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Pediatric Research May 2024The pathogenesis of congenital diaphragmatic hernia (CDH) depends on multiple factors. Activation of the DNA-sensing cyclic-GMP-AMP-synthase (cGAS) and...
BACKGROUND
The pathogenesis of congenital diaphragmatic hernia (CDH) depends on multiple factors. Activation of the DNA-sensing cyclic-GMP-AMP-synthase (cGAS) and Stimulator-of-Interferon-Genes (STING) pathway by double-stranded DNA (dsDNA) links environmental stimuli and inflammation. We hypothesized that nitrofen exposure alters cGAS and STING in human bronchial epithelial cells and fetal rat lungs.
METHODS
We used the Quant-IT™-PicoGreen™ assay to assess dsDNA concentration in BEAS-2B cells after 24 h of nitrofen-exposure and performed immunofluorescence of cGAS/STING. We used nitrofen to induce CDH and harvested control and CDH lungs at embryonic day E15, E18 and E21 for cGAS/STING immunofluorescence, RT-qPCR and RNA-Scope™ in-situ-hybridization (E18, E21).
RESULTS
We found a higher concentration of dsDNA following nitrofen treatment. Nitrofen-exposure to BEAS-2B cells increased cGAS and STING protein abundance. cGAS abundance was higher in nitrofen lungs at E15, E18 and E21. RNA-Scope in-situ-hybridization showed higher cGAS and STING expression in E18 and E21 lungs. RT-qPCR revealed higher mRNA expression levels of STING in E21 nitrofen-induced lungs.
CONCLUSION
Our data suggest that nitrofen-exposure increases dsDNA content which leads to stimulation of the cGAS/STING pathway in human BEAS-2B cells and the nitrofen rat model of CDH. Consequently, DNA sensing and the cGAS-STING-pathway potentially contribute to abnormal lung development in CDH.
IMPACT STATEMENT
We found an alteration of DNA sensing targets cGAS and STING in human BEAS-2B cells and experimental congenital diaphragmatic hernia with higher protein abundance and mRNA expression in cells and lung sections of nitrofen-treated rat pups. This is the first study to investigate DNA sensing, a potential link between environmental stimuli and inflammation, in experimental CDH. Our study extends the knowledge on the pathogenesis of experimental CDH.
PubMed: 38816442
DOI: 10.1038/s41390-024-03277-2 -
General Thoracic and Cardiovascular... Mar 2024Thoracic endometriosis syndrome gives rise to various clinical and radiological manifestations. We reviewed the records of patients operated for intrathoracic migration...
BACKGROUND
Thoracic endometriosis syndrome gives rise to various clinical and radiological manifestations. We reviewed the records of patients operated for intrathoracic migration of abdominal viscera through a diaphragmatic hernia secondary to thoracic endometriosis.
METHODS
We retrospectively reviewed the single-center prospective collected database of all patients operated for thoracic endometriosis during the twenty years. All cases in which an abdominal organ was found to be herniated into the thoracic cavity were retrieved. Clinical and pathological data are presented and analyzed.
RESULTS
Twenty women of median age 36 (range 25-58) years were operated for endometriosis-related diaphragmatic hernia. The hernia was diagnosed concomitantly with endometriosis-related pneumothorax in 13 cases and during the exploration of catamenial thoracic pain in seven cases. There were 18 cases on the right side and two cases on the left side. The median diameter of the hernia was 8 cm (2.5-20 cm). In seventeen cases, the hernia was repaired by direct suture, and in three cases a heterologous prosthesis was positioned. At follow-up, two patients had an episode of recurrent pneumothorax.
CONCLUSIONS
Diaphragmatic hernia should be ruled out in the presence of endometriosis-related pneumothorax or catamenial thoracic pain. Surgery is indicated to make a pathological diagnosis, restore anatomy, and prevent recurrence in patients presenting with pneumothorax.
PubMed: 38461451
DOI: 10.1007/s11748-024-02016-y -
Children (Basel, Switzerland) Dec 2023Congenital diaphragmatic hernia (CDH) repair can be challenging, particularly when a larger defect is present. Barbed sutures prevent the suture from slipping back after...
