Multidisciplinary follow-up in a patient with Morgagni hernia leads to diagnosis of Marfan syndrome.

BACKGROUND: congenital diaphragmatic hernia (CDH) is a birth defect occurring in isolated or syndromic (chromosomal or monogenic) conditions. The diaphragmatic defect can be the most common one: left-sided posterolateral, named Bochdalek hernia; or it can be an anterior-retrosternal defect, named Morgagni hernia. Marfan syndrome (MFS) is a rare autosomal dominant inherited condition that affects connective tissue, caused by mutations in fibrillin-1 gene on chromosome 15. To date various types of diaphragmatic defects (about 30 types) have been reported in association with MFS, but they are heterogeneous, including CDH and paraesophageal hernia. CASE PRESENTATION: We describe the case of a child incidentally diagnosed with Morgagni hernia through a chest X-ray performed due to recurrent respiratory tract infections. Since the diagnosis of CDH, the patient underwent a clinical multidisciplinary follow-up leading to the diagnosis of MFS in accordance with revised Ghent Criteria: the child had typical clinical features and a novel heterozygous de novo single-base deletion in exon 26 of the FBN1 gene, identified by Whole-Exome Sequencing. MFS diagnosis permitted to look for cardiovascular complications and treat them, though asymptomatic, in order to prevent major cardiovascular life-threatening events. CONCLUSION: Our case shows the importance of a long-term and multidisciplinary follow-up in all children with diagnosis of CDH.

Management of Congenital Hernias in Adults: Foramen of Morgagni Hernia.

Morgagni hernias may range from asymptomatic incidental findings to surgical emergencies. An abdominal approach is ideal in the majority of cases, although surgeons should understand alternatives for repair.

Cryo-EM structures elucidate the multiligand receptor nature of megalin.

Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. Saito, Int. J. Biochem. Cell Biol. 157, 106393 (2023)]. It is expressed predominantly in renal proximal tubule epithelial cells, as well as in the brain, lungs, eyes, inner ear, thyroid gland, and placenta. Megalin is also known to mediate the endocytosis of toxic compounds, particularly those that cause renal and hearing disorders [Y. Hori et al., J. Am. Soc. Nephrol. 28, 1783-1791 (2017)]. Genetic megalin deficiency causes Donnai-Barrow syndrome/facio-oculo-acoustico-renal syndrome in humans. However, it is not known how megalin interacts with such a wide variety of ligands and plays pathological roles in various organs. In this study, we elucidated the dimeric architecture of megalin, purified from rat kidneys, using cryoelectron microscopy. The maps revealed the densities of endogenous ligands bound to various regions throughout the dimer, elucidating the multiligand receptor nature of megalin. We also determined the structure of megalin in complex with receptor-associated protein, a molecular chaperone for megalin. The results will facilitate further studies on the pathophysiology of megalin-dependent multiligand endocytic pathways in multiple organs and will also be useful for the development of megalin-targeted drugs for renal and hearing disorders, Alzheimer's disease [B. V. Zlokovic et al., Proc. Natl. Acad. Sci. U.S.A. 93, 4229-4234 (1996)], and other illnesses.

An acute gastric volvulus in a child with congenital left diaphragmatic hernia: a case report.

BACKGROUND: Acute complete gastric volvulus is a rare and life-threatening disease, which is prone to gastric wall ischemia, perforation, and necrosis. If it is not treated by surgery in time, the mortality rate can range from 30 to 50%. Clinical presentations of acute gastric volvulus are atypical and often mimic other abdominal conditions such as gastritis, gastroesophageal reflux, gastric dilation, and pancreatitis. Imaging studies are crucial for diagnosis, with barium meal fluoroscopy being the primary modality for diagnosing gastric volvulus. Cases of acute gastric volvulus diagnosed by ultrasound are rarely reported. CASE PRESENTATION: We reported a rare case of acute gastric volvulus in a 4-year-old Chinese girl who presented with vomiting and abdominal pain. Ultrasound examination revealed the "whirlpool sign" in the cardia region, raising suspicion of gastric volvulus. Diagnosis was confirmed by X-ray barium meal fluoroscopy, which indicated left-sided diaphragmatic hernia and obstruction at the cardia region. Surgical intervention confirmed our suspicion of acute complete gastric volvulus combined with diaphragmatic hernia. CONCLUSION: In this case, we reported an instance of acute complete gastric volvulus. Ultrasound revealed a "whirlpool sign" in the cardia, which is likely to be a key sign for the diagnosis of complete gastric volvulus.

