Abbreviations: CF, cystic fibrosis; FEV1(%), forced expiratory volume in 1 second (as percent of predicted); NBS, newborn screening; PI, pancreatic insufficient; PS, pancreatic sufficient. AbstractAim: Denmark has a high standard cystic fibrosis care. However, newborn screening was not implemented until 2016. This article describes the clinical status of cystic fibrosis patients at time of diagnosis prior to newborn screening. Methods:Patients diagnosed with cystic fibrosis in Denmark in 2010-2014 were reviewed using the Danish Cystic Fibrosis Registry as well as patient files. Parameters collected were age at diagnosis, gender, weight, height, forced expiratory volume at 1 second, cystic fibrosis transmembrane regulator-genotype, lung bacteriology at diagnosis and previous diagnoses. Results:A total of 63 patients were diagnosed in the study period. The most typical pre-cystic fibrosis diagnoses were asthma and pneumonia. The median age at diagnosis was 1.4 years for the pancreatic insufficient and 27.3 years for the pancreatic sufficient patients. Of the pancreatic insufficient patients, 21% had moderate to severe malnutrition with BMI below minus 2 SD and 40% had moderate to severe stunting with height below minus 2 SD.
BackgroundTo determine complications during outpatient parenteral antimicrobial therapy (OPAT) administrated through a peripheral venous line, PICC-line or PORT-A-CATH (PAC).MethodsCatheter related complications in patients with cystic fibrosis during OPAT were identified through a retrospective review of patient files supplemented by an interview.ResultsIn 64 treatment episodes with a peripheral venous line, 51 (79.7 %) used bolus injection and 13 (20.3 %) used infusion pump. 27 out of 51 (53.0 %) bolus injection episodes experienced complications, which required removal. None were observed for infusion pump treatments.The infectious complications requiring removal of peripheral venous line were 9 out of 23 (39.1 %) for the PICC line and 11 out of 26 (42.3 %) for the PAC.No anaphylaxis was observed during the OPAT treatments.ConclusionsOur data indicate that using an infusion pump to administer the antibiotic treatment minimized peripheral venous line complications. The frequency of complications leading to removal of the catheter is about the same for PICC-lines and PACs, but the average life-time of the latter is much longer. Allergic reactions are not a major problem.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1019-4) contains supplementary material, which is available to authorized users.
The emergence and global spread of a new plasmid-mediated resistance mechanism to colistin, the mcr-1 gene, can have significant implications for the treatment of pulmonary infections in cystic fibrosis (CF) patients. The polymyxins, colistin (polymyxin E) and polymyxin B, are antimicrobial peptides with broad-spectrum activity against Gram negative bacteria, including common CF pathogens as Pseudomonas aeruginosa and Achromobacter species and are frequently administered as inhaled antimicrobial therapy to CF patients. A transfer of colistin resistance to multidrug-resistant CF pathogens would limit treatment options.A transferable colistin resistance gene, designated mcr-1, was recently detected in Enterobacteriaceae isolated from foodproducing animals and patients from China [1]. The plasmidborne mcr-1 gene encodes a lipid A phosphoethanolamine transferase that can modify Lipid A in the outer membrane of Gram negative bacteria, thus conferring resistance to colistin [2]. Subsequent investigations have revealed a worldwide dissemination of the mcr-1 gene, also including patient isolates from Denmark dating back to 2011 ([3,4];unpublished observation). So far the mcr-1 gene has only been detected in Enterobacteriaceae; however, in vitro transfer of mcr-1 to P. aeruginosa has proven stable [1]. Due to the daily selective pressure in patients receiving colistin by inhalation, a transfer of the mcr-1 gene to P. aeruginosa could be more likely to occur in the CF population.We performed a study to evaluate the occurrence of the mcr-1 gene in colistin resistant P. aeruginosa and Achromobacter species isolated from respiratory samples obtained from CF patients from Aarhus University Hospital, Denmark between 2008 and 2016. Of the 216 patients affiliated with the CF center during those 9 years, 134 patients (62%) had at least one culture with P. aeruginosa, while 50 patients (23%) had at least one culture with Achromobacter sp. During the period, an increase in colistin resistance in P. aeruginosa and Achromobacter spp. was observed. Colistin resistant P. aeruginosa strains increased from 3 of 44 (7%) in 2008 to 10 of 76 (13%) in 2016, and 4 of 11
Following the success of the anti-CD19 chimeric antigen receptor (CAR) T-cell therapies against B-cell malignancies, the CAR T-cell approach is being developed towards other malignancies like acute myeloid leukemia (AML). Treatment options for relapsed AML patients are limited, and the upregulation of the FMS-like tyrosine kinase 3 (FLT3) in malignant T-cells is currently not only being investigated as a prognostic factor, but also as a target for new treatment options. In this review, we provide an overview and discuss different approaches of current anti-FLT3 CAR T-cells under development. In general, these therapies are effective both in vitro and in vivo, however the safety profile still needs to be further investigated. The first clinical trials have been initiated, and the community now awaits clinical evaluation of the approach of targeting FLT3 with CAR T-cells.
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