Patient preference for needleless factor VIII reconstitution device: the Italian experience

Background: Needlestick injuries, mostly due to unsafe needle devices, are a frequent adverse event among health care workers and patients on chronic treatment, such as hemophiliacs. To improve the safety of these procedures, a needleless reconstitution system, Bio-Set\uae has been implemented for the sucrose-formulated recombinant factor VIII (rFVIII-FS) Kogenate\uae Bayer (Bayer Healthcare, Berlin, Germany). The aim of this study was to collect patients' satisfaction and safety data regarding the administration of rFVIII-FS with this new device. Methods: This was a multicenter, prospective, postmarketing surveillance study collecting data from seven Italian Haemophilia Centers within the framework of an international project involving patients from nine European countries. The patients were asked to fill out two preference questionnaires (one assessing the old method and one assessing the new method) directly after the training and two further preference questionnaries (assessing the new method) after a period of about 3 and 12 months. Results: A total of 44 male hemophilia A patients were included in the analysis. At the end of the 12-month observation period, physicians assessed the patients' satisfaction with Kogenate\uae Bayer with Bio-Set\uae in 40.9% (n = 18) as "very satisfied" and in 45.5% (n = 20) as "satisfied", whereas "not satisfied" ratings were given for 9.1% (n = 4) of patients (data missing from two patients, 4.5%). The compliance of the patients compared with the last method before switch to the Bio-Set\uae device was rated as "better", "equal", and "worse" in 72.7% (n = 32), 20.5% (n = 9), and 2.3% (n = 1) of patients, respectively. Three patients (6.8%) experienced adverse events, but only one event was related to rFVIII infusion (inhibitor development in a patient who had little prior exposure to rFVIII) itself and not to the new device per se. Conclusions: The great majority of Italian patients who switched from an older method of rFVIII reconstitution to rFVIII-FS with the new reconstitution method preferred the new method. The ease of use, perceived safety from needlesticks, and the speed of reconstitution were identified as main advantages by the majority patients

False-Positive Aspergillus Galactomannan Enzyme-Linked Immunosorbent Assay Results In Vivo during Amoxicillin-Clavulanic Acid Treatment

Positive Platelia Aspergillus test results were observed in consecutive serum samples from an immunocompromised host during amoxicillin-clavulanic acid treatment, and a correlation between plasmatic amoxicillin concentration and galactomannan optical density index was observed. Amoxicillin-clavulanic acid vials tested positive for galactomannan but were negative for Aspergillus DNA

Human Monocytes Constitutively Express Membrane-Bound, Biologically Active, and Interferon-γ–Upregulated Interleukin-15

Interleukin-15 (IL-15) is a potent regulator of T-, B-, and natural killer cell proliferation and displays unusually tight controls of secretion. Even though IL-15 mRNA is constitutively expressed in monocytes/macrophages and is upregulated by a variety of stimuli, evidence for IL-15 cytokine secretion is only found exceptionally, eg, conditions of pathological, chronic inflammation. This raises the possibility that monocytes express membrane-bound IL-15 rather than secrete it. The current study explores this hypothesis. We demonstrate here that biologically active IL-15 is indeed detectable in a constitutively expressed, membrane-bound form on normal human monocytes, as well as on monocytic cell lines (MONO-MAC-6, THP-1, and U937), but not on human T or B cells (MT4, M9, C5966, JURKAT, DAUDI, RAJI, and Epstein-Barr virus-immortalized B-cell clones). Furthermore, cell surface-bound IL-15 is upregulated upon interferon-γ stimulation. Interestingly, monocyte/macrophage inhibitory cytokines such as IL-4 and IL-13 fail to downregulate both constitutive and induced cell-surface expression of IL-15. Membrane-bound IL-15 does not elute with acetate buffer or trypsin treatment, suggesting that it is an integral membrane protein and that it is not associated with the IL-15 receptor complex. Finally, membrane-bound IL-15 stimulates T lymphocytes to proliferate in vitro, indicating that it is biologically active. These findings enlist IL-15 in the fairly small family of cytokines for which the presence of a biologically active membrane-bound form has been demonstrated (eg, IL-1, tumor necrosis factor-, and IL-10) and invites the speculation that most of the biological effects of IL-15 under physiological conditions are exerted by the cell surface-bound form