Postoperative pulmonary vascular growth in patients with congenital diaphragmatic hernia.

BACKGROUND: Postoperative pulmonary growth in congenital diaphragmatic hernias (CDH) remains unclear. We investigated postoperative pulmonary vascular growth using serial lung perfusion scintigraphy in patients with CDH. METHODS: Neonates with left CDH who underwent surgery and postoperative lung perfusion scintigraphy at our institution between 2001 and 2020 were included. Patient demographics, clinical courses, and lung scintigraphy data were retrospectively analyzed by reviewing medical records. RESULTS: Twenty-one patients with CDH were included. Of these, 10 underwent serial lung scintigraphy. The ipsilateral perfusion rate and median age on the 1st and serial lung scintigraphy were 32% (34 days) and 33% (3.6 years), respectively. Gestational age at prenatal diagnosis (p = 0.02), alveolar-arterial oxygen difference (A-aDO2) at birth (p = 0.007), and preoperative nitric oxide (NO) use (p = 0.014) significantly correlated with the 1st lung scintigraphy. No other variables, including operative approach, were significantly correlated with the 1st or serial scintigraphy findings. All patients improved lung perfusion with serial studies [Difference: + 7.0 (4.3-13.25) %, p = 0.001, paired t-test]. This improvement was not significantly correlated with preoperative A-aDO2 (p = 0.96), NO use (p = 0.28), or liver up (p = 0.90). The difference was significantly larger in patients who underwent thoracoscopic repair than in those who underwent open abdominal repair [+ 10.6 (5.0-17.1) % vs. + 4.25 (1.2-7.9) %, p = 0.042]. CONCLUSION: Our study indicated a postoperative improvement in ipsilateral lung vascular growth, which is possibly enhanced by a minimally invasive approach, in patients with CDH.

Congenital Hernias in Adults: Bochdalek Hernias.

Bochdalek hernias are a rare occurrence in adults and usually asymptomatic, resulting in incidental discovery. However, surgical intervention is recommended for both symptomatic and asymptomatic Bochdalek hernias due to the risk of acute morbidity and mortality. There are various possible surgical approaches that may be appropriate depending on the circumstance, with robotic repair becoming increasingly popular. To date, the rarity of the condition has limited the available data on postoperative outcomes.

Diaphragmatic Defects in Infants: Acute Management and Repair.

Congenital diaphragmatic hernia (CDH) is a complex and highly variable disease process that should be treated at institutions with multidisciplinary teams designed for their care. Treatment in the neonatal period focuses on pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Extracorporeal membrane oxygenation (ECMO) can be considered in patients refractory to medical management. Repair of CDH early during the ECMO course seems to improve mortality compared with other times for surgical intervention. The choice of surgical approach to CDH repair should consider the patient's physiologic status and the surgeon's familiarity with the operative approaches available, recognizing the pros/cons of each technique.

[Treatment of recurrent incarcerated Bochdalek hernia in an adult]. / Recidív, kizáródott, felnottkori Bochdalek-sérv mutéti megoldása.

