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https://www.readbyqxmd.com/read/30101632/new-anti-pseudomonal-agents-for-cystic-fibrosis-still-needed-in-the-era-of-small-molecule-cftr-modulators
#1
Jane C Davies, Isaac Martin
Cystic fibrosis is characterized by bacterial lung infection, a majority of adults being chronically infected with Pseudomonas aeruginosa. Treatment is a major challenge, with frequent courses of antibiotics contributing to antimicrobial resistance. New approaches are clearly required. Over the last few years, a major shift in our approach to treating CF has occurred with the availability of the first drugs targeting the CFTR protein and leading to improvements in lung function, weight gain and frequency of exacerbations...
August 12, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/30100257/antisense-oligonucleotide-targeting-of-mrnas-encoding-enac-subunits-%C3%AE-%C3%AE-and-%C3%AE-improves-cystic-fibrosis-like-disease-in-mice
#2
Chenguang Zhao, Jeff Crosby, Tinghong Lv, Dong Bai, Brett P Monia, Shuling Guo
BACKGROUND: The epithelial sodium channel ENaC consists of three subunits encoded by Scnn1a, Scnn1b, and Scnn1g and increased sodium absorption through this channel is hypothesized to lead to mucus dehydration and accumulation in cystic fibrosis (CF) patients. METHODS: We identified potent and specific antisense oligonucleotides (ASOs) targeting mRNAs encoding the ENaC subunits and evaluated these ASOs in mouse models of CF-like lung disease. RESULTS: ASOs designed to target mRNAs encoding each ENaC subunit or a control ASO were administered directly into the lungs of mice...
August 10, 2018: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/30100108/no-gender-differences-in-growth-patterns-in-a-cohort-of-children-with-cystic-fibrosis-born-between-1986-and-1995
#3
Gianfranco Alicandro, Arianna Bisogno, Matteo Rota, Rita Padoan, Carla Colombo
BACKGROUND & AIMS: A higher mortality rate at young ages has been reported in cystic fibrosis (CF) girls compared to boys. The reasons of this gap remain unclear but may be related to a different evolution of the disease, in terms of growth and lung function throughout childhood and adolescence. This study aimed at investigating gender differences in growth patterns in a cohort of children with CF through a longitudinal study, and as secondary objectives, to evaluate gender differences in forced expiratory volume in one second (FEV1 ) trend and transplant-free survival...
July 31, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/30095492/emerging-gram-negative-bacteria-pathogenic-or-innocent-bystanders
#4
Heather Green, Andrew M Jones
PURPOSE OF REVIEW: The current review examines the current literature around 'emerging' Gram-negative bacteria other than Pseudomonas aeruginosa in cystic fibrosis (CF), paying particular focus on the recent literature for those that are more frequently encountered: Pandoraea, Achromobacter, Ralstonia and Stenotrophomonas species. RECENT FINDINGS: The recent literature is evolving our understanding of the clinical consequences of infection with an 'emerging' Gram-negative bacteria in CF...
August 7, 2018: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/30095491/the-lung-clearance-index-as-a-monitoring-tool-in-cystic-fibrosis-ready-for-the-clinic
#5
Lucy Perrem, Jonathan H Rayment, Felix Ratjen
PURPOSE OF REVIEW: In cystic fibrosis, (CF) there is an urgent need for objective tests that can capture and track preclinical lung disease. The lung clearance index (LCI), the primary outcome measure of the multiple breath washout test, is an established endpoint in clinical trials but the clinical utility of the test remains poorly defined. The purpose of this review is to examine the key studies over the past years that have advanced our understanding of the role of the LCI in clinical practice...
