-
Pediatric Research May 2021Congenital diaphragmatic hernia (CDH)-related deaths are the largest contributor to in-hospital neonatal deaths in children with congenital malformations. Morbidity and... (Review)
Review
Congenital diaphragmatic hernia (CDH)-related deaths are the largest contributor to in-hospital neonatal deaths in children with congenital malformations. Morbidity and mortality in CDH are directly related to the development of pulmonary hypertension (PH). Current treatment consists of supportive measures. To date, no pharmacotherapy has been shown to effectively reverse the hallmark finding of pulmonary vascular remodeling that is associated with pulmonary hypertension in CDH (CDH-PH). As such, there is a great need for novel therapies to effectively manage CDH-PH. Our review aims to evaluate emerging therapies, and specifically focuses on those that are still under investigation and not approved for clinical use by the Food and Drug Administration. Therapies were categorized into antenatal pharmacotherapies or antenatal regenerative therapies and assessed on their method of administration, safety profile, the effect on pulmonary vascular pathophysiology, and overall efficacy. In general, emerging antenatal pharmaceutical and regenerative treatments primarily aim to alleviate pulmonary vascular remodeling by restoring normal function and levels of key regulatory factors involved in pulmonary vascular development and/or in promoting angiogenesis. Overall, while these emerging therapies show great promise for the management of CDH-PH, most require further assessment of safety and efficacy in preclinical models before translation into the clinical setting. IMPACT: Emerging antenatal therapies for congenital diaphragmatic hernia-induced pulmonary hypertension (CDH-PH) show promise to effectively mitigate vascular remodeling in preclinical models. Further investigation is needed in preclinical and human studies to evaluate safety and efficacy prior to translation into the clinical arena. This review offers a comprehensive and up-to-date summary of emerging therapies currently under investigation in experimental animal models. There is no cure for CDH-PH. This review explores emerging therapeutic options for the treatment of CDH-PH and evaluates their impact on key molecular pathways and clinical markers of disease to determine efficacy in the preclinical stage.
Topics: Animals; Disease Models, Animal; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary
PubMed: 33038872
DOI: 10.1038/s41390-020-01191-x -
The Journal of Obstetrics and... Aug 2022To review new challenges of fetal therapy in Japan after the establishment of four existing fetal therapies as standard prenatal care with National Health Insurance...
AIM
To review new challenges of fetal therapy in Japan after the establishment of four existing fetal therapies as standard prenatal care with National Health Insurance coverage over the past 20 years.
METHODS
Reported studies and our current research activities related to four fetal therapies newly performed in Japan were reviewed.
RESULTS
Fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) aims to occlude the trachea using a detachable balloon to promote lung growth. Following the recent successful completion of an international randomized controlled trial for CDH, in which we participated, FETO is offered for severe left CDH to perform balloon insertion at 27-29 weeks and removal at 34 weeks of gestation. Fetal cystoscopy (FC) for low urinary tract obstruction was introduced to overcome the demerits of vesicoamniotic shunting. FC may provide a proper diagnosis by visual observation of the urethra and physiological treatment of the posterior urethral valve. The effectiveness of open fetal surgery for myelomeningocele (MMC), direct surgery with laparotomy and hysterotomy, for ameliorating hindbrain herniation and the motor function was demonstrated, but it was also associated with substantial maternal and fetal risks. Fetal aortic valvuloplasty (FAV), ultrasound-guided fetal aortic balloon dilation for critical aortic stenosis with evolving hypoplastic left heart syndrome may improve left heart development and maintain biventricular circulation. Feasibility and safety studies for FC, MMC open fetal surgery, and FAV are currently ongoing.
CONCLUSIONS
Clinical research on FETO, FC, MMC open fetal surgery, and FAV has proceeded with careful preparations in Japan.
Topics: Female; Fetal Therapies; Fetoscopy; Hernias, Diaphragmatic, Congenital; Humans; Japan; Pregnancy; Trachea
PubMed: 35676616
DOI: 10.1111/jog.15320 -
PloS One 2019Controversy persists regarding many aspects of traumatic diaphragmatic hernia (TDH). We aimed to understand why some traumatic diaphragmatic injuries present with...