Az igen ritka felnottkori nem hiatális, azaz nem paraoesophagealis típusú transdiaphragmaticus sérveket - a veleszületett rekeszizom defektusok mintájára - általánosan Bochdalek, ill. Larey-Morgagni-sérveknek nevezik. Etiológia tekintetében a nem diagnosztizált és kezelt veleszületett eredet, a traumás kontúziós-szakadásos, az iatrogen, ill. a recidív típus említendo meg.Esetismertetésünkben egy felnottkori recidív, kizáródott Bochdalek-sérv sikeres mutéti ellátását ismertetjük. A 23 éves férfi beteg kórelozményében 11 éves korában bal oldali Bochdalek-sérv miatt végzett thoracoscopos rekeszizom sutura szerepel. Epigastrialis fájdalmak, hányinger, hányás, akut hasi megbetegedés klinikai tünetei miatt jelentkezett Intézetünkben. Az elvégzett sürgos mellkasi és hasi CT-vizsgálat a bal mellüregben elhelyezkedo, kizáródott, vékonybélkacsokat tartalmazó Bochdalek-sérvet igazolt. Sürgos laparotomia során az életképesnek bizonyult sérvtartalmat (a vékonybéltraktus 2/3 része, a colon flexura lienalisa és a pancreas farok) a hasüregbe reponáltuk, a sérvkaput direkt suturával zártuk, és szövetszeparáló sebészi hálóval fedtük, valamint a mellüreget draináltuk. A postoperatív szak eseménytelenül zajlott. Kontroll-CT-vizsgálat a reconstruált rekeszizom és pleuro-peritonealis rétegek folytonosságát mutatta. A 10. posztoperatív napon panaszmentesen bocsátottuk otthonába.Megbeszélés: Mint minden kizáródott sérv esetében, a diagnózis mihamarabbi felállítása és az idoben elvégzett mutét kulcsfontosságú. A mellkasi drenázs szükségességét minden esetnél körültekintoen mérlegelni kell. A mutét után a mell- és hasüregben kialakult új anatómiai viszonyok miatt cardialis és respiratoricus szövodmények alakulhatnak ki. Álláspontunk szerint a betegség ritkasága miatt centrumban kezelendo. Ezen ritka állapot sikeres gyógyítása többszakmás együttmuködésen alapul, melynek meghatározó eleme a helyesen megválasztott rekeszi felszínt helyreállító mutéti technika alkalmazása.

[Congenital diaphragmatic hernia : Imaging-from diagnosis to aftercare]. / Kongenitale Zwerchfellhernie : Bildgebung von der Diagnose bis zur Nachsorge.

STANDARD RADIOLOGICAL METHODS: Fetal: Ultrasound and magnetic resonance imaging (MRI); postnatal: conventional X­ray diagnostics, computed tomography (CT) and MRI. METHODICAL INNOVATIONS: MRI-based lung ventilation and perfusion measurement. PRACTICAL RECOMMENDATIONS: Lifelong follow-up care should be provided, in which radiology is part of the treatment team.

A clinical consensus guideline for nutrition in infants with congenital diaphragmatic hernia from birth through discharge.

OBJECTIVE: To develop a consensus guideline to meet nutritional challenges faced by infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: The CDH Focus Group utilized a modified Delphi method to develop these clinical consensus guidelines (CCG). Topic leaders drafted recommendations after literature review and group discussion. Each recommendation was sent to focus group members via a REDCap survey tool, and members scored on a Likert scale of 0-100. A score of > 85 with no more than 25% outliers was designated a priori as demonstrating consensus among the group. RESULTS: In the first survey 24/25 recommendations received a median score > 90 and after discussion and second round of surveys all 25 recommendations received a median score of 100. CONCLUSIONS: We present a consensus evidence-based framework for managing parenteral and enteral nutrition, somatic growth, gastroesophageal reflux disease, chylothorax, and long-term follow-up of infants with CDH.

Reasons for conversions in thoracoscopic repairs of neonatal congenital diaphragmatic hernias: a systematic review.

PURPOSE: This systematic review focused on reasons for conversions in neonates undergoing thoracoscopic congenital diaphragmatic hernia (CDH) repair. METHODS: Systematic search of Medline/Pubmed and Embase was performed for English, Spanish and Portuguese reports, according to PRISMA guidelines. RESULTS: Of the 153 articles identified (2003-2023), 28 met the inclusion criteria and offered 698 neonates for analysis. Mean birth weight and gestational age were 3109 g and 38.3 weeks, respectively, and neonates were operated at a mean age of 6.12 days. There were 278 males (61.50%; 278/452) and 174 females (38.50%; 174/452). The reasons for the 137 conversions (19.63%) were: (a) defect size (n = 22), (b) need for patch (n = 21); (c) difficulty in reducing organs (n = 14), (d) ventilation issues (n = 10), (e) bleeding, organ injury, cardiovascular instability (n = 3 each), (f) bowel ischemia and defect position (n = 2 each), hepatopulmonary fusion (n = 1), and (g) reason was not specified for n = 56 neonates (40.8%). The repair was primary in 322 neonates (63.1%; 322/510) and patch was used in 188 neonates (36.86%; 188/510). There were 80 recurrences (12.16%; 80/658) and 14 deaths (2.48%; 14/565). Mean LOS and follow-up were 20.17 days and 19.28 months, respectively. CONCLUSIONS: Neonatal thoracoscopic repair for CDH is associated with conversion in 20% of cases. Based on available data, defect size and patch repairs have been identified as the predominant reasons, followed by technical difficulties to reduce the herniated organs and ventilation related issues. However, data specifically relating to conversion is poorly documented in a high number of reports (40%). Accurate data reporting in future will be important to better estimate and quantify reasons for conversions in neonatal thoracoscopy for CDH.

