A case report of an unusual non-mucinous papillary variant of CPAM type 1 with KRAS mutations

BACKGROUND: congenital pulmonary airway malformation (CPAM) is the most frequent congenital lung disorder. CPAM type 1 is the most common subtype, typically having a cystic radiological and histological appearance. Mucinous clusters in CPAM type 1 have been identified as premalignant precursors for mucinous adenocarcinoma. These mucinous adenocarcinomas and the mucinous clusters in CPAM commonly harbor a specific KRAS mutation. CASE PRESENTATION: we present a case of a 6-weeks-old girl with CPAM type 1 where evaluation after lobectomy revealed a highly unusual complex non-mucinous papillary architecture in all cystic parts, in which both mucinous clusters and non-mucinous papillary areas harbored the known KRAS mutation. CONCLUSIONS: we found that a KRAS mutation thought to be premalignant in mucinous clusters only, was also present in the other cyst lining epithelial cells of this unusual non-mucinous papillary variant of CPAM type 1, warranting clinical follow-up because of uncertain malignant potential

Ciclesonide versus other inhaled corticosteroids for chronic asthma in children

Background Inhaled corticosteroids (ICS) are the cornerstone of asthma maintenance treatment in children. Particularly among parents, there is concern about the safety of ICS as studies in children have shown reduced growth. Small-particle-size ICS targeting the smaller airways have improved lung deposition and effective asthma control might be achieved at lower daily doses. Ciclesonide is a relatively new ICS. This small-particle ICS is a pro-drug that is converted in the airways to an active metabolite and therefore with potentially less local (throat infection) and systemic (reduced growth) side effects. It can be inhaled once daily, thereby possibly improving adherence. Objectives To assess the efficacy and adverse effects of ciclesonide compared to other ICS in the management of chronic asthma in children. Search methods We searched the Cochrane Airways Group Register of trials with pre-defined terms. Additional searches of MEDLINE (via PubMed), EMBASE and Clinicalstudyresults. org were undertaken. Searches are up to date to 7 November 2012. Selection criteria Randomised controlled parallel or cross-over studies were eligible for the review. We included studies comparing ciclesonide with other corticosteroids both at nominally equivalent doses or lower doses of ciclesonide. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. Main results Six studies were included in this review (3256 children, 4 to 17 years of age). Two studies were published as conference abstracts only. Ciclesonide was compared to budesonide and fluticasone. Ciclesonide compared to budesonide (dose ratio 1: 2): asthma symptoms and adverse effect were similar in both groups. Pooled results showed no significant difference in children who experience an exacerbation (risk ratio (RR) 2.20, 95% confidence interval (CI) 0.75 to 6.43). Both studies reported that 24-hour urine cortisol levels showed a statistically significant decrease in the budesonide group compared to the ciclesonide group. Ciclesonide compared to fluticasone (dose ratio 1: 1): no significant differences were found for the outcome asthma symptoms. Pooled results showed no significant differences in number of patients with exacerbations (RR 1.37, 95% CI 0.58 to 3.21) and data from a study that could not be pooled in the meta-analysis reported similar numbers of patients with exacerbations in both groups. None of the studies found a difference in adverse effects. No significant difference was found for 24-hour urine cortisol levels between the groups (mean difference 0.54 nmol/mmol, 95% CI -5.92 to 7.00). Ciclesonide versus fluticasone (dose ratio 1: 2) was assessed in one study and showed similar results between the two corticosteroids for asthma symptoms. The number of children with exacerbations was significantly higher in the ciclesonide group (RR 3.57, 95% CI 1.35 to 9.47). No significant differences were found in adverse effects (RR 0.98, 95% CI 0.81 to 1.14) and 24-hour urine cortisol levels (mean difference 1.15 nmol/mmol, 95% CI 0.07 to 2.23). The quality of evidence was judged 'low' for the outcomes asthma symptoms and adverse events and 'very low' for the outcome exacerbations for ciclesonide versus budesonide (dose ratio 1: 1). The quality of evidence was graded 'moderate' for the outcome asthma symptoms, 'very low' for the outcome exacerbations and 'low' for the outcome adverse events for ciclesonide versus fluticasone (dose ratio 1: 1). For ciclesonide versus fluticasone (dose ratio 1: 2) the quality was rated 'low' for the outcome asthma symptoms and 'very low' for exacerbations and adverse events (dose ratio 1: 2). Authors' conclusions An improvement in asthma symptoms, exacerbations and side effects of ciclesonide versus budesonide and fluticasone could be neither demonstrated nor refuted and the trade-off between benefits and harms of using ciclesonide instead of budesonide or fluticasone is unclear. The resource use or costs of different ICS should therefore also be considered in final decision making. Longer-term superiority trials are needed to identify the usefulness and safety of ciclesonide compared to other ICS. Additionally these studies should be powered for patient relevant outcomes (exacerbations, asthma symptoms, quality of life and side effects). There is a need for studies comparing ciclesonide once daily with other ICS twice daily to assess the advantages of ciclesonide being a pro-drug that can be administered once daily with possibly increased adherence leading to increased control of asthma and fewer side effects

Tolerance to exercise in high-altitude in organ transplant recipients

Op het congres van de Britisch Transplant Society en de Nederlandse Transplantatie Vereniging dat gehouden werd in Bournemouth, Engeland is deze bijgevoegde poster gepresenteerd. De poster beschrijft het onderzoek naar de inspanningstolerantie van mensen na een orgaantransplantatie op grote hoogte, tijdens de beklimming van de Kilimanjaro

