Pathological Roles for Endothelial Colony-Forming Cells in Neonatal and Adult Lung Disease.

Endothelial colony-forming cells (ECFCs) are vascular resident and circulating endothelial cell subtypes with potent angiogenic capacity, a hierarchy of single-cell clonogenic potentials, and the ability to participate in de novo blood vessel formation and endothelial repair. Existing literature regarding ECFCs in neonatal and adult pulmonary diseases is confounded by the study of ambiguously defined "endothelial progenitor cells," which are often not true ECFCs. This review contrasts adult and fetal ECFCs, discusses the effect of prematurity on ECFCs, and examines their different pathological roles in neonatal and adult pulmonary diseases, such as bronchopulmonary dysplasia, congenital diaphragmatic hernia, pulmonary artery hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease. Therapeutic potential is also discussed in light of available preclinical data.

Short-term outcomes of thoracoscopic versus open lobectomy for congenital lung malformations.

PURPOSE: Thoracoscopic and open approaches for the management of congenital lung malformations (CLM) has been debated. The aim of this study is to compare 30-day outcomes for non-emergent lobectomies in children. METHODS: The National Surgical Quality Improvement Program-Pediatric database was queried for patients undergoing CLM resection from 2013 to 2020. Outcomes were compared by operative technique in an intention-to-treat model and then propensity matched. RESULTS: 2157 patients met inclusion criteria and underwent non-emergent pulmonary lobectomy for CLM. The intended operative approach was thoracoscopic in 57.7% of patients. Patients in the open group compared to the thoracoscopic were more likely to be born premature, have chronic lung disease, require preoperative oxygen support, and be ventilator dependent. After propensity matching, there was no statistically significant difference in 30-day mortality, unplanned readmission, and other complications between the thoracoscopic and open groups. Thoracoscopic approach was associated with a shorter length of stay. The proportion of cases approached via thoracoscopy increased over time from 48.8% in 2013 to 69.9% in 2020. CONCLUSIONS: This large multicenter retrospective matched analysis demonstrates thoracoscopic lobectomy in children has similar favorable 30-day outcomes and shorter length of stay for the non-emergent management of CLM, compared to open thoracotomy. LEVEL OF EVIDENCE: Level III.

Acute kidney injury in necrotizing enterocolitis predicts mortality.

BACKGROUND: Morbidity and mortality with necrotizing enterocolitis (NEC) remains a significant challenge. Acute kidney injury (AKI) has been shown to worsen survival in critically ill neonates. To our knowledge, this study is the first to evaluate the prevalence of AKI and its impact on outcomes in neonatal NEC. METHODS: We carried out a single-center retrospective chart review of all neonates treated for NEC between 2003 and 2015 (N = 181). AKI is defined as a rise in serum creatinine (SCr) from a previous trough according to neonatal modified KDIGO criteria (stage 1 = SCr rise 0.3 mg/dL or SCr 150 < 200%, stage 2 = SCr rise 200 < 300%, stage 3 = SCr rise ≥300%, SCr 2.5 mg/dL or dialysis). Primary outcome was in-hospital mortality and secondary outcomes were hospital length of stay (LOS) and need for and type of surgery. RESULTS: Acute kidney injury occurred in 98 neonates (54%), with 39 stage 1 (22%), 31 stage 2 (18%), and 28 stage 3 (16%), including 5 requiring dialysis. Non-AKI and AKI groups were not statistically different in age, weight, Bell's NEC criteria, and medication exposure (vasopressors, vancomycin, gentamicin, or diuretic). Neonates with AKI had higher mortality (44% vs 25.6%, p = 0.008) and a higher chance of death (HR 2.4, CI 1.2-4.8, p = 0.009), but the effect on LOS on survivors did not reach statistical significance (79 days, interquartile range [IQR] 30-104 vs 54 days, IQR 30-92, p = 0.09). Overall, 48 (27.9%) patients required surgical intervention. CONCLUSIONS: This study shows that AKI not only occurs in over half of patients with NEC, but that it is also associated with more than a two-fold higher mortality, highlighting the importance of early recognition and potentially early intervention for AKI.

Steroid use for refractory hypotension in congenital diaphragmatic hernia.