Controversy persists regarding many aspects of traumatic diaphragmatic hernia (TDH). We aimed to understand why some traumatic diaphragmatic injuries present with chronic hernia and to evaluate diagnosis and treatment options. Fifty acute and 19 chronic TDH patients were diagnosed and treated at our institution over a 10-year period. Clinical data from these two groups were analyzed statistically and compared. Chronic TDH patients had a significantly lower Injury Severity Score than acute TDH patients (10.26 ± 2.68 vs. 26.92 ± 4.79, P < 0.001). The most common surgical approach for acute and chronic TDH was thoracotomy and laparotomy, respectively. The length of the diaphragmatic rupture was significantly shorter in chronic TDH patients than acute TDH patients (6.00 ± 1.94 cm vs. 10.71 ± 3.30 cm, P < 0.001). The mean length of hospital stay was significantly longer for acute TDH patients than chronic TDH patients (41.18 ± 31.02 days vs. 16.65 ± 9.61 days, P = 0.002). In conclusion, milder trauma and a smaller diaphragmatic rupture were associated with delayed diagnosis. A thoraco-abdominal computed tomography scan is needed for patients with periphrenic injuries to avoid delayed diagnosis of TDH. Improved awareness and understanding of diaphragmatic injuries will increase the rate of early diagnosis and improve prognosis.
Topics: Abdominal Injuries; Acute Disease; Adolescent; Adult; Aged; Chronic Disease; Delayed Diagnosis; Female; Hernia, Diaphragmatic, Traumatic; Humans; Injury Severity Score; Laparotomy; Male; Middle Aged; Thoracic Injuries; Thoracotomy; Young Adult
PubMed: 31830097
DOI: 10.1371/journal.pone.0226364 -
Scientific Reports Jun 2023Congenital diaphragmatic hernia (CDH) is a neonatal anomaly that includes pulmonary hypoplasia and hypertension. We hypothesized that microvascular endothelial cell (EC)...
Congenital diaphragmatic hernia (CDH) is a neonatal anomaly that includes pulmonary hypoplasia and hypertension. We hypothesized that microvascular endothelial cell (EC) heterogeneity is different in CDH lungs and related to lung underdevelopment and remodeling. To test this, we evaluated rat fetuses at E21.5 in a nitrofen model of CDH to compare lung transcriptomes among healthy controls (2HC), nitrofen-exposed controls (NC) and nitrofen-exposed subjects with CDH. Single-cell RNA sequencing with unbiased clustering revealed 3 distinct microvascular EC clusters: a general population (mvEC), a proliferative population and a population high in hemoglobin. Only the CDH mvEC cluster had a distinct inflammatory transcriptomic signature as compared to the 2HC and NC endothelial cells, e.g. greater activation and adhesion of inflammatory cells and production of reactive oxygen species. Furthermore, CDH mvECs had downregulated Ca4, Apln and Ednrb gene expression. Those genes are markers for ECs important to lung development, gas exchange and alveolar repair (mvCa4+). mvCa4+ ECs were reduced in CDH (2HC [22.6%], NC [13.1%] and CDH [5.3%], p < 0.0001). Overall, these findings identify transcriptionally distinct microvascular endothelial cell clusters in CDH, including the distinctly inflammatory mvEC cluster and the depleted group of mvCa4+ ECs, which together may contribute to pathogenesis.
Topics: Humans; Rats; Animals; Hernias, Diaphragmatic, Congenital; Endothelial Cells; Transcriptome; Rats, Sprague-Dawley; Lung; Disease Models, Animal
PubMed: 37330615
DOI: 10.1038/s41598-023-37050-y -
American Journal of Respiratory and... May 2023
Topics: Humans; Hernias, Diaphragmatic, Congenital; NF-kappa B; Respiratory System; Thorax
PubMed: 36883942
DOI: 10.1164/rccm.202302-0290ED -
Indian Journal of Thoracic and... Sep 2021Complex long-standing diaphragmatic hernia presenting in adults is often managed through an open approach. Minimal invasive approach by either laparoscopy or...
Complex long-standing diaphragmatic hernia presenting in adults is often managed through an open approach. Minimal invasive approach by either laparoscopy or thoracoscopy is limited by its ability to tackle these complex hernias with large defects and thoraco-mediastinal adhesions. Thus, standard laparoscopic or thoracoscopic approach is associated with high conversion to open approach. We herein describe a novel combined thoraco-laparoscopic approach to repair complex diaphragmatic hernias in a series of three adults.
PubMed: 34511764
DOI: 10.1007/s12055-021-01142-z -
International Journal of Molecular... Oct 2022The lung originates from the ventral foregut and develops into an intricate branched structure of airways, alveoli, vessels and support tissue. As the lung develops,... (Review)
Review
The lung originates from the ventral foregut and develops into an intricate branched structure of airways, alveoli, vessels and support tissue. As the lung develops, cells become specified and differentiate into the various cell lineages. This process is controlled by specific transcription factors, such as the SRY-related HMG-box genes and , that are activated or repressed through intrinsic and extrinsic signals. Disturbances in any of these processes during the development of the lung may lead to various pediatric lung disorders, such as Congenital Diaphragmatic Hernia (CDH), Congenital Pulmonary Airway Malformation (CPAM) and Broncho-Pulmonary Dysplasia (BPD). Changes in the composition of the airways and the alveoli may result in reduced respiratory function and eventually lead to chronic lung disorders. In this concise review, we describe different intrinsic and extrinsic cellular processes required for proper differentiation of the epithelium during development and regeneration, and the influence of the microenvironment on this process with special focus on SOX2 and SOX21.
