Senescence of lung mesenchymal stem cells of preterm infants by cyclic stretch and hyperoxia via p21.

Phenotype distortion of lung resident mesenchymal stem cells (MSC) in preterm infants is a hallmark event in the pathogenesis of bronchopulmonary dysplasia (BPD). Here, we evaluated the impact of cyclic mechanical stretch (CMS) and hyperoxia (HOX). The negative action of HOX on proliferation and cell death was more pronounced at 80% than at 40%.

Highlighting fibroblast plasticity in lung fibrosis: the WI-38 cell line as a model for investigating the myofibroblast and lipofibroblast switch.

Myofibroblasts (MYFs) are generally considered the principal culprits in excessive extracellular matrix deposition and scar formation in the pathogenesis of lung fibrosis. Lipofibroblasts (LIFs), on the other hand, are defined by their lipid-storing capacity and are predominantly found in the alveolar regions of the lung. They have been proposed to play a protective role in lung fibrosis.

GLI1+ Cells Contribute to Vascular Remodeling in Pulmonary Hypertension.

Background: The precise origin of newly formed ACTA2+ (alpha smooth muscle actin-positive) cells appearing in nonmuscularized vessels in the context of pulmonary hypertension is still debatable although it is believed that they predominantly derive from preexisting vascular smooth muscle cells (VSMCs).

Methods: mice were used to lineage trace GLI1+ (glioma-associated oncogene homolog 1-positive) cells in the context of pulmonary hypertension using 2 independent models of vascular remodeling and reverse remodeling: hypoxia and cigarette smoke exposure. Hemodynamic measurements, right ventricular hypertrophy assessment, flow cytometry, and histological analysis of thick lung sections followed by state-of-the-art 3-dimensional reconstruction and quantification using Imaris software were used to investigate the contribution of GLI1+ cells to neomuscularization of the pulmonary vasculature.

Anthropometric parameters as a tool for the prediction of metabolic and cardiovascular risk in childhood brain tumor survivors.

Purpose: To assess the prevalence of alterations in anthropometric parameters predictive of metabolic syndrome and cardiovascular risk among childhood brain tumor survivors.

Methods: Anthropometric parameters predictive of metabolic syndrome and cardiovascular risk were analyzed [height, weight, BMI, waist circumference, hip circumference, waist-height ratio (WHtR), waist-hip ratio (WHR, blood pressure] of 25 patients who survived childhood brain tumors.

Results: 21 patients (84%) showed alteration of at least one predictive anthropometric parameter.

Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients.

Aminoglycosides are broad-spectrum antibiotics largely used in children, but they have potential toxic side effects, including ototoxicity. Ototoxicity from aminoglycosides is permanent and is a consequence of its action on the inner ear cells via multiple mechanisms. Both uncontrollable risk factors and controllable risk factors are involved in the pathogenesis of aminoglycoside-related ototoxicity and, because of the irreversibility of ototoxicity, an important undertaking for preventing ototoxicity includes antibiotic stewardship to limit the use of aminoglycosides.

Early and Long-Term Ototoxicity Noted in Children Due to Platinum Compounds: Prevalence and Risk Factors.

Background: Platinum compounds are a group of fundamental chemotherapeutics used in the treatment of solid tumors, but they are burdened by side effects, such as ototoxicity. The objective of this study was to evaluate the incidence of ototoxicity caused by platinum compounds and the risk factors affecting its appearance/progression.

Methods: Data from 53 patients who received platinum compounds and who had been off therapy for at least 5 years were analyzed.

Insights into the Black Box of Intra-Amniotic Infection and Its Impact on the Premature Lung: From Clinical and Preclinical Perspectives.

Intra-amniotic infection (IAI) is one major driver for preterm birth and has been demonstrated by clinical studies to exert both beneficial and injurious effects on the premature lung, possibly due to heterogeneity in the microbial type, timing, and severity of IAI. Due to the inaccessibility of the intra-amniotic cavity during pregnancies, preclinical animal models investigating pulmonary consequences of IAI are indispensable to elucidate the pathogenesis of bronchopulmonary dysplasia (BPD). It is postulated that on one hand imbalanced inflammation, orchestrated by lung immune cells such as macrophages, may impact on airway epithelium, vascular endothelium, and interstitial mesenchyme, resulting in abnormal lung development.

