Int J Mol Sci. 2022 Nov 4;23(21):13494. doi: 10.3390/ijms232113494.

ABSTRACT

Pseudomonas aeruginosa is an opportunistic pathogen causing several chronic infections resistant to currently available antibiotics. Its pathogenicity is related to the production of different virulence factors such as biofilm and protease secretion. Pseudomonas communities can persist in biofilms that protect bacterial cells from antibiotics. Hence, there is a need for innovative approaches that are able to counteract these virulence factors, which play a pivotal role, especially in chronic infections. In this context, antimicrobial peptides are emerging drugs showing a broad spectrum of antibacterial activity. Here, we tested the anti-virulence activity of a chionodracine-derived peptide (KHS-Cnd) on five P. aeruginosa clinical isolates from cystic fibrosis patients. We demonstrated that KHS-Cnd impaired biofilm development and caused biofilm disaggregation without affecting bacterial viability in nearly all of the tested strains. Ultrastructural morphological analysis showed that the effect of KHS-Cnd on biofilm could be related to a different compactness of the matrix. KHS-Cnd was also able to reduce adhesion to pulmonary cell lines and to impair the invasion of host cells by P. aeruginosa. A cytotoxic effect of KHS-Cnd was observed only at the highest tested concentration. This study highlights the potential of KHS-Cnd as an anti-biofilm and anti-virulence molecule against P. aeruginosa clinical strains.

PMID:36362282 | DOI:10.3390/ijms232113494

Int J Mol Sci. 2022 Nov 2;23(21):13405. doi: 10.3390/ijms232113405.

ABSTRACT

Elevated levels of matrix metalloprotease 9 (MMP-9) and neutrophil elastase (NE) are associated with bronchiectasis and lung function decline in patients with cystic fibrosis (CF). MMP-9 is a potent extracellular matrix-degrading enzyme which is activated by NE and has been implicated in structural lung damage in CF. However, the role of MMP-9 in the in vivo pathogenesis of CF lung disease is not well understood. Therefore, we used β-epithelial Na+ channel-overexpressing transgenic (βENaC-Tg) mice as a model of CF-like lung disease and determined the effect of genetic deletion of Mmp9 (Mmp9-/-) on key aspects of the pulmonary phenotype. We found that MMP-9 levels were elevated in the lungs of βENaC-Tg mice compared with wild-type littermates. Deletion of Mmp9 had no effect on spontaneous mortality, inflammatory markers in bronchoalveolar lavage, goblet cell metaplasia, mucus hypersecretion and emphysema-like structural lung damage, while it partially reduced mucus obstruction in βENaC-Tg mice. Further, lack of Mmp9 had no effect on increased inspiratory capacity and increased lung compliance in βENaC-Tg mice, whereas both lung function parameters were improved with genetic deletion of NE. We conclude that MMP-9 does not play a major role in the in vivo pathogenesis of CF-like lung disease in mice.

PMID:36362203 | DOI:10.3390/ijms232113405

Int J Mol Sci. 2022 Oct 29;23(21):13146. doi: 10.3390/ijms232113146.

ABSTRACT

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). The newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. The regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

PMID:36361933 | DOI:10.3390/ijms232113146

Int J Environ Res Public Health. 2022 Oct 27;19(21):14014. doi: 10.3390/ijerph192114014.

ABSTRACT

BACKGROUND: Telemedicine is an effective, widely used strategy in the field of cystic fibrosis management. The objective of this scoping review is to summarize and analyze the scientific literature with the special focus on the tools and the strategies used in patients with a chronic disease, such as cystic fibrosis.

METHODS: This scoping review will be performed in accordance with the Joanna Briggs Institute methodology. In this context, the planned scoping review is a research synthesis that will map the literature on the applications of telemedicine and telemonitoring to the management of cystic fibrosis, with the aim to identify key concepts in the research and work to be conducted that may impact clinical practice. Studies will be included if they meet the following population, concept, and context criteria: all patients with cystic fibrosis receiving treatment with the tools of telemedicine and telemonitoring. No study design, publication type, or data restrictions will be applied. MEDLINE, Scopus, CINHAL, Pedro, Embase, Web of Science, ACM Digital Library, Health Technology Assessment Database (HTA), and Cochrane Central will be searched up to September 2022.

