The spectrum of pneumonia among intubated neonates in the neonatal intensive care unit.

We review the pathophysiology, epidemiology, diagnosis, treatment, and prevention of ventilator-associated pneumonia (VAP) in neonates. VAP has been studied primarily in adult ICU patients, although there has been more focus on pediatric and neonatal VAP (neo-VAP) in the last decade. The definition as well as diagnosis of VAP in neonates remains a challenge to date. The neonatal intensivist needs to be familiar with the current diagnostic tools and prevention strategies available to treat and reduce VAP to reduce neonatal morbidity and the emergence of antibiotic resistance. This review also highlights preventive strategies and old and emerging treatments available.

Pharmacotherapy of BPD: Current status & future perspectives.

Bronchopulmonary dysplasia (BPD) is a disease exclusive to prematurity and has changed in its definition since Northway first described it in 1967. There have been countless clinical trials evaluating the efficacy of drugs in the treatment and prevention of BPD in human subjects, and an even larger number of animal studies. Despite these, only a handful of drugs are used at the bedside today, primarily due to the lack of consistent efficacy seen in clinical trials or due to reports of adverse effects. This review summarizes the list of the most commonly used drugs and emerging new therapies which target BPD and BPD-related pulmonary hypertension (BPD-PH), including those which have shown promise in human trials but are not yet used routinely.

Factors Associated with Hospital Readmission One Year Post-Discharge in Infants with Gastroschisis.

INTRODUCTION: Gastroschisis is the most common congenital abdominal wall defect with a rising prevalence. Infants with gastroschisis are at risk for multiple complications, leading to a potential increased risk for hospital readmission after discharge. We aimed to find the frequency and factors associated with an increased risk of readmission. METHODS: A retrospective analysis of infants born with gastroschisis between 2013 and 2019 who received initial surgical intervention and follow-up care in the Children's Wisconsin health system was performed. The primary outcome was the frequency of hospital readmission within 1 year of discharge. We also compared maternal and infant clinical and demographic variables between those readmitted for reasons related to gastroschisis, and those readmitted for other reasons or not readmitted. RESULTS: Forty of 90 (44%) infants born with gastroschisis were readmitted within 1-year of the initial discharge date, with 33 (37%) of the 90 infants being readmitted due to reasons directly related to gastroschisis. The presence of a feeding tube (p < 0.0001), a central line at discharge (p = 0.007), complex gastroschisis (p = 0.045), conjugated hyperbilirubinemia (p = 0.035), and the number of operations during the initial hospitalization (p = 0.044) were associated with readmission. Maternal race/ethnicity was the only maternal variable associated with readmission, with Black race being less likely to be readmitted (p = 0.003). Those who were readmitted were also more likely to be seen in outpatient clinics and utilize emergency healthcare resources. There was no statistically significant difference in readmission based on socioeconomic factors (all p > 0.084). CONCLUSION: Infants with gastroschisis have a high hospital readmission rate, which is associated with a variety of risk factors including complex gastroschisis, multiple operations, and the presence of a feeding tube or central line at discharge. Improved awareness of these risk factors may help stratify patients in need of increased parental counseling and additional follow-up.

Fetal pulmonary hypertension: dysregulated microRNA-34c-Notch1 axis contributes to impaired angiogenesis in an ovine model.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) occurs when pulmonary vascular resistance (PVR) fails to decrease at birth. Decreased angiogenesis in the lung contributes to the persistence of high PVR at birth. MicroRNAs (miRNAs) regulate gene expression through transcript binding and degradation. They were implicated in dysregulated angiogenesis in cancer and cardiovascular disease. METHODS: We investigated whether altered miRNA levels contribute to impaired angiogenesis in PPHN. We used a fetal lamb model of PPHN induced by prenatal ductus arteriosus constriction and sham ligation as controls. We performed RNA sequencing of pulmonary artery endothelial cells (PAECs) isolated from control and PPHN lambs. RESULTS: We observed a differentially expressed miRNA profile in PPHN for organ development, cell-cell signaling, and cardiovascular function. MiR-34c was upregulated in PPHN PAECs compared to controls. Exogenous miR34c mimics decreased angiogenesis by control PAEC and anti-miR34c improved angiogenesis of PPHN PAEC in vitro. Notch1, a predicted target for miR-34c by bioinformatics, was decreased in PPHN PAECs, along with Notch1 downstream targets, Hey1 and Hes1. Exogenous miR-34c decreased Notch1 expression in control PAECs and anti-miR-34c restored Notch1 and Hes1 expression in PPHN PAECs. CONCLUSION: We conclude that increased miR-34c in PPHN contributes to impaired angiogenesis by decreasing Notch1 expression in PAECs. IMPACT: Adds a novel mechanism for the regulation of angiogenesis in persistent pulmonary hypertension of the newborn. Identifies non-coding RNAs that are involved in the altered angiogenesis in PPHN and thus the potential for future studies to identify links between known pathways regulating angiogenesis. Provides preliminary data to conduct studies targeting miR34c expression in vivo in animal models of pulmonary hypertension to identify the mechanistic role of miR34c in angiogenesis in the lung vasculature.

Pediatric Pulmonary Hypertension: Definitions, Mechanisms, Diagnosis, and Treatment.

Pediatric pulmonary hypertension (PPH) is a multifactorial disease with diverse etiologies and presenting features. Pulmonary hypertension (PH), defined as elevated pulmonary artery pressure, is the presenting feature for several pulmonary vascular diseases. It is often a hidden component of other lung diseases, such as cystic fibrosis and bronchopulmonary dysplasia. Alterations in lung development and genetic conditions are an important contributor to pediatric pulmonary hypertensive disease, which is a distinct entity from adult PH. Many of the causes of pediatric PH have prenatal onset with altered lung development due to maternal and fetal conditions. Since lung growth is altered in several conditions that lead to PPH, therapy for PPH includes both pulmonary vasodilators and strategies to restore lung growth. These strategies include optimal alveolar recruitment, maintaining physiologic blood gas tension, nutritional support, and addressing contributing factors, such as airway disease and gastroesophageal reflux. The outcome for infants and children with PH is highly variable and largely dependent on the underlying cause. The best outcomes are for neonates with persistent pulmonary hypertension (PPHN) and reversible lung diseases, while some genetic conditions such as alveolar capillary dysplasia are lethal. © 2021 American Physiological Society. Compr Physiol 11:2135-2190, 2021.

Epidemiology and outcomes of primary pediatric lung malignancies: Updates from the SEER database.

BACKGROUND: Primary pediatric lung malignancies are rare tumors. We provide an updated analysis of the epidemiology and prognosis of these tumors since the last SEER series published in 2009. METHODS: The SEER 18 database from 1975 to 2016 was analyzed for patients ages 0-19 years with primary lung and/or bronchus neoplasms. RESULTS: 348 patients met inclusion criteria. The majority were white and ≥12 years of age. The most common histologies were neuroendocrine (41.4%) and blastoma (16.4%). 75.4% of patients had local-regional disease and 81.4% underwent surgery. Significant differences between histologies were seen for age, year at diagnosis, tumor laterality and location, stage, and treatment type. Median survival was 36.6 years (95% CI 33.3-37.4). Blastoma (HR 3.47) and squamous cell (HR 6.26) carried a significantly higher risk of death than neuroendocrine cancer diagnosis. CONCLUSION: Primary pediatric lung malignancies are rare, long-term survival is favorable but histology-dependent. Surgery continues to be an important treatment modality.

Frequency and duration of phototherapy in preterm infants <35 weeks gestation.

OBJECTIVE: To evaluate the frequency, age at phototherapy (PT) initiation, and duration of PT use in infants 230/7 to 346/7 weeks of gestation in two neonatal intensive care units (NICUs) over 4 time periods. STUDY DESIGN: We reviewed the charts of all infants born at 230/7-346/7 weeks of gestational age (GA) and admitted to the NICUs of two hospitals between January 2009 and September 2015. We calculated the proportion of infants who received PT and the total duration of PT exposure. RESULTS: Overall 2023 (81.8%) received PT, and PT use was inversely related to GA and birthweight. More infants received PT when GA was added as a criterion for initiating PT. The median duration (interquartile range (IQR)) of PT for all infants was 50 (27-85) h and in the lowest GA group was 74 (42-111) h. CONCLUSIONS: Recent US consensus guidelines appear to have led to an increased use of PT in our NICUs and studies from Norway indicate that we use PT considerably more frequently and for longer durations than do our Norwegian colleagues.

Primary intracranial soft tissue sarcomas in children, adolescents, and young adults: single institution experience and review of the literature.

There is a paucity of literature reporting the outcome of intracranial sarcomas (IS) in children, adolescents, and young adults (CAYA). A multimodal therapeutic approach is commonly used, with no well-established treatment consensus. We conducted a retrospective review of CAYA with IS, treated at our institution, to determine their clinical findings, treatments, and outcomes. Immunohistochemistry (PDGFRA and EGFR) and DNA sequencing were performed on 5 tumor samples. A literature review of IS was also conducted. We reviewed 13 patients (median age, 7 years) with a primary diagnosis of IS between 1990 and 2015. Diagnoses included unclassified sarcoma (n = 9), chondrosarcoma (n = 2), and rhabdomyosarcoma (n = 2). Five patients underwent upfront gross total resection (GTR) of the tumor. The 5-drug regimen (vincristine, doxorubicin, cyclophosphamide, etoposide, and ifosfamide) was the most common treatment used. Nine patients died due to progression or recurrence (n = 8) or secondary malignancy (n = 1). The median follow-up period of the 4 surviving patients was 1.69 years (range 1.44-5.17 years). The 5-year progression-free survival and overall survival rates were 21 and 44 %, respectively. BRAF, TP53, KRAS, KIT, ERBB2, MET, RET, ATM, and EGFR mutations were detected in 4 of the 5 tissue samples. All 5 samples were immunopositive for PDGFRA, and only 2 were positive for EGFR. IS remain a therapeutic challenge due to high progression and recurrence rates. Collaborative multi-institutional studies are warranted to delineate a treatment consensus and investigate tumor biology to improve the disease outcome.