Ewingringgaard9508

P. aeruginosa bloodstream infection (BSI) is associated with high hospital mortality. Empirical combination therapy is commonly used, but its benefit remains debated. The purpose of this study was to describe in a paediatric population, demographical characteristics and outcome of children treated for P. aeruginosa BSI receiving either a combined or single antibacterial therapy. We performed a retrospective, single-centre, cohort study of hospitalized children with P. aeruginosa BSI from 2007 to 2015. A total of 118 bloodstream infections (BSI) were analysed (102 (86.4%) hospital-acquired, including 52 (44.1%) hospitalized in intensive care unit). In immunocompromised children, 52% of BSI episodes were recorded. Recent medical history revealed that 68% were hospitalized, 31% underwent surgery and 67% had a prior antibiotic therapy within the last 3 months. In-hospital mortality was similar for patients receiving single or combined anti-Pseudomonas therapy (p = 0.78). In multivariate analysis, independent risk factors for in-hospital mortality were neutropenia (OR = 6.23 [1.94-20.01], hospitalization in ICU (OR = 5.24 [2.04-13.49]) and urinary tract infection (OR = 4.40 [1.02-19.25]).Conclusion P. aeruginosa BSI mainly occurred in immunocompromised children. Most infections were hospital-acquired and associated with high mortality. Combination therapy did not improve survival.What is Known• P. aeruginosa bloodstream infection (BSI) is associated with high hospital mortality. Empirical combination therapy is commonly used but its benefit remains debated.What is New• This is the largest cohort of Pseudomonas aeruginosa bacteraemia in children ever published. P. aeruginosa Bloodstream mainly occurred in immunocompromised children. Most infections were hospital-acquired and associated with high mortality. Combination therapy did not improve survival.Polyhexamethylene guanidine phosphate (PHMG-p) was used as a humidifier disinfectant in Korea. PHMG induced severe pulmonary fibrosis in Koreans. The objective of this study was to elucidate mechanism of pulmonary toxicity caused by PHMG-p in rats using multi-omics analysis. Wistar rats were intratracheally instilled with PHMG-p by single (1.5 mg/kg) administration or 4-week (0.1 mg/kg, 2 times/week) repeated administration. Histopathologic examination was performed with hematoxylin and eosin staining. Alveolar macrophage aggregation and granulomatous inflammation were observed in rats treated with single dose of PHMG-p. Pulmonary fibrosis, chronic inflammation, bronchiol-alveolar fibrosis, and metaplasia of squamous cell were observed in repeated dose group. Next generation sequencing (NGS) was performed for transcriptome profiling after mRNA isolation from bronchiol-alveoli. Bronchiol-alveoli proteomic profiling was performed using an Orbitrap Q-exactive mass spectrometer. Serum and urinary metabolites were related to pulmonary damage by PHMG-p.Cadmium is a xenobiotic involved in neoplastic transformation. Cadmium enters the cells through divalent cation transporters including the Transient Receptor Potential Melastatin-related 7 (TRPM7) which is known to be involved in cancer cell fate. This work aimed to study the role of TRPM7 in neoplastic transformation induced by cadmium exposure in non-cancer epithelial cells. Non-cancer epithelial cells were chronically exposed to low-dose of cadmium. TRPM7 expression and function were studied by Western-Blot, Patch-Clamp and calcium and magnesium imaging. Finally, cell migration and invasion were studied by Boyden chamber assays. Chronic cadmium exposure induced TRPM7 overexpression and increased the membrane currents (P  less then  0.001). Cells exposed to cadmium had higher intracellular calcium and magnesium levels (P  less then  0.05). TRPM7 silencing restored calcium levels but strongly decreased intracellular magnesium concentration (P  less then  0.001). Moreover, cadmium exposure enhanced both cell migration and invasion, but TRPM7 silencing strongly decreased these features (P  less then  0.001). Furthermore, mammary epithelial cells exposed to cadmium became rounded and had less cell-to-cell junctions. Cadmium exposure decreased epithelial markers while the mesenchymal ones were increased. Importantly, TRPM7 silencing was able to reverse these phenotypic modifications (P  less then  0.05). To summarize, our data show that chronic cadmium exposure enhanced TRPM7 expression and activity in non-cancer epithelial cells. TRPM7 overexpression induced intracellular magnesium increase and stimulated cell migration and invasion. These neoplastic properties could be linked to a TRPM7-dependent epithelial-to-mesenchymal transition reprogramming in cell exposed to cadmium. These findings provide new insights into the regulation of cell fates by cadmium exposure.Mobile fracture prevention services, with DXA, significantly improved access to care for those at high risk of fracture living in rural areas. Introduction of mobile services facilitated access to fracture liaison services and development of integrated of care pathways across community- and secondary-based care. MMP inhibitor INTRODUCTION The ageing population is growing faster in rural areas, yet most fracture prevention services are located in urban areas. As part of a wider study, evaluating the introduction of mobile fracture prevention services, we focus on whether mobile services improve access to care for those at highest risk of fracture. METHODS Services outcomes were assessed against the Royal Osteoporosis Society clinical standards for fracture liaison services. This included standardised, age-specific referral rates, FRAX 10-year probability of major osteoporotic and hip fracture of referrals, pre- and post-introduction of the mobile service across two island and one rural mainland sites. This was compared with referrals from a similar rural mainland region with local access to a comprehensive service. RESULTS Greatest impact occurred in areas with most limited service provision at baseline. Mean age of patients referred increased from 59 to 68 years (CI 6.8-10.1, p  less then  0.001). Referral rates increased from 2.8 to 5.4 per 1000 population between 2011 and 2018, with a 5-fold rise in those ≥ 75 years (0.4 to 2.0 per 1000). Mean FRAX 10-year risk of major osteoporotic fracture increased from 12.7 to 17.7% (CI 3.2-5.7, p  less then  0.001). Mean hip fracture risk probability increased from 3.0 to 5.7% (CI 2.0-3.4, p  less then  0.001). However, referral rates from the mobile sites remained lower than the comparator site. CONCLUSIONS Mobile fracture prevention services, including DXA, greatly improved uptake amongst high-risk individuals. Mobile services facilitated development of integrated of care pathways, including fracture liaison services, across community- and secondary-based care.