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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 -
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 -
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 -
European Journal of Pediatric Surgery :... Sep 2023Despite advances in neonatal intensive care, fetuses with congenital diaphragmatic hernia (CDH) remain to have a poor prognosis. Exclusive postnatal treatment is...
INTRODUCTION
Despite advances in neonatal intensive care, fetuses with congenital diaphragmatic hernia (CDH) remain to have a poor prognosis. Exclusive postnatal treatment is inadequate in patients with moderate CDH (observed than expected lung-to-head ratio [O/E LHR] 26-45%) and can lead to respiratory failure at birth, requiring extracorporeal membrane oxygenation in 75% of cases. An ex-utero intrapartum treatment (EXIT) procedure may be beneficial in these cases, improving the fetal-neonatal transition.
MATERIAL AND METHODS
We review all pregnancies with fetal isolated left CDH with moderate O/E LHR delivered by EXIT in our center from January 2007 to December 2022. Maternal and neonatal variables were analyzed. As primary outcomes, we included neonatal survival and mortality rates, surgical and infectious complications, uterine scar dehiscence, and blood loss during EXIT. As secondary outcomes, we studied recurrences of the diaphragmatic defect, long-term evolution, subsequent pregnancies, and mode of delivery.
RESULTS
A total of 14 patients were delivered by the EXIT procedure, with a neonatal survival rate of 85.7%. All these children had optimal physical and neurocognitive development and no pulmonary morbidity. We found no major complications and 7.1% of minor maternal complications. There were no cases of surgical wound infection or endometritis. The median decrease in hemoglobin during the EXIT procedure was 1.9 mg/dL, and only one case required postoperative transfusion. Two out of the 14 women became pregnant again, and both pregnancies were uneventful.
CONCLUSIONS
In our series, the EXIT procedure allows for adequate airway management associated with a high neonatal survival rate in patients with moderate O/E LHR CDH, with a low rate of neonatal and maternal complications.
PubMed: 37473779
DOI: 10.1055/a-2133-8380 -
American Journal of Physiology. Lung... Oct 2023Abnormal pulmonary vascular development and function in congenital diaphragmatic hernia (CDH) is a significant factor leading to pulmonary hypertension. The lung is a...
Abnormal pulmonary vascular development and function in congenital diaphragmatic hernia (CDH) is a significant factor leading to pulmonary hypertension. The lung is a very heterogenous organ and has marked cellular diversity that is differentially responsive to injury and therapeutic agents. Spatial transcriptomics provides the unmatched capability of discerning the differences in the transcriptional signature of these distinct cell subpopulations in the lung with regional specificity. We hypothesized that the distal lung parenchyma (selected as a region of interest) would show a distinct transcriptomic profile in the CDH lung compared with control (normal lung). We subjected lung sections obtained from male and female CDH and control neonates to spatial transcriptomics using the Nanostring GeoMx platform. Spatial transcriptomic analysis of the human CDH and control lung revealed key differences in the gene expression signature. Increased expression of alveolar epithelial-related genes ( and ) and angiogenesis-related genes ( and ) was seen in control lungs compared with CDH lungs. Response to vitamin A was enriched in the control lungs as opposed to abnormality of the coagulation cascade and TNF-alpha signaling via NF-kappa B in the CDH lung parenchyma. In male patients with CDH, higher expression of (ECM remodeling) and CD163 was seen. Increased type 2 alveolar epithelial cells (AT-2) and arterial and lung capillary endothelial cells were seen in control lung samples compared with CDH lung samples. To the best of our knowledge, this is the first use of spatial transcriptomics in patients with CDH that identifies the contribution of different lung cellular subpopulations in CDH pathophysiology and highlights sex-specific differences. This is the first use of spatial transcriptomics in patients with congenital diaphragmatic hernia (CDH) that identifies the contribution of different lung cellular subpopulations in CDH pathophysiology and highlights sex-specific differences.