August 7, 2018: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/30093906/construction-of-a-protective-vaccine-against-lipopolysaccharide-heterologous-pseudomonas-aeruginosa-strains-based-on-expression-profiling-of-outer-membrane-proteins-during-infection
#6
Chang Liu, Xiaolei Pan, Bin Xia, Fei Chen, Yongxin Jin, Fang Bai, Gregory Priebe, Zhihui Cheng, Shouguang Jin, Weihui Wu
Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen, which causes infectious disease in patients with cystic fibrosis and compromised immunity. P. aeruginosa is difficult to eradicate because of its intrinsic resistance to most traditional antibiotics as well as acquired resistance mechanisms after decades of antibiotic usage. A full understanding of the P. aeruginosa pathogenesis mechanisms is necessary for the development of novel prevention and treatment strategies. To identify novel vaccine candidates, here we comprehensively examined the expression levels of all the known outer membrane proteins in two P...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30093360/sleep-disturbances-and-their-impact-in-pediatric-cystic-fibrosis
#7
REVIEW
Aarti Shakkottai, Louise M O'Brien, Samya Z Nasr, Ronald D Chervin
Cystic fibrosis is a chronic, life-shortening illness that affects multiple systems and results in frequent respiratory infections, chronic cough, fat malabsorption and malnutrition. Poor sleep is often reported by patients with cystic fibrosis. Although objective data to explain these complaints have been limited, they do show poor sleep efficiency and frequent arousals. Abnormalities in gas exchange are also observed during sleep in patients with cystic fibrosis. The potential impact of these abnormalities in sleep on health and quality of life remains largely unstudied...
July 6, 2018: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/30093322/-real-world-effectiveness-of-ivacaftor-in-children-with-cystic-fibrosis-and-the-g551d-mutation
#8
David Gomez-Pastrana, Chinedu Nwokoro, Mike McLean, Sarah Brown, Nanna Christiansen, Caroline S Pao
INTRODUCTION: Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has been shown to improve the nutritional status and lung function of cystic fibrosis patients with the G551D mutation in clinical trials. The objective of this study was to describe the real-world progress of children receiving ivacaftor. METHODS: We describe the real-world progress of four children with cystic fibrosis and the F508del/G551D genotype comparing data during ivacaftor treatment with baseline and with the year before commencing treatment...
August 6, 2018: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
https://www.readbyqxmd.com/read/30091146/vitamin-a-and-beta-%C3%AE-carotene-supplementation-for-cystic-fibrosis
#9
REVIEW
Jorrit Jv de Vries, Anne B Chang, Catherine M Bonifant, Elizabeth Shevill, Julie M Marchant
BACKGROUND: People with cystic fibrosis (CF) and pancreatic insufficiency are at risk of a deficiency in fat-soluble vitamins, including vitamin A. Vitamin A deficiency predominantly causes eye and skin problems, while excessive levels of vitamin A can harm the respiratory and skeletal systems in children and interfere with the metabolism of other fat-soluble vitamins. Most CF centres administer vitamin A as supplements to reduce the frequency of vitamin A deficiency in people with CF and to improve clinical outcomes such as growth, although the recommended dose varies between different guidelines...
August 9, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/30089726/ivacaftor-induced-sweat-chloride-reductions-correlate-with-increases-in-airway-surface-liquid-ph-in-cystic-fibrosis
#10
Mahmoud H Abou Alaiwa, Jan L Launspach, Brenda Grogan, Suzanne Carter, Joseph Zabner, David A Stoltz, Pradeep K Singh, Edward F McKone, Michael J Welsh
BACKGROUND: Disruption of cystic fibrosis transmembrane conductance regulator (CFTR) anion channel function causes cystic fibrosis (CF), and lung disease produces most of the mortality. Loss of CFTR-mediated HCO3- secretion reduces the pH of airway surface liquid (ASL) in vitro and in neonatal humans and pigs in vivo. However, we previously found that, in older children and adults, ASL pH does not differ between CF and non-CF. Here, we tested whether the pH of CF ASL increases with time after birth...