BACKGROUND
Congenital diaphragmatic hernia (CDH) repair can be challenging, particularly when a larger defect is present. Barbed sutures prevent the suture from slipping back after approximation of the tissues. Although introduced almost 2 decades ago, barbed sutures have not been widely used for CDH repair. We report our initial experience and pitfalls.
METHODS
All patients presenting with CDH from 2021 onward underwent repair using barbed sutures. Demographics, operative parameters, complications, and outcomes were prospectively recorded.
RESULTS
A total of 13 patients underwent CDH repair during the study interval (median age 6 days, range 3 days to 5.75 years). Median operative time was 89 min (range 46 to 288 min). Five thoracoscopic and eight open procedures were performed. Severe pulmonary hypertension and ECMO (extracorporeal membrane oxygenation) were considered contraindications for thoracoscopic repair. The included patients were compared to a historic controlled group performed without barbed sutures. The barbed suture facilitated easy and quick closure of the defects in most cases and obviated the need for knot tying. One patient in the thoracoscopic group had a patch placed due to high tension after the barbed sutures tore the diaphragm. At a median follow-up time of 15 months (range 2 to 34 months), one patient had died, and one patient with complete diaphragmatic agenesis was home-ventilated. There were no recurrences. Median operative time trended lower (89 min) than in the historic control group repaired without barbed sutures (119 min, < 0.06) after eliminating outliers with large, complex patch repairs.
CONCLUSIONS
Barbed sutures simplify congenital diaphragmatic hernia repair regardless of whether a minimal-invasive or open approach is performed. Patch repair is not a contraindication for using barbed sutures. The resulting potential time savings make them particularly useful in patients with cardiac or other severe co-morbidities in which shorter operative times are essential. In cases with high tension, though, the barbs may tear through and produce a "saw" effect on the tissue with subsequent damage.
PubMed: 38255349
DOI: 10.3390/children11010035 -
European Journal of Pediatric Surgery :... Apr 2024The Congenital Diaphragmatic Hernia Study Group (CDHSG) is an international consortium of medical centers actively collecting and voluntarily contributing data... (Review)
Review
The Congenital Diaphragmatic Hernia Study Group (CDHSG) is an international consortium of medical centers actively collecting and voluntarily contributing data pertaining to live born congenital diaphragmatic hernia (CDH) patients born and/or managed at their institutions. These data are aggregated to construct a comprehensive registry that participating centers can access to address specific clinical inquiries and track patient outcomes. Since its establishment in 1995, 147 centers have taken part in this initiative, including 53 centers from 17 countries outside the United States, with 95 current active centers across the globe. The registry has amassed data on over 14,000 children, resulting in the creation of over 75 manuscripts based on registry data to date. International, multicenter consortia enable health care professionals managing uncommon, complex, and diverse diseases to formulate evidence-based hypotheses and draw meaningful and generalizable conclusions for clinical inquiries. This review will explore the formation and structure of the CDHSG and its registry, outlining their functions, center participation, and the evolution of data collection. Additionally, we will provide an overview of the evidence generated by the CDHSG, with a particular emphasis on contributions post-2014, and look ahead to the future directions the study group will take in addressing CDH.
Topics: Child; Humans; Hernias, Diaphragmatic, Congenital; Registries; Multicenter Studies as Topic
PubMed: 38242150
DOI: 10.1055/s-0043-1778021 -
European Journal of Pediatrics Oct 2023Morgagni hernias account for less than 5% of congenital diaphragmatic hernias. They are characteristically retrosternal and bilateral, with right-sided predominance. An...
UNLABELLED
Morgagni hernias account for less than 5% of congenital diaphragmatic hernias. They are characteristically retrosternal and bilateral, with right-sided predominance. An association between Trisomy 21 and diaphragmatic hernias resembling Morgagni hernia has been reported, but the effect of cardiac surgery on its formation has not been investigated. The purpose of this study was to determine whether there is a higher incidence of anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery. We compared the prevalence of anterior diaphragmatic hernias in 92 patients with Trisomy 21 who underwent cardiac surgery with its prevalence in 100 children without Trisomy 21 who underwent cardiac surgery. All available CXRs of all children underwent revision for the presence of an anterior diaphragmatic hernia by a pediatric radiologist. Within the study group, four cases of an anterior diaphragmatic hernia were detected, all upon presentation to the emergency room due to breathing difficulties. No cases of an anterior diaphragmatic hernia were found in the control group (P = 0.0094).
