Introduction: Neonates with congenital diaphragmatic hernia (CDH) who undergo repair while on extracorporeal membrane oxygenation (ECMO) are at risk of developing post-operative bleeding complications. Balanced anticoagulation is critical to maintain ECMO flow and avoid bleeding. Heparin has historically been our first-line anticoagulant; however, recently, we transitioned to bivalirudin, a direct thrombin inhibitor. The objective of this pilot study was to compare post-operative surgical bleeding complications between the two groups. Methods: We performed a single center retrospective cohort study of patients who underwent CDH repair while on ECMO between 2008 and 2023. Neonates were stratified based on the type of anticoagulant initiated after CDH repair. Outcomes included bleeding requiring surgical re-operation, intracranial hemorrhage, volume of blood products transfused, number of circuit changes, days on ECMO, and overall survival. Results: Among 62 neonates with CDH who underwent repair on ECMO, 44 (71%) were managed post-CDH repair with heparin and 18 (29%) with bivalirudin. One (5.6%) neonate managed with bivalirudin underwent re-operation following CDH repair for a bleeding complication compared to 17 (38.6%) managed with heparin (p = 0.022). In addition, the bivalirudin cohort utilized half of the total blood product volume compared to the heparin cohort (p = 0.020). Despite these benefits, there were no significant differences between groups for incidence of intracranial hemorrhage, number of circuit changes, days on ECMO, and overall survival. Conclusion: Anticoagulation with bivalirudin in neonates who underwent CDH repair while on ECMO was associated with decreased surgical bleeding complications and less total blood product transfused. This pilot analysis is the first to compare heparin to bivalirudin and stresses the importance of a multicenter study.

Inflammation and oxidative stress are implicated in the pathogenesis of Crohn’s disease. Cerium oxide nanoparticle (CNP) conjugated to microRNA 146a (miR146a) (CNP-miR146a) is a novel compound with anti-inflammatory and antioxidative properties. We hypothesized that local administration of CNP-miR146a would improve colitis in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS) mouse model for Crohn’s disease by decreasing colonic inflammation. Balb/c mice were instilled with TNBS enemas to induce colitis. Two days later, the mice received cellulose gel enema, cellulose gel with CNP-miR146a enema, or no treatment. Control mice received initial enemas of 50% ethanol and PBS enemas on day two. The mice were monitored daily for weight loss and clinical disease activity. The mice were euthanized on days two or five to evaluate their miR146a expression, inflammation on histology, and colonic IL-6 and TNF gene expressions and protein concentrations. CNP-miR146a enema successfully increased colonic miR146a expression at 12 h following delivery. At the end of five days from TNBS instillation, the mice treated with CNP-miR146a demonstrated reduced weight loss, improved inflammation scores on histology, and reduced gene expressions and protein concentrations of IL-6 and TNF. The local delivery of CNP-miR146a in a TNBS mouse model of acute Crohn’s colitis dramatically decreased inflammatory signaling, resulting in improved clinical disease.

Introduction: Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among extremely premature infants. Approximately 50% of cases progress to surgery, frequently resulting in resection of necrotic bowel and ostomy creation. Premature neonates are at risk for bronchopulmonary dysplasia and feeding failure; surgery in these patients is higher risk. We evaluated the incidence of gastrostomy tube (GT) placement after ostomy reversal in surgical NEC to define a subset of patients who would benefit from concurrent ostomy reversal and GT placement.Methods: A single-center retrospective study of infants with surgical NEC requiring ostomy creation between 2007 and 2021 was performed.Results: Eighty patients met inclusion criteria. A GT was placed in 45/80 (56.3%), of which 3/ 45 (6.7%) were placed before, 20/45 (44.4%) concurrently with, and 22/45 (48.9%) after ostomy reversal. Between those who did and did not require GT placement, there were no significant differences in gestational age (27 versus 27 wk, P = 0.94) or birth weight (830 g versus 1055 g, P = 0.36). Hospital length of stay was longer in the GT group (128.2 versus 70.9 d, P < 0.0001). Time from ostomy reversal to hospital discharge was shorter when performed concurrently with GT (56 versus 77 d, P = 0.02). There were no differences in short-term or long-term GT related complications based on timing of GT placement. Conclusions: GT placement occurred in approximately 50% of patients with surgical NEC and GT may be accomplished safely at the time of ostomy reversal thus reducing the need for an additional procedure.(c) 2023 Elsevier Inc. All rights reserved.