August 9, 2018: JCI Insight
https://www.readbyqxmd.com/read/30088315/from-general-to-specific-can-primary-metabolism-in-pseudomonas-be-exploited-for-narrow-spectrum-antibiotics
#11
Justin A Shapiro, Anna Kaplan, William M Wuest
The spread of antimicrobial resistance is a major threat to human health and patients requiring prolonged antibiotic exposure are in desperate need of new therapeutic strategies. It has been hypothesized that tailoring our antibiotics to inhibit molecular targets specific to pathogens may stem the spread of resistance. A prime candidate for such a strategy is Pseudomonas aeruginosa, which can be found in the lungs of nearly all adult cystic fibrosis patients and, due to chronic exposure to antibiotics, has a high rate of multi-drug resistant strains...
August 7, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/30087066/hyperpolarized-gas-magnetic-resonance-imaging-of-pediatric-cystic-fibrosis-lung-disease
#12
Giles Santyr, Nikhil Kanhere, Felipe Morgado, Jonathan H Rayment, Felix Ratjen, Marcus J Couch
Conventional pulmonary function tests appear normal in early cystic fibrosis (CF) lung disease. Therefore, new diagnostic approaches are required that can detect CF lung disease in children and monitor treatment response. Hyperpolarized (HP) gas (129 Xe and 3 He) magnetic resonance imaging (MRI) is a powerful, emergent tool for mapping regional lung function and may be well suited for studying pediatric CF. HP gas MRI is well tolerated, reproducible, and it can be performed longitudinally without the need for ionizing radiation...
August 4, 2018: Academic Radiology
https://www.readbyqxmd.com/read/30086099/effect-of-donor-age-on-outcome-of-lung-transplantation-stratified-by-recipient-diagnosis-a-nordic-multicenter-study
#13
H Auråen, M T Durheim, G Dellgren, P Hämmäinen, H Larsson, O Geiran, H H Lawaetz Schultz, I Leuckfeld, M Iversen, A E Fiane, A M Holm
BACKGROUND: Organs from older donors are increasingly used in lung transplantation, and studies have demonstrated that this could be safe in selected recipients. However, which recipient groups that have the largest benefit of older organs are unclear. This multicenter study reviews all bilateral lung transplantations (BLTx) from donors ≥55 years stratified by recipient diagnosis, and compares outcomes with transplantations from younger donors. METHODS: All BLTx recipients (excluding ReTx) at 5 Scandiatransplant centers between 2000 and 2013 were included (n=913)...
August 6, 2018: Transplantation
https://www.readbyqxmd.com/read/30084977/lung-donation-after-circulatory-determined-death-a-single-centre-experience
#14
Cristina Barbero, Simon Messer, Ayyaz Ali, David P Jenkins, John Dunning, Steven Tsui, Jasvir Parmar
OBJECTIVES: Donor organ utilization and shortage remain the major limitations to the opportunity of a lung transplantation (LTx). Donation after circulatory determined death (DCD) has been adopted as a source of additional organs worldwide. However, concerns about organ quality and ischaemia-reperfusion injury have limited its application. The aim of this study was to retrospectively analyse a single-centre experience in the DCD LTx and compare early and mid-term outcomes with those from a standard donation after brain death (DBD)...
August 1, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/30081420/-differential-diagnosis-of-cystic-lung-diseases
#15
Omar M Albtoush, Asma'a Al-Mnayyis, Kloth Christopher, Spengler Werner, Hetzel Jürgen, Marius Horger
No abstract text is available yet for this article.