Disease severity impacts perceived quality of life in congenital diaphragmatic hernia: a prospective observational study.

BACKGROUND: While research indicates comparable quality of life (QOL) in congenital diaphragmatic hernia (CDH) and healthy populations, the effect of CDH severity on patients' health perceptions remains unexplored. We aimed to assess QOL perception in CDH, hypothesising a decline correlated with increased disease severity. METHODS: In this prospective observational study, we analysed patients with CDH aged 5 years and above participating in a longitudinal outpatient programme. We excluded bilateral CDH, genetic/syndromic conditions, prematurity and late diagnosis. Participants self-administered the age-adapted Pediatric Quality of Life Inventory (PedsQL) survey, covering four domains (physical, emotional, social, school). After enrolment, data were collected blind to severity status (larger defects denoting significant/'severe' disease). Repeated measurements were managed using a random mixed-effects model. RESULTS: Of 34 participants (50% males) who completed the PedsQL, 10 provided measurements at two visits. Eight required a patch (type C), while 26 had primary repairs (type A=8; type B=18). Age at first evaluation was comparable across groups (no patch: median 11 (7-16), patch: 13 (8-15) years, p=0.78). Severe CDH correlated significantly with lower PedsQL scores (adjusted ß: -18%, 95% CI -28%; -7%, adjusted for age at visit and sex). Lower scores specifically occurred in walking, exercising, social and academic functioning. CONCLUSION: Severe CDH significantly lowers QOL. This finding is crucial for resource allocation in long-term CDH health surveillance and advocates for regular inclusion of patient experiences in quality improvement efforts.

Antenatally Detected Thoracic Lesions: Prognosis, Management and Outcome.

BACKGROUND: Foetal thoracic lesions are uncommon, with the incidence of 1 in 15,000 live births. Antenatal monitoring of these lesions is required to prognosticate the parents about the postnatal outcome of the lesions and about the well-being of the baby. Foetal ultrasound and magnetic resonance imaging (MRI) are the modalities to detect these lesions and follow-up during pregnancy and postnatally. Congenital pulmonary adenomatoid malformations (CPAM), congenital diaphragmatic hernia (CDH) and bronchopulmonary sequestrations (BPS) are the commonly detected foetal thoracic lesions. Parameters such as congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) and lung-to-head ratio (LHR) determine the prognosis of these lesions. With this background, we planned to study the prognosis and outcome of antenatally detected thoracic lesions. MATERIALS AND METHODS: This was a prospective study carried out for 2 years (January 2017 to December 2018). Pregnant females with foetuses diagnosed to have thoracic lesions on the second- and third-trimester ultrasound and foetal MRI were enrolled for the study. CVR and LHR were noted. Outcomes were analysed in terms of the need of termination of pregnancy, foetal or neonatal demise and need of surgery or conservative management. RESULTS: Of a total of 521 pregnancies, thoracic lesions were detected in 22 (4.22%) cases. Individually, the incidence of each lesion was: CPAM-10 (45.45%), BPS-5 (22.73%), CDH-5 (22.73%) and congenital higher airway obstruction-2 (9.1%). Chromosomal screening was normal in 100% of cases. Follow-up was done for 2 years. Termination of pregnancy was required in 3 (13.64%) cases, postnatal death occurred in 4 (18.2%) cases, surgery was required in three cases of CDH soon after birth and two cases of extralobar BPS at 2 years of age. 10 (45.45%) cases were managed conservatively, who are doing well at 2-year follow-up. CONCLUSION: CPAMs, BPSs and CDH are the commonly detected antenatal thoracic lesions. Ultrasonography and MRI help detect and prognosticate the parents about the outcomes of these lesions. CVR and LHR with associated congenital malformations are important prognostic markers for these lesions. There is a need of long-term prospective studies to delineate the natural history of these lesions.

