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Cardiac dysfunction is a key determinant of outcome in congenital diaphragmatic hernia (CDH). Pro-b-type natriuretic peptide (proBNP) is used as a prognosticator in heart failure and cardiomyopathy. We hypothesized that proBNP levels would be associated with ventricular dysfunction and high-risk disease in CDH.Patients in the CDH Study Group (CDHSG) from 2015-2019 with at least one proBNP value were included. Ventricular function was determined using echocardiograms from the first 48 h of life.A total of 2,337 patients were identified, and 212 (9%) had at least one proBNP value. Of those, 3 (1.5%) patients had CDHSG stage A defects, 58 (29.6%) B, 111 (56.6%) C, and 24 (12.2%) D. Patients with high-risk defects (Stage C/D) had higher proBNP compared with low-risk defects (Stage A/B) (14,281 vs. 5,025, p = 0.007). ProBNP was significantly elevated in patients who died (median 14,100, IQR 4,377-22,900 vs 4,911, IQR 1,883-9,810) (p0.001). Ventricular dysfunction was associated with higher proBNP than normal ventricular function (8,379 vs. 4,778, p = 0.005). No proBNP value was both sensitive and specific for ventricular dysfunction (AUC=0.61).Among CDH patients, elevated proBNP was associated with high-risk defects, ventricular dysfunction, and mortality. ProBNP shows promise as a biomarker in CDH-associated cardiac dysfunction.

The purpose of this study was to analyze the clinical characteristics and outcomes of low birthweight (LBW) infants with congenital diaphragmatic hernia (CDH) compared to normal birthweight (NBW) infants with CDH. We hypothesized that LBW was associated with increased mortality, decreased extracorporeal life support (ECLS) utilization, and increased pulmonary morbidity in CDH patients. Patients in the CDH Study Group from 2007 to 2018 were included. LBW was defined as p = .03). LBW infants had longer durations of mechanical ventilation and were more likely to require supplemental oxygen at 30 days and at the time of discharge. LBW is a risk factor for mortality and pulmonary morbidity in CDH. Prolonged oxygen requirement and increased length of stay are important considerations when managing this population.

Objective Abnormal pulmonary vasculature directly affects the development and progression of congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension (PH). Though overarching structural and cellular changes in CDH-affected pulmonary arteries have been documented, the precise role of the extracellular matrix (ECM) in the pulmonary artery (PA) pathophysiology remains undefined. Here, we quantify the structural, compositional, and mechanical CDH-induced changes in the main and distal PA ECM and investigate the efficacy of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) as a therapy to ameliorate pathological vascular ECM changes. Methods Pregnant Sprague-Dawley rodents were administered nitrofen to induce CDH-affected pulmonary vasculature in the offspring. A portion of CDH-affected pups was treated with intravenous infusion of MSC-EVs (1 × 1010 /mL) upon birth. A suite of histological, mechanical, and transmission electron microscopic analyses were utilized to characterize the PA ECM. Results The CDH model main PA presented significantly altered characteristics-including greater vessel thickness, greater lysyl oxidase (LOX) expression, and a relatively lower ultimate tensile strength of 13.6 MPa compared to control tissue (25.1 MPa), suggesting that CDH incurs ECM structural disorganization. MSC-EV treatment demonstrated the potential to reverse CDH-related changes, particularly through rapid inhibition of ECM remodeling enzymes (LOX and MMP-9). Additionally, MSC-EV treatment bolstered structural aspects of the PA ECM and mitigated pathological disorganization as exhibited by increased medial wall thickness and stiffness that, while not significantly altered, trends away from CDH-affected tissue. Conclusions These data demonstrate notable ECM remodeling in the CDH pulmonary vasculature, along with the capacity of MSC-EVs to attenuate pathological ECM remodeling, identifying MSC-EVs as a potentially efficacious therapeutic for CDH-associated pulmonary hypertension.

There is a known association between Cornelia de Lange syndrome (CdLS) and congenital diaphragmatic hernia (CDH), with CDH being the cause of death in 5%-20% of CdLS cases. We aimed to identify and describe patients with CDLS and CDH. We hypothesized that CdLS would be associated with high-risk CDH and poor outcomes.CDH Study Group patients from 1995 to 2019 were included. Those with CdLS were reviewed retrospectively. Rates of repair and outcomes were compared between patients with and without CdLS.We identified 9,251 CDH patients. Of those, 21 had confirmed CdLS. CdLS patients had a lower birth weight (2.2±0.57 kg) than non-CdLS patients (2.9±0.64 kg) (p0.001). 5-min Apgar scores were lower in CdLS patients (6, 4-7) than non-CdLS patients (7, 5-8) (p=0.014). Only 33% of CdLS patients underwent diaphragmatic repair compared to 84.2% of non-CdLS patients (p0.001). Mortality was 76% for CdLS patients compared with 29% for non-CdLS patients (p0.001). Of the 7 CdLS patients who underwent repair, 5 survived to hospital discharge.Infants with CdLS and CDH have a poor prognosis. However, CdLS patients who undergo repair can survive to discharge; therefore, the concomitant diagnosis of CdLS and CDH is not necessarily a contraindication to repair. Early recognition of these anomalies can assist with counseling and prognostication.Retrospective comparative study LEVEL OF EVIDENCE: III.

