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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 -
Frontiers in Pediatrics 2024Bronchopulmonary foregut malformation (BPFM) is an uncommon condition, with few case reports documented in both national and international literature. This scarcity...
BACKGROUND
Bronchopulmonary foregut malformation (BPFM) is an uncommon condition, with few case reports documented in both national and international literature. This scarcity underscores the importance of utilizing effective imaging techniques to improve our understanding and diagnostic precision concerning this disorder.
CASE DESCRIPTION
In the first case report, a neonate, born at full term and aged 15 days, presented with symptoms including dyspnea, coughing, wheezing, cyanosis, and vomiting. Initial diagnostic evaluations, which included chest radiography and upper gastrointestinal tract radiography, led to an erroneous initial diagnosis of a left-sided diaphragmatic hernia, accompanied by a suspicion of infection. In the second case report, another neonate, also born at full term but aged 5 days, exhibited symptoms such as coughing, choking, and mild vomiting. Utilizing a combination of computed tomography (CT) scans (plain, enhanced, and reconstructed), chest x-ray, and upper gastrointestinal tract radiography, the diagnosis of BPFM was accurately determined.
CONCLUSION
Comprehensive imaging examinations play a crucial role in reducing misdiagnosis and diagnostic oversights in cases of BPFM. Given its rarity, BPFM often manifests as a sequestered lung accompanied by gastrointestinal abnormalities. Hence, the integration of CT scans with gastrointestinal tract radiography can substantially improve diagnostic precision in such cases.
PubMed: 38813545
DOI: 10.3389/fped.2024.1400124 -
Cureus Apr 2024Diaphragmatic hernia (DH) is an uncommon cause of small bowel obstruction (SBO), particularly in the absence of trauma. This rarity can pose a diagnostic challenge,...
Diaphragmatic hernia (DH) is an uncommon cause of small bowel obstruction (SBO), particularly in the absence of trauma. This rarity can pose a diagnostic challenge, leading to significant delays in treatment and increased morbidity. We report a case of a 79-year-old male patient who presented with acute signs of small bowel obstruction. The patient had no reported history of trauma. Computed tomography (CT) of the abdomen revealed a diaphragmatic hernia causing small bowel obstruction. The patient underwent an initial laparoscopy, which was converted to laparotomy, small bowel resection, and subsequent hernia repair. The patient made a good recovery, and two weeks after his initial presentation, he was discharged home. This case highlights the importance of considering diaphragmatic hernia in differential diagnosis for small bowel obstruction, even in the absence of trauma.
PubMed: 38813327
DOI: 10.7759/cureus.59279 -
Journal of Robotic Surgery May 2024Emergency treatment of paraesophageal hernias can be carried out through laparotomy or minimally invasive approaches, however, evidence in this regard is weak. The aim...
Emergency treatment of paraesophageal hernias can be carried out through laparotomy or minimally invasive approaches, however, evidence in this regard is weak. The aim of our study was to assess safety and feasibility of the robotic-assisted treatment of paraesophageal hernias in the emergency setting. At the Bellinzona e Valli Regional Hospital, Switzerland, we conducted a retrospective analysis of patients operated on from January 2020 to January 2024 with robotic surgery for emergency presentation of paraesophageal hernias. Demographic and clinical details, operative techniques, and postoperative outcomes were collected and analyzed. Out of 82 patients who underwent robotic-assisted paraesophageal hernia repair, 17 were treated in the emergency setting. Median age was 79 years (IQR 77-85), 3 (17.6%) patients were male, and median BMI was 23.9 kg/m (IQR 21.0-26.0). Most frequent presentation symptoms were pain (100%), regurgitation (88.2%), and dyspnea (17.6%). No intraoperative complication, conversion to open surgery or stomach resections were recorded. Two complications of grade 3 according to the Clavien-Dindo classification and one of grade 2 occurred; all were successfully treated until resolution. The median length of hospital stay was 8 days (IQR 5-16). After a mean follow-up of 15.9 months (IQR 6.5-25.6) only two small axial asymptomatic recurrences that required no treatment. Despite limitations, our study demonstrated a very low rate of intra- and postoperative complications, likely supporting the safety and feasibility of robotic-assisted treatment for paraesophageal hernias in emergency settings. Larger studies with a control arm are needed to validate our initial findings.
