Enforcing surveillance of antimicrobial resistance and antibiotic use to drive stewardship: experience in a paediatric setting.

BACKGROUND: Antibiotic stewardship (AS) interventions in paediatrics are still not standardized regarding methodology, metrics, and outcomes. We report the results of an AS intervention in the paediatric area based on education and guideline provision via an electronic App. MATERIALS AND METHODS: The AS intervention was conducted in 2021 through observation, education, audit and feedback and provision of an electronic App (Firstline.org) to support antibiotic prescription based on local susceptibility data. The primary outcome was the antibiotic consumption in the 12 months following the intervention (year 2022) compared with a historical 12-month control (year 2019) via an interrupted time series analysis. Secondary outcomes were appropriateness of therapy, length of stay, 30-day readmission, transfers to the paediatric intensive care unit, in-hospital mortality, and prevalence of antimicrobial resistance (AMR). RESULTS: During the post-intervention phase, 29 cross-sectional audits and feedback were conducted including 467 patients. Prescriptions were appropriate according to the guidelines in 85.7% of cases, with a stable trend over time. A significant decrease in antibiotic consumption was measured in terms of defined daily doses per 1000 patient days (-222.13; P<0.001) and days of therapy per 1000 patient days (-452.49; P<0.001) in the post-intervention period with a clear inversion of the Access to Watch ratio (from 0.7 to 1.7). Length of stay, in-hospital mortality, intensive care unit transfers, and incidence of AMR infections remained stable, while 30-day readmission decreased from 4.9 per 100 admissions to 2.8 per 100 admissions (P<0.001). CONCLUSIONS: The intervention was associated with a significant reduction in antimicrobial consumption and an increase in the appropriateness of prescriptions. Electronic tools can be of value in promoting adherence to guidelines and ensuring the sustainability of results.

Role of adipose tissue in melanoma cancer microenvironment and progression.

BACKGROUND: An epidemiological association between excess weight and increased risk of cancer has been described in melanoma, for which the physiopathological mechanisms are still unknown. The study of tumor microenvironment and of the role of adipocytes in cancer development, progression and metastasis has recently received great interest. However, the role of peritumoral adipocytes has been characterized only in a few types of cancer, and in melanoma it still remains to be defined. METHODS: We investigated the interactions between adipocytes and melanoma cells using an in vitro co-culture system. We studied the morphological and functional properties of 3T3-L1 adipocytes before and after co-culture with A375 melanoma cells, in order to assess the role of adipocytes on melanoma migration. RESULTS: Morphological analysis showed that after 6 days of co-culture 3T3-L1 adipocytes were reduced in number and size. Moreover, we observed the appearance of dedifferentiated cells with a fibroblast-like phenotype that were not present in controls and that had lost the expression of some adipocyte-specific genes, and increased the expression of collagen, metalloproteinases and genes typical of dedifferentiation processes. Through the Matrigel Invasion Test, as well the Scratch Test, it was possible to observe that co-culture with adipocytes induced in melanoma cells increased migratory capacity, as compared with controls. In particular, the increase in migration observed in co-culture was suppressed after adding the protein SFRP-5 in the medium, supporting the involvement of the Wnt5a pathway. The activation of this pathway was further characterized by immunofluorescence and western blot analysis, showing in melanocytes in co-culture the activation of ß-catenin and LEF-1, two transcription factors involved in migration processes, neo-angiogenesis and metastasis. CONCLUSIONS: These data allow us to hypothesize a dedifferentiation process of adipocytes toward fibroblast-like cells, which can promote migration of melanoma cells through activation of Wnt5a and the intracellular pathways of ß-catenin and LEF-1.