Objectives Electronic cigarette or vaping product use-associated lung injury is a clinical entity that can lead to respiratory failure and death. Despite the severity of electronic cigarette or vaping product use-associated lung injury, the role of extracorporeal life support in its management remains unclear. Our objective was to describe the clinical characteristics and outcomes of patients with electronic cigarette or vaping product use-associated lung injury who received extracorporeal life support. Design We performed a retrospective review of records of electronic cigarette or vaping product use-associated lung injury patients who received extracorporeal life support. Standardized data were collected via direct contact with extracorporeal life support centers. Data regarding presentation, ventilatory management, extracorporeal life support details, and outcome were analyzed. Setting This was a multi-institutional, international case series with patients from 10 different institutions in three different countries. Patients Patients who met criteria for confirmed electronic cigarette or vaping product use-associated lung injury (based on previously reported diagnostic criteria) and were placed on extracorporeal life support were included. Patients were identified via literature review and by direct contact with extracorporeal life support centers. Measurements and main results Data were collected for 14 patients ranging from 16 to 45 years old. All had confirmed vape use within 3 months of presentation. Nicotine was the most commonly used vaping product. All patients had respiratory symptoms and radiographic evidence of bilateral pulmonary opacities. IV antibiotics and corticosteroids were universally initiated. Patients were intubated for 1.9 days (range, 0-6) prior to extracorporeal life support initiation. Poor oxygenation and ventilation were the most common indications for extracorporeal life support. Five patients showed evidence of ventricular dysfunction on echocardiography. Thirteen patients (93%) were placed on venovenous extracorporeal life support, and one patient required multiple rounds of extracorporeal life support. Total extracorporeal life support duration ranged from 2 to 37 days. Thirteen patients survived to hospital discharge; one patient died of septic shock. Conclusions Electronic cigarette or vaping product use-associated lung injury can cause refractory respiratory failure and hypoxemia. These data suggest that venovenous extracorporeal life support can be an effective treatment option for profound, refractory respiratory failure secondary to electronic cigarette or vaping product use-associated lung injury.

Background Bronchopulmonary sequestration (BPS) has long been identified in patients with congenital diaphragmatic hernia (CDH), however the reported incidence in the literature varies widely and is not based on large series. Methods Version 4 of the Congenital Diaphragmatic Hernia Study Group (CDHSG) included questions specifically identifying BPS-associated cases. The data were prospectively collected between 2015 and 2020. Clinical characteristics and outcomes for CDH+BPS patients were compared to patients without BPS using univariate and multiple regression analyses. Results Out of 2118 total patients, 72 had a pulmonary sequestration (3.4%). The amount of CDH+BPS with high-risk (CDHSG type C and D) defects was significantly greater than those without BPS (68.0% vs 49.3%, respectively; p = 0.001). The need for ECLS (35/72, 48.6%) and overall mortality (21/72, 29.2%) was significantly higher in CDH+BPS. When corrected for hernia size, cardiac and chromosomal anomalies, the need for ECLS (OR 2.2, p = 0.004) and mortality (OR 2.0, p = 0.015) was significantly greater in CDH+BPS. Conclusions This is the largest series to look at the incidence of BPS in children with CDH. They are associated with larger defect sizes, a greater need for ECLS and higher mortality than those patients without BPS.

Rotational anomalies of the intestine are well described in the pediatric surgical literature. The deep understanding of these anomalies their surgical management differentiate the pediatric surgeons from their adult surgery colleagues. The diagnostic and operative approaches to these problems have developed consistently over the last several decades as techniques and understanding have progressed. The potentially devastating outcomes of malrotation, nonrotation, and volvulus generally necessitate operative repair. The open technique was originally described by William Ladd in the 1930s, hence the eponymous “Ladd’s Procedure.” Since then, although the principles of the operation have remained the same, minimally invasive approaches have also been applied. Herein, we provide a review of the laparoscopic approach to surgical correction of abdominal rotation anomalies. Included in this chapter are a discussion of the preoperative workup, anesthetic considerations, and peri-operative pearls and pitfalls of laparoscopic repair.