Comparative in vitro evaluation of four corticosteroid metered dose inhalers:Consistency of delivered dose and particle size distribution

SummaryIntroductionRecent developments concerning pressurized metered dose inhalers (pMDIs) with inhaled corticosteroids (ICS) are the introduction of ciclesonide and the replacement of propellants. As the results of in vivo studies depend on pMDIperformance, it is necessary to evaluate pMDIs in vitro for delivered dose and particle size distributions under different conditions.MethodsFluticasone 125μg, budesonide 200μg, beclomethasone HFA100μg, and ciclesonide 160μg were compared for delivered dose and particle size using laser diffraction analysis with inspiratory flow rates of 10, 20 and 30l/s.ResultsThe volume median diameter of budesonide was 3.5μm, fluticasone 2.8μm, beclomethasone and ciclesonide both 1.9μm. The mouthpiece retention was up to 30% of the nominal dose for beclomethasone and ciclesonide, 11–19% for the other pMDIs. Lifespan, flow rate, and air humidity had no significant influence on particle size distribution. The delivered dose of beclomethasone, budesonide, and ciclesonide remained constant over the lifespan. The delivered dose of fluticasone 125 decreased from 106% to 63%; fluticasone 250 also decreased whereas fluticasone 50 remained constant.ConclusionsThere is a significant difference in median particle size distribution between the different ICS pMDIs. Air humidity and inspiratory flow rate have no significant influence on particle size distribution. Ciclesonide 160 and beclomethasone 100 deliver the largest fine particle fractions of 1.1–3.1μm. The changes in delivered dose during the lifespan for the fluticasone 125 and 250 may have implications for patient care

Електрофізичні властивості системи політетрафторетилен – вуглецеві нанотрубки

Проведено дослідження комплексної діелектричної проникності та електропровідності в надвисокочастотному діапазоні (9 ГГц) і на низьких частотах (0,1; 1 та 10 кГц) двох систем політетрафторетилен – багатошарові вуглецеві нанотрубки з вихідними та диспергованими у водному середовищі . Введення диспергованих нанотрубок в полімер знижує поріг перколяції з 4,5 % до 2,6 % (мас.) за рахунок рівномірного розподілу наповнювача у полімері, що призводить до зростання міжфазної поверхні взаємодії полімер – вуглецеві нанотрубки, яка проявляється в збільшенні значень дійсної та уявної складової комплексної діелектричної проникності.Проведены исследования комплексной диэлектрической проницаемости и электропроводности в сверхвысокочастотном диапазоне (9 ГГц) и на низких частотах (0,1; 1; 10 кГц) двух систем политетрафторэтилен–многослойные углеродные нанотрубки с исходными и диспергированными у водной среде. Введение диспергированных нанотрубок в полимер снижает порог перколяции с 4,5% до 2,6 % (масс.) за счет равномерного распределения наполнителя в полимере, что приводит к возрастанию межфазной поверхности взаимодействия полимер – углеродные нанотрубки, которая проявляется в увеличении значений действительной и мнимой составляющей комплексной диэлектрической проницаемости.Complex dielectric permeability and conductivity of two systems, namely polytetrafluorethylene – intact carbon nanotubes and polytetrafluorethylene – carbon nanotubes dispersed in aqueous media, has been studied in super high-frequency range (9 GHz) and at low frequencies (0,1; 1 and 10 kHz). Doping of the polymer with the dispersed nanotubes decreases percolation threshold (limit ) from 4,5 wt. % to 2,6 wt. % due to uniform distribution of the filler in the polymer. This results to increase of interface interaction polymer - carbon nanotubes that is demonstrated by increase of value of real and imaginary component of complex dielectric permeability

Eradication of Pseudomonas aeruginosa in cystic fibrosis patients with inhalation of dry powder tobramycin

BACKGROUND: Pseudomonas aeruginosa (Pa) is the predominant pulmonary pathogen in patients with cystic fibrosis (CF). Tobramycin nebulization is used for the eradication of Pa infection. Nowadays, tobramycin dry powder inhalation (DPI) is available as well. This study reports the results of eradicating Pa with tobramycin DPI versus nebulization. METHODS: Adult CF patients with a Pa isolation between September 2010 and September 2017 from the University Medical Centre Groningen (UMCG), the Netherlands, were included in this retrospective study. RESULTS: In total 27 Pa isolations were recorded. In 13 of these, eradication was attempted with tobramycin, 7 with DPI and 6 with nebulization. DPI eradicated Pa successfully in six isolations (85.7%). Of these, one patient received additional oral ciprofloxacin and one received intravenous ceftazidime. Nebulization eradicated three Pa isolations (50.0%), in two of these, additional oral ciprofloxacin was given. CONCLUSION: Eradication rates of DPI tobramycin are comparable with those for nebulized tobramycin reported in the literature. This study suggests that DPI tobramycin is an alternative to nebulized tobramycin for eradication of Pa. TRIAL REGISTRATION: The Medical Ethics Committee of the UMCG granted a waiver (METC2017-349), as they concluded that this study was not subject to the Medical Research Involving Human Subjects Act. The reviews of this paper are available via the supplemental material section