Para-chloro-2-[18F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging.

Introduction: [11C]Metomidate ([11C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [11C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting. Objectives: The aim of this study was to further evaluate the previously published fluorine-18 (T1/2=109.5 min) etomidate analogue, para-chloro-2-[18F]fluoroethyl etomidate; [18F]CETO, as an adrenal PET tracer. Methods: In vitro experiments included autoradiography on human and cynomolgus monkey (non-human primate, NHP) tissues and binding studies on adrenal tissue from NHPs. In vivo studies with [18F]CETO in mice, rats and NHP, using PET and CT/MRI, assessed biodistribution and binding specificity in comparison to [11C]MTO. Results: The binding of [18F]CETO in the normal adrenal cortex, as well as in human adrenocortical adenomas and adrenocortical carcinomas, was shown to be specific, both in vitro (in humans) and in vivo (in rats and NHP) with an in vitro Kd of 0.66 nM. Non-specific uptake of [18F]CETO in NHP liver was found to be low compared to that of [11C]MTO. Conclusions: High specificity of [18F]CETO to the adrenal cortex was demonstrated, with in vivo binding properties qualitatively surpassing those of [11C]MTO. Non-specific binding to the liver was significantly lower than that of [11C]MTO. [18F]CETO is a promising new PET tracer for imaging of adrenocortical disease and should be evaluated further in humans.

The Sum of Kidney Donor Profile Index and Estimated Post-Transplant Survival Scale and Their Correlation with eGFR Decline in Deceased Donor Kidney Recipients.

BACKGROUND: The impact of donor quality on post-kidney transplant survival may vary by candidate condition. OBJECTIVE: Analyzing the combined use of the Kidney Donor Profile Index (KDPI) and the estimated post-transplant survival (EPTS) scale and their correlation with the estimated glomerular filtration rate (eGFR) decline in deceased-donor kidney recipients (DDKR). METHODS: This was a retrospective, observational cohort study. We included DDKRs between 2015 and 2017 at a national third-level hospital. RESULTS: We analyzed 68 DDKR. The mean age at transplant was 41 ± 14 years, 47 (69%) had sensitization events, 18 (26%) had delayed graft function, and 16 (23%) acute rejection. The graft survival at 12 and 36 months was 98.1% (95% CI 94-100) and 83.7% (95% CI 65-100), respectively. The Pearson correlation coefficient between the percentage reduction in the annual eGFR and the sum of EPTS and KDPI scales was r = 0.61, p < 0.001. The correlation coefficient between the percentage reduction in the annual eGFR and the EPTS and KDPI scales separately was r = 0.55, p < 0.001, and r = 0.53, p < 0.001, respectively. CONCLUSIONS: The sum of EPTS and KDPI scales can provide a better donor-recipient relationship and has a moderately positive correlation with the decrease in eGFR in DDKR.

Factors associated with ventilator-associated events: an international multicenter prospective cohort study.

A secondary analysis of a prospective multicenter cohort was performed in six intensive care units (ICU) in four European countries (France, Greece, Spain and Turkey). The main objective was to identify factors associated with ventilator-associated events (VAEs) in adults who underwent mechanical ventilation (MV) ≥ 48 h. Secondary objectives were to identify: variables influencing VAE in the subpopulation with endotracheal intubation and in those subjects who were ventilated > 7 days. Subjects who had undergone MV ≥ 48 h were included. In subjects with multiple episodes of MV, only the first one was eligible. The adult definitions for VAEs were adjusted to the 2015 update of the CDC's 2013 National Healthcare Safety Network Association. Factors associated with VAE were estimated through multivariate Cox proportional hazards analysis. Among 163 adults (42 tracheostomies), 76 VAEs (34.9 VAEs/1,000 ventilator-days) were documented: 9 were Ventilator-Associated Conditions (VAC) and 67 Infection-related Ventilator-Associated Complications (IVAC)-plus (9 only IVAC and 58 Possible Ventilator-Associated Pneumonia). VAEs developed after a median of 6 days (interquartile range: 4-9). VAEs were independently associated with long-acting sedative/analgesic drugs (Hazard Ratio [HR]: 4.30), selective digestive decontamination (SDD) (HR: 0.38), and surgical/trauma admission (HR: 2.30). Among 116 subjects with endotracheal tube, SDD (HR: 0.21) and surgical/trauma admission (HR: 3.11) remained associated with VAE. Among 102 subjects ventilated >7 days, only long-acting sedative/analgesic agents (HR: 8.69) remained independently associated with VAE. In summary, SDD implementation and long-acting analgesic/sedative agents restriction prescription may prevent early and late VAEs, respectively. Bundles developed to prevent VAEs should include these two interventions.