DISCUSSION: To the best of our knowledge, this will be the first scoping review to provide a comprehensive overview of the topic. The results could add meaningful information for future research and, especially, for clinical practice, when implementing telerehabilitation in cystic fibrosis treatment. Furthermore, we expect that our work may identify possible knowledge gaps on the topic. The results of this research will be published in a peer-reviewed journal and will be presented at relevant international scientific events, such as in congress or meetings.

PMID:36360894 | DOI:10.3390/ijerph192114014

Healthcare (Basel). 2022 Nov 3;10(11):2205. doi: 10.3390/healthcare10112205.

ABSTRACT

Objective: Physical exercise is associated with several benefits in the treatment of cystic fibrosis (CF), associated with a reduction in patient mortality. The aim of this systematic review was to determine the effectiveness of exercise interventions on physical condition and lung function in children and adults with CF to establish the most appropriate type and dose of physical exercise used so far. Methods: The studies included were randomized controlled trials with physical exercise interventions performed with children or adults with CF, analyzing the effects on pulmonary function, cardiorespiratory capacity, and muscle strength. The variables analyzed in at least four studies in the same population (children or adults) with the same measuring test were included in the meta-analysis. Results:Pulmonary function: There were no changes in the forced expiratory volume 1 s, but mouth expiratory/inspiratory pressures were improved in some studies. Physical fitness: In children, the interventions did not manage to improve the VO2peak (SMD = 0.22; 95%CI: -0.25 to 0.68; p = 0.73) but improved muscle strength. In adults, physical exercise interventions based on high-intensity aerobic training showed positive results in the VO2peak, and in some muscle strength outcomes. Conclusions: Exercise interventions in children and adults with CF are effective in improving muscle strength, cardiovascular capacity, and respiratory muscle function. However, they do not achieve improvements in lung function. The most effective programs are those using strength training or cardiovascular high-intensity interval training, although to date there have been few such interventions.

PMID:36360546 | DOI:10.3390/healthcare10112205

Children (Basel). 2022 Nov 5;9(11):1700. doi: 10.3390/children9111700.

ABSTRACT

Children with medical complexity (CMCs) represent a subgroup of children who may have congenital or acquired multisystemic disease. CMCs are frequently predisposed to respiratory problems and often require long-term mechanical ventilation (LTMV). The indications for LTMV in CMCs are increasing, but gathering evidence about indications, titration, and monitoring is currently the most difficult challenge due to the absence of validated data. The aim of this review was to examine the clinical indications and ethical considerations for the initiation, continuation, or withdrawal of LTMV among CMCs. The decision to initiate long-term ventilation should always be based on clinical and ethical considerations and should be shared with the parents.

PMID:36360427 | DOI:10.3390/children9111700

Children (Basel). 2022 Oct 31;9(11):1665. doi: 10.3390/children9111665.

ABSTRACT

BACKGROUND: Physical activity (PA) improves exercise capacity, slows the decline in lung function, and enhances Quality of Life (QoL) in patients with cystic fibrosis (pwCF).

OBJECTIVES: The study aimed to evaluate PA and QoL among children with CF compared to healthy controls; the secondary aim was to assess the correlation between PA, QoL, and lung function (FEV1).

METHODS: Forty-five children and adolescents with CF and 45 age-matched controls completed two self-administered validated questionnaires: The Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the DISABKIDS for QoL. Moreover, pwCF performed spirometry and multiple breath washout tests (MBW). In addition, weight, height, and BMI were recorded. The Godin Leisure-Time Exercise Questionnaire was used to evaluate physical activity; QOL was assessed using the DISABKIDS Questionnaire. The correlation of PA with QOL was assessed as well.

RESULTS: Mean age of the CF population was 13.22 (±4.6) years, mean BMI 19.58 (±4.1) kg/m2, mean FEV1% 91.15 ± 20.46%, and mean LCI 10.68 ± 4.08. 68% of the CF group were active, 27% were medium active, 5% were sedentary, while 83% of the control group were active and 17% were medium active. PwCF with higher PA scores showed significantly higher emotional health (r2: 0.414, p: 0.006) and total QOL score (r2: 0.372; p: 0.014). The PA score showed no significant correlation with FEV1% or LCI.

