The pharmacokinetics of antibiotics in cystic fibrosis.

Expert Opin Drug Metab Toxicol. 2020 Nov 19;:

Authors: Akkerman-Nijland AM, Akkerman OW, Grasmeijer F, Hagedoorn P, Frijlink HW, Rottier BL, Koppelman GH, Touw DJ

Abstract
INTRODUCTION: Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration and increasing presence of antimicrobial resistance.
AREAS COVERED: The purpose of this work is to critically review original data as well as previous reviews and guidelines on pharmacokinetics of systemic and inhaled antibiotics in CF, with the aim to propose strategies for optimization of antibacterial therapy in both children and adults with CF.Expert opinion: For systemic antibiotics, absorption is comparable in CF patients and non-CF controls. The volume of distribution (Vd) of most antibiotics is similar between people with CF with normal body composition and healthy individuals. However, there are a few exceptions, like cefotiam and tobramycin. Many antibiotic class dependent changes in drug metabolism and excretion are reported, with an increased total body clearance for ß-lactam antibiotics, aminoglycosides, fluoroquinolones and trimethoprim. We therefore recommend following class specific guidelines for CF, mostly resulting in higher dosages per kg bodyweight in CF compared to non-CF controls.Higher local antibiotic concentrations in the airways can be obtained by inhalation therapy, with which eradication of bacteria may be achieved while minimizing systemic exposure and risk of toxicity.

PMID: 33213220 [PubMed - as supplied by publisher]

The Impact of Hospital Ward Ventilation on Airborne Pathogen Exposure.

Am J Respir Crit Care Med. 2020 Nov 19;:

Authors: Mingotti N, Grogono D, Dello Ioio G, Curran M, Barbour K, Taveira M, Rudman J, Haworth CS, Floto RA, Woods AW

PMID: 33211973 [PubMed - as supplied by publisher]

Cystic fibrosis year in review 2019: Section 3 multisystem-based care and research.

Pediatr Pulmonol. 2020 Nov 19;:

Authors: Savant AP, McColley SA

Abstract
During the year 2019, numerous research studies and other reports were published that are interesting and instructive to professionals who care for people with cystic fibrosis (CF) and their families.  This report is the third of 3 CF year in review articles and focuses on the multisystem manifestations of CF care. Previous articles have addressed cystic fibrosis transmembrane regulator modulators and reports on CF pulmonary disease and airway infections. It is an exciting time to be involved in care and research that aims to improve care for people with CF and their families.

PMID: 33210843 [PubMed - as supplied by publisher]

Repeat Dosing of AAV2.5T to Ferret Lungs Elicits an Antibody Response That Diminishes Transduction in an Age-Dependent Manner.

Mol Ther Methods Clin Dev. 2020 Dec 11;19:186-200

Authors: Tang Y, Yan Z, Lin S, Huntemann ED, Feng Z, Park SY, Sun X, Yuen E, Engelhardt JF

Abstract
Readministration of recombinant adeno-associated virus (rAAV) may be necessary to treat cystic fibrosis (CF) lung disease using gene therapy. However, little is known about rAAV-mediated immune responses in the lung. Here, we demonstrate the suitability of the ferret for testing AAV2.5T-mediated CFTR delivery to the lung and characterization of neutralizing-antibody (NAb) responses. AAV2.5T-SP183-hCFTRΔR efficiently transduced both human and ferret airway epithelial cultures and complemented CFTR Cl- currents in CF airway cultures. Delivery of AAV2.5T-hCFTRΔR to neonatal and juvenile ferret lungs produced hCFTR mRNA at 200%-300% greater levels than endogenous fCFTR. Single-dose (AAV2.5T-SP183-gLuc) or repeat dosing (AAV2.5T-SP183-fCFTRΔR followed by AAV2.5T-SP183-gLuc) of AAV2.5T was performed in neonatal and juvenile ferrets. Repeat dosing significantly reduced transgene expression (11-fold) and increased bronchoalveolar lavage fluid (BALF) NAbs only in juvenile, but not neonatal, ferrets, despite near-equivalent plasma NAb responses in both age groups. Notably, both age groups demonstrated a reduction in BALF anti-capsid binding immunoglobulin (Ig) G, IgM, and IgA antibodies after repeat dosing. Unique to juvenile ferrets was a suppression of plasma anti-capsid-binding IgM after the second vector administration. Thus, age-dependent immune system maturation and isotype switching may affect the development of high-affinity lung NAbs after repeat dosing of AAV2.5T and may provide a path to blunt AAV-neutralizing responses in the lung.