Microencapsulation of cocoa liquor nanoemulsion with whey protein using spray drying to protection of volatile compounds and antioxidant capacity.

The aim of this study was microencapsulated a nanoemulsion of cocoa liquor with whey protein by spray drying, and evaluate the effect of different inlet drying temperatures on the properties of microcapsules. The nanoemulsion showed a particle size of 202.13 nm, PdI of 0.424, and ζ-potential of -25.20 mV. The inlet drying temperature showed differences in physicochemical properties of microcapsules. Microcapsules presented good thermal stability and protection against the melting of cocoa liquor. Microcapsules obtained showed excellent yields of polyphenolic compounds (78-93%), and high retention of volatile compounds, especially of pyrazines. Greater microencapsulation yield of bioactive compounds and retention of volatile compounds was obtained at higher drying temperature (180 °C). Excellent stability of polyphenols content, antioxidant capacity, and volatile compounds of cocoa liquor were observed during storage of the microcapsules at different temperature conditions, indicating the feasibility of this powder for its incorporation into functional foods.

The thermophilic biomass-degrading fungus Thielavia terrestris Co3Bag1 produces a hyperthermophilic and thermostable ß-1,4-xylanase with exo- and endo-activity.

A hyperthermophilic and thermostable xylanase of 82 kDa (TtXynA) was purified from the culture supernatant of T. terrestris Co3Bag1, grown on carboxymethyl cellulose (CMC), and characterized biochemically. TtXynA showed optimal xylanolytic activity at pH 5.5 and at 85 °C, and retained more than 90% of its activity at a broad pH range (4.5-10). The enzyme is highly thermostable with a half-life of 23.1 days at 65 °C, and active in the presence of several metal ions. Circular dichroism spectra strongly suggest the enzyme gains secondary structures when temperature increases. TtXynA displayed higher substrate affinity and higher catalytic efficiency towards beechwood xylan than towards birchwood xylan, oat-spelt xylan, and CMC. According to its final hydrolysis products, TtXynA displays endo-/exo-activity, yielded xylobiose, an unknown oligosaccharide containing about five residues of xylose and a small amount of xylose on beechwood xylan. Finally, this report represents the description of the first fungal hyperthermophilic xylanase which is produced by T. terrestris Co3Bag1. Since TtXynA displays relevant biochemical properties, it may be a suitable candidate for biotechnological applications carried out at high temperatures, like the enzymatic pretreatment of plant biomass for the production of bioethanol.

Strategic Actions to Value, Conserve, and Restore the Natural Capital of Megadiversity Countries: The Case of Mexico.

Decisionmakers need updated, scientifically sound and relevant information to implement appropriate policy measures and make innovative commitments to halt biodiversity loss and improve human well-being. Here, we present a recent science-based synthesis on the biodiversity and ecosystem services of Mexico, intended to be a tool for policymakers. We describe the methodological approach used to undertake such an assessment and highlight the major findings. Organized into five volumes and originally written in Spanish (Capital Natural de México), it summarizes the available knowledge on the components, structure, and functioning of the biodiversity of Mexico; the threats and trajectories of anthropogenic impact, together with its conservation status; and the policies, institutions, and instruments available for its sustainable management. We stress the lessons learned that can be useful for similar exercises in other megadiverse developing countries and identify major gaps and strategic actions to conserve the natural capital in light of the challenges of the Anthropocene.

Synthesis and labeling of a piperazine-based library of ¹¹C-labeled ligands for imaging of the vesicular acetylcholine transporter.