CONCLUSIONS: The children with CF showed satisfactory PA levels, which positively correlated to their QoL. More research is needed on the effect of increased levels of habitual physical activity to establish the decline in pulmonary function among pwCF.

PMID:36360393 | DOI:10.3390/children9111665

Children (Basel). 2022 Oct 26;9(11):1625. doi: 10.3390/children9111625.

ABSTRACT

BACKGROUND: Dornase alfa (DNase) is the only mucus-degrading agent that has proven efficacy in cystic fibrosis (CF). Few studies have evaluated the effects of DNase on the lung clearance index (LCI). We report the experience of two CF centers in which LCI monitoring was used to evaluate the efficacy of DNase therapy.

METHODS: This is a prospective and observational study, evaluating the effects of DNase therapy on LCI values in three CF children followed at CF centers in Florence and Catania, Italy. In both centers, LCI was performed routinely, every 3-6 months, based on the clinical picture and severity of the lung disease. In this study, we evaluated the LCI before and after long-term DNase therapy.

RESULTS: DNase improved LCI values in the absence of respiratory exacerbations: in case n. 1 LCI decreased by 39% in 16 months (from 11.1 to 6.8); in case n. 2 by 20% in 12 months (from 9.3 to 7.4); in case n. 3 by 24% in 16 months (from 9.3 to 7.0).

CONCLUSIONS: This case series confirms the efficacy of DNase therapy in CF children, as demonstrated by the LCI reduction in treated patients. Furthermore, our results suggest that LCI is a sensitive marker of disease and can be used for the evaluation of response to treatment.

PMID:36360353 | DOI:10.3390/children9111625

Biomedicines. 2022 Nov 10;10(11):2886. doi: 10.3390/biomedicines10112886.

ABSTRACT

Cystic fibrosis (CF) is a disorder causing dysfunctional ion transport resulting in the accumulation of viscous mucus. This environment fosters a chronic bacterial biofilm-associated infection in the airways. Achromobacter xylosoxidans, a gram-negative aerobic bacillus, has been increasingly associated with antibiotic resistance and chronic colonisation in CF. In this study, we aimed to create a reproducible model of CF infection using an artificial sputum medium (ASMDM-1) with bronchial (BEAS-2B) and macrophage (THP-1) cells to test A. xylosoxidans infection and treatment toxicity. This study was conducted in three distinct stages. First, the tolerance of BEAS-2B cell lines and two A. xylosoxidans strains against ASMDM-1 was optimised. Secondly, the cytotoxicity of combined therapy (CT) comprising N-acetylcysteine (NAC) and the antibiotics colistin or ciprofloxacin was tested on cells alone in the sputum model in both BEAS-2B and THP-1 cells. Third, the efficacy of CT was assessed in the context of a bacterial infection within the live cell/sputum model. We found that a model using 20% ASMDM-1 in both cell populations tolerated a colistin-NAC-based CT and could significantly reduce bacterial loads in vitro (~2 log10 CFU/mL compared to untreated controls). This pilot study provides the foundation to study other bacterial opportunists that infect the CF lung to observe infection and CT kinetics. This model also acts as a springboard for more complex co-culture models.

PMID:36359406 | DOI:10.3390/biomedicines10112886

Biomedicines. 2022 Nov 1;10(11):2771. doi: 10.3390/biomedicines10112771.

ABSTRACT

BACKGROUND: The impact of COVID-19 on respiratory outcomes in people with cystic fibrosis (pwCF) has not been clearly characterized. We evaluated changes in respiratory function indicators derived from spirometry and pulmonary exacerbation rates 6 months after SARS-CoV-2 infection.

METHODS: This multicentre prospective study was based on pwCF enrolled between October, 2020 and June, 2021 in the DECO COVID-19 project. PwCF complaining of COVID-like symptoms were tested with real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab. Mean changes in respiratory function indicators and time to first episode of pulmonary exacerbation were compared in RT-PCR-positive and RT-PCR-negative patients. Regression models were used to adjust for baseline percent predicted forced expiratory volume in one second (ppFEV1) values, number of comorbidities, and initiation of CFTR modulator therapy during the follow-up.