Topics: Humans; Child; Cell Differentiation; Transcription Factors; Pulmonary Alveoli; Lung; Hernias, Diaphragmatic, Congenital; Lung Diseases; SOXB1 Transcription Factors
PubMed: 36361852
DOI: 10.3390/ijms232113064 -
JAMA Pediatrics Jun 2023Prostacyclin (PGI2) is a therapeutic option to treat congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension in neonates. Its use may decrease the need...
IMPORTANCE
Prostacyclin (PGI2) is a therapeutic option to treat congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension in neonates. Its use may decrease the need for extracorporeal life support (ECLS).
OBJECTIVE
To evaluate the association of early PGI2 therapy with ECLS use and outcomes among patients with CDH.
DESIGN, SETTING, AND PARTICIPANTS
This was a cohort study from the CDH Study Group (CDHSG) registry of patients born from January 2007 to December 2019. Patients were from 88 different tertiary pediatric referral centers worldwide that contributed data to the CDHSG. Patients were included in the study if they were admitted within the first week of life. Propensity score matching was performed using estimated gestational age, birth weight, transfer status, 1-minute and 5-minute Apgar scores, highest and lowest partial pressure of arterial carbon dioxide in the first 24 hours of life, and degree of pulmonary hypertension as covariates to generate a matched cohort of exposed and unexposed patients. Data were analyzed from January 2021 to December 2022.
EXPOSURES
Early PGI2 therapy was defined as initiation of PGI2 within the first week of life. Patients who received ECLS were included in the early PGI2 group if PGI2 was started prior to ECLS.
MAIN OUTCOMES AND MEASURES
The primary outcome of the study was the proportion of patients receiving ECLS in the exposed and unexposed groups.
RESULTS
Of 6227 patients who met inclusion criteria (mean [SD] gestational age, 37.4 [2.36] weeks; 2618 [42%] female), 206 (3.3%) received early PGI2 therapy. ECLS was used in 46 of 206 patients who received PGI2 (22.2%) and 1682 of 6021 who did not (27.9%). After propensity score matching, there were 147 patients in the treatment and control groups. Thirty-four patients who received PGI2 (23.3%) and 63 who did not (42.9%) received ECLS. Those who received PGI2 were less likely to receive ECLS (adjusted odds ratio, 0.39; 95% CI, 0.22-0.68) and had shorter mean (SD) duration of ECLS (8.6 [3.73] days vs 12.6 [6.61] days; P < .001), although there was no significant difference in in-hospital mortality.
CONCLUSIONS AND RELEVANCE
In this study, there was decreased use of ECLS and decreased ECLS duration among patients with CDH who started PGI2 therapy during the first week of life. These results identify a potential advantage of early prostacyclin therapy in this population.
Topics: Infant, Newborn; Humans; Female; Child; Adult; Male; Hernias, Diaphragmatic, Congenital; Extracorporeal Membrane Oxygenation; Cohort Studies; Hypertension, Pulmonary; Epoprostenol; Retrospective Studies
PubMed: 37036717
DOI: 10.1001/jamapediatrics.2023.0405 -
Acta Paediatrica (Oslo, Norway : 1992) Aug 2022To review the selection, measurement and reporting of outcomes in studies of interventions in Congenital Diaphragmatic Hernia (CDH). (Review)
Review
AIM
To review the selection, measurement and reporting of outcomes in studies of interventions in Congenital Diaphragmatic Hernia (CDH).
METHODS
We searched the Cochrane Central Register of Controlled Trials from 2000-2020 for randomised trials and observational studies. Outcomes reported were classified into seven key domains modelled on the patient journey.
RESULTS
Our search yielded 118 papers; 27 were eligible. The most frequent domains measured were 'short-term markers of disease activity' (17/27), whereas long-term outcomes (3/27) and outcomes relating to functional health status (8/27) were reported infrequently. There was heterogeneity in the methods and timing of outcome reporting. Primary outcomes were varied and not always clearly stated.
CONCLUSION
Long-term health and functional outcomes involving interventional studies in CDH are infrequently reported, which hinders the process of shared decision-making and evidence-based healthcare. A CDH core outcome set is needed to standardise outcome reporting that is relevant to both families and healthcare teams.
Topics: Hernias, Diaphragmatic, Congenital; Humans; Outcome Assessment, Health Care
PubMed: 35567507
DOI: 10.1111/apa.16409 -
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