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OBJECTIVES: The impressive improvements of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) function by elexacaftor/tezacaftor/ivacaftor (ETI) result in changes in the detection frequencies of Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). We assessed determinants of the response to ETI with regards to SA and PA detection frequencies as documented in the German CF registry for people with CF (pwCF) ≥12 years. METHODS: We evaluated changes in the detection frequencies of SA and PA for 21 months before and after initiation of ETI and used different statistical tests to identify determinants of detection changes. RESULTS: We included data from 1092 pwCF with results from culture-dependent diagnostics for SA and PA detection from 7944 microbiological samples before and 6.845 microbiological samples after initiation of ETI. Detections of SA decreased from 54.3% to 44.3% and 40.2% and those of PA from 39.9% to 31.9% and 22.6% 3 and 21 months after initiation of therapy, respectively (all P <0.001). Reduction of SA and PA were observed in throat swabs and sputa, associated significantly with age, previous lung function, and were dependent on pre-ETI colonization status. CONCLUSIONS: The different patterns of reductions of SA and PA suggest that pathogen-specific biological processes govern the responsiveness of microbiological colonization towards ETI in pwCF.

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Background: Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves multiple clinical outcomes in people with cystic fibrosis (pwCF) with at least one F508del allele. This study evaluated the real-world impact of ETI on lung function, nutritional status, pulmonary exacerbation frequency, and sweat chloride concentrations in a large group of pwCF. Methods: This observational cohort study used data from the German CF Registry for pwCF who received ETI therapy and were followed up for a period of 12 months. Findings: The study included 2645 pwCF from 67 centres in Germany (mean age 28.0 ± 11.5 years). Over the first year after ETI was initiated, percent predicted forced expiratory volume in 1 s (ppFEV1) increased by 11.3% (95% confidence interval [CI] 10.8-11.8, p < 0.0001), body mass index (BMI) z-score increased by 0.3 (95% CI 0.3-0.4, p < 0.0001) in individuals aged 12 to <18 years and BMI in adults increased by 1.4 kg/m2 (95% CI 1.3-1.4, p < 0.0001), pulmonary exacerbations decreased by 75.9% (p < 0.0001) and mean sweat chloride concentration decreased by 50.9 mmol/L (95% CI -52.6, -49.3, p < 0.0001). Improvements in ppFEV1 over the first year of therapy were greater in pwCF who had not previously received cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (12.6% [95% CI 11.9-13.4] vs. 9.7% [95% CI 9.0-10.5] in those with prior CFTR modulator treatment. Interpretation: These real-world data are consistent with the findings of randomised clinical trials, and support the use of ETI as a highly effective treatment option for pwCF who have at least one F508del allele. Funding: None.

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Since the introduction of CFTR modulator therapies, longitudinal real-life data of lung clearance index (LCI) during treatment is scarce. In this single-centre, post-approval setting, we report data of 51 patients with different stages of lung disease, age 2-52 years with repeated measurements of forced expiratory volume as a percentage of the predicted value (ppFEV1) and LCI after 2, 4, and 16 weeks of CFTR modulator treatment and at baseline. In 25 patients during elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) treatment, significant improvements of LCI (median -1.4) and ppFEV1 (median +8.3%) were observed after only 2 weeks, and were maintained after 4 and 16 weeks of treatment (LCI: -2.0, -2.2; ppFEV1: +7.2%, +11.8%). We observed a significant correlation between LCI improvement at week 16 and lower baseline LCI. In 26 younger and healthier patients receiving lumacaftor/ivacaftor (LUM/IVA) treatment, no significant changes of LCI and ppFEV1 occured. With ELX/TEZ/IVA, our data shows rapid, significant improvements of LCI and ppFEV1 already after 2 weeks. Early LCI measurements can help to assess the patient's response to this high-cost therapy.

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INTRODUCTION: The objective of this study was to analyze patients' perceptions of their headaches both before and after Pipeline flow diversion treatment of their unruptured intracranial aneurysms, with the goal of identifying prognostic factors associated with headache patterns to improve predictions of overall outcomes. METHODS: We retrospectively identified 133 patients treated with the Pipeline embolization device (PED) between January 1, 2014, and December 31, 2016, at an academic institution in the United States. Patients with at least 6 months of clinical follow-up, who had completed a validated telephone survey assessing their headache perceptions before and after treatment of their UIAs, were included. RESULTS: Sixty patients (57.7%) responded to the questionnaire. Median aneurysm size was 6.3 mm. Thirty-two patients (53.3%) presented with headaches before treatment, which had a median intensity of 7 out of 10 (range, 3-10). On postprocedural evaluation, 8 patients (25%) had complete resolution of their headaches. Of the 24 (75%) patients with persistent headaches, the frequency and severity of the headaches decreased or remained the same in most (58.3%) patients. Eleven (18.3%) patients had new-onset headaches. This study found an association between aneurysm size and a reduction in headache frequency and severity after PED treatment. No significant association was found between headache persistence, severity, or frequency and patient demographics, aneurysm characteristics, and other comorbidities. CONCLUSION: An overall improvement of headaches in patients with UIAs who underwent treatment with the PED was observed, particularly in patients harboring large aneurysms and who had presented with daily headaches.

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BACKGROUND: The configuration of the anterior communicating artery (AcomA) complex is important in the endovascular treatment of AcomA complex aneurysms. In cases of codominant anterior cerebral arteries (ACA), coil embolization may result in inadvertent occlusion of the contralateral ACA due to poor visualization. A second diagnostic catheter in the contralateral carotid artery may help with visualization of this angiographic blind spot. To our knowledge, the safety and efficacy of this dual diagnostic catheter technique have never been assessed. METHODS: A cohort of consecutive patients that underwent coil embolization of an AcomA complex aneurysm at a major academic institution in the United States between 2007 and 2014 were retrospectively reviewed. RESULTS: Eighty-two patients who had an AcomA complex aneurysm treated with coil embolization were identified. The dual diagnostic catheter technique was used in 17 (20.7%) patients. Aneurysms treated with the dual diagnostic catheter technique were less frequently ruptured and had less favorable dome-to-neck ratios as well as neck width for primary coil embolization. The rate of codominant ACAs was significantly higher and stent-assisted coil embolization was performed more frequently. The rate of thromboembolic complications, angiographic outcome, and retreatment did not differ between both the groups. CONCLUSIONS: The dual diagnostic catheter technique is a safe and effective method during coil embolization of AcomA complex aneurysms and preferred for aneurysms with codominant ACAs, incorporation of either A1 or A2 segments into the aneurysm, and aneurysms with a wide neck and low dome-to-neck ratios.