PMID: 33209961 [PubMed]

Coinfection with Pseudomonas aeruginosa and Aspergillus fumigatus in cystic fibrosis.

Eur Respir Rev. 2020 Dec 31;29(158):

Authors: Keown K, Reid A, Moore JE, Taggart CC, Downey DG

Abstract
OBJECTIVES: Cystic fibrosis (CF) lung disease is characterised by mucus stasis, chronic infection and inflammation, causing progressive structural lung disease and eventual respiratory failure. CF airways are inhabited by an ecologically diverse polymicrobial environment with vast potential for interspecies interactions, which may be a contributing factor to disease progression. Pseudomonas aeruginosa and Aspergillus fumigatus are the most common bacterial and fungal species present in CF airways respectively and coinfection results in a worse disease phenotype.
METHODS: In this review we examine existing expert knowledge of chronic co-infection with P. aeruginosa and A. fumigatus in CF patients. We summarise the mechanisms of interaction and evaluate the clinical and inflammatory impacts of this co-infection.
RESULTS: P. aeruginosa inhibits A. fumigatus through multiple mechanisms: phenazine secretion, iron competition, quorum sensing and through diffusible small molecules. A. fumigatus reciprocates inhibition through gliotoxin release and phenotypic adaptations enabling evasion of P. aeruginosa inhibition. Volatile organic compounds secreted by P. aeruginosa stimulate A. fumigatus growth, while A. fumigatus stimulates P. aeruginosa production of cytotoxic elastase.
CONCLUSION: A complex bi-directional relationship exists between P. aeruginosa and A. fumigatus, exhibiting both mutually antagonistic and cooperative facets. Cross-sectional data indicate a worsened disease state in coinfected patients; however, robust longitudinal studies are required to derive causality and to determine whether interspecies interaction contributes to disease progression.

PMID: 33208485 [PubMed - in process]

Engineered mutant α-ENaC subunit mRNA delivered by lipid nanoparticles reduces amiloride currents in cystic fibrosis-based cell and mice models.

Sci Adv. 2020 Nov;6(47):

Authors: Mukherjee A, MacDonald KD, Kim J, Henderson MI, Eygeris Y, Sahay G

Abstract
Cystic fibrosis (CF) results from mutations in the chloride-conducting CF transmembrane conductance regulator (CFTR) gene. Airway dehydration and impaired mucociliary clearance in CF is proposed to result in tonic epithelial sodium channel (ENaC) activity, which drives amiloride-sensitive electrogenic sodium absorption. Decreasing sodium absorption by inhibiting ENaC can reverse airway surface liquid dehydration. Here, we inhibit endogenous heterotrimeric ENaC channels by introducing inactivating mutant ENaC α mRNA (αmutENaC). Lipid nanoparticles carrying αmutENaC were transfected in CF-based airway cells in vitro and in vivo. We observed a significant decrease in macroscopic as well as amiloride-sensitive ENaC currents and an increase in airway surface liquid height in CF airway cells. Similarly, intranasal transfection of αmutENaC mRNA decreased amiloride-sensitive nasal potential difference in CFTRKO mice. These data suggest that mRNA-based ENaC inhibition is a powerful strategy for reducing mucus dehydration and has therapeutic potential for treating CF in all patients, independent of genotype.

PMID: 33208364 [PubMed - in process]

Defective immunometabolism pathways in cystic fibrosis macrophages.