Mechanical ventilation in special populations.

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.

The RNA-binding protein quaking is upregulated in nitrofen-induced congenital diaphragmatic hernia lungs at the end of gestation.

BACKGROUND: The RNA-binding protein Quaking (QKI) increases during epithelial-to-mesenchymal transition and its expression is controlled by microRNA-200 family members. Here, we aimed to describe the expression of QKI in the developing lungs of control and nitrofen-induced congenital diaphragmatic hernia lungs (CDH). METHODS: To investigate the expression of QKI, we dissected lungs from control and nitrofen-induced CDH rats on embryonic day 15, 18, 21 (E15, E18, E21). We performed immunofluorescence (IF) and quantitative reverse transcription PCR (RT-qPCR) for QKI expression. Additionally, we assessed Interleukin-6 (IL-6) abundance using IF. RESULTS: On E21, IF showed that the abundance of all three QKI isoforms and IL-6 protein was higher in CDH lungs compared to control lungs (QKI5: p = 0.023, QKI6: p = 0.006, QKI7: p = 0.014, IL-6: p = 0.045, respectively). Furthermore, RT-qPCR data showed increased expression of QKI5, QKI6, and QKI7 mRNA in E21 nitrofen lungs by 1.63 fold (p = 0.001), 1.63 fold (p = 0.010), and 1.48 fold (p = 0.018), respectively. CONCLUSIONS: Our data show an increase in the abundance and expression of QKI at the end of gestation in nitrofen-induced CDH lungs. Therefore, a disruption in the regulation of QKI during the late stage of pregnancy could be associated with the pathogenesis of abnormal lung development in CDH.

Unmasking a hidden culprit: late-presenting congenital diaphragmatic hernia beyond infancy: A case report and literature review.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly with abnormal diaphragm development, typically diagnosed prenatally or soon after birth. Late-presenting CDH presents diagnostic challenges due to nonspecific symptoms that can lead to misdiagnoses. METHODS: This report discusses a 35-month-old female initially presenting with predominant gastrointestinal symptoms and minimal respiratory distress. Initial radiographic findings suggested a left tension pneumothorax, prompting further investigation. RESULTS: Subsequent diagnostic efforts revealed a Bochdalek-type left CDH, with several abdominal organs herniated into the thoracic cavity. The case was managed through laparotomy, where herniated contents were successfully repositioned into the abdominal cavity. This intervention underscores the need for high clinical suspicion and the importance of distinguishing between similar presentations, such as tension pneumothorax and tension gastrothorax, which require different management strategies. CONCLUSION: The case illustrates the importance of considering CDH in differential diagnoses for older pediatric patients with atypical symptoms. Early recognition and appropriate management are key to improving patient outcomes.

Pulmonary vasculature development in congenital diaphragmatic hernia: a novel automated quantitative imaging analysis.

PURPOSE: Impaired fetal lung vasculature determines the degree of pulmonary hypertension in the congenital diaphragmatic hernia (CDH). This study aims to demonstrate the morphometric measurements that differ in pulmonary vessels of fetuses with CDH. METHODS: Nitrofen-induced CDH Sprague-Dawley rat fetuses were scanned with microcomputed tomography. The analysis of the pulmonary vascular tree was performed with artificial intelligence. RESULTS: The number of segments in CDH was significantly lower than that in the control group on the left (U = 2.5, p = 0.004) and right (U = 0, p = 0.001) sides for order 1(O1), whereas there was a significant difference only on the right side for O2 and O3. The pooled element numbers in the control group obeyed Horton's law (R2 = 0.996 left and R2 = 0.811 right lungs), while the CDH group broke it. Connectivity matrices showed that the average number of elements of O1 springing from elements of O1 on the left side and the number of elements of O1 springing from elements of O3 on the right side were significantly lower in CDH samples. CONCLUSION: According to these findings, CDH not only reduced the amount of small order elements, but also destroyed the fractal structure of the pulmonary arterial trees.

Multicentre, randomised controlled trial of physiological-based cord clamping versus immediate cord clamping in infants with a congenital diaphragmatic hernia (PinC): statistical analysis plan.

BACKGROUND: Infants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial). DESIGN: The PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4-8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved. TRIAL REGISTRATION: ClinicalTrials.gov NCT04373902 (registered April 2020).