Oncological pediatric early warning score: a dedicated tool to predict patient's clinical deterioration and need for pediatric intensive care treatment.

Pediatric oncohematological patients frequently require PICU admission during their clinical history. The O-PEWS is a specific score developed to predict the need for PICU admission of oncohematological children. This study aimed at i) describing the trend of the O-PEWS in a cohort of patients hospitalized in the Pediatric Oncohematology ward and transferred to the PICU of Padua University Hospital, measured at different time-points in the 24 hours before PICU admission and to evaluate its association with mortality and presence of organ failure; ii) investigating the association between the recorded O-PEWS, and PIM3, number of organ failure and the need for ventilation, dialysis and inotropes.

Evaluation of GSK2789917-induced TRPV4 inhibition in animal models of fluid induced lung injury.

Administration of bolus intravenous fluids, common in pre-hospital and hospitalised patients, is associated with increased lung vascular permeability and mortality outside underlying disease states. In our laboratory, the induction of lung injury and oedema through rapid administration of intravenous fluid in rats was reduced by a non-specific antagonist of transient receptor potential vanilloid 4 (TRPV4) channels. The aims of this study were to determine the effect of selective TRPV4 inhibition on fluid-induced lung injury (FILI) and compare the potency of FILI inhibition to that of an established model of TRPV4 agonist-induced lung oedema.

[F]FDG PET-MR in the Evaluation and Follow-Up of Incidental Bone Ischemic Lesions in a Mono-Center Cohort of Pediatric Patients Affected by Hodgkin's Lymphoma.

Hodgkin's lymphoma (HL) is one of the neoplasms with the best prognosis in children, adolescents and young adults, but sufferers are burdened by the possibility of developing adverse effects such as Bone Ischemic Lesions (BILs) which are lesions of the bone caused by the loss of/reduction in blood flow. The main goal of this retrospective study was to evaluate the role of [F]FDG-PET-MR in the early detection of BILs in a single-center cohort of uniformly treated pediatric HL patients. BILs were assessed through PET-MR images as the appearance of medullary lesion surrounded by a serpiginous, tortuous border.

Bolus intravenous 0.9% saline leads to interstitial permeability pulmonary edema in healthy volunteers.

Purpose: Bolus intravenous administration of 0.9% saline has been associated with the development of pulmonary edema, and increased mortality. An animal model has previously demonstrated that rapid intravenous administration of 0.

Induced hypernatremia in patients with moderate-to-severe ARDS: a randomized controlled study.

Background: Induced hypernatremia and hyperosmolarity is protective in animal models of lung injury. We hypothesized that increasing and maintaining plasma sodium between 145 and 150 mmol/l in patients with moderate-to-severe ARDS would be safe and will reduce lung injury. This was a prospective randomized feasibility study in moderate-to-severe ARDS, comparing standard care with intravenous hypertonic saline to achieve and maintain plasma sodium between 145 and 150 mmol/l for 7 days (HTS group).

Treatment strategy introducing immunosuppressive drugs with glucocorticoids ab initio or very early in giant cell arteritis: A multicenter retrospective controlled study.

Objective: Glucocorticoids (GC) are associated with side effects in giant cell arteritis (GCA). Immunosuppressive therapies (ITs) have given conflicting results in GCA, regarding GC sparing effect. Primary endpoint is to evaluate whether very early introduction of ITs in GCA minimize the rate of GC-induced adverse events, in terms of infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures.

Comparison of Early vs. Delayed Anakinra Treatment in Patients With Adult Onset Still's Disease and Effect on Clinical and Laboratory Outcomes.

Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment. One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences ( < 0.

Data linkage analysis of giant cell arteritis in Italy: Healthcare burden and cost of illness in the Italian region of Friuli Venezia Giulia (2001-2017).

Giant cell arteritis (GCA) is the most common vasculitis in adults. However, comprehensive analyses of the healthcare burden are still scarce. The aim of the study is to report the healthcare burden and cost of illness of GCA in the Friuli Venezia Giulia (FVG) region of Italy, based on a data linkage analysis.

Hyperechoic bands detected by salivary gland ultrasonography are related to salivary impairment in established Sjögren's syndrome.

Objectives: In primary Sjögren's syndrome (pSS) dryness of eye and mouth is the cardinal referred symptom. Assessing the rate of activity and damage in the salivary glands of pSS patients is essential to improve disease management. Up to now, a differentiation of activity and damage ultrasonographic (US) lesions is an open issue.

One year in review 2019: vasculitis.

Systemic vasculitis are disabling complex disorders potentially involving any organ and system. Tremendous efforts have been made recently in this field with novel insights into pathogenesis and new therapy in the pipeline. Following the previous annual reviews of this one year in review series, in this paper we provide a critical digest of the most recent literature regarding pathogenesis, clinical manifestations and therapy, with the ultimate aim of addressing whether the existing data may open new avenues for precision medicine in these disorders.

Immune biomarkers predicting bronchiolitis disease severity: A systematic review.

Bronchiolitis is one of the leading causes of hospitalisation in infancy, with highly variable clinical presentations ranging from mild disease safely managed at home to severe disease requiring invasive respiratory support. Identifying immune biomarkers that can predict and stratify this variable disease severity has important implications for clinical prognostication/disposition. A systematic literature search of the databases Embase, PubMed, ScienceDirect, Web of Science, and Wiley Online Library was performed.