The cholinergic system is involved in neurodegenerative diseases, and visualization of cholinergic innervations with positron emission tomography (PET) would be a useful tool in understanding these diseases. A ligand for the vesicular acetylcholine transporter (VAChT), acknowledged as a marker for cholinergic neurons, could serve as such a PET tracer. The aim was to find a VAChT PET tracer using a library concept to create a small but diverse library of labeled compounds. From the same precursor and commercially available aryl iodides 6a-f, six potential VAChT PET tracers, [(11)C]-(±)5a-f, were (11)C-labeled by a palladium (0)-mediated aminocarbonylation, utilizing a standard protocol. The labeled compounds [(11)C]-(±)5a-f were obtained in radiochemical purities >95% with decay-corrected radiochemical yields and specific radioactivities between 4-25% and 124-597 GBq/µmol, respectively. Autoradiography studies were then conducted to assess the compounds binding selectivity for VAChT. Labeled compounds [(11)C]-(±)5d and [(11)C]-(±)5e showed specific binding but not enough to permit further preclinical studies. To conclude, a general method for a facile synthesis and labeling of a small piperazine-based library of potential PET tracers for imaging of VAChT was shown, and in upcoming work, another scaffold will be explored using this approach.

Ventilator-associated events in adults: A secondary analysis assessing the impact of monitoring ventilator settings on outcomes.

BACKGROUND: Ventilator-associated events (VAE) is a tier implemented for surveillance by the CDC in the USA. Implementation usefulness for clinical decisions is unknown. METHODS: We conducted a secondary analysis from a prospective, multicentre, international study, to assess the impact on outcomes of using tiers with shorter follow-up (VAE24), lower oxygenation requirements (light-VAE) or both (light VAE24). RESULTS: A cohort of 261 adults with 2706 ventilator-days were included. The median (IQR) duration of mechanical ventilation (MV) was 9 days (5-21), and the median (IQR) length of stay in the intensive care unit (ICU) was 14 days (8-26). A VAE tier was associated with a trend to increase from 32% to 44% in the ICU mortality rates. VAE Incidence was 24 per 1,000 ventilator-days, being increased when reduced the oxygenation settings requirement (35 per 1,000 ventilator-days), follow-up (41 per 1,000 ventilator-days) or both (55 per 1,000 ventilator-days). A VAE tier was associated with 13 extra (21 vs. 8) days of ventilation, 11 (23 vs. 12) ICU days and 7 (31 vs. 14) hospitalization days, outperforming the modified tiers' performance. CONCLUSIONS: The modification of ventilator settings (consistent with ventilator-associated events) was associated with worse outcomes among adults with prolonged mechanical ventilation. Monitoring ventilator-associated events at the bedside represents a new tool for quality improvement.

A novel approach to model exposure of coastal-marine ecosystems to riverine flood plumes based on remote sensing techniques.

Increased loads of land-based pollutants are a major threat to coastal-marine ecosystems. Identifying the affected marine areas and the scale of influence on ecosystems is critical to assess the impacts of degraded water quality and to inform planning for catchment management and marine conservation. Studies using remotely-sensed data have contributed to our understanding of the occurrence and influence of river plumes, and to our ability to assess exposure of marine ecosystems to land-based pollutants. However, refinement of plume modeling techniques is required to improve risk assessments. We developed a novel, complementary, approach to model exposure of coastal-marine ecosystems to land-based pollutants. We used supervised classification of MODIS-Aqua true-color satellite imagery to map the extent of plumes and to qualitatively assess the dispersal of pollutants in plumes. We used the Great Barrier Reef (GBR), the world's largest coral reef system, to test our approach. We combined frequency of plume occurrence with spatially distributed loads (based on a cost-distance function) to create maps of exposure to suspended sediment and dissolved inorganic nitrogen. We then compared annual exposure maps (2007-2011) to assess inter-annual variability in the exposure of coral reefs and seagrass beds to these pollutants. We found this method useful to map plumes and qualitatively assess exposure to land-based pollutants. We observed inter-annual variation in exposure of ecosystems to pollutants in the GBR, stressing the need to incorporate a temporal component into plume exposure/risk models. Our study contributes to our understanding of plume spatial-temporal dynamics of the GBR and offers a method that can also be applied to monitor exposure of coastal-marine ecosystems to plumes and explore their ecological influences.

Ventilator-associated events: From surveillance to optimizing management.

