A survey of pediatric hematology/oncology specialists regarding management of central line associated venous thrombosis

Central venous catheters (CVCs) account for the largest proportion of thrombotic events in pediatric patients. Questions remain regarding adequate treatment and prevention methods. We surveyed pediatric hematology/oncology specialists, using hypothetical cases to assess management strategies for acute CVC thrombosis and secondary prevention. Survey respondents varied in the use of the thrombophilia evaluation (33.3%, 41/123) and duration of treatment (6 weeks: 54.1%, 66/122). Secondary CVC prophylaxis was utilized by 36.6% (45/123) of respondents and by 24.4% (30/123) but only if there was a documented thrombophilia. This heterogeneity highlights the need for clinical studies to address these important clinical questions.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137422/1/pbc26383_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137422/2/pbc26383.pd

Rifampicin-loaded electrospun polycaprolactone membranes: Characterization of stability, antibacterial effects and urotheliocytes proliferation

Pathological conditions such as infections, cancer, inflammation, or iatrogenic lesions, can hinder the cor-rect functionality of the ureter and its structural integrity. Several strategies for the regeneration of the ureter and the restoration of its functionality are available but the best strategy has not been reached yet. Among the proposed strategies, a promising one is the development of tubular scaffolds, in particular exploiting electrospinning technique. In this work, antibacterial electrospun polycaprolactone/rifampicin (PCL/Rif) membranes were prepared and characterized. The membranes are characterized by randomly oriented nanofibers with a homogeneous diameter, as determined by scanning electron microscopy. The mechanical characterization, performed with uniaxial tensile tests, showed a suitable stability over time and a proper deformability. The rifampicin release, investigated by UV spectrophotometry, showed a burst release in the first part of the experiment and a sustained release over time. The membranes are biocompatible and able to support the adhesion and proliferation of urotheliocytes. Moreover, PCL/Rif membranes showed an antibacterial activity against Escherichia coli and other bacterial strains belonging to the "ESKAPE" group. Considering the possibility to use the electrospinning for the production of tubu-lar scaffolds, the described membranes represent a promising starting point for the preparation of uret-eral scaffolds with antibacterial properties.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Antibacterial rifampicin-loaded electrospun polycaprolactone membranes for ureteral regeneration

Author of the study: Nowadays partial or complete ureteral loss following resection or injuries of various etiology is managed with different surgical techniques involving local tissue flaps or autologous tissues interposition. In the last years ureteral tissue engineering using membranes, tubular scaffolds or decellularized matrices has shown promising results for ureteral substitution. The aim of this study is to evaluate the use of antibacterial electrospun polycaprolactone/ rifampicin (PCL/RIF) membranes for the production of ureteral scaffolds with antibacterial properties. Materials and methods: Electrospinning processwas used to produce the membranes that were subsequently impregnated with rifampicin. Membranes stability was evaluated by immersion in Simulated Body Fluid (SBF) at 37 °C. Mechanical properties were evaluated by uniaxial tensile tests, Young’s modulus was calculated for each sample. UV spectrophotometry was used to evaluate in vitro release of rifampicin. The ability of PCL/Rif membranes to sustain cell adhesion and proliferation was evaluated by seeding human urothelial bladder carcinoma cells on the membranes. In order to investigate the antibacterial effect of PCL/Rif membranes, in vitro antibacterial tests were performed using bacterial strains belonging to the “ESKAPE” group. Results: PCL/Rif membranes are characterized by a random distribution of fibers with an average diameter of 0.52 μm.Water contact angle for PCL and PCL/Rif membranes is around 125° and decreases to 0° after air-plasma treatment. When culture medium is used as testing fluid PCL and PCL/Rif contact angles are 116° and 12° respectively. Membranes are deformable up to 300% of their initial dimension and possess an elastic Young modulus of about 20 kPa; after 3 weeks membranes gain the property to sustain a 100% deformation before rupture. The 72% of rifampicin load is released by the membranes in the first 24 hours. Proliferation assay showed a seven-fold increase of cell number adhered on the membranes after 7 days of culture. At the same time in presence of PCL/Rif membranes, rates of bacterial proliferation inhibition ranged from 75 to 94% compared to controls. Conclusions: PCL/Rif membranes represent a promising starting point in the production of ureteral scaffolds with antibacterial properties for ureteral substitution

Apixaban overdose in children: case report and proposed management. A brief communication from the Pediatric and Neonatal Thrombosis and Hemostasis SSC of ISTH

\ua9 2024 The Authors. Background: Direct oral anticoagulants are commonly prescribed for adults and increasingly also for children requiring anticoagulation therapy. While household medications should not be accessible to children, accidental, and intentional overdoses occur. Key Clinical Question: How should apixaban overdose in children be managed?. Clinical Approach: We present a case of an accidental overdose with the factor Xa antagonist apixaban in a young child and propose an approach to the management of cases of apixaban overdose in children. Conclusion: Given the increasing use of direct oral anticoagulants, it is important to have an approach to the management of overdose of these medications

Human and animal integrated influenza surveillance: a novel sampling approach for an additional transmission way in the aquatic bird reservoir.