J Cyst Fibros. 2020 Nov 15;:

Authors: Hamilton K, Krause K, Badr A, Daily K, Estfanous S, Eltobgy M, Khweek AA, Anne MNK, Carafice C, Baetzhold D, Tonniges JR, Zhang X, Gavrilin MA, Parinandi NL, Amer AO

Abstract
BACKGROUND: Mitochondria play a key role in immune defense pathways, particularly for macrophages. We and others have previously demonstrated that cystic fibrosis (CF) macrophages exhibit weak autophagy activity and exacerbated inflammatory responses. Previous studies have revealed that mitochondria are defective in CF epithelial cells, but to date, the connection between defective mitochondrial function and CF macrophage immune dysregulation has not been fully elucidated. Here, we present a characterization of mitochondrial dysfunction in CF macrophages.
METHODS: Mitochondrial function in wild-type (WT) and CF F508del/F508del murine macrophages was measured using the Seahorse Extracellular Flux analyzer. Mitochondrial morphology was investigated using transmission electron and confocal microscopy. Mitochondrial membrane potential (MMP) as well as mitochondrial reactive oxygen species (mROS) were measured using TMRM and MitoSOX Red fluorescent dyes, respectively. All assays were performed at baseline and following infection by Burkholderia cenocepacia, a multi-drug resistant bacterium that causes detrimental infections in CF patients.
RESULTS: We have identified impaired oxygen consumption in CF macrophages without and with B. cenocepacia infection. We also observed increased mitochondrial fragmentation in CF macrophages following infection. Lastly, we observed increased MMP and impaired mROS production in CF macrophages following infection with B. cenocepacia.
CONCLUSIONS: The mitochondrial defects identified are key components of the macrophage response to infection. Their presence suggests that mitochondrial dysfunction contributes to impaired bacterial killing in CF macrophages. Our current study will enhance our understanding of the pathobiology of CF and lead to the identification of novel mitochondrial therapeutic targets for CF.

PMID: 33208300 [PubMed - as supplied by publisher]

Antibacterial Effects of Bicarbonate in Media Modified to Mimic Cystic Fibrosis Sputum.

Int J Mol Sci. 2020 Nov 16;21(22):

Authors: Jaikumpun P, Ruksakiet K, Stercz B, Pállinger É, Steward M, Lohinai Z, Dobay O, Zsembery Á

Abstract
Cystic fibrosis (CF) is a hereditary disease caused by mutations in the gene encoding an epithelial anion channel. In CF, Cl- and HCO3- hyposecretion, together with mucin hypersecretion, leads to airway dehydration and production of viscous mucus. This habitat is ideal for colonization by pathogenic bacteria. We have recently demonstrated that HCO3- inhibits the growth and biofilm formation of Pseudomonas aeruginosa and Staphylococcus aureus when tested in laboratory culture media. Using the same bacteria our aim was to investigate the effects of HCO3- in artificial sputum medium (ASM), whose composition resembles CF mucus. Control ASM containing no NaHCO3 was incubated in ambient air (pH 7.4 or 8.0). ASM containing NaHCO3 (25 and 100 mM) was incubated in 5% CO2 (pH 7.4 and 8.0, respectively). Viable P. aeruginosa and S. aureus cells were counted by colony-forming unit assay and flow cytometry after 6 h and 17 h of incubation. Biofilm formation was assessed after 48 h. The data show that HCO3- significantly decreased viable cell counts and biofilm formation in a concentration-dependent manner. These effects were due neither to extracellular alkalinization nor to altered osmolarity. These results show that HCO3- exerts direct antibacterial and antibiofilm effects on prevalent CF bacteria.

PMID: 33207565 [PubMed - in process]

Evaluation of the health-related quality of life in Turkish cystic fibrosis patients.