Mechanical ventilation (MV) is a life-support therapy that may predispose to morbid and lethal complications, with ventilator-associated pneumonia (VAP) being the most prevalent. In 2013, the Center for Disease Control (CDC) defined criteria for ventilator-associated events (VAE). Ten years later, a growing number of studies assessing or validating its clinical applicability and the potential benefits of its inclusion have been published. Surveillance with VAE criteria is retrospective and the focus is often on a subset of patients with higher than lower severity. To date, it is estimated that around 30% of ventilated patients in the intensive care unit (ICU) develop VAE. While surveillance enhances the detection of infectious and non-infectious MV-related complications that are severe enough to impact the patient's outcomes, there are still many gaps in its classification and management. In this review, we provide an update by discussing VAE etiologies, epidemiology, and classification. Preventive strategies on optimizing ventilation, sedative and neuromuscular blockade therapy, and restrictive fluid management are warranted. An ideal VAE bundle is likely to minimize the period of intubation. We believe that it is time to progress from just surveillance to clinical care. Therefore, with this review, we have aimed to provide a roadmap for future research on the subject.

PET Imaging of Neutrophil Elastase with 11C-GW457427 in Acute Respiratory Distress Syndrome in Pigs.

Today, there is a lack of clinically available imaging techniques to detect and quantify specific immune cell populations. Neutrophils are one of the first immune cells at the site of inflammation, and they secrete the serine protease neutrophil elastase (NE), which is crucial in the fight against pathogens. However, the prolonged lifespan of neutrophils increases the risk that patients will develop severe complications, such as acute respiratory distress syndrome (ARDS). Here, we evaluated the novel radiolabeled NE inhibitor 11C-GW457427 in a pig model of ARDS, for detection and quantification of neutrophil activity in the lungs. Methods: ARDS was induced by intravenous administration of oleic acid to 5 farm pigs, and 4 were considered healthy controls. The severity of ARDS was monitored by clinical parameters of lung function and plasma biomarkers. Each pig was studied with 11C-GW457427 and PET/CT, before and after pretreatment with the NE inhibitor GW311616 to determine in vivo binding specificity. PET image data were analyzed as SUVs and correlated with immunohistochemical staining for NE in biopsies. Results: The binding of 11C-GW457427 was increased in pig lungs with induced ARDS (median SUVmean, 1.91; interquartile range [IQR], 1.67-2.55) compared with healthy control pigs (P < 0.05 and P = 0.03, respectively; median SUVmean, 1.04; IQR, 0.66-1.47). The binding was especially strong in lung regions with high levels of NE and ongoing inflammation, as verified by immunohistochemistry. The binding was successfully blocked by pretreatment of an NE inhibitor drug, which demonstrated the in vivo specificity of 11C-GW457427 (P < 0.05 and P = 0.04, respectively; median SUVmean, 0.60; IQR, 0.58-0.77). The binding in neutrophil-rich tissues such as bone marrow (P < 0.05 and P = 0.04, respectively; baseline median SUVmean, 5.01; IQR, 4.48-5.49; block median SUVmean, 1.57; IQR, 0.95-1.85) and spleen (median SUVmean, 2.14; IQR, 1.19-2.36) was also high in all pigs. Conclusion: 11C-GW457427 binds to NE in a porcine model of oleic acid-induced lung inflammation in vivo, with a specific increase in regional lung, bone marrow, and spleen SUV. 11C-GW457427 is a promising tool for localizing, tracking, and quantifying neutrophil-facilitated inflammation in clinical diagnostics and drug development.

Prevention of ventilator-associated pneumonia through care bundles: A systematic review and meta-analysis.

Background: Ventilator-associated pneumonia (VAP) represents a common hospital-acquired infection among mechanically ventilated patients. We summarized evidence concerning ventilator care bundles to prevent VAP. Methods: A systematic review and meta-analysis were performed. Randomized controlled trials and controlled observational studies of adults undergoing mechanical ventilation (MV) for at least 48 h were considered for inclusion. Outcomes of interest were the number of VAP episodes, duration of MV, hospital and intensive care unit (ICU) length of stay, and mortality. A systematic search was conducted in the MEDLINE, the Cochrane Library, and the Web of Science between 1985 and 2022. Results are reported as odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI). The PROSPERO registration number is CRD42022341780. Results: Thirty-six studies including 116,873 MV participants met the inclusion criteria. A total of 84,031 participants underwent care bundles for VAP prevention. The most reported component of the ventilator bundle was head-of-bed elevation (n=83,146), followed by oral care (n=80,787). A reduction in the number of VAP episodes was observed among those receiving ventilator care bundles, compared with the non-care bundle group (OR=0.42, 95% CI: 0.33, 0.54). Additionally, the implementation of care bundles decreased the duration of MV (MD=-0.59, 95% CI: -1.03, -0.15) and hospital length of stay (MD=-1.24, 95% CI: -2.30, -0.18) in studies where educational activities were part of the bundle. Data regarding mortality were inconclusive. Conclusions: The implementation of ventilator care bundles reduced the number of VAP episodes and the duration of MV in adult ICUs. Their application in combination with educational activities seemed to improve clinical outcomes.