Background: infectious low pathogenic avian influenza viruses (LPAIVs) have been recently detected on feathers of wild ducks. Laboratory trial results suggested that the preen oil gland secretion, covering waterbirds\u2019 feathers, may attract and concentrate virus particles from AIV-contaminated waters to birds\u2019 bodies. We evaluated whether ducks can become infected by the ingestion of preen oil-associated viral particles, experimentally smeared on their plumage. In addition, we compared virologic and serologic results obtained from mallards whose feathers were experimentally infected, with those from wild mallards naturally carrying AIVs on feathers. Methods: we experimentally coated 7 mallards (Anas plathyrynchos) using preen oil mixed with a LPAIV (H10N7 subtype), and housed them for 45 days with a control, uncoated duck. Cloacal, oropharyngeal and feather swabs were collected from all birds and examined for AIV molecular detection and isolation. Blood samples were also taken to detect influenza specific antibodies. In addition, sera from 10 wild mallards, carrying on feathers infectious LPAIV H10N7, were examined. Results: virologic and serologic results indicated that through self- and allopreening all the birds experimentally coated with the preen oil/AIV mix and the control duck ingested viruses covering feathers and became infected. Virus isolation from feathers was up to 32 days post-coating treatment. One out of 8 wild mallards showing antibodies against type A influenza virus was seropositive for H10 subtype too. Conclusions: our experimental and field results show evidences suggesting that uninfected birds carrying viruses on their feathers, including immune ones, might play an active role in spreading AIV infection in nature. For this reason, routine AIV surveillance programs, aimed at detecting intestinal and/or respiratory viruses, should include the collection of samples, such as feather swabs, enabling the detection of viruses sticky to preened birds\u2019 bodies

Serologic evidence of occupational exposure to avian influenza viruses at the wildfowl/poultry/human interface

Ecological interactions between wild aquatic birds and outdoor-housed poultry can enhance spillover events of avian influenza viruses (AIVs) from wild reservoirs to domestic birds, thus increasing the related zoonotic risk to occupationally exposed workers. To assess serological evidence of AIV infection in workers operating in Northern Italy at the wildfowl/poultry interface or directly exposed to wildfowl, serum samples were collected between April 2005 and November 2006 from 57 bird-exposed workers (BEWs) and from 7 unexposed controls (Cs), planning three sample collec-tions from each individual. Concurrently, AIV surveillance of 3587 reared birds identified 4 AIVs belonging to H10N7, H4N6 and H2N2 subtypes while serological analysis by hemagglutination inhibition (HI) assay showed recent infections caused by H1, H2, H4, H6, H10, H11, H12, and H13 subtypes. Human sera were analyzed for specific antibodies against AIVs belonging to antigenic subtypes from H1 to H14 by using HI and virus microneutralization (MN) assays as a screening and a confirmatory test, respectively. Overall, antibodies specific to AIV-H3, AIV-H6, AIV-H8, and AIV-H9 were found in three poultry workers (PWs) and seropositivity to AIV-11, AIV-H13—still detectable in October 2017—in one wildlife professional (WP). Furthermore, seropositivity to AIV-H2, accounting for previous exposure to the “extinct” H2N2 human influenza viruses, was found in both BEWs and Cs groups. These data further emphasize the occupational risk posed by zoonotic AIV strains and show the possible occurrence of long-lived antibody-based immunity following AIV infections in humans

Identification of Two DNMT3A Mutations Compromising Protein Stability and Methylation Capacity in Acute Myeloid Leukemia

Somatic mutations of DNMT3A occur in about 20% of acute myeloid leukemia (AML) patients. They mostly consist in heterozygous missense mutations targeting a hotspot site at R882 codon, which exhibit a dominant negative effect and are associated with high myeloblast count, advanced age, and poor prognosis. Other types of mutations such as truncations, insertions, or single-nucleotide deletion also affect the DNMT3A gene, though with lower frequency. The present study aimed to characterize two DNMT3A gene mutations identified by next-generation sequencing (NGS), through analysis of protein stability and DNA methylation status at CpG islands. The first mutation was a single-nucleotide variant of DNMT3A at exon 20 causing a premature STOP codon (c.2385G > A; p.Trp795 17; NM-022552.4). The DNMT3A mutation load increased from 4.5% to 38.2% during guadecitabine treatment, with a dominant negative effect on CpG methylation and on protein expression. The second mutation was a novel insertion of 35 nucleotides in exon 22 of DNMT3A (NM-022552.4) that introduced a STOP codon too, after the amino acid Glu863 caused by a frameshift insertion (c.2586-2587insTCATGAATGAGAAAGAGGACATCTTATGGTGCACT; p. Thr862-Glu863fsins). The mutation, which was associated with reduced DNMT3A expression and CpG methylation, persisted at relapse with minor changes in the methylation profile and at protein level. Our data highlight the need to better understand the consequences of DNMT3A mutations other than R882 substitutions in the leukemogenic process in order to tailor patient treatments, thus avoiding therapeutic resistance and disease relapse

The usability attributes and evaluation measurements of mobile media AR (augmented reality)

This research aims to develop a tool for creating user-based design interfaces in mobile augmented reality (MAR) education. To develop a design interface evaluation tool, previous literature was examined for key design elements in the educational usage of MAR. The evaluation criteria identified were presence, affordance, and usability. The research used a focus group interview with 7 AR experts to develop a basic usability evaluation checklist, which was submitted to factor analysis for reliability by 122 experts in practice and academia. Based on this checklist, a MAR usability design interface test was conducted with seven fourth-grade elementary students. Then, it conducted follow-up structured interviews and questionnaires. This resulted in 29 questions being developed for the MAR interface design checklist.ope