Topics: Infant, Newborn; Humans; Male; Female; Hernias, Diaphragmatic, Congenital; Transcriptome; Endothelial Cells; Lung; Hypertension, Pulmonary; Phenyl Ethers; Muscle Proteins; Intracellular Signaling Peptides and Proteins; LIM Domain Proteins
PubMed: 37605849
DOI: 10.1152/ajplung.00154.2023 -
Radiographics : a Review Publication of... Jun 2024Acute diaphragmatic abnormalities encompass a broad variety of relatively uncommon and underdiagnosed pathologic conditions, which can be subdivided into nontraumatic... (Review)
Review
Acute diaphragmatic abnormalities encompass a broad variety of relatively uncommon and underdiagnosed pathologic conditions, which can be subdivided into nontraumatic and traumatic entities. Nontraumatic abnormalities range from congenital hernia to spontaneous rupture, endometriosis-related disease, infection, paralysis, eventration, and thoracoabdominal fistula. Traumatic abnormalities comprise both blunt and penetrating injuries. Given the role of the diaphragm as the primary inspiratory muscle and the boundary dividing the thoracic and abdominal cavities, compromise to its integrity can yield devastating consequences. Yet, diagnosis can prove challenging, as symptoms may be vague and findings subtle. Imaging plays an essential role in investigation. Radiography is commonly used in emergency evaluation of a patient with a suspected thoracoabdominal process and may reveal evidence of diaphragmatic compromise, such as abdominal contents herniated into the thoracic cavity. CT is often superior, in particular when evaluating a trauma patient, as it allows rapid and more detailed evaluation and localization of pathologic conditions. Additional modalities including US, MRI, and scintigraphy may be required, depending on the clinical context. Developing a strong understanding of the acute pathologic conditions affecting the diaphragm and their characteristic imaging findings aids in efficient and accurate diagnosis. Additionally, understanding the appearance of diaphragmatic anatomy at imaging helps in differentiating acute pathologic conditions from normal variations. Ultimately, this knowledge guides management, which depends on the underlying cause, location, and severity of the abnormality, as well as patient factors. RSNA, 2024 Supplemental material is available for this article.
Topics: Humans; Diaphragm; Diagnosis, Differential; Acute Disease; Female; Hernias, Diaphragmatic, Congenital
PubMed: 38781091
DOI: 10.1148/rg.230110 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Dec 2023Congenital and traumatic diaphragmatic hernias (DH) can lead to respiratory and gastrointestinal complications that can be the cause of serious morbidity and mortality....
BACKGROUND
Congenital and traumatic diaphragmatic hernias (DH) can lead to respiratory and gastrointestinal complications that can be the cause of serious morbidity and mortality. In this study, we aimed to share our experience with the surgical repair of complicated or non-complicated DH.
METHODS
Patients who were operated on under emergency or elective conditions with the diagnosis of DH between 2009 and 2023 were analyzed retrospectively. Demographic characteristics, histories, symptoms, etiology of DH, computed tomography find-ings, surgical techniques, and postoperative outcomes of the patients were recorded.
RESULTS
The mean age of the cases was 51.5±18.5, and 29 were female and 41 were male. Hernia etiology was found to be con-genital (40%), traumatic (32.8%), spontaneous (14.3%), and iatrogenic (12.8%), respectively. The mean diameter of the defects was 7.3±2.76 cm (range: 3-15 cm), and 84% of the defects were on the left side. Sixty percent of the cases were treated by laparoscopic surgery and 11.4% by laparotomy. The conversion rate from laparoscopic to open was 24.3%. Dual mesh was used in 48% of the pa-tients, and primary suturing was applied in 34%. The postoperative mortality rate was 7.1%.
CONCLUSION
DH is an important cause of morbidity and mortality due to abdominal organ strangulation and pulmonary and cardiac complications. When a DH is diagnosed, laparoscopic or open surgery is the treatment that should be preferred.
Topics: Humans; Male; Female; Retrospective Studies; Herniorrhaphy; Hernia, Diaphragmatic; Hernia, Diaphragmatic, Traumatic; Laparoscopy; Surgical Mesh
PubMed: 38073460
DOI: 10.14744/tjtes.2023.98029 -
Archives of Disease in Childhood. Fetal... Apr 2024
Topics: Humans; Hernias, Diaphragmatic, Congenital; Retrospective Studies
PubMed: 38253468
DOI: 10.1136/archdischild-2023-326267