Background: Open fetal resection for large lung lesions has virtually been replaced by maternal steroid administration. Despite this paradigm shift, little is known about the effects steroids have on lung lesion growth in utero. Methods: A 10 -year retrospective review of all prenatally diagnosed lung lesions cared for at our fetal care center was performed. We evaluated the effects of prenatal steroids on congenital pulmonary airway malformation (CPAM)-volume-ratio (CVR), distinguishing change in CVR among CPAMs, bronchopulmonary sequestrations (BPS), and bronchial atresias. We also correlated fetal ultrasound and MRI findings with pathology to determine the accuracy of prenatal diagnosis. Results: We evaluated 199 fetuses with a prenatal lung lesion. Fifty-four (27 %) were treated with prenatal steroids with a subsequent 21 % mean reduction in the CVR (2.1 +/- 1.4 to 1.1 +/- 0.4, p = 0.003). Fetuses with hydrops and mediastinal shift who were treated with steroids rarely had resolution of these radiographic findings. Postnatal pathology was available for 91/199 patients (45.7 %). The most common diagnosis was CPAM (42/91, 46 %), followed by BPS (30/91, 33 %), and bronchial atresia (14/91, 15 %). Fetuses who received steroids and had pathology consistent with CPAM were more likely to have a reduction in their CVR (p = 0.02). Fetal ultrasound correctly diagnosed the type of lung lesion in 75 % of cases and fetal MRI in 81 % of cases. Conclusions: Prenatally diagnosed CPAMs are more likely to respond to maternal steroids than BPS or bronchial atresias. Knowing the diagnosis in utero could aid to steward steroid usage, however, fetal imagining modalities are not perfect in distinguishing subtype. Level of evidence: III. (c) 2023 Elsevier Inc. All rights reserved.

Diabetes mellitus is a morbid condition affecting a growing number of the world population, and approximately one third of diabetic patients are afflicted with diabetic foot ulcers (DFU), which are chronic non-healing wounds that frequently progress to require amputation. The treatments currently used for DFU focus on reducing pressure on the wound, staving off infection, and maintaining a moist environment, but the impaired wound healing that occurs in diabetes is a constant obstacle that must be faced. Aberrant angiogenesis is a major contributor to poor wound healing in diabetes and surgical intervention is often necessary to establish peripheral blood flow necessary for healing wounds. Over recent years, microRNAs (miRNAs) have been implicated in the dysregulation of angiogenesis in multiple pathologies including diabetes. This review explores the pathways of angiogenesis that become dysregulated in diabetes, focusing on miRNAs that have been identified and the mechanisms by which they affect angiogenesis.

Introduction: Prosthetic patches (patch) and muscle flaps (flap) are techniques used for repair of congenital diaphragmatic hernia (CDH) with a large defect unamenable to primary closure. We hypothesized that the flap technique for CDH repair while on extra-corporeal membrane oxygenation (onECMO) would have decreased bleeding complications compared to patch due to the hemostatic advantage of native tissue. Methods: A single-center retrospective comparative study of patients who underwent on-ECMO CDH repair between 2008 and 2022 was performed. Results: Fifty-two patients met inclusion criteria: 18 patch (34.6%) and 34 flap (65.4%). There was no difference in CDH severity between groups. On univariate analysis, reoperation for surgical bleeding was lower following flap repair compared to patch (23.5% vs 55.6%, respectively; p = 0.045), 48-h postoperative blood product transfusion was lower after flap repair (132 mL/kg vs 273.5 mL/kg patch; p = 0.006), and two-year survival was increased in the flap repair group compared to patch (53.1% vs 17.7%, respectively; p = 0.036). On multivariate analysis adjusting for CDH side, day on ECMO repaired, and day of life CDH repaired, flap repair was significantly associated with lower five-day postoperative packed red blood cell transfusion amount, improved survival to hospital discharge, and improved twoyear survival. Conclusions: Our experience suggests that the muscle flap technique for on-ECMO CDH repair is associated with reduced bleeding complications compared to prosthetic patch repair, which may in part be responsible for the improved survival seen in the flap repair group. These results support the flap repair technique as a favored method for on-ECMO CDH repair. Level of Evidence: Level III.