RESULTS: We enrolled 26 pwCF with RT-PCR-confirmed infection and 42 with a RT-PCR-negative test. After 6 months of follow-up, mean ppFEV1 changes were not significantly different between groups (+0.3% in positive vs. +0.2% in negative patients, p = 0.19). The 6-month cumulative probabilities of a first episode of pulmonary exacerbation were: 0.425 among RT-PCR-negative patients and 0.465 among those with a positive test (adjusted hazard ratio: 0.88, 95% CI: 0.44-1.75).

CONCLUSIONS: COVID-19 did not appear to negatively influence respiratory outcomes of pwCF at 6 months from infection.

PMID:36359291 | DOI:10.3390/biomedicines10112771

Biology (Basel). 2022 Oct 27;11(11):1582. doi: 10.3390/biology11111582.

ABSTRACT

The analysis of blood samples from mice treated with the PDE4 inhibitor Roflumilast revealed an unexpected reduction in serum potassium levels, while sodium and chloride levels were unaffected. Treatment with several structurally distinct PAN-PDE4 inhibitors, including Roflumilast, Rolipram, RS25344, and YM976 dose-dependently reduced serum potassium levels, indicating the effect is a class-characteristic property. PDE4 inhibition also induces hypothermia and hypokinesia in mice. However, while general anesthesia abrogates these effects of PDE4 inhibitors, potassium levels decrease to similar extents in both awake as well as in fully anesthetized mice. This suggests that the hypokalemic effects of PDE4 inhibitors occur independently of hypothermia and hypokinesia. PDE4 inhibition reduces serum potassium within 15 min of treatment, consistent with a rapid transcellular shift of potassium. Catecholamines promote the uptake of potassium into the cell via increased cAMP signaling. PDE4 appears to modulate these adrenoceptor-mediated effects, as PDE4 inhibition has no additional effects on serum potassium in the presence of saturating doses of the β-adrenoceptor agonist Isoprenaline or the α2-blocker Yohimbine, and is partially blocked by pre-treatment with the β-blocker Propranolol. Together, these data suggest that PDE4 inhibitors reduce serum potassium levels by modulating the adrenergic regulation of cellular potassium uptake.

PMID:36358283 | DOI:10.3390/biology11111582

NPJ Vaccines. 2022 Nov 10;7(1):143. doi: 10.1038/s41541-022-00562-1.

ABSTRACT

Whole cell vaccines are complex mixtures of antigens, immunogens, and sometimes adjuvants that can trigger potent and protective immune responses. In some instances, such as whole cell Bordetella pertussis vaccination, the immune response to vaccination extends beyond the pathogen the vaccine was intended for and contributes to protection against other clinically significant pathogens. In this study, we describe how B. pertussis whole cell vaccination protects mice against acute pneumonia caused by Pseudomonas aeruginosa. Using ELISA and western blot, we identified that B. pertussis whole cell vaccination induces production of antibodies that bind to lab-adapted and clinical strains of P. aeruginosa, regardless of immunization route or adjuvant used. The cross-reactive antigens were identified using immunoprecipitation, mass spectrometry, and subsequent immunoblotting. We determined that B. pertussis GroEL and OmpA present in the B. pertussis whole cell vaccine led to production of antibodies against P. aeruginosa GroEL and OprF, respectively. Finally, we showed that recombinant B. pertussis OmpA was sufficient to induce protection against P. aeruginosa acute murine pneumonia. This study highlights the potential for use of B. pertussis OmpA as a vaccine antigen for prevention of P. aeruginosa infection, and the potential of broadly protective antigens for vaccine development.

PMID:36357402 | DOI:10.1038/s41541-022-00562-1

J Imaging. 2022 Nov 9;8(11):305. doi: 10.3390/jimaging8110305.

ABSTRACT

Ultrasound education traditionally involves theoretical and practical training on patients or on simulators; however, difficulty accessing training equipment during the COVID-19 pandemic has highlighted the need for home-based training systems. Due to the prohibitive cost of ultrasound probes, few medical students have access to the equipment required for at home training. Our proof of concept study focused on the development and assessment of the technical feasibility and training performance of an at-home training solution to teach the basics of interpreting and generating ultrasound data. The training solution relies on monitor-based augmented reality for displaying virtual content and requires only a marker printed on paper and a computer with webcam. With input webcam video, we performed body pose estimation to track the student's limbs and used surface tracking of printed fiducials to track the position of a simulated ultrasound probe. The novelty of our work is in its combination of printed markers with marker-free body pose tracking. In a small user study, four ultrasound lecturers evaluated the training quality with a questionnaire and indicated the potential of our system. The strength of our method is that it allows students to learn the manipulation of an ultrasound probe through the simulated probe combined with the tracking system and to learn how to read ultrasounds in B-mode and Doppler mode.

