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Background: Chronic lung infection with Pseudomonas aeruginosa is associated with increased exacerbations and mortality in people with bronchiectasis. The PROMIS-I and PROMIS-II trials investigated the efficacy and safety of 12-months of inhaled colistimethate sodium delivered via the I-neb., Methods: Two randomised, double-blind, placebo-controlled trials of twice per day colistimethate sodium versus placebo were conducted in patients with bronchiectasis with P aeruginosa and a history of at least two exacerbations requiring oral antibiotics or one requiring intravenous antibiotics in the previous year in hospitals in Argentina, Australia, Belgium, Canada, France, Germany, Greece, Israel, Italy, Netherlands, New Zealand, Poland, Portugal, Spain, Switzerland, the UK, and the USA. Randomisation was conducted through an interactive web response system and stratified by site and long term use of macrolides. Masking was achieved by providing colistimethate sodium and placebo in identical vials. After random assignment, study visits were scheduled for 1, 3, 6, 9, and 12 months (the end of the treatment period); and telephone calls were scheduled for 7 days after random assignment and 2 weeks after the end of treatment. The primary endpoint was the mean annual exacerbation rate. These trials are registered with EudraCT: number 2015-002743-33 (for PROMIS-I) and 2016-004558-13 (for PROMIS-II), and are now completed., Findings: 377 patients were randomly assigned in PROMIS-I (177 to colistimethate sodium and 200 to placebo; in the modified intention-to-treat population, 176 were in the colistimethate sodium group and 197 were in the placebo group) between June 6, 2017, and April 8, 2020. The annual exacerbation rate was 0·58 in the colistimethate sodium group versus 0·95 in the placebo group (rate ratio 0·61; 95% CI 0·46-0·82; p=0·0010). 287 patients were randomly assigned in PROMIS-II (152 were assigned to colistimethate sodium and 135 were assigned to placebo, in the modified intention-to-treat population), between Feb 12, 2018, and Oct 22, 2021. PROMIS-II was then prematurely terminated due to the effect of the COVID-19 pandemic. No significant difference was observed in the annual exacerbation rate between the colistimethate sodium and placebo groups (0·89 vs 0·89; rate ratio 1·00; 95% CI 0·75-1·35; p=0·98). No major safety issues were identified. The overall frequency of adverse events was 142 (81%) patients in the colistimethate sodium group versus 159 (81%) patients in the placebo group in PROMIS-I, and 123 (81%) patients versus 104 (77%) patients in PROMIS-II. There were no deaths related to study treatment., Interpretation: The data from PROMIS-I suggest a clinically important benefit of colistimethate sodium delivered via the I-neb adaptive aerosol delivery system in patients with bronchiectasis and P aeruginosa infection. These results were not replicated in PROMIS-II, which was affected by the COVID-19 pandemic and prematurely terminated., Funding: Zambon., Competing Interests: Declaration of interests CSH reports consultancy or speakers fees from 30 Technology, AstraZeneca, CSL Behring, Chiesi, Infex, Insmed, Janssen, Lifearc, Meiji, Mylan, Pneumagen, Shionogi, Vertex, and Zambon. MS reports research grants from Glaxosmithkline, Trudell, and Tel Aviv League for Lung Disease; consulting fees or speaker fees for Astrazeneca, Boehringer Ingelheim, Dexcel, Kamada, Rafa, Synchrony Medical, Trumed, Vertex, Zambon, and Sanofi Insmed; and data safety monitoring board participation for Bonus Biotherapeutics and Boehringer Ingelheim. KW reports research grants from Insmed, Paratek, Red Hill Biopharma, AN2, Spero, and Renovion; consulting fees from Insmed, Paratek, Red Hill Biopharma, AN2, Renovion, Spero, Zambon, and Janssen; and data safety monitoring board participation for Janssen and Red Hill Biopharma. AB declares research funding from Zambon; and contributed to UptoDate. FB reports research funding from Astrazeneca, Glaxosmithkline, Chiesi, and Insmed; and consulting fees or speakers fees from Astrazeneca, Chiesi, Glaxosmithkline, Menarini, Grifols, Insmed, Novartis, Pfizer, Sanofi, Vertex, Viatris, and Zambon. KD reports payments for consultancy or lectures from Boehringer Ingelheim, GSK, Menarini, Novartis, Norma Hellas, Chiesi, Astrazeneca, and Zambon. LCM reports a leadership role with Lung Foundation Australia; research grants from Boehringer Ingelheim, Astrazeneca, Zambon, Insmed, and Glaxosmithkline; and consultancy or speaker fees from Boehringer Ingelheim, Astrazeneca, Zambon, Insmed, Sequirius, and Glaxosmithkline. AEO reports research