Introduction: Pulmonary hypertension (PH) is the major pathophysiologic consequence of congenital diaphragmatic hernia (CDH). We aimed to evaluate the association between early CDH-associated PH (CDH-PH) and inpatient outcomes. Methods: The CDH Study Group registry was queried for infants born 2015–2019 with echocardiograms before 48h of life. PH was categorized using echocardiographic findings: none, mild (right ventricular systolic pressure Results: Of 1,472 patients, 86.5% had CDH-PH: 13.9% mild (n = 193), 44.4% moderate (n = 631), and 33.2% severe (n = 468). On adjusted analysis, the primary outcome of mortality or oxygen support at 30 days occurred more frequently in infants with moderate (incidence rate ratio [IRR] 1.8, 95% confidence interval [CI], 1.2–2.6) and severe CDH-PH (IRR 2.0, 95% CI, 1.3–2.9). Extracorporeal life support (ECLS) utilization was associated only with severe CDH-PH after adjustment (IRR 1.8, 95% CI, 1.0–3.3). Discussion/Conclusion: Early, postnatal CDH-PH is independently associated with increased risk for mortality or oxygen support at 30 days and utilization of ECLS. Early echocardiogram is a valuable prognostic tool for early, inpatient outcomes in neonates with CDH.

Congenital diaphragmatic hernia (CDH) leads to pathophysiologic pulmonary vasoreactivity. Previous studies show that mesenchymal stromal cell-derived extracellular vesicles (MSCEv) inhibit lung inflammation and vascular remodeling. We characterize MSCEv and human pulmonary artery endothelial cell (HPAEC) interaction, as well as the pulmonary artery (PA) response to MSCEv treatment. HPAECs were cultured with and without exposure to nitrofen (2,4-dichloro-phenyl-p-nitrophenylether) and treated with MSCEv. HPAEC viability, architecture, production of reactive oxygen species (ROS), endothelial dysfunction-associated protein levels (PPARγ, LOX-1, LOX-2, nuclear factor-κB [NF-κB], endothelial NO synthase [eNOS], ET-1 [endothelin 1]), and the nature of MSCEv-cellular interaction were assessed. Newborn rodents with and without CDH (nitrofen model and Sprague-Dawley) were treated with intravascular MSCEv or vehicle control, and their PAs were isolated. Contractility was assessed by wire myography. The contractile (KCL and ET-1) and relaxation (fasudil) responses were evaluated. HPAEC viability correlated inversely with nitrofen dose, while architectural compromise was directly proportional. There was a 2.1 × increase in ROS levels in nitrofen HPAECs (

Congenital diaphragmatic hernia (CDH) is a neonatal pathology in which intrathoracic herniation of abdominal viscera via diaphragmatic defect results in aberrant pulmonary and cardiovascular development. Despite decades of study and many advances in the diagnosis and treatment of CDH, morbidity and mortality remain high, largely due to pulmonary hypertension (PH), along with pulmonary hypoplasia and cardiac dysfunction. In patients with CDH, hypoplastic pulmonary vasculature and alterations in multiple molecular pathways lead to pathophysiologic pulmonary vasculopathy and, for severe CDH, sustained, elevated pulmonary arterial pressures. This review addresses the multiple anatomic and physiologic changes that underlie CDH-associated PH (CDH-PH), along with the multimodal treatment strategies that exist currently and future therapies currently under investigation.

Background The purpose of this study was to identify patient and treatment characteristics associated with early (in hospital) hernia recurrence after congenital diaphragmatic hernia (CDH) repair. Methods Data from the Congenital Diaphragmatic Hernia Study Group registry were queried from 2007 to 2015. Recurrence of the diaphragmatic hernia after initial repair and prior to death or discharge was determined at the time of reoperation. Minimally invasive surgery (MIS) approaches included laparoscopy or thoracoscopy, and open approaches consisted of laparotomy or thoracotomy. Multivariate regression analysis was performed. Results Of 3984 patients, 3332 (84%) underwent CDH repair. 76 (2.3%) patients had an early recurrence. The rate of recurrence was less variable over time for patients undergoing laparotomy vs thoracoscopy (range: 1.1–3.7% vs 1.7–8.9% annually). Timing of repair, whether performed after, during, or before ECMO did not significantly alter recurrence rates (0% vs 4.2% vs 3.0%, p =0.116). Larger defect size (C: OR 4.3, 95% CI 1.2–15.4; D: OR 7.1, 95% CI 1.7–29.1) and an MIS approach (OR 3.2, 95% CI 1.7–6.0) were the only independent predictors of recurrence. Conclusion Larger defect size and an MIS approach were associated with higher rates of early recurrence, while ECMO use and timing of repair with ECMO were not. Type of study Treatment study. Level of evidence II.