August 6, 2018: RöFo: Fortschritte Auf Dem Gebiete der Röntgenstrahlen und der Nuklearmedizin
https://www.readbyqxmd.com/read/30080520/smoking-related-diffuse-cystic-lung-disease
#16
Nishant Gupta, Thomas V Colby, Cristopher A Meyer, Francis X McCormack, Kathryn A Wikenheiser-Brokamp
Exposure to cigarette smoke can lead to a variety of parenchymal lung diseases, including diffuse cystic lung diseases (DCLDs). Lymphangioleiomyomatosis (LAM) is the prototypical DCLD and has a characteristic appearance on high-resolution CT (HRCT). We present a series of four patients with DCLD on HRCT who were referred to our institution with a presumed diagnosis of LAM and who were found instead to have smoking-related injury of the small airways on histopathological analysis. We submit that cigarette smoke-induced small airway injury can present as DCLD on HRCT in a pattern that can mimic LAM...
August 2018: Chest
https://www.readbyqxmd.com/read/30079241/case-report-first-report-of-elizabethkingia-miricola-infection-in-a-patient-with-cystic-fibrosis
#17
Freddy Frost, Dilip Nazareth
Elizabethkingia miricola is a rare non-fermenting Gram-negative rod that has previously been reported to be associated with blood stream and pulmonary abscess infections, but never before in cystic fibrosis (CF). Here we present the first reported case of Elizabethkingia miricola infection in a patient with CF and discuss the management options. We describe a patient with CF in whom we observed clinical and spirometric evidence of pulmonary exacerbation with the associated growth of E. miricola in sputum culture...
2018: F1000Research
https://www.readbyqxmd.com/read/30076968/lung-mesenchymal-stem-cells-derived-extracellular-vesicles-attenuate-the-inflammatory-profile-of-cystic-fibrosis-epithelial-cells
#18
Aida Zulueta, Michela Colombo, Valeria Peli, Monica Falleni, Delfina Tosi, Mario Ricciardi, Alessandro Baisi, Gaetano Bulfamante, Raffaella Chiaramonte, Anna Caretti
BACKGROUND: Mesenchymal stromal/stem cells (MSCs) are multi-potent non-hematopoietic stem cells, residing in most tissues including the lung. MSCs have been used in therapy of chronic inflammatory lung diseases such as Cystic Fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD) but the main beneficial effects reside in the anti-inflammatory potential of the released extracellular vesicles (EVs). Recent reports demonstrate that EVs are effective in animal model of asthma, E...
August 1, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/30075493/significance-of-mri-in-the-diagnosis-and-differentiation-of-clear-cell-sarcoma-of-tendon-and-aponeurosis-ccsta-a-case-report
#19
Kalyan Sharma, Sudhir Kumar Yadav, Bimbadhar Valluru, Ling Liu
RATIONALE: Clear cell sarcoma of tendon and aponeurosis (CCSTA) or soft parts is a rare malignant melanin producing tumor entity that is derived from the neural crest cells originating from soft tissues displaying melanocytic differentiation. Diagnosis of CCSTA is difficult as it is dependent on age, size, location, necrosis, calcifications, cystic degeneration, and local to distant metastatic deposits. These tumors have very poor prognosis with a survival rate of 5-10 years because of local recurrence, early to late metastasis to lymph nodes, lungs, bones, and liver...
August 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/30075071/virtual-screening-against-carbohydrate-binding-proteins-evaluation-and-application-to-bacterial-burkholderia-ambifaria-lectin
#20
Tamir Dingjan, Émilie Gillon, Anne Imberty, Serge Perez, Alexander Titz, Paul A Ramsland, Elizabeth Yuriev
Bacterial adhesion to human epithelia via lectins constitutes a therapeutic opportunity to prevent infection. Specifically, BambL (the lectin from Burkholderia ambifaria) is implicated in cystic fibrosis, where lectin-mediated bacterial adhesion to fucosylated lung epithelia is suspected to play an important role. We have employed structure-based virtual screening to identify inhibitors of BambL-saccharide interaction with potential therapeutic value. In order to enable such discovery, a virtual screening protocol has been iteratively developed via 194 retrospective screening protocols against four bacterial lectins (BambL, BC2L-A, FimH and LecA) with known ligands...
August 3, 2018: Journal of Chemical Information and Modeling
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