grants from Zambon, Insmed, Boehringer Ingelheim, Armata, and the US COPD foundation; consultancy or speaker fees from Insmed, Boehringer Ingelheim, Zambon, and Electromed; participation in a data safety monitoring board for Paraxel; and fees from Academic CME, Vindico Medical Education, Answers in CME, Peer Review Institute, CE, and RMEI. FCR reports grant from the German Centre for Lung Research, German Centre for Infection Research, EU Innovative Medicines Initiative, Mukoviszidose Institute, Novartis, Insmed, Grifols, Bayer, and InfectoPharm; consulting fees or lecture fees from Parion, Grifols, Zambon, Insmed, Helmholtz-Zentrum fur Infektionsforschung, Astrazeneca, Insmed, and Grifols; participation in data safety monitoring board for Insmed, Grifols, Shionogi, and Boehringer Ingelheim; provided expert testimony to the Social Court Cologne; received support to attend meetings from German Kartagener Syndrome and Primary Ciliary Dyskinesia Patient Advocacy Group and Mukoviszidose; was a coordinator of the ERN-LUNG Bronchiectasis Core Network; was the chair of the German Bronchiectasis Registry PROGNOSIS; was a member of the SteerCo of the European Bronchiectasis Registry EMBARC and SteerCo of the European Nontuberculous Mycobacterial Pulmonary Disease Registry EMBARC-NTM; was a co-speaker of the Medical Advisory Board of the German Kartagener Syndrome and PCD Patient Advocacy Group; was a speaker of the Respiratory Infections and TB group of the German Respiratory Society, the Cystic Fibrosis group of German Respiratory Society (DGP); was a principal investigator of the German Center for Lung Research, Member of the Protocol Review Committee of the PCD-CTN, Member of Physician Association of the German Cystic Fibrosis Patient Advocacy Group; and declares fees to institution from clinical trial work from AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, German Center for Lung Research/KKS Marburg, Insmed, Novartis, Parion, University of Dundee, Vertex, and Zambon. RMT reports research grants from Australian Institute of Infectious Diseases, Herston Infectious Diseases Institute, Metro South Health, and the Asia Pacific Society of Respirology Gallipoli Medical Research Foundation; an eductional grant from Insmed; support for attending a meeting from Beyond Air; and consulting fees from AN2 Therapeutics, Beyond Air, and Insmed. KJC reports consulting fees from Zambon. FP is an employee of Zambon. PC is an employee of Zambon; and reports an international patent application WO 23/012280 in the name of Zambon, designating PC as the inventor. JDC has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed, and Trudell; and received consultancy or speaker fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell, and Zambon. OS declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic progressive respiratory disorder occurring at a rate ranging from 4.2 to 278.1 cases per 100,000 persons, depending on age, in the United States. For many patients with NCFB, the presence of Pseudomonas aeruginosa (PA) makes treatment more complicated and typically has worse outcomes. Management of NCFB can be challenging, warranting a better understanding of the burden of illness for NCFB, treatments applied, healthcare resources used, and subsequent treatment costs. Comparing patients diagnosed with exacerbated NCFB, with or without PA on antibiotic utilization, treatments, and healthcare resources utilization and costs was the purpose of this study., Materials and Methods: This was a retrospective cohort study of commercial claims from IQVIA's PharMetrics Plus database (January 1,2006-December 31, 2020). Study patients with a diagnosis of NCFB were stratified into two groups based on the presence or absence of PA, then followed to identify demographic characteristics, comorbid conditions, antibiotic treatment regimen prescribed, healthcare resources utilized, and costs of care., Results: The results showed that patients with exacerbated NCFB who were PA + had significantly more oral antibiotic fills per patient per year, more inpatient admissions with a longer length of stay, and more outpatient encounters than those who were PA - . For costs, PA + patients also had significantly greater total healthcare costs per patient when compared to those who were PA - ., Conclusion: Exacerbated NCFB with PA + was associated with increased antibiotic usage, greater resource utilization, and increased costs. The major contributor to the cost differences was the use of inpatient services. Treatment strategies aimed at reducing the need for inpatient treatment could lessen the disparities observed in patients with NCFB.

