Pediatric Intensive Care Unit admission criteria for haemato-oncological patients: a basis for clinical guidelines implementation

Recent advances in supportive care and progress in the development and use of chemotherapy have considerably improved the prognosis of many children with malignancy, thus the need for intensive care admission and management is increasing, reaching about 40% of patients throughout the disease course. Cancer remains a major death cause in children, though outcomes have considerably improved over the past decades. Prediction of outcome for children with cancer in Pediatric Intensive Care Unit (PICU) obviously requires clinical guidelines, and these are not well defined, as well as admission criteria. Major determinants of negative outcomes remain severe sepsis/septic shock association and respiratory failure, deserving specific approach in children with cancer, particularly those receiving a bone marrow transplantation. A nationwide consensus should be achieved among pediatric intensivists and oncologists regarding the threshold clinical conditions requiring Intensive Care Unit (ICU) admission as well as specific critical care protocols. As demonstrated for the critically ill non-oncologic child, it appears unreasonable that pediatric patients with malignancy can be admitted to an adult Intensive Care Unit ICU. On a national basis a pool of refecence institutions should be identified and early referral to an oncologic PICU is warranted

Role of MicroRNA Profile Modifications in Hepatitis C Virus-Related Mixed Cryoglobulinemia

Hepatitis C virus infection is closely related to lymphoproliferative disorders (LPDs), including mixed cryoglobulinemia (MC) and some lymphomas. Modification of the expression of specific microRNAs (miRNAs) has been associated with different autoimmune diseases and/or LPDs. No data exist about the modifications in miRNA expression in HCV-associated LPDs. The aim of this study was to analyze the expression levels of a panel of miRNAs previously associated with autoimmune/LPDs in a large population of HCV patients with and without MC or non-Hodgkin’s lymphoma (NHL), to identify potential markers of evolution of HCV infection. PBMC expression of miR-Let-7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 was evaluated by real-time PCR in 167 HCV patients (75 with MC [MC-HCV], 11 with HCV-associated NHL [NHL-HCV], 81 without LPD [HCV]) and in 35 healthy subjects (HS). A significant increase in miR-21 (p<0.001), miR-16 (p<0.01) and miR-155 (p<0.01) expression was detected in PBMCs from only NHL patients whereas a significant decrease in miR-26b was detected in both MC and NHL subjects (p<0.01) when compared to HS and HCV groups. A restoration of miR-26b levels was observed in the post-treatment PBMCs of 35 HCV-MC patients experiencing complete virological and clinical response following antiviral therapy. This study, for the first time, shows that specific microRNAs in PBMC from HCV patients who developed MC and/or NHL are modulated differently. The specific, reversible downregulation of miR-26b strongly suggests the key role it plays in the pathogenesis of HCV-related LPDs and its usefulness as a biomarker of the evolution of HCV infection to these disorders

Development of a Novel Passive-Dynamic Custom AFO for Drop-Foot Patients: Design Principles, Manufacturing Technique, Mechanical Properties Characterization and Functional Evaluation

Ankle foot orthoses (AFOs) are medical devices prescribed to support the foot and ankle of drop-foot patients. Passive-dynamic AFOs (PD-AFOs) are an effective solution for less severe cases. While off-the-shelf PD-AFOs are rather inexpensive, they provide poor anatomical fit and do not account for the required patient-specific biomechanical support. Three-dimensional (3D) scanning and manufacturing technologies allow manufacturing PD-AFOs customized for the patient's anatomy and functional needs. This paper aimed to report the overall procedure for designing and manufacturing a novel, fiberglass-reinforced polyamide, custom PD-AFO. The feasibility of the proposed procedure was tested in a case study. The methodology can be divided into the following steps: (i) foot and leg scanning, (ii) 3D design, and (iii) additive manufacturing via selective laser sintering. A custom PD-AFO was designed and manufactured for a 67-year-old male drop-foot patient following paraparesis in severe discarthrosis after spine stabilization surgery. AFO mechanical properties were measured via an ad hoc setup based on a servohydraulic testing machine. The functional outcome was assessed via gait analysis in three conditions: shod (no AFO), wearing an off-the-shelf PD-AFO, and wearing the patient-specific PD-AFO. As expected, wearing the PD-AFO resulted in increased ankle dorsiflexion in the swing phase with respect to the shod condition. Sagittal rotations of the hip, knee, and ankle joints were similar across PD-AFO conditions, but the custom PD-AFO resulted in faster walking speed with respect to the off-the-shelf (walking speed: 0.91 m/s versus 0.85 m/s). Additionally, the patient scored the custom PD-AFO as more comfortable (VAS score: 9.7 vs. 7.3). While the present analysis should be extended to a larger cohort of drop-foot patients, the novel PD-AFO seems to offer a valid, custom solution for drop-foot patients not satisfied with standard orthotics