Background: Acute arterial thrombosis can be life-and limb-threatening. Most pediatric patients with iliofemoral arterial thrombosis are treated successfully with medical therapy; however, expert consensus is limited, and many recommendations are based on the extrapolation of adult data. We aim to understand treatment patterns and long-term outcomes after pediatric acute iliofemoral arterial thrombosis, from which management recommendations can be informed.Methods: A single-institution retrospective study of pediatric patients diagnosed with iliofemoral arterial thrombosis from 2009 to 2018 was performed. Multiple parameters of management and follow-up were evaluated. Children anticoagulated for <= 28 days versus >28 days were compared. Data analysis used Fisher exact and Mann-Whitney U tests.Results: Two hundred thirty-six children were included. Median age at diagnosis was 65 days (inter quartile range 17-163), with 207 diagnosed as infants, 15 diagnosed between 1 to 2 years, and 14 diagnosed between 2 to 16 years. The median treatment duration was 28 days (interquartile range 13-42); patients treated for >28 days had a longer time for thrombus resolution, and more follow-up ultrasounds were performed. Limb length discrepancy did not differ between the groups (1.0% vs 6.3%, P 1/4 .06), and no patients were documented to have developed peripheral arterial disease over a median 6.5-year follow-up. Multiple treatment strategies were employed, the most common being heparin bridged to enoxaparin (25.0%) and enoxaparin monotherapy (21.6%). Eight patients (3.4%) underwent surgical intervention.Conclusion: Pediatric iliofemoral arterial thrombosis is primarily a disease of infants treated adequately with heparin or enoxaparin, infrequently requires surgical intervention, and is rarely associated with long-term complications. When guided by thrombus resolution on ultrasound, a four-week or shorter course of anticoagulation does not increase the need for surgical intervention or long-term complications.(c) 2023 Elsevier Inc. All rights reserved.

Introduction: Pericardial teratomas are rare mediastinal tumors that can lead to pericardial effusions with subsequent tamponade physiology and progression to hydrops. While overall outcomes can be favorable, prognosis is poor in the setting of hydrops, particularly at an early gestational age. Case presentation:We present a case in which a 29-year-old female presented at 26 3/7 weeks' gestation carrying a fetus with a prenatally diagnosed pericardial teratoma. During a period of outpatient monitoring with twice-weekly ultrasounds and echocardiograms, the fetus developed a rapidly expanding pericardial effusion with cardiac compromise, prompting admission. Following admission, the fetus developed early signs of hydrops including ascites and pulmonary effusions at 27 6/7 weeks, and after a multidisciplinary discussion underwent open fetal resection two days later. This resulted in the resolution of hydrops with delivery at 29 3/7 weeks and ultimately neonatal survival without the need for any additional postnatal procedures. Conclusion:In this case report, we discuss current fetal interventions utilized in the management of pericardial teratomas, including the few prior attempts at open fetal resection. We also highlight the potential benefit of open fetal resection in the setting of early hydrops to optimize further in-utero development while simultaneously addressing the tamponade physiology of pericardial teratomas that can lead to hydrops and fetal demise. Here, we demonstrate that open fetal resection is a feasible and effective treatment option for carefully selected patients with pericardial teratomas, particularly in the setting of early hydrops.