Long-Term Retention Rate of Anakinra in Adult Onset Still's Disease and Predictive Factors for Treatment Response.

Anakinra (ANA) is an effective treatment choice in patients with adult onset Still's disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission. Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission.

Fluid resuscitation associated with elevated angiopoietin-2 and length of mechanical ventilation after cardiac surgery.

Background: Fluid restriction in patients with acute respiratory distress syndrome increases ventilator-free days while lowering plasma angiopoietin-2 (Ang-2), a marker of pulmonary endothelial injury. We hypothesised that fluid resuscitation may lead to endothelial injury after cardiac surgery and analysed Ang-2, angiopoietin-1 (Ang-1) and phospholipase A (PLA) levels and the impact of fluid management on ventilation time.

Methods: Patients enrolled in a single-centre, prospectively randomised interventional study of liberal or conservative fluid resuscitation strategy had plasma Ang-2, Ang-1 and PLA levels measured at baseline (pre-operative), 6 and 24 hours after commencement of cardiopulmonary bypass, and analysed by linear mixed models as liberal conservative (intention to treat) or high low fluid group (actual treatment, ≥ 3250 mL of fluid administered), and further subclassified as EuroSCORE (European System for Cardiac Operative Risk Evaluation) II ≥ 0.

One year in review 2018: systemic vasculitis.

Systemic vasculitis are heterogeneous, complex and disabling disorders. Following the previous annual reviews of this series, this paper gives a brief overview on current knowledge about recent literature on small- and large-vessel systemic vasculitis, with a specific focus on pathogenetic and clinical aspects, novel possible disease-related biomarkers and current and future therapies that are in the pipeline.

Safety profile of the interleukin-1 inhibitors anakinra and canakinumab in real-life clinical practice: a nationwide multicenter retrospective observational study.

A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and adults, based on data from a real-life setting. Demographic, clinical, and therapeutic data from patients treated with ANA and CAN were retrospectively collected and analyzed.

Response to Interleukin-1 Inhibitors in 140 Italian Patients with Adult-Onset Still's Disease: A Multicentre Retrospective Observational Study.

Interleukin (IL)-1 plays a crucial role in the pathogenesis of Adult onset Still's disease (AOSD). To evaluate the efficacy and safety of anakinra (ANA) and canakinumab (CAN) in a large group of AOSD patients. Data on clinical, serological features, and concomitant treatments were retrospectively collected at baseline and after 3, 6, and 12 months from AOSD patients (Yamaguchi criteria) referred by 18 Italian centers.

Lung fluid clearance in chronic heart failure patients.

Chronic elevation of pulmonary microvascular pressure (Pmv) consistently leads to alveolocapillary barrier thickening and reduction in the filtration coefficient. In animal models of chronic heart failure (CHF) the lung remains dry despite hydrostatic forces. As fluid flux is bi-directional, it has been postulated that an increase in alveolar fluid clearance may facilitate the dry lung when Pmv is chronically elevated.

A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide Multi-Center Retrospective Observational Study.

Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis. To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults. We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016.

Neutrophil infiltration and activation in bronchiolitic airways are independent of viral etiology.

Background: Hospitalization with bronchiolitis is linked to the development of early childhood chronic wheeze and asthma. Viral etiology and severity of inflammation are potential contributing factors. Previously we observed reduced airway neutrophil infiltration in breastfed bronchiolitic infants, with a corresponding reduction in disease severity.

In Vivo Genetic Screens of Patient-Derived Tumors Revealed Unexpected Frailty of the Transformed Phenotype.

Unlabelled: The identification of genes maintaining cancer growth is critical to our understanding of tumorigenesis. We report the first in vivo genetic screen of patient-derived tumors, using metastatic melanomas and targeting 236 chromatin genes by expression of specific shRNA libraries. Our screens revealed unprecedented numerosity of genes indispensable for tumor growth (∼50% of tested genes) and unexpected functional heterogeneity among patients (<15% in common).

USP9X Controls EGFR Fate by Deubiquitinating the Endocytic Adaptor Eps15.

Following activation by its cognate ligand(s), the epidermal growth factor receptor (EGFR) is rapidly routed to the lysosome for degradation in a ubiquitination-dependent fashion. This pathway represents the major mechanism of long-term attenuation of EGFR signaling, and its deregulation is a significant feature in different types of cancers. Here we demonstrate, through a systematic RNAi-based approach, that several deubiquitinating (DUB) enzymes extend or decrease EGFR half-life upon EGF stimulation.

Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation.

Clathrin-mediated endocytosis (CME) is the major pathway of epidermal growth factor receptor (EGFR) internalization. It is commonly believed that CME mediates long-term attenuation of EGFR signaling by targeting the receptor for degradation. However, the EGFR can also be internalized through (a) clathrin-independent pathway(s), and it remains unclear why distinct mechanisms of internalization have evolved.

Molecular mechanisms of coupled monoubiquitination.

Many proteins contain ubiquitin-binding domains or motifs (UBDs), such as the UIM (ubiquitin-interacting motif) and are referred to as ubiquitin receptors. Ubiquitin receptors themselves are frequently monoubiquitinated by a process that requires the presence of a UBD and is referred to as coupled monoubiquitination. Using a UIM-containing protein, eps15, as a model, we show here that coupled monoubiquitination strictly depends on the ability of the UIM to bind to monoubiquitin (mUb).