Use of microbiology tests in the era of increasing AMR rates- a multicentre hospital cohort study

Background: Effective use of microbiology test results may positively influence patient outcomes and limit the use of broad-spectrum antibiotics. However, studies indicate that their potential is not fully utilized. We investigated microbiology test ordering practices and the use of test results for antibiotic decision-making in hospitals. Methods: A multicentre cohort study was conducted during five months in 2014 in Medical departments across three hospitals in Western Norway. Patients treated with antibiotics for sepsis, urinary tract infections, skin and soft tissue infections, lower respiratory tract infections or acute exacerbations of chronic obstructive pulmonary disease were included in the analysis. Primary outcome measures were degree of microbiology test ordering, compliance with microbiology testing recommendations in the national antibiotic guideline and proportion of microbiology test results used to inform antibiotic treatment. Data was obtained from electronic- and paper medical records and charts and laboratory information systems. Results: Of the 1731 patient admissions during the study period, mean compliance with microbiology testing recommendations in the antibiotic guideline was 89%, ranging from 81% in patients with acute exacerbations of chronic obstructive pulmonary disease to 95% in patients with sepsis. Substantial additional testing was performed beyond the recommendations with 298/606 (49%) of patients with lower respiratory tract infections having urine cultures and 42/194 (22%) of patients with urinary tract infections having respiratory tests. Microbiology test results from one of the hospitals showed that 18% (120/672) of patient admissions had applicable test results, but only half of them were used for therapy guidance, i.e. in total, 9% (63/672) of patient admissions had test results informing prescription of antibiotic therapy. Conclusions: This study showed that despite a large number of microbiology test orders, only a limited number of tests informed antibiotic treatment. To ensure that microbiology tests are used optimally, there is a need to review the utility of existing microbiology tests, test ordering practices and use of test results through a more targeted and overarching approach

Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS:Results from the nordic NMDSG08A phase II trial

This prospective phase II study evaluated the efficacy of azacitidine (Aza) + erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo + granulocyte colony stimulation factors for 48 weeks and a transfusion need of ≥ 4 units over 8 weeks were included. Aza 75mgm -2 d-1, 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received ≥ one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza + Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n = 3) and DNMT3A (n = 4) were only observed in nonresponders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations

Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation

Background Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells. Methods We developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders. Results We observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC. Conclusions This study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation

Exploration of plant growth and development using the European Modular Cultivation System facility on the International Space Station

Plant Biol.ISI Document Delivery No.: AE5RITimes Cited: 1Cited Reference Count: 35Kittang, A. -I. Iversen, T. -H. Fossum, K. R. Mazars, C. Carnero-Diaz, E. Boucheron-Dubuisson, E. Le Disquet, I. Legue, V. Herranz, R. Pereda-Loth, V. Medina, F. J.French Space Agency (CNES); Norwegian Research Council; Spanish National Plan for Research, Development and Innovation; ELIPS Programme of the European Space Agency (ESA); ESAWe thank Prof. John Z. Kiss (University of Mississippi, USA), Prof. Gerald Perbal (University P. and M. Curie, France) and Dr. Imara Y. Perera (North Carolina State University, USA) for their contribution to some parts of this article. Experimental work reported in this paper and performed in the authors' laboratories was supported by the French Space Agency (CNES), the Norwegian Research Council, the Spanish National Plan for Research, Development and Innovation (different grants) and the ELIPS Programme of the European Space Agency (ESA). Specifically, the activities related to the 'Arabidopsis Topical team' were supported by an ESA grant.Wiley-blackwellHobokenSpace experiments provide a unique opportunity to advance our knowledge of how plants respond to the space environment, and specifically to the absence of gravity. The European Modular Cultivation System (EMCS) has been designed as a dedicated facility to improve and standardise plant growth in the International Space Station (ISS). The EMCS is equipped with two centrifuges to perform experiments in microgravity and with variable gravity levels up to 2.0g. Seven experiments have been performed since the EMCS was operational on the ISS. The objectives of these experiments aimed to elucidate phototropic responses (experiments TROPI-1 and -2), root gravitropic sensing (GRAVI-1), circumnutation (MULTIGEN-1), cell wall dynamics and gravity resistance (Cell wall/Resist wall), proteomic identification of signalling players (GENARA-A) and mechanism of InsP(3) signalling (Plant signalling). The role of light in cell proliferation and plant development in the absence of gravity is being analysed in an on-going experiment (Seedling growth). Based on the lessons learned from the acquired experience, three preselected ISS experiments have been merged and implemented as a single project (Plant development) to study early phases of seedling development. A Topical Team initiated by European Space Agency (ESA), involving experienced scientists on Arabidopsis space research experiments, aims at establishing a coordinated, long-term scientific strategy to understand the role of gravity in Arabidopsis growth and development using already existing or planned new hardware