Cardiac microcalcifications in transthyretin (ATTR) amyloidosis.

BACKGROUND: Bone tracers bind to amyloid-containing heart of most patients with ATTR amyloidosis. Amyloid deposits outside the heart are often scarce and bone scintigraphy is increasingly often used to diagnose cardiac involvement. However, the nature of the binding of bone tracers to the heart is not clear. OBJECTIVE: To identify possible calcium deposits in hearts with amyloid, explaining bone tracer binding. METHODS AND RESULTS: Formalin-fixed and paraffin embedded cardiac specimens from three patients with ATTR and one with AL amyloidosis, all with cardiac deposits, were studied. The specimens covered large parts of the heart. Sections were stained immunohistochemically for ATTR deposits and according to von Kóssa for calcifications. The study identified in all hearts, but particularly in the ATTR materials, focal, tight swarms of tiny calcifications. These were sometimes associated with amyloid but found as frequent in areas without such deposits. Autoradiography with [99mTc]Tc labelled 3,3-disphos-phono-1,2-propanodicarboxylic acid (DPD) revealed labelling in von Kóssa positive areas. Electron microscopically the particles were not amorphous but had a complex structured appearance and were often surrounded by a membrane, indicating a cellular origin. Labelling with antibodies against ubiquitin and P62 pointed to result from autophagy. CONCLUSIONS: Our study indicates that binding of skeletal probes to amyloid-containing hearts depends on an irregular presence of clouds of very tiny calcifications, which seem not to be directly associated with amyloid fibrils. Therefore, [99mTc]Tc-DPD bone scans can be considered surrogate markers of ATTR amyloid but have to be used carefully to estimate amyloid amount or disease progression.

Imaging of the Glucose-Dependent Insulinotropic Polypeptide Receptor Using a Novel Radiolabeled Peptide Rationally Designed Based on Endogenous GIP and Synthetic Exendin-4 Sequences.

Imaging and radiotherapy targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) could potentially benefit the management of neuroendocrine neoplasms (NENs), complementing clinically established radiopharmaceuticals. The aim of this study was to evaluate a GIPR-targeting positron emission tomography (PET) radioligand with receptor-specific binding, fast blood clearance, and low liver background uptake. The peptide DOTA-bioconjugate, C803-GIP, was developed based on the sequence of the endogenous GIP(1-30) and synthetic exendin-4 peptides with selective amino acid mutations to combine their specificity for the GIPR and in vivo stability, respectively. The 68Ga-labeled bioconjugate was evaluated in vitro in terms of binding affinity, specificity, and internalization in HEK293 cells transfected with the human GIPR, GLP1, or GCG receptors and in sections of human insulinoma and NENs. In vivo binding specificity, biodistribution, and tissue background were investigated in mice bearing huGIPR-HEK293 xenografts and in a pig. Ex vivo organ distribution, pharmacokinetics, and dosimetry were studied in normal rats. [68Ga]Ga-C803-GIP was stable and demonstrated a high affinity to the huGIPR-HEK293 cells. Binding specificity was demonstrated in vitro in frozen sections of NENs and huGIPR-HEK293 cells. No specific uptake was observed in the negative controls of huGLP1R and huGCGR cells. A novel rationally designed PET radioligand, [68Ga]Ga-C803-GIP, demonstrated promising binding characteristics and specificity towards the GIPR.

Preclinical evaluation of [11C]GW457427 as a tracer for neutrophil elastase.

