Every CFTR variant counts - Target-capture based next-generation-sequencing for molecular diagnosis in the German CF Registry.

BACKGROUND: In times of genotype guided therapy options, a total of 3.2 % of people with CF (pwCF) in the German CF Registry[1] only have one or no CFTR-variant detected after genetic analysis. Additionally, genetic data in the Registry can be documented as free text and can therefore be prone to error. In order to allow the greatest possible amount of pwCF access to modern therapies, we conducted a re-evaluation of free text entries and established a custom-whole-CFTR-locus NGS-approach for all pwCF who remained without genetic confirmation afterwards. METHODS: To this end, we assembled 731 free text variants of 655 pwCF in the German CF Registry. All variants were evaluated using ClinVar, HGMD and CFTR1/2, corrected in the Registries' database and uploaded to ClinVar. PwCF whose diagnosis remained uncertain as well as additional pwCF or pwCFTR-RD that were assembled through a nationwide call for testing of unclear cases were offered genetic analysis. Samples were analysed using a target-capture based NGS-custom-design-panel covering the entire CFTR-locus. RESULTS: Evaluation of free text variants led to the discovery of 43 variants not formerly reported in the context of CF. The Registries' dropdown list was extended by 497 variants and over 500 pwCF were provided with their most up-to-date genotype. Samples of 47 pwCF/pwCFTR-RD were sequenced via NGS with an overall success rate of 61.7 %, resulting in implementation of entire CFTR-genotyping into routine diagnostics. CONCLUSION: Entire CFTR-genotyping can greatly increase the genetic diagnostic rate of pwCF/pwCFTR-RD and should be considered after inconspicuous CFTR screening panels in CFTR-diagnostics.

Easy measurement of health related quality of life in patients with cystic fibrosis by the COPD assessment test (CAT) - A pilot study.

BACKGROUND: Quality of life (QOL) is an important patient-related outcome (PRO) in patients with cystic fibrosis (CF). There are several QOL questionnaires like the "Cystic Fibrosis Questionnaire Revised" (CFQ-R) or the "St George's Respiratory Questionnaire" (SGRQ) that are well validated in CF. The aim of the study was to evaluate whether the easily applicable "COPD assessment test" (CAT) can be used in CF patients. METHODS: 42 CF patients were recruited within the PulmoHOM study, a prospective, observational cohort study. The CAT, the SGRQ and the CFQ-R were handed out to the patients. The spearman's rank correlation coefficient and the Cronbach's α coefficient were used for the statistical analysis. RESULTS: The internal consistencies of the CAT, SGRQ and the CFQ-R were high (Cronbach's α coefficients = 0.89, 0.91 and 0.83). There were significant correlations between the CAT and the total score of the SGRQ (r = 0.851, p < 0.01), between the CAT and many items of the CFQ-R (physical score of the CFQ-R and total score of the CAT: r = -0.872, p < 0.01) and between the SGRQ and the CFQ-R (physical score of the CFQ-R and total score of the SGRQ: r = -0.878, p < 0.01). CONCLUSION: The main finding was the high correlation between the CAT and the validated questionnaires in CF. The CAT is a PRO instrument that can be filled quickly and that correlates well with the CFQ-R. The CAT or similar tools might be applicable in the care of CF patients.

The Phagocytosis of Blood Leukocytes from Cystic Fibrosis Patients is not Impaired in General.

Impaired phagocytosis of Pseudomonas aeruginosa was found in isolated monocytes of peripheral blood of cystic fibrosis patients, but not in their neutrophils, as reported some years ago. In the present study, we analysed the phagocytic capacity of peripheral blood neutrophils and monocytes of cystic fibrosis patients and of healthy controls. Phagocytosis was determined using a commercial phagocytosis "in whole blood" assay on the basis of fluorescence-labelled opsonized Escherichia coli bacteria and flow cytometry. Venous blood of cystic fibrosis patients and of healthy controls was collected and the phagocytosis assay was performed. No differences in the percentage of phagocytic cells or in the overall phagocytic capacity were found between samples of cystic fibrosis patients and healthy controls either in monocytes or in neutrophils. Thus, our results did not support the hypothesis of a generally reduced phagocytic ability in the peripheral blood immune cells of cystic fibrosis patients.

[Modern variant of hanging: use of a time-programmed winch]. / Eine moderne Variante des Erhängens: Einsatz einer zeitprogrammierten Seilwinde.

Hanging is one of the most frequent types of suicide. Descriptions of unusual ligatures can be read about again and again. The paper reports the suicide of a 41-year-old electrician, who, using an electric winch, hung himself in nearly free suspension. The winch that was secured to the timberwork of the attic had been programmed by an electric time clock, the toggle switch of the remote control was fixed in the on-position using adhesive tape. The man had handcuffed his hands behind his back against any attempts to save himself. The noose was partly cushioned with a bike tube with the obvious aim of reducing the pain. Due to the state, in which he was found and the results of the post-mortem examination, a third party responsibility was excluded. The case shows that not only certain types of knots and nooses can be associated with various occupational groups, but the choice of a special strangulation device can possibly also come from the occupational sphere. As a modern variation of hanging, the presented casuistry can partly complete the familiar documentation of historical cases with the use of block and tackle and similar constructions.