PMID:36354878 | DOI:10.3390/jimaging8110305

Pediatr Pulmonol. 2022 Nov 10. doi: 10.1002/ppul.26235. Online ahead of print.

ABSTRACT

The coronavirus disease 2019 (COVID-19) outbreak has evolved with different waves corresponding to subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations. While the most severe cases have been observed in the elderly and in individuals with underlying comorbidities, severe pediatric and young adult cases have been observed, as well as post-infectious inflammatory syndromes and persistent symptoms leading to long-COVID. This manuscript describes the experience of a pediatric respiratory unit during the first year of the pandemic and reviews the corresponding literature with a special emphasis on children and young people with underlying conditions, such as immunosuppression, sickle cell disease, and cystic fibrosis. This article is protected by copyright. All rights reserved.

PMID:36353967 | DOI:10.1002/ppul.26235

Rev Esp Enferm Dig. 2022 Nov 10;114. doi: 10.17235/reed.2022.9289/2022. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic Fibrosis Liver Disease is a poorly understood entity, especially in adults, in terms of its real prevalence, natural history and diagnostic criteria, despite being the most important extrapulmonary cause of mortality. The aim was to evaluate the prevalence, characteristics and potential risk factors of liver disease in adults with cystic fibrosis, according to two diagnostic criteria accepted in the scientific literature.

METHODS: Patients were recruited in a tertiary referral hospital, and laboratory, ultrasound, non-invasive liver fibrosis tests (AST to Platelet Ratio Index; Fibrosis-4 Index) and transient elastography (Fibroscan) were performed. The proportion of patients with liver disease according to the Debray and Koh criteria were evaluated.

RESULTS: 95 patients were included, 48 (50.5%) females, with a mean age of 30.4 (28.6-32.2) years. According to the Debray criteria, 6 (6.3%) patients presented liver disease. According to the Koh criteria, prevalence increased up to 8.4%, being statistically different from the 25% value described in other published series (p = 0.005). Seven (7.5%) presented ultrasonographic chronic liver disease. Eleven (13%) presented liver fibrosis according to the APRI score; 95 (100%) had a normal FIB-4 value. Mean liver stiffness value was 4.4 (4.1-4.7) kPa. FEV1 (OR=0.16, p 0.05), meconium ileus (OR=14.16, p 0.002), platelets (Pearson coefficient -0.25, p 0.05) and younger age (Pearson coefficient -0.19, p 0.05) were risk factors.

CONCLUSIONS: Prevalence and severity of liver disease in adult cystic fibrosis patients were lower than expected. Meconium ileus, platelets, age and respiratory function were confirmed as risk factors associated to cystic fibrosis liver disease.

PMID:36353964 | DOI:10.17235/reed.2022.9289/2022

Front Mol Biosci. 2022 Oct 24;9:1026724. doi: 10.3389/fmolb.2022.1026724. eCollection 2022.

ABSTRACT

Pseudomonas aeruginosa is a wide-spread opportunistic human pathogen and a high-risk factor for immunodeficient people and patients with cystic fibrosis. The extracellular lipase A belongs to the virulence factors of P. aeruginosa. Prior to the secretion, the lipase undergoes folding and activation by the periplasmic foldase LipH. At this stage, the enzyme is highly prone to aggregation in mild and high salt concentrations typical for the sputum of cystic fibrosis patients. Here, we demonstrate that the periplasmic chaperone Skp of P. aeruginosa efficiently prevents misfolding of the lipase A in vitro. In vivo experiments in P. aeruginosa show that the lipase secretion is nearly abolished in absence of the endogenous Skp. Small-angle X-ray scattering elucidates the trimeric architecture of P. aeruginosa Skp and identifies two primary conformations of the chaperone, a compact and a widely open. We describe two binding modes of Skp to the lipase, with affinities of 20 nM and 2 μM, which correspond to 1:1 and 1:2 stoichiometry of the lipase:Skp complex. Two Skp trimers are required to stabilize the lipase via the apolar interactions, which are not affected by elevated salt concentrations. We propose that Skp is a crucial chaperone along the lipase maturation and secretion pathway that ensures stabilization and carry-over of the client to LipH.