For diagnostic purposes, cryofixation of tissues is a daily routine technique to investigate rapidly about the presence of tumours during a surgical procedure in patients. We performed morphometric analysis of cryofixed muscular tissues according to different techniques. About 1,000 muscle fibers and 1,493 nuclei, were automatically examined. After freezing, ice tissue interfaces shrinkage of the cells were present. Liquid isopentane or liquid nitrogen produced a statistical increase of fractal dimension, D, of the ice-tissue interfaces, P < 0.001 respect to the formalin-fixed samples, cryofixation performed inside the cryostat chamber at t = -20°C produced a D value close to the formalin-fixed samples. Shrinkage of the muscle fibers was higher in the samples cryofixed inside the cryostat chamber (P < 0.001). Cryofixation inside cryostat or by liquid nitrogen caused decreases of the nuclei dimensions and altered nuclear morphology (P < 0.01), liquid isopentane appeared not affecting the nuclei of the fibers. Cryofixation inside the cryostat chamber produced the highest shrinkage but it was reduced performing cryofixation in liquid nitrogen or isopentane. Freezing damage inside the muscle cells was absent in the samples cryofixed inside the cryostat, it was present after cryofixation by liquid nitrogen or isopentane. Subcellular components like the nuclei were preserved by isopentane. This paper present, for the first time, an objective method able to quantify and characterize the damages produced by cryofixation in biological sample for intraoperative consultation., (© 2016 Wiley Periodicals, Inc.)

Purpose: To investigate the safety of trypan blue, brilliant blue G (BBG), Evans blue (EB), patent blue, Chicago blue (CB), and bromophenol blue (BB), with and without halogen and xenon light exposure., Methods: All dyes were diluted in a balanced saline solution at a concentration of 0.5%. Cells of the human RPE line ARPE-19 and rat RGC5 were exposed to vital dyes for 5 min. Experiments with and without xenon or halogen illumination were performed. The viability of ARPE-19 and RGC5 cells was determined at 12, 24, or 120 h by a cell proliferation assay using WST-1 reagent. The apoptotic events as well as cell numbers were registered for 72 h and counted by time-lapse videomicroscopy., Results: There was no evidence of ARPE-19 or RGC5 toxicity, immediate (0 and 24 h) or delayed (120 h), following exclusive exposure to each single dye. After halogen light exposure, ARPE-19 cell lines did not show any significant toxicity, except for when they were exposed to EB. After xenon illumination, ARPE-19 cells showed a marked decrease in cell viability when exposed to EB or CB and a moderate decrease when exposed to BBG and BB. After xenon illumination, RGC5 cells showed the highest decrease in cell viability when exposed to EB and CB; BB caused the same decrease in cell viability as in ARPE-19 cells., Conclusion: Interaction of light from endo-illumination source and blue vital dyes may increase the risk of retinal toxicity.