistic regression.
RESULTS
Of 105 included patients, 19 (18%) underwent FETO and 25 (24%) received surfactant. Overall, surfactant recipients were born at earlier gestational ages and lower birthweights regardless of FETO history. Surfactant recipients possessed significantly worse prenatal prognostic features such as observed to expected total fetal lung volume, observed to expected lung to head ratio, and percent liver herniation. In CDH patients without FETO history, surfactant recipients demonstrated worse outcomes than nonrecipients. This association is notably absent in the FETO population, where surfactant recipients have more favorable survival and comparable outcomes. When controlling for defect severity or surfactant usage, as a proxy for respiratory status, surfactant recipients that underwent FETO trended toward improved survival and decreased ECMO use.
CONCLUSIONS
Surfactant administration is not associated with increased morbidity and mortality and may be beneficial in CDH patients that have undergone FETO.
Topics: Pregnancy; Infant; Female; Humans; Hernias, Diaphragmatic, Congenital; Retrospective Studies; Surface-Active Agents; Trachea; Fetoscopy
PubMed: 38295711
DOI: 10.1016/j.jss.2023.12.003 -
World Journal of Clinical Cases Sep 2023Diaphragmatic hernia (DH) is extremely rarely described during pregnancy. Due to the rarity, there is no diagnostic or treatment algorithm for DH in pregnancy.
BACKGROUND
Diaphragmatic hernia (DH) is extremely rarely described during pregnancy. Due to the rarity, there is no diagnostic or treatment algorithm for DH in pregnancy.
AIM
To summarize and define the most appropriate diagnostic methods and therapeutic options for DH in pregnancy based on scarce literature.
METHODS
Literature search of English-, German-, Spanish-, and Italian-language articles were performed using PubMed (1946-2021), PubMed Central (1900-2021), and Google Scholar. The PRISMA protocol was followed. The search terms included: Maternal diaphragmatic hernia, congenital hernia, pregnancy, cardiovascular collapse, mediastinal shift, abdominal pain in pregnancy, hyperemesis, diaphragmatic rupture during labor, puerperium, hernie diaphragmatique maternelle, hernia diafragmática congenital. Additional studies were identified by reviewing reference lists of retrieved studies. Demographic, imaging, surgical, and obstetric data were obtained.
RESULTS
One hundred and fifty-eight cases were collected. The average maternal age increased across observed periods. The proportion of congenital hernias increased, while the other types appeared stationary. Most DHs were left-sided (83.8%). The median number of herniated organs declined across observed periods. A working diagnosis was correct in 50%. DH type did not correlate to maternal or neonatal outcomes. Laparoscopic access increased while thoracotomy varied across periods. Presentation of less than 3 days carried a significant risk of strangulation in pregnancy.
CONCLUSION
The clinical presentation of DH is easily confused with common chest conditions, delaying the diagnosis, and increasing maternal and fetal mortality. Symptomatic DH should be included in the differential diagnosis of pregnant women with abdominal pain associated with dyspnea and chest pain, especially when followed by collapse. Early diagnosis and immediate intervention lead to excellent maternal and fetal outcomes. A proposed algorithm helps manage pregnant women with maternal DH. Strangulated DH requires an emergent operation, while delivery should be based on obstetric indications.
PubMed: 37900237
DOI: 10.12998/wjcc.v11.i27.6440 -
The Journal of Pediatrics Oct 2023To evaluate associations between cardiac catheterization (cath) hemodynamics, quantitative measures of right ventricular (RV) function by echocardiogram, and survival in...
OBJECTIVE
To evaluate associations between cardiac catheterization (cath) hemodynamics, quantitative measures of right ventricular (RV) function by echocardiogram, and survival in patients with congenital diaphragmatic hernia (CDH).