Topics: Humans; Hernia, Hiatal; Robotic Surgical Procedures; Retrospective Studies; Aged; Male; Female; Aged, 80 and over; Herniorrhaphy; Feasibility Studies; Treatment Outcome; Length of Stay; Postoperative Complications; Emergencies
PubMed: 38809354
DOI: 10.1007/s11701-024-01975-x -
Journal of Pediatric Surgery May 2024Our study examines if the disease severity profile of our Congenital Diaphragmatic Hernia (CDH) patient cohort adherent to long-term follow-up differs from patients lost...
OBJECTIVES
Our study examines if the disease severity profile of our Congenital Diaphragmatic Hernia (CDH) patient cohort adherent to long-term follow-up differs from patients lost to follow-up after discharge and examines factors associated with health care utilization.
METHODS
Retrospective review identified CDH survivors born 2005-2019 with index repair at our institution. Primary outcome was long-term follow-up status: "active" or "inactive" according to clinic guidelines. Markers of CDH disease severity including CDH defect classification, oxygen use, tube feeds at discharge, and sociodemographic factors were examined as exposures.
RESULTS
Of the 222 included patients, median age [IQR] was 10.2 years [6.7-14.3], 61% male, and 57 (26%) were insured by Medicaid. Sixty-three percent (139/222) of patients were adherent to follow-up. Seventy-six percent of patients discharged on tube feeds had active follow-up compared to 55% of patients who were not, with similar findings for oxygen at discharge (76% vs. 55%). Kaplan-Meier analysis showed patients with smaller defect size had earlier attrition compared to patients with larger defect size. Other race (Hispanic, Asian, Middle Eastern) patients had 2.87 higher odds of attrition compared to white patients (95% CI 1.18-7.0). Medicaid patients had 2.64 higher odds of attrition compared to private insurance (95% CI 1.23-5.66).
CONCLUSION
Loss to follow-up was associated with race and insurance type. Disease severity was similar between the active and inactive clinic cohorts. Long-term CDH clinic publications should examine attrition to ensure reported outcomes reflect the discharged population. This study identified important factors to inform targeted interventions for follow-up adherence.
LEVEL OF EVIDENCE
Level III.
PubMed: 38806317
DOI: 10.1016/j.jpedsurg.2024.04.023 -
Ultrasound in Obstetrics & Gynecology :... May 2024
PubMed: 38804564
DOI: 10.1002/uog.27711 -
Prenatal Diagnosis May 2024We aim to provide a template structured report of fetal Magnetic Resonance Imaging in congenital diaphragmatic hernia (CDH) that was locally validated by the CDH study...
OBJECTIVE
We aim to provide a template structured report of fetal Magnetic Resonance Imaging in congenital diaphragmatic hernia (CDH) that was locally validated by the CDH study group in Mannheim.
METHODS
A selection of 50 fetal MRIs of patients with an isolated diaphragmatic hernia and associated radiology reports from five different senior radiologists from a single center resulted in a primary structured report, which was put into practice by using dedicated software. A questionnaire survey of the interdisciplinary CDH study group Mannheim was used to adapt the report to the clinical requirements.
RESULTS
There was a huge variability in how deep the free text reports go into detail. The side of the hernia was named in 94% of cases. In 58%, both the lung volume and the total lung volume were reported. A comparison with the expected lung volume was reported in 66% of cases. Additional findings, such as herniated organs, were reported in 96% of cases. Overall satisfaction with the newly established structured report was high within the CDH study group with a mean of 4.7.