INTRODUCTION: Neutrophils are part of the innate immune system and function as a first line of defense against invading microorganisms. Overactivity of the immune system may result in a devastating immuno-inflammation with extensive damage to tissue leading to organ damage and/or failure. The literature suggests several human diseases in which neutrophil elastase (NE) is postulated to be important in the pathophysiology including inflammatory bowel disease (IBD), chronic obstructive pulmonary disorder (COPD), abdominal aortic aneurysms (AAA), breast and lung cancer, and recently also in Sars-cov-2 virus infection (Covid-19). In particular, the lungs are affected by the destructive power of the protease neutrophil elastase (NE). In this paper, we report the pre-clinical development of a selective and specific positron emission tomography (PET) tracer, [11C]GW457427, as an in vivo biomarker for the study of NE, now available for human studies. METHODS: [11C]GW457427 was produced by methylation of GW447631 using [11C]methyl triflate and GMP validated production and quality control methods were developed. Chemical purity was high with no traces of the precursor GW611437 or other uv-absorbing compounds. A method for the determination of intact [11C]GW457427 in plasma was developed and the binding characteristics were evaluated in vitro and in vivo. An animal model for lung inflammation was used to investigate the specificity and sensitivity of the [11C]GW457427 tracer for neutrophil elastase (NE) in pulmonary inflammation, verified by blockade using two structurally different elastase inhibitors. RESULTS: [11C]GW457427 was obtained in approximately 45% radiochemical yield and with a radiochemical purity higher than 98%. Molar activity was in the range 130-360 GBq/µmol. Binding to NE was shown to be highly specific both in vitro and in vivo and a significantly higher uptake of tracer was found in a lipopolysaccharide mouse model of pulmonary inflammation compared with control animals. The uptake in lung tissue measured as standardized uptake value (SUV) strongly correlated with tissue NE content as measured by ELISA. In vitro studies also showed specific tracer binding in aortic tissue of patients with abdominal aorta aneurysm (AAA). The rate of metabolism in rats was appropriate considering the critical balance between available tracer for binding and requirement for blood clearance with about 40% and 20% intact [11C]GW457427 in plasma at 5 and 40 min, respectively. Radioactivity was cleared from blood and organs in control animals with mainly hepatobiliary excretion with distribution in the intestines and the urinary bladder; but without retention of the tracer in healthy organs of interests such as the lung, liver, kidneys or in the cardiovascular system. A dosimetry study in rat indicated that the whole-body effective dose was 2.2 µSv/MBq with bone marrow as the limiting organ. It is estimated that up to five PET-CT investigations could be performed in humans without exceeding a total dose of 10 mSv. CONCLUSION: [11C]GW457427 is a promising in vivo PET-biomarker for NE with high specific binding demonstrated both in vitro and in vivo. A GMP validated production method including quality control has been developed and a microdosing toxicity study performed with no adverse signs. [11C]GW457427 is currently being evaluated in a First-In-Man PET study.

Safety and Efficacy of Devices Delivering Inhaled Antibiotics among Adults with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and a Network Meta-Analysis.

It remains unknown whether the type of aerosol generating device is affecting efficacy and safety among non-cystic fibrosis bronchiectasis (NCFB) adults. The proposal of this network meta-analysis (NMA) is to evaluate effectiveness and safety of inhaled antibiotics administered via dry powder inhaler (DPI) and via nebulizers (SVN) among adult patients with NCFB. Inclusion criteria were randomized-controlled trials, adults (≥18 years) with NCFB, and inhaled antibiotics administered via DPI as intervention. Search strategy was performed in PubMed, Web of Science, and Cochrane Library from 2000 to 2019. Sixteen trials (2870 patients) were included. Three trials (all ciprofloxacin) used DPIs and thirteen used SVN (three ciprofloxacin). Both DPI and SVN devices achieved similar safety outcomes (adverse events, antibiotic discontinuation, severe adverse events, and bronchospasm). Administration of ciprofloxacin via DPI significantly improved time to first exacerbation (87 days, 95% CI 34.3-139.7) and quality of life (MD -7.52; 95% CI -13.06 to -1.98) when compared with via SVN. No other significant differences were documented in clinical efficacy (at least one exacerbation, FEV1% predicted) and microbiologic response (bacterial eradication, emergence of new potential pathogens, and emergence of antimicrobial resistance) when comparing devices. Our NMA documented that time to first exacerbation and quality of life, were more favorable for DPIs. Decisions on the choice of devices should incorporate these findings plus other criteria, such as simplicity, costs or maintenance requirements.