Pediatr Int. 2020 Nov 18;:

Authors: Alishbayli G, Kilinc AA, Cokugras H

Abstract
BACKGROUND: Prolongation of life expectancy in cystic fibrosis (CF) to the 4th decade makes the health-related quality of life (HRQOL) an important issue in this population. This study aims to evaluate the effects of clinical and socio-demographic characteristics of patients on different aspects of HRQOL in pediatric CF population. We also intend to assess some measures of reliability and validity of the Turkish CFQ-R forms.
METHODS: 54 CF patients and 46 parents/caregivers filled the appropriate CF Questionnaire-Revised (CFQ-R) forms. Disease severity was evaluated via modified Shwachman Kulczycki (SK) score, and additional clinical information was obtained from patient records.
RESULTS: 43% (n=23) of patients were female, the mean age of patients being 13.3 ± 3.96 years. Self and proxy reported points showed a strong correlation (Spearman's rho>0.6) on more observable domains of HRQOL (e.g. physical functioning). No significant difference was found on any HRQOL domain between sexes. When compared between age groups, treatment burden appeared to worsen with age, while social functioning improved. All 3 forms of the CFQ-R Turkish version showed acceptable internal consistency reliability and convergence with disease severity measures.
CONCLUSIONS: CFQ-R showed a fair correlation with the SK score and FEV1% value, which makes its longitudinal use possible in clinical practice. It is important to make self-reported, as well as parent/caregiver reported HRQOL evaluation, especially in young children. More studies are needed to assess the psychometric properties of Turkish CFQ-R forms.

PMID: 33207026 [PubMed - as supplied by publisher]

Oxidative stress-induced inflammation in susceptible airways by anthropogenic aerosol.

PLoS One. 2020;15(11):e0233425

Authors: Leni Z, Cassagnes LE, Daellenbach KR, El Haddad I, Vlachou A, Uzu G, Prévôt ASH, Jaffrezo JL, Baumlin N, Salathe M, Baltensperger U, Dommen J, Geiser M

Abstract
Ambient air pollution is one of the leading five health risks worldwide. One of the most harmful air pollutants is particulate matter (PM), which has different physical characteristics (particle size and number, surface area and morphology) and a highly complex and variable chemical composition. Our goal was first to comparatively assess the effects of exposure to PM regarding cytotoxicity, release of pro-inflammatory mediators and gene expression in human bronchial epithelia (HBE) reflecting normal and compromised health status. Second, we aimed at evaluating the impact of various PM components from anthropogenic and biogenic sources on the cellular responses. Air-liquid interface (ALI) cultures of fully differentiated HBE derived from normal and cystic fibrosis (CF) donor lungs were exposed at the apical cell surface to water-soluble PM filter extracts for 4 h. The particle dose deposited on cells was 0.9-2.5 and 8.8-25.4 μg per cm2 of cell culture area for low and high PM doses, respectively. Both normal and CF HBE show a clear dose-response relationship with increasing cytotoxicity at higher PM concentrations. The concurrently enhanced release of pro-inflammatory mediators at higher PM exposure levels links cytotoxicity to inflammatory processes. Further, the PM exposure deregulates genes involved in oxidative stress and inflammatory pathways leading to an imbalance of the antioxidant system. Moreover, we identify compromised defense against PM in CF epithelia promoting exacerbation and aggravation of disease. We also demonstrate that the adverse health outcome induced by PM exposure in normal and particularly in susceptible bronchial epithelia is magnified by anthropogenic PM components. Thus, including health-relevant PM components in regulatory guidelines will result in substantial human health benefits and improve protection of the vulnerable population.

PMID: 33206642 [PubMed - in process]

Host-Pathogen Interactions after Lung Transplant: Are Cystic Fibrosis Patients Unique?

Cell Rep Med. 2020 Jul 21;1(4):100061

Authors: Morrell ED, Lease ED

Abstract
The impact of Pseudomonas aeruginosa airway colonization on lung allografts is not entirely clear. In this issue of Cell Reports Medicine, Dugger et al.1 identify distinct clinical outcomes and lung allograft biology in recipients with and without cystic fibrosis.

PMID: 33205066 [PubMed]

Frequency of Tiotropium Bromide Use and Clinical Features of Patients with Severe Asthma in a Real-Life Setting: Data from the Severe Asthma Network in Italy (SANI) Registry.