PMID:36353734 | PMC:PMC9638971 | DOI:10.3389/fmolb.2022.1026724

Front Med (Lausanne). 2022 Oct 24;9:1022981. doi: 10.3389/fmed.2022.1022981. eCollection 2022.

ABSTRACT

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows the assessment of pulmonary perfusion, which may play a key role in the development of muco-obstructive lung disease. One problem with quantifying pulmonary perfusion is the high variability of metrics. Quantifying the extent of abnormalities using unsupervised clustering algorithms in residue function maps leads to intrinsic normalization and could reduce variability.

PURPOSE: We investigated the reproducibility of perfusion defects in percent (QDP) in clinically stable patients with cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).

METHODS: 15 CF (29.3 ± 9.3y, FEV1%predicted = 66.6 ± 15.8%) and 20 COPD (66.5 ± 8.9y, FEV1%predicted = 42.0 ± 13.3%) patients underwent DCE-MRI twice 1 month apart. QDP, pulmonary blood flow (PBF), and pulmonary blood volume (PBV) were computed from residue function maps using an in-house quantification pipeline. A previously validated MRI perfusion score was visually assessed by an expert reader.

RESULTS: Overall, mean QDP, PBF, and PBV did not change within 1 month, except for QDP in COPD (p < 0.05). We observed smaller limits of agreement (± 1.96 SD) related to the median for QDP (CF: ± 38%, COPD: ± 37%) compared to PBF (CF: ± 89%, COPD: ± 55%) and PBV (CF: ± 55%, COPD: ± 51%). QDP correlated moderately with the MRI perfusion score in CF (r = 0.46, p < 0.05) and COPD (r = 0.66, p < 0.001). PBF and PBV correlated poorly with the MRI perfusion score in CF (r =-0.29, p = 0.132 and r =-0.35, p = 0.067, respectively) and moderately in COPD (r =-0.57 and r =-0.57, p < 0.001, respectively).

CONCLUSION: In patients with muco-obstructive lung diseases, QDP was more robust and showed a higher correlation with the MRI perfusion score compared to the traditionally used perfusion metrics PBF and PBV.

PMID:36353218 | PMC:PMC9637664 | DOI:10.3389/fmed.2022.1022981

Magn Reson Med. 2022 Nov 9. doi: 10.1002/mrm.29518. Online ahead of print.

ABSTRACT

PURPOSE: To enable efficient hyperpolarized 129 Xe diffusion imaging using 2D and 3D (Fermat Looped, ORthogonally Encoded Trajectories, FLORET) spiral sequences and demonstrate that 129 Xe ADCs obtained using these sequences are comparable to those obtained using a conventional, 2D gradient-recalled echo (GRE) sequence.

THEORY AND METHODS: Diffusion-weighted 129 Xe MRI (b-values = 0, 7.5, 15 s/cm2 ) was performed in four healthy volunteers and one subject with lymphangioleiomyomatosis using slice-selective 2D-GRE (scan time = 15 s), slice-selective 2D-Spiral (4 s), and 3D-FLORET (16 s) sequences. Experimental SNRs from b-value = 0 images ( SNR 0 EX $$ SNR{0}_{EX} $$ ) and mean ADC values were compared across sequences. In two healthy subjects, a second b = 0 image was acquired using the 2D-Spiral sequence to map flip angle and correct RF-induced, hyperpolarized signal decay at the voxel level, thus improving regional ADC estimates.

RESULTS: Diffusion-weighted images from spiral sequences displayed image quality comparable to 2D-GRE and produced sufficient SNR 0 EX $$ SNR{0}_{EX} $$ (16.8 ± 3.8 for 2D-GRE, 21.2 ± 3.5 for 2D-Spiral, 20.4 ± 3.5 for FLORET) to accurately calculate ADC. Whole-lung means and SDs of ADC obtained via spiral were not significantly different (P > 0.54) from those obtained via 2D-GRE. Finally, 2D-Spiral images were corrected for signal decay, which resulted in a whole-lung mean ADC decrease of ˜15%, relative to uncorrected images.