A serum metabolomic analysis of HCV-infected patients successfully treated with IFN-free DAA regimens

HCV infects about 170 million of subjects worldwide. The virus has a high propensity to persist in the host, leading to cirrhosis and liver cancer. Metabolomics is the study of metabolic changes in biological systems and may identify specific profiles associated with subtle alterations induced by diseases. Few studies are available on metabolitic changes in liver injuries, and since none of which was focused on HCV-infected patients before and after reaching a SVR following treatment with direct acting antivirals (DAAs), the aim of this study was to perform a serum metabolomics analysis in this setting Sera were collected from 52 HCV patients (18 men, mean age 65±9,7) successfully undergoing different IFN-free DAA regimens, before therapy (baseline) and at post-treatment week 12 (SVR12). HCV genotype was 1a/1b in 70%, 2a/2c in 23%, 3 in 4.7% and 4 in 2.3%. METAVIR score indicated F3-F4 score in 55% of patients, the remaining 45% had F0-F2 We also analyzed a small group of 12 sera from healthy subjects in order to localize them in the PLS plot respect to baseline and SVR12 as a preliminary negative control for both groups. Samples were analyzed using proton nuclear magnetic resonance spectroscopy (1H-NMR). Partial Least Squares (PLS) and the canonical analysis (CA) were applied, demonstrating a significant pair-wise discrimination (96% of accuracy) for the two time-points of each patient and highlighting a metabolic shift Several metabolites with unequivocal assignment (i e amino acids, organic acids, creatine, creatinine, lactate and choline) differed comparing baseline with SVR12. Baseline featured higher level of formate and acetate (p&lt;0.05) and methionine was higher in SVR12 (p&lt;0.05). Preliminary analysis revealed also a progressive nearing of SVR12 to the healthy fingerprint. The serum metabolomic analysis of pre- and post-treatment samples showed remarkable profile changes from baseline to SVR12. We found variations, with opposite directions, in formate (produced in adults only by hepatocytes) and methionine. These metabolites take part in biochemical ways (i e glucose metabolism) also involving acetate and other amino acids, going through the synthesis of folates These alterations could be implied in the metabolic impairment previously observed in chronically infected HCV-patients. Also, since methionine is the major source of methyl groups, an understanding of its variation, could reveal important dysfunctions in liver essential pathways requiring methylation (i e epigenetic regulation of DNA) in HCV-related chronic infection

Overexpression of N-ras oncogene and epidermal growth factor receptor gene in human glioblastomas.

Five human glioblastoma cell lines were analyzed for oncogene activation with a panel of probes. Abnormal expression of the epidermal growth factor receptor (EGFr) gene was detected in four of five lines; N-ras oncogene overexpression was found in all five cell lines. These results were subsequently confirmed with fresh brain tumor and nonneoplastic brain tissue biopsy samples; increased expression of the N-ras proto-oncogene was observed in five of five glioblastomas, all of which also showed EGFr gene overexpression, but not in well-differentiated gliomas or in nonneoplastic brain tissue specimens. No significant differences in Ha-ras and Ki-ras expression were observed. Preliminary histochemical observations showed that intracellular levels of transforming growth factor alpha, a putative biochemical link between these two oncogenes, were significantly higher in glioblastoma cells than in controls