Interleukin-15 Activates Proinflammatory and Antimicrobial Functions in Polymorphonuclear Cells

Interleukin-15 (IL-15) is a recently discovered cytokine produced by a wide range of different cell types including fibroblasts, keratinocytes, endothelial cells, and macrophages in response to lipopolysaccharide or microbial infection. This suggests that IL-15 may play a crucial role in the activation of phagocytic cells against pathogens. We studied polymorphonuclear leukocyte (PMN) activation by IL-15, evaluated as enhancement of PMN anti-Candida activity as well as IL-8 production, following stimulation with the cytokine. The PMN response to IL-15 depends on binding to the IL-15 receptor. Our experiments show that binding of a biotinylated human IL-15–immunoglobulin G2b IgG2b fusion protein was competed by the addition of human recombinant IL-15 (rIL-15) or of human rIL-2, suggesting that IL-15 binding to PMN might involve the IL-2Rβ and IL-2Rγ chains, which have been shown to be constitutively expressed by PMN. In addition, we show by reverse transcription-PCR and by flow cytometry with a specific anti-IL-15Rα chain monoclonal antibody that PMN express the IL-15Rα chain at the mRNA and protein levels. Incubation with IL-15 activated PMN to secrete the chemotactic factor IL-8, and the amount secreted was increased by costimulation with heat-inactivated Candida albicans. In addition, IL-15 primed the metabolic burst of PMN in response to formyl-methionyl-leucyl-phenylalanine but was not sufficient to trigger the respiratory burst or to increase the production of superoxide in PMN exposed to C. albicans. IL-15 also increased the ability of PMN to phagocytose heat-killed C. albicans organisms in a dose-dependent manner, without opsonization by antibodies or complement-derived products. In the same concentration range, IL-15 was as effective as gamma interferon (IFN-γ) and IL-2 in increasing the C. albicans growth-inhibitory activity of PMN. Taken together, these results suggest that IL-15 is a potent stimulant of both proinflammatory and antifungal activities of PMN, activating several antimicrobial functions of PMN involved in the cellular response against C. albicans

Musei italiani del dopoguerra (1945-1977). Ricognizioni storiche e prospettive future

Gli anni della ricostruzione nel secondo dopoguerra hanno consegnato al Paese una stagione irripetibile del museo, rinnovato nella sua forma così come nei contenuti. Di quel periodo il volume intende fornire una riflessione storico-critica relativa alla tenuta odierna della proposta culturale e al contempo sui problemi di restauro e di rifunzionalizzazione di quei musei attualmente in corso. L’importanza, riconosciuta a livello internazionale, dei progetti di architetti quali Carlo Scarpa, Franco Albini, Franco Minissi, non sottrae infatti le istituzioni museali nate all’epoca dalle esigenze contemporanee di una loro riorganizzazione dettata da mutati livelli qualitativi e standard di comunicazione aggiornati.Quali possano essere le soluzioni da adottare, nel dovuto rispetto di quanto costituisce tuttora un modello esemplare della museologia e della museografia italiane, è quanto si propongono di verificare i saggi raccolti nel libro, tenendo conto del cambiamento radicale della missione del museo sempre più orientato verso un’ampia accessibilità, nuove pratiche e uno statuto nuovo delle proprie collezioni. Il volume raccoglie i contributi scientifici del primo anno del Corso di Alta Formazione di Museologia e Museografia tenuto a Palazzo Butera a Palermo nel 2020, diretto da Valter Curzi e organizzato dal Dipartimento SARAS dell'Università di Roma "La Sapienza" in convenzione con Palazzo Butera, Francesca & Massimo Valsecchi Collection, con il patrocinio di Fondazione Roma Sapienza, MAXXI, SISCA