PURPOSE: Guidelines for diagnosis and treatment of adrenal insufficiency (AI) in newborns with congenital diaphragmatic hernia (CDH) are poorly defined. METHODS: From 2002 to 2016, 155 infants were treated for CDH at our institution. Patients with shock refractory to vasopressors (clinically diagnosed AI) were treated with hydrocortisone (HC). When available, random cortisol levels <10 µg/dL were considered low. Outcomes were compared between groups. RESULTS: Hydrocortisone was used to treat AI in 34% (53/155) of patients. That subset of patients was demonstrably sicker, and mortality was expectedly higher for those treated with HC (37.7 vs. 17.6%, p = 0.0098). Of the subset of patients with random cortisol levels measured before initiation of HC, 67.7% (21/31) had low cortisol levels. No significant differences were seen in survival between the high and low groups, but mortality trended higher in patients with high cortisol levels that received HC. After multivariate analysis, duration of HC stress dose administration was associated with increased risk of mortality (OR 1.11, 95% CI 1.02-1.2, p = 0.021), and total duration of HC treatment was associated with increased risk of sepsis (OR 1.04, 95% CI 1.005-1.075, p = 0.026). CONCLUSION: AI is prevalent amongst patients with CDH, but prolonged treatment with HC may increase risk of mortality and sepsis.

Sensory Recovery Following Intercostal Nerve Cryoablation for the Nuss Procedure.

BACKGROUND: Intercostal nerve cryoablation (CRYO) during the Nuss procedure is effective for postoperative pain control, but little is known about patterns of sensory recovery following its use. METHODS: A single institution, prospective study of 121 patients undergoing Nuss bar placement with CRYO for pectus excavatum was conducted to assess sensory recovery. Patients received CRYO from T3-T8 and were followed at scheduled intervals. The primary outcome was time to return of normal chest wall sensation. Secondary outcomes included alterations in sensation, permanent numbness, and chronic neuropathic pain. RESULTS: Following CRYO, median time to normal sensation was 6.0 (range 1-12) months. This was achieved postoperatively by 14.9% at 3 months, 62.3% at 6 months, 85.1% at 9 months, and 98.3% at 12 months. 1.7% had a small area of persistent/permanent numbness in the lower central sternum. The most common altered sensation was hypersensitivity which occurred in 20.7%. Hypersensitivity began on average at 3.0 months postoperatively (range 0.25-6 months) and lasted a median of 1.0 (range 0.5-9) months. Only 5.8% described their altered sensation as painful, and all of these were successfully treated with gabapentin and/or capsaicin cream. All others resolved spontaneously. There were no cases of chronic neuropathic pain. CONCLUSIONS: Sensory recovery following CRYO is a slow process that ultimately leads to normal sensation in virtually all patients by one year. Hypersensitivity is more common than expected but is rarely described as painful and always resolves. Permanent numbness can occur but is very rare and limited in scope. LEVEL OF EVIDENCE: Therapeutic.

Surgical techniques used for the treatment of atrial fibrillation.

The use of surgical lesion sets for the treatment of atrial fibrillation has been increasing, particularly in patients with complicated anatomical substrates and those undergoing concomitant surgery. Preferences in terms of lesion set, surgical approach and ablation technology vary by center. This review discusses both the surgical techniques and the outcomes for the most commonly performed procedures in the context of recent consensus guidelines. The Cox-Maze IV, pulmonary vein isolation, extended left atrial lesion sets, the hybrid approach and ganglionated plexus ablation are each reviewed in an attempt to provide insight into current clinical practice and patient selection.

Single-cell transcriptomic profiling of microvascular endothelial cell heterogeneity in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a neonatal anomaly that includes pulmonary hypoplasia and hypertension. We hypothesized that microvascular endothelial cell (EC) heterogeneity is different in CDH lungs and related to lung underdevelopment and remodeling. To test this, we evaluated rat fetuses at E21.5 in a nitrofen model of CDH to compare lung transcriptomes among healthy controls (2HC), nitrofen-exposed controls (NC) and nitrofen-exposed subjects with CDH. Single-cell RNA sequencing with unbiased clustering revealed 3 distinct microvascular EC clusters: a general population (mvEC), a proliferative population and a population high in hemoglobin. Only the CDH mvEC cluster had a distinct inflammatory transcriptomic signature as compared to the 2HC and NC endothelial cells, e.g. greater activation and adhesion of inflammatory cells and production of reactive oxygen species. Furthermore, CDH mvECs had downregulated Ca4, Apln and Ednrb gene expression. Those genes are markers for ECs important to lung development, gas exchange and alveolar repair (mvCa4+). mvCa4+ ECs were reduced in CDH (2HC [22.6%], NC [13.1%] and CDH [5.3%], p < 0.0001). Overall, these findings identify transcriptionally distinct microvascular endothelial cell clusters in CDH, including the distinctly inflammatory mvEC cluster and the depleted group of mvCa4+ ECs, which together may contribute to pathogenesis.

Use of Image Guidance During Pediatric Venovenous Extracorporeal Membrane Oxygenation Cannulation: A Survey of the American Pediatric Surgical Association.

This study evaluated practices for image guidance during placement of bicaval dual-lumen (BCDL) venovenous extracorporeal membrane oxygenation (VV-ECMO) cannulas in pediatric and adolescent patients and elucidates reasoning behind surgeon practices. A survey covering VV-ECMO practice and opinions was distributed by the American Pediatric Surgical Association (APSA) to all attending members. A total of 110 pediatric surgeons responded (11.3%). During initial BCDL cannula placement, 67.7% of surgeons reported using bimodal imaging with either fluoroscopy (38.4%) or x-ray (29.3%) plus echocardiography. Although 37.4% of surgeons used serial x-rays during cannula placement, only 5.9% believed it was best practice to do so ( P < 0.0001). Rather, 60.4% believed that fluoroscopy was the standard. Among surgeons not using fluoroscopy, 27.6% (13.3% of respondents) reported fluoroscopy added unnecessary complexity or that they preferred another modality. More frequently, reasons for not using fluoroscopy are related to resource limitations. Echocardiography use to confirm cannula position was considered best practice by 92.1% of surgeons, with 86.9% utilization. Therefore, most pediatric surgeons use multimodal imaging during cannulation and consider it best practice. Fluoroscopy is preferred, but its use is frequently limited by hospital resources. Echocardiography is widely available and used. These data represent increased consensus among surgeons and present opportunities for modernization of hospital resources and standards.

Discontinuation of the OriGen® Dual-Lumen Right Atrial Cannula Decreased Venovenous ECMO Usage in Neonates and Older Children: A Survey of the American Pediatric Surgical Association.

INTRODUCTION: Dual-lumen cannulas for venovenous (VV)-ECMO are widely used in pediatric patients. The popular OriGen® dual-lumen right atrial cannula was discontinued in 2019 without a comparable replacement. METHODS: A survey covering VV-ECMO practice and opinions was distributed to attending members of the American Pediatric Surgical Association. RESULTS: 137 pediatric surgeons responded (14%). Prior to discontinuation of the OriGen®, 82.5% offered VV-ECMO to neonates, and 79.6% cannulated with the OriGen®. Following its discontinuation, those that offered only venoarterial (VA)-ECMO to neonates increased to 37.6% from 17.5% (p = 0.0002). An additional 33.8% changed their practice to sometimes use VA-ECMO when VV-ECMO was indicated. Reasons for not incorporating dual-lumen bi-caval cannulation into practice included risk of cardiac injury (51.7%), inexperience with bi-caval cannulation in neonates (36.8%), difficulty with placement (31.0%), and recirculation and/or positioning problems (27.6%). For the pediatric/adolescent population, 95.5% of surgeons offered VV-ECMO prior to OriGen® discontinuation. Few switched to exclusive VA-ECMO (1.9%) when the OriGen® was discontinued, but 17.8% of surgeons began to incorporate selective use of VA-ECMO. CONCLUSION: Discontinuation of the OriGen® cannula drove pediatric surgeons to alter their cannulation practices, dramatically increasing VA-ECMO use for neonatal and pediatric respiratory failure. These data may suggest a need for targeted education accompanying major technological shifts. LEVEL OF EVIDENCE: Level IV.

Are pediatric surgery fellowship websites ready for the changing paradigms in the virtual interview era?

Purpose: With the COVID-19 pandemic, in-person fellowship interviews were curtailed, leading candidates to seek information from other resources. Our main purposes were (1) to determine what information recent participants in the match needed to evaluate programs and (2) to assess which of these were available online. Methods: A focus group of ten recent graduates/applicants identified information that was important in choosing a fellowship program. In August 2020 and December 2021, websites belonging to the American Pediatric Surgical Association (APSA) and individual programs were assessed. Results: Recent applicants identified 55 pieces of information considered important to their decision making. Of 57 pediatric surgery fellowships, 98% were listed on APSA's website. Program descriptions on APSA's website listed on average 60% of program information desired by applicants. All listed fellowship director, accreditation status, faculty list, and current fellow(s). Other descriptors frequently noted were alumni (95%), graduate's board performance (83%), ECMO exposure (77%), and curriculum (70%). Information desired but less frequently available were fellow case logs (63%), trauma center designation (53%), burn center designation (40%), research opportunities (30%), candidate interview assistance (25%), and supplemental fellowships (12%). There were 7% of program descriptions that were not updated for at least a year. Conclusions: APSA and individual program websites were complimentary. Websites often lacked data that applicants sought to inform their rank list. To best adapt to the evolving virtual interview paradigm, we suggest reporting key information on a central APSA website with more nuanced information available via links to program specific websites. Supplementary Information: The online version contains supplementary material available at 10.1007/s44186-023-00104-w.