J Asthma Allergy. 2020;13:599-604

Authors: Puggioni F, Brussino L, Canonica GW, Blasi F, Paggiaro P, Caminati M, Latorre M, Heffler E, Senna G, Severe Asthma Network in Italy (SANI) group

Abstract
Purpose: Patients with uncontrolled asthma despite high doses of inhaled corticosteroid therapy plus another controller are defined as severe asthmatics. Tiotropium bromide respimat (TBR) is the only long-acting muscarinic antagonists (LAMA) approved for severe asthma. The aim of this study was to explore the frequency of severe asthmatics treated with TBR and characterize their clinical features in a real-life, registry-based setting.
Materials and Methods: Baseline data from the Severe Asthma Network in Italy (SANI) registry have been analyzed to determine the use of TBR and other LAMA, and to compare clinical, functional and inflammatory features associated with the use of LAMA.
Results: Among a total of 698 enrolled patients, 35.9% were treated with LAMA (23.3% TBR, 4.5% tiotropium bromide handihaler, 4.5% aclidinium, 3.4% glycopyrronium bromide 0.3% umeclidinium bromide). Age of asthma onset was higher in patients taking LAMA, whom, compared to others were more frequently former smokers. They also had a higher annual exacerbation rate, experienced worst asthma control, worst disease-related quality of life and poorer lung function. Bronchiectasis was more frequently found in LAMA users (25.9% vs 13.1%).
Conclusion: TBR is still underused in severe asthma in a real-life setting, while a relevant proportion of patients are treated with other LAMA that are not approved for severe asthma treatment. Patients taking LAMA have features characteristic of even more severe asthma.

PMID: 33204116 [PubMed]

Crystal Structure of Isoform CBd of the Basic Phospholipase A2 Subunit of Crotoxin: Description of the Structural Framework of CB for Interaction with Protein Targets.

Molecules. 2020 Nov 13;25(22):

Authors: Nemecz D, Ostrowski M, Ravatin M, Saul F, Faure G

Abstract
Crotoxin, from the venom of the South American rattlesnake Crotalus durissus terrificus, is a potent heterodimeric presynaptic β-neurotoxin that exists in individual snake venom as a mixture of isoforms of a basic phospholipase A2 (PLA2) subunit (CBa2, CBb, CBc, and CBd) and acidic subunit (CA1-4). Specific natural mutations in CB isoforms are implicated in functional differences between crotoxin isoforms. The three-dimensional structure of two individual CB isoforms (CBa2, CBc), and one isoform in a crotoxin (CA2CBb) complex, have been previously reported. This study concerns CBd, which by interaction with various protein targets exhibits many physiological or pharmacological functions. It binds with high affinity to presynaptic receptors showing neurotoxicity, but also interacts with human coagulation factor Xa (hFXa), exhibiting anticoagulant effect, and acts as a positive allosteric modulator and corrector of mutated chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR), implicated in cystic fibrosis. Thus, CBd represents a novel family of agents that have potential in identifying new drug leads related to anticoagulant and anti-cystic fibrosis function. We determined here the X-ray structure of CBd and compare it with the three other natural isoforms of CB. The structural role of specific amino acid variations between CB isoforms are analyzed and the structural framework of CB for interaction with protein targets is described.

PMID: 33202772 [PubMed - in process]

NMR Profiling of Exhaled Breath Condensate Defines Different Metabolic Phenotypes of Non-Cystic Fibrosis Bronchiectasis.

Int J Mol Sci. 2020 Nov 14;21(22):

Authors: Paris D, Palomba L, Mirra V, Borrelli M, Corcione A, Santamaria F, Maniscalco M, Motta A

Abstract
Nuclear-magnetic-resonance (NMR) profiling of exhaled breath condensate (EBC) provides insights into the pathophysiology of bronchiectasis by identifying specific biomarkers. We evaluated whether NMR-based metabolomics discriminates the EBC-derived metabolic phenotypes ("metabotypes") of 41 patients with non-cystic fibrosis (nCF) bronchiectasis of various etiology [24 subjects with Primary Ciliary Dyskinesia (PCD); 17 patients with bronchiectasis not associated with PCD (nCF/nPCD)], who were compared to 17 healthy subjects (HS). NMR was used for EBC profiling, and Orthogonal Projections to Latent Structures with partial least-squares discriminant analysis (OPLS-DA