CONCLUSIONS: Relative to GRE, efficient spiral sequences allow 129 Xe diffusion images to be acquired with isotropic lung coverage (3D), higher SNR $$ SNR $$ (2D and 3D), and three-fold faster (2D) within a single breath-hold. In turn, shortened breath-holds enable flip-angle mapping, and thus, allow RF-induced signal decay to be corrected, increasing ADC accuracy.

PMID:36352793 | DOI:10.1002/mrm.29518

Arch Dis Child Fetal Neonatal Ed. 2022 Sep 8:fetalneonatal-2021-323549. doi: 10.1136/archdischild-2021-323549. Online ahead of print.

ABSTRACT

OBJECTIVE: Newborn screening (NBS) for cystic fibrosis (CF) was introduced in Switzerland in 2011 based on an immunoreactive trypsinogen (IRT)-DNA-IRT protocol. CF diagnosis was confirmed by sweat test and/or genetics but remained inconclusive for some newborns (cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS)/CF screen positive, inconclusive diagnosis (CFSPID)). We aimed to (1) Describe IRT levels in healthy newborns in the first year of life and by gestational age (GA), and (2) Compare IRT at two time points between healthy newborns and newborns with CF and CRMS/CFSPID.

DESIGN: Retrospective study.

SETTING: National NBS database.

PATIENTS: All children with an IRT measurement by heel prick test from 2011 to 2019.

INTERVENTIONS: None.

MAIN OUTCOME MEASURES: IRT values were extracted from the National NBS Laboratory, and clinical characteristics of positively screened children from the CF-NBS database. Second IRT assessment in positively screened children was usually performed after 18-24 days. We calculated internal IRT Z-Scores and multiples of the median to compare our results across different laboratory tools.

RESULTS: Among 815 899 children; 232 were diagnosed with CF, of whom 36 had meconium ileus (MI); 27 had CRMS/CFSPID. Among all samples analysed, mean IRT Z-Scores were higher for newborns with GA <33 weeks and ≥43 weeks (all Z-Scores >0.11) compared with term babies (all Z-Scores ≤0.06). Repeated IRT Z-Scores after a median (IQR) of 19 (17-22) days remained high for infants with CF with or without MI but decreased for infants with CRMS/CFSPID.

CONCLUSIONS: Measurement of a second IRT value can help distinguish between children with CRMS/CFSPID and CF, early in life.

PMID:36351789 | DOI:10.1136/archdischild-2021-323549

J Palliat Med. 2022 Nov 9. doi: 10.1089/jpm.2022.0349. Online ahead of print.

ABSTRACT

Background: Cystic fibrosis (CF) is a progressive genetic disease characterized by multisystem symptom burden. Specialist palliative care (PC), as a model of care, has been shown to be effective in improving quality of life and reducing symptom burden in other conditions, but has not been tested in CF. Objectives: To develop and test the feasibility and acceptability of a specialist PC intervention embedded within an outpatient CF clinic. Design: Single-site, equal-allocation randomized pilot study comparing usual care with addition of four protocolized quarterly visits with a PC nurse practitioner. Participants: Adults with CF age ≥18 years with any of the following: FEV1% predicted ≤50, ≥2 CF-related hospitalizations in the past 12 months, supplemental oxygen use, or noninvasive mechanical ventilation use, and moderate-or-greater severity of any symptoms on the Edmonton Symptom Assessment Scale. Measurements: Randomization rate, intervention visit completion, data completements, participant ratings of intervention acceptability and benefit, and intervention delivery fidelity. Results: We randomized 50 adults with CF of 65 approached (77% randomization rate) to intervention (n = 25) or usual care (n = 25), mean age 38, baseline mean FEV1% predicted 41.8 (usual care), and 41.2 (intervention). No participants withdrew, five were lost to follow-up, and two died (88% retention). In the intervention group, 23 of 25 completed all study visits; 94% stated the intervention was not burdensome, and 97.6% would recommend the intervention to others with CF. More than 90% of study visits addressed topics prescribed by intervention manual. Conclusions: Adding specialist PC to standard clinic visits for adults with CF is feasible and acceptable.

PMID:36350712 | DOI:10.1089/jpm.2022.0349