CONCLUSIONS
A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed. In light of our findings, the surgical technique has been modified in patients with DS in our medical center.
WHAT IS KNOWN
• Several studies reported an association between Trisomy 21 and diaphragmatic hernia resembling Morgagni hernia, but the effect of cardiac surgery on its formation has not been investigated.
WHAT IS NEW
• There is a higher incidence of anterior diaphragmatic hernia resembling a Morgagni hernia in children with Trisomy 21 after cardiac surgery. • A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed.
Topics: Humans; Child; Hernias, Diaphragmatic, Congenital; Down Syndrome; Radiography; Cardiac Surgical Procedures; Laparoscopy
PubMed: 37507598
DOI: 10.1007/s00431-023-05127-5 -
Pediatric Pulmonology Sep 2023Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidities. The objective of this study was to delineate the...
INTRODUCTION
Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidities. The objective of this study was to delineate the histopathological features observed in necropsies of CDH patients and correlate these with their clinical manifestations.
METHODS
We retrospectively reviewed the postmortem findings and corresponding clinical characteristics in eight CDH cases from 2017 to July 2022.
RESULTS
The median survival time was 46 (8-624) hours. Autopsy reports showed that diffuse alveolar damage (congestion and hemorrhage) and hyaline membrane formation were the primary pathological lung changes observed. Notably, despite significant reduction in lung volume, the lung development appeared normal in 50% of the cases, while lobulated deformities were present in three (37.5%) cases. All patients displayed a large patent ductus arteriosus (PDA) and a patent foramen ovale, resulting in increased right ventricle (RV) volume, and myocardial fibers appeared slightly congested and swollen. The pulmonary vessels indicated thickening of the arterial media and adventitia. Lung hypoplasia and diffuse lung damage resulted in impaired gas exchange, while PDA and pulmonary hypertension led to RV failure, subsequent organ dysfunction and ultimately death.
CONCLUSIONS
Patients with CDH typically succumb to cardiopulmonary failure, a condition driven by a complex interplay of pathophysiological factors. This complexity accounts for the unpredictable response to currently available vasodilators and ventilation therapies.
Topics: Humans; Hernias, Diaphragmatic, Congenital; Retrospective Studies; Lung; Hypertension, Pulmonary; Research Design
PubMed: 37378468
DOI: 10.1002/ppul.26565 -
European Journal of Pediatric Surgery :... Dec 2023Nutritional support during the neonatal and postoperative period in congenital diaphragmatic hernia (CDH) is challenging and controversial. We aimed to report on...
OBJECTIVES
Nutritional support during the neonatal and postoperative period in congenital diaphragmatic hernia (CDH) is challenging and controversial. We aimed to report on early enteral nutritional support in symptomatic CDH patients during the pre- and postoperative period, including feasibility, associated factors with established full enteral nutrition, and weight at birth, discharge, and 18 months.
METHODS
We retrospectively collected data on nutrition: type and volume of enteral nutrition and parental support. Enteral feeding was introduced preoperatively from day 1 after birth, increased step-wised (breastmilk preferred), and resumed after CDH repair on the first postoperative day. Baseline data were available from our CDH database.
RESULTS
From 2011 to 2020, we identified 45 CDH infants. Twenty-two were girls (51.1%), 35 left sided (77.8%), and 40 underwent CDH repair (88.9%). Median (interquartile range) length of stay in the pediatric intensive care unit was 14.6 days (6.0-26.5), and 1-year mortality was 17.8%.Postoperatively, 120 and 160 mL/kg/d of enteral nutrition was achieved after a median of 6.5 (3.6-12.6) and 10.6 (7.6-21.7) days, respectively. In total, 31 (68.9%) needed supplemental parenteral nutrition in a median period of 8 days (5-18), and of those 11 had parenteral nutrition initiated before CDH repair. No complications to enteral feeding were reported.
CONCLUSION
Early enteral nutrition in CDH infants is feasible and may have the potential to reduce the need for parental nutrition and reduce time to full enteral nutrition in the postoperative period.
Topics: Infant, Newborn; Infant; Child; Female; Humans; Male; Enteral Nutrition; Hernias, Diaphragmatic, Congenital; Retrospective Studies; Parenteral Nutrition; Postoperative Period
PubMed: 36929125
DOI: 10.1055/s-0043-1767829 -
Journal of Ultrasound Dec 2023Hepatopulmonary fusion (HPF) is an extremely rare condition characterized by a fusion between the herniated liver and lung right parenchyma. Knowledge about this...
Hepatopulmonary fusion (HPF) is an extremely rare condition characterized by a fusion between the herniated liver and lung right parenchyma. Knowledge about this condition comes from the few cases reported in the literature (less than 40 cases). While diagnostic evaluation as X-Ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Single Photon Emission Computed Tomography (SPECT) were described, poor ultrasound findings are available. In this paper, the authors provide the detailed chest ultrasound findings of this rare condition.
Topics: Humans; Hernias, Diaphragmatic, Congenital; Lung; Liver; Tomography, X-Ray Computed; Ultrasonography
PubMed: 37730971
DOI: 10.1007/s40477-023-00828-x -
Archives of Disease in Childhood. Fetal... Nov 2023Prognostication of mortality and decision to offer extracorporeal membrane oxygenation (ECMO) treatment in infants with congenital diaphragmatic hernia (CDH) can inform... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prognostication of mortality and decision to offer extracorporeal membrane oxygenation (ECMO) treatment in infants with congenital diaphragmatic hernia (CDH) can inform clinical management.
OBJECTIVE
To summarise the prognostic value of echocardiography in infants with CDH.
METHODS
Electronic databases Ovid MEDLINE, Embase, Scopus, CINAHL, the Cochrane Library and conference proceedings up to July 2022 were searched. Studies evaluating the prognostic performance of echocardiographic parameters in newborn infants were included. Risk of bias and applicability were assessed using the Quality Assessment of Prognostic Studies tool. We used a random-effect model for meta-analysis to compute mean differences (MDs) for continuous outcomes and relative risk (RR) for binary outcomes with 95% CIs. Our primary outcome was mortality; secondary outcomes were need for ECMO, duration of ventilation, length of stay, and need for oxygen and/or inhaled nitric oxide.
RESULTS
Twenty-six studies were included that were of acceptable methodological quality. Increased diameters of the right and left pulmonary arteries at birth (mm), MD 0.95 (95% CI 0.45 and 1.46) and MD 0.79 (95% CI 0.58 to 0.99), respectively) were associated with survival. Left ventricular (LV) dysfunction, RR 2.40, (95% CI 1.98 to 2.91), right ventricular (RV) dysfunction, RR 1.83 (95% CI 1.29 to 2.60) and severe pulmonary hypertension (PH), RR 1.69, (95% CI 1.53 to 1.86) were associated with mortality. Left and RV dysfunctions, RR 3.30 (95% CI 2.19 to 4.98) and RR 2.16 (95% CI 1.85 to 2.52), respectively, significantly predicted decision to offer ECMO treatment. Limitations are lack of consensus on what parameter is optimal and standardisation of echo assessments.
CONCLUSIONS
LV and RV dysfunctions, PH and pulmonary artery diameter are useful prognostic factors among patients with CDH.
Topics: Infant, Newborn; Infant; Humans; Hernias, Diaphragmatic, Congenital; Prognosis; Echocardiography; Lung; Hypertension, Pulmonary; Retrospective Studies
PubMed: 37130729
DOI: 10.1136/archdischild-2022-325257 -
Thoracic Surgery Clinics May 2024Diaphragm injuries are rarely seen injuries in trauma patients and are difficult to diagnose. With improving technology, computed tomography has become more reliable,...
Diaphragm injuries are rarely seen injuries in trauma patients and are difficult to diagnose. With improving technology, computed tomography has become more reliable, but with increasing rates of non-operative management of both penetrating and blunt trauma, the rate of missed diaphragmatic injury has increased. The long-term complications of missed injury include bowel obstruction and perforation, which can carry a mortality rate as high as 85%. When diagnosed, injuries should be repaired to reduce the risk of future complications.
Topics: Humans; Diaphragm; Tomography, X-Ray Computed; Wounds, Nonpenetrating
PubMed: 38705665
DOI: 10.1016/j.thorsurg.2024.01.008