STUDY DESIGN
This single-center retrospective cohort study enrolled patients with CDH who underwent index cath from 2003 to 2022. Tricuspid annular plane systolic excursion z score, RV fractional area change, RV free wall and global longitudinal strain, left ventricular (LV) eccentricity index, RV/LV ratio, and pulmonary artery acceleration time were measured from preprocedure echocardiograms. Associations between hemodynamic values, echocardiographic measures, and survival were evaluated by Spearman correlation and Wilcoxon rank sum test, respectively.
RESULTS
Fifty-three patients (68% left-sided, 74% liver herniation, 57% extracorporeal membrane oxygenation, 93% survival) underwent cath (39 during index hospitalization, 14 later) including device closure of a patent ductus arteriosus in 5. Most patients (n = 31, 58%) were on pulmonary hypertension treatment at cath, most commonly sildenafil (n = 24, 45%) and/or intravenous treprostinil (n = 16, 30%). Overall, hemodynamics were consistent with precapillary pulmonary hypertension. Pulmonary capillary wedge pressure was >15 mm Hg in 2 patients (4%). Lower fractional area change and worse ventricular strain were associated with higher pulmonary artery pressure while higher LV eccentricity index and higher RV/LV ratio were associated with both higher pulmonary artery pressure and higher pulmonary vascular resistance. Hemodynamics did not differ based on survival status.
CONCLUSIONS
Worse RV dilation and dysfunction by echocardiogram correlate with higher pulmonary artery pressure and pulmonary vascular resistance on cath in this CDH cohort. These measures may represent novel, noninvasive clinical trial targets in this population.
Topics: Humans; Hernias, Diaphragmatic, Congenital; Retrospective Studies; Hypertension, Pulmonary; Ventricular Dysfunction, Right; Echocardiography; Cardiac Catheterization; Hemodynamics; Ventricular Function, Right
PubMed: 37329980
DOI: 10.1016/j.jpeds.2023.113564 -
Translational Pediatrics Jul 2023Congenital diaphragmatic hernia (CDH) is an anomaly of the cardiopulmonary system maturation process that results from both a global embryopathy and concomitant... (Review)
Review
BACKGROUND AND OBJECTIVE
Congenital diaphragmatic hernia (CDH) is an anomaly of the cardiopulmonary system maturation process that results from both a global embryopathy and concomitant mechanical compression of the cardiopulmonary system from the abdominal contents during fetal maturation. This results in pulmonary hypertension, pulmonary hypoplasia, and cardiac dysfunction, requiring intense critical care management. The patients with highest risk CDH are the most challenging, resource-intensive, and bear most of the mortality. Advances at the basic, translational, and clinical research levels are leading to novel therapies and management strategies for complex, high-risk CDH. Our objective is to review novel approaches in thinking and management for the most complex and high-risk CDH patients. These include patients with prenatal and postnatal indicators of high-risk defects, those receiving extracorporeal life support (ECLS), and those with concomitant anomalies such as complex cardiac and/or chromosomal abnormalities.
METHODS
PubMed was searched in late 2022 and early 2023 to identify relevant evidence. Search terms included congenital diaphragmatic hernia (CDH)", "extracorporeal life support (ECLS)", "pulmonary hypertension", "dual-hit hypothesis", "risk reduction", "cardiac/chromosomal anomalies", and "novel therapies". We included trials, multicenter studies (prospective and retrospective), single-center reports, and review articles/expert opinion.
KEY CONTENT AND FINDINGS
CDH is a congenital anomaly of the cardiopulmonary and diaphragmatic systems that represents a spectrum of disease. High-risk or complex patients are defined by prenatal/postnatal risk stratification, receipt of ECLS, and/or having concomitant anomalies, representing the severe end of that spectrum. Overall survival of high-risk CDH is about 50% and comprises the vast majority of mortality, mandating special emphasis. The development of risk-stratification processes, best practices or guidelines of management, and novel therapies is critical to optimize the care of these infants.
CONCLUSIONS
CDH patients with high-risk disease remain a challenging subset of CDH patients. Increasing opportunities for survival are being realized with novel, investigational approaches.
PubMed: 37575897
DOI: 10.21037/tp-23-240