Purpose: Fetal repair of myelomeningocele (MMC) and myeloschisis leads to improved neurologic out-comes compared to postnatal repair, but the effects of modifications in closure techniques have not been extensively studied. Previous work has suggested that a watertight repair is requisite for improvement in hindbrain herniation (HBH) and to decrease postnatal hydrocephalus (HCP). Our institution adopted the myofascial closure technique for open fetal MMC repair in July 2019, which we hypothesized would result in decreased need for patch closure, improved HBH, and decreased rate of surgically-treated HCP.Methods: A single-center retrospective study of patients who underwent fetal MMC or myeloschisis re-pair between March 2013 and February 2022 was performed. Outcomes were evaluated ( n = 70 prior to July 2019, n = 34 after July 2019). Statistical significance was determined by Fisher's exact and Chi square tests ( p < 0.05 significant).Results: Patients who underwent myofascial closure were less likely to require a patch for skin closure (14.7% vs 58.6%, p < 0.0 0 01). Myofascial closure was also associated with an increased rate of HBH im-provement on two-week postoperative fetal MRI (93.9% vs 65.7%, p = 0.002). Surgically-treated HCP at one year was lower in the myofascial closure group ( n = 21), however this did not reach statistical sig-nificance (23.8% vs 41.9%, p = 0.19).Conclusions: We conclude that the myofascial closure technique for repair of fetal MMC and myeloschisis is associated with significantly decreased need for patch closure and improvement in hindbrain herni-ation compared to our previous skin closure technique. These results support a surgical approach that employs a multilayer watertight closure.(c) 2022 Elsevier Inc. All rights reserved.

Acute respiratory distress syndrome (ARDS) has high mortality (~40 %) and requires the lifesaving intervention of mechanical ventilation. A variety of systemic inflammatory insults can progress to ARDS, and the inflamed and injured lung is susceptible to ventilator-induced lung injury (VILI). Strategies to mitigate the inflammatory response while restoring pulmonary function are limited, thus we sought to determine if treatment with CNP-miR146a, a conjugate of novel free radical scavenging cerium oxide nanoparticles (CNP) to the anti-inflammatory microRNA (miR)-146a, would protect murine lungs from acute lung injury (ALI) induced with intratracheal endotoxin and subsequent VILI. Lung injury severity and treatment efficacy were evaluated via lung mechanical function, relative gene expression of inflammatory biomarkers, and lung morphometry (stereology). CNP-miR146a reduced the severity of ALI and slowed the progression of VILI, evidenced by improvements in inflammatory biomarkers, atelectasis, gas volumes in the parenchymal airspaces, and the stiffness of the pulmonary system.

Acute respiratory distress syndrome (ARDS) has approximately 40% in-hospital mortality, and treatment is limited to supportive care. Pneumonia is the underlying etiology in many cases with unrestrained inflammation central to the pathophysiology. We have previously shown that CNP-miR146a, a radical scavenging cerium oxide nanoparticle (CNP) conjugated to the anti-inflammatory microRNA(miR)-146a, reduces bleomycin- and endotoxin-induced acute lung injury (ALI) by decreasing inflammation. We therefore hypothesized that CNP-miR146a would decrease inflammation in murine infectious ALI. Mice were injured with intratracheal (IT) MRSA or saline followed by treatment with IT CNP-miR146a or saline control. Twenty-four hours post-infection, bronchoalveolar lavage fluid (BALF) and whole lungs were analyzed for various markers of inflammation. Compared to controls, MRSA infection significantly increased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p < 0.05), BALF proinflammatory cytokines (IL-6, IL-8, TNFα, IL-1β; p < 0.01), and inflammatory cell infiltrate (p = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p < 0.05), bronchoalveolar proinflammatory protein leak (IL-6, IL-8, TNFα; p < 0.05), and inflammatory infiltrate (p = 0.01). CNP-miR146a decreases inflammation and improves alveolar–capillary barrier integrity in the MRSA-infected lung and has significant promise as a potential therapeutic for ARDS.