CONCLUSIONS
The use of the structured report of this study can optimize the interdisciplinary dialog, the standardization of report content, increase report completeness and improve quality.
PubMed: 38797992
DOI: 10.1002/pd.6593 -
Journal of Perinatology : Official... May 2024Fetal Centers use imaging studies to predict congenital diaphragmatic hernia (CDH) prognosis and the need for fetal therapy. Given improving CDH survival, we...
BACKGROUND
Fetal Centers use imaging studies to predict congenital diaphragmatic hernia (CDH) prognosis and the need for fetal therapy. Given improving CDH survival, we hypothesized that current fetal imaging severity predictions no longer reflect true outcomes and fail to justify the risks of fetal therapy.
METHODS
We analyzed our single-center contemporary data in a left-sided CDH cohort (n = 58) by prognostic criteria determined by MRI observed-to-expected total fetal lung volumes: severe <25%, moderate 25-35%, and mild >35%. We compared contemporary survival to prior studies and the TOTAL trials.
RESULTS
Contemporary survival was significantly higher than past studies for all prognostic classifications (mild 100% vs 80-94%, moderate 95% vs 59-75%, severe 79% vs 13-25%; P < 0.01), and to either control or fetal therapy arms of the TOTAL trials.
CONCLUSIONS
Current fetal imaging criteria are overly pessimistic and may lead to unwarranted fetal intervention. Fetal therapies remain experimental. Future studies will require updated prognostic criteria.
PubMed: 38796522
DOI: 10.1038/s41372-024-02008-z -
Hernia : the Journal of Hernias and... May 2024To determine the relationship between abdominal hernia and obesity. Although obesity is frequently cited as a risk factor for abdominal hernia, few studies have...
PURPOSE
To determine the relationship between abdominal hernia and obesity. Although obesity is frequently cited as a risk factor for abdominal hernia, few studies have confirmed this association (Menzo et al. Surg Obes Relat Dis 14:1221-1232. 10.1016/j.soard.2018.07.005, 2018).
METHODS
A cross-sectional study of primary care ambulatory patients aged older than 16 years treated at UCLA Health from 01/01/2018 to 06/06/2023. Abdominal hernia was identified by clinic encounter ICD-10 codes (K40-K46).
RESULTS
There were 41,703 hernias identified among 1,362,440 patients (306.1 per10,000) with a mean age of 62.5 ± 16.1 years, and 57.6% were men. Nearly half (44.7%) of all abdominal hernias were diaphragmatic. There was an approximately equal distribution of the ventral (28.7%) and inguinal (24.3%) hernia. Each hernia type had a different relationship with obesity: The odds of having a ventral hernia increased with BMI in both sexes: BMI 25-29.9 kg/m odds ratio (OR) = 1.65, (CI 1.56-1.74); BMI 30-39.9 kg/m OR = 2.42 (CI 2.29-2.56), BMI 40-49.9 kg/m OR = 2.28 (CI 2.05-2.54) and BMI > = 50 kg/m OR = 2.54 (CI 2.03-3.17) all relative to normal BMI. In contrast, the odds of having an inguinal hernia decreased with obesity relative to normal weight [obesity (BMI 30-39.9 kg/m): OR = 0.60 (CI 0.56-0.65)], morbid obesity (BMI 40-49.9 kg/m): OR = 0.29 (CI 0.23-0.37). The OR for diaphragmatic hernia peaks with obesity in women and overweight status in men but was found to decrease with morbid obesity [OR = 1.18 (CI 1.07-1.30)]. There was no significant difference between men and women in the prevalence of femoral hernia (men: 0.7/per10,000, women: 0.9/per10,000, p = 0.19).
CONCLUSIONS
The relationship between hernia and obesity is complex with some hernias decreasing in prevalence as obesity increases. Further research is needed to better understand this paradoxical relationship.
PubMed: 38795218
DOI: 10.1007/s10029-024-03034-8