Transplacental Passage and Fetal Effects of Antineoplastic Treatment during Pregnancy.

The incidence of PAC is relatively infrequent among pregnant women. However, it has gradually increased in recent years, becoming a challenging area for clinicians that should take into account in the same way maternal benefits and fetal potential risks correlated to the antineoplastic treatment. None of the antineoplastic drugs is completely risk-free during the pregnancy, the timing of exposure and transplacental transfer properties influence the toxicity of the fetus.

Biomarkers Predictive of Metabolic Syndrome and Cardiovascular Disease in Childhood Cancer Survivors.

The improvement in childhood cancer treatments resulted in a marked improvement in the survival of pediatric cancer patients. However, as survival increased, it was also possible to observe the long-term side effects of cancer therapies. Among these, metabolic syndrome is one of the most frequent long-term side effects, and causes high mortality and morbidity.

Fgfr2b signaling is essential for the maintenance of the alveolar epithelial type 2 lineage during lung homeostasis in mice.

Fibroblast growth factor receptor 2b (Fgfr2b) signaling is essential throughout lung development to form the alveolar epithelial lineage. However, its role in alveolar epithelial type 2 cells (AT2s) homeostasis was recently considered dispensable. Sftpc; Fgfr2b; tdTomato mice were used to delete Fgfr2b expression in cells belonging to the AT2 lineage, which contains mature AT2s and a novel Sftpc lineage-traced population called "injury activated alveolar progenitors" or IAAPs.

When inflammation meets lung development-an update on the pathogenesis of bronchopulmonary dysplasia.

Even more than 50 years after its initial description, bronchopulmonary dysplasia (BPD) remains one of the most important and lifelong sequelae following premature birth. Tremendous efforts have been undertaken since then to reduce this ever-increasing disease burden but a therapeutic breakthrough preventing BPD is still not in sight. The inflammatory response provoked in the immature lung is a key driver of distorted lung development and impacts the formation of alveolar, mesenchymal, and vascular structures during a particularly vulnerable time-period.

FGF10 Triggers De Novo Alveologenesis in a Bronchopulmonary Dysplasia Model: Impact on Resident Mesenchymal Niche Cells.

Bronchopulmonary dysplasia (BPD) is a neonatal lung disease developing in premature babies characterized by arrested alveologenesis and associated with decreased Fibroblast growth factor 10 (FGF10) expression. One-week hyperoxia (HYX) exposure of newborn mice leads to a permanent arrest in alveologenesis. To test the role of Fgf10 signaling to promote de novo alveologenesis following hyperoxia, we used transgenic mice allowing inducible expression of Fgf10 and recombinant FGF10 (rFGF10) protein delivered intraperitoneally.

Mechanisms, Characteristics, and Treatment of Neuropathic Pain and Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients.

Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti-GD2 monoclonal antibody (ch14.18) dinutuximab.

Early spontaneous pneumothorax, pneumomediastinum and pneumorrhachis in an adolescent with SARS-CoV-2 infection.

We report a case of spontaneous pneumomediastinum, pneumothorax, emphysema subcutaneous and pneumorrhachis, occurring in an adolescent resulting positive to SARS-CoV-2 nasopharyngeal swab. At the admission in Emergency Department, the child presented with left cervical and sternal pain, without respiratory symptoms. Radiological studies showed sizeable pneumomediastinum, bilateral apical pneumothorax, massive emphysema subcutaneous and pneumorrhachis.

Identification of a novel subset of alveolar type 2 cells enriched in PD-L1 and expanded following pneumonectomy.

Alveolar type 2 (AT2) cells are heterogeneous cells, with specialised AT2 subpopulations within this lineage exhibiting stem cell properties. However, the existence of quiescent, immature cells within the AT2 lineage that are activated during lung regeneration is unknown. mice were used for the labelling of AT2 cells and labelled subpopulations were analysed by flow cytometry, quantitative PCR, assay for transposase-accessible chromatin using sequencing (ATAC-seq), gene arrays, pneumonectomy and culture of precision-cut lung slices.

Utility of a pediatric observation unit for the management of children admitted to the emergency department.

Background: Observation Units (OU), as part of emergency department (ED), are areas reserved for short-term treatment or observation of patients with selected diagnoses to determine the need for hospitalization or home referral.

Methods: In this retrospective cohort study, we analyzed similarities and differences of children admitted to the pediatric ED of the Fondazione Policlinico Universitario A. Gemelli IRCCS hospital in the first 2 years of OU activity, analyzing general patient characteristics, access modalities, diagnosis, triage, laboratory and instrumental examinations, specialist visits, outcome of OU admission and average time spent in OU.

Identification of a Repair-Supportive Mesenchymal Cell Population during Airway Epithelial Regeneration.

Tissue regeneration requires coordinated and dynamic remodeling of stem and progenitor cells and the surrounding niche. Although the plasticity of epithelial cells has been well explored in many tissues, the dynamic changes occurring in niche cells remain elusive. Here, we show that, during lung repair after naphthalene injury, a population of PDGFRα cells emerges in the non-cartilaginous conducting airway niche, which is normally populated by airway smooth muscle cells (ASMCs).

Use of the Reversible Myogenic to Lipogenic Transdifferentiation Switch for the Design of Pre-clinical Drug Screening in Idiopathic Pulmonary Fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is an end-stage lung disease characterized by excessive extracellular matrix (ECM) deposition from activated myofibroblasts (MYFs) and tissue scarring. Eventually leading to stiffening of the lung, capable of assuming only limited gas exchange function. So far two drugs, pirfenidone [acting via TGF-β (transforming growth factor beta) inhibition] and nintedanib (a pan-tyrosine kinase receptor inhibitor) have been approved for IPF patients.

Fgf10/Fgfr2b Signaling in Mammary Gland Development, Homeostasis, and Cancer.

Fibroblast growth factor 10 (Fgf10) is a secreted ligand acting via the Fibroblast growth factor receptor 2b (Fgfr2b). Fgf10/Fgfr2b signaling plays important roles both in the epithelium and in the mesenchyme during mammary gland development. Evidence in mice show that Fgf10 is critical for the induction of four out of five of the mammary placodes and for the formation of the white adipose tissue.

Food Protein-Induced Enterocolitis Syndrome: Proposals for New Definitions.

Acute food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated allergy and is characterized by repetitive profuse vomiting episodes, often in association with pallor, lethargy, and diarrhea, presenting within 1-4 h from the ingestion of a triggering food. In 2017, the international consensus guidelines for the diagnosis and management of FPIES were published. They cover all aspects of this syndrome, which in recent decades has attracted the attention of pediatric allergists.

Impact of Fgf10 deficiency on pulmonary vasculature formation in a mouse model of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD), characterized by alveoli simplification and dysmorphic pulmonary microvasculature, is a chronic lung disease affecting prematurely born infants. Pulmonary hypertension (PH) is an important BPD feature associated with morbidity and mortality. In human BPD, inflammation leads to decreased fibroblast growth factor 10 (FGF10) expression but the impact on the vasculature is so far unknown.

A comparative study of physical image quality in digital and synthetic mammography from commercially available mammography systems.

We present a comparison between full field digital mammography and synthetic mammography, performed on several mammography systems from four different manufacturers. The analysis is carried out on both the digital and synthetic images of two commercially available mammography phantoms, and focuses on a set of objective metrics that encode the geometrical appearance of imaging features of diagnostic interest. In particular, we measured sizes and contrasts of several clusters of microcalcification specks, shapes and contrasts of circular masses, and the power spectrum of background regions mimicking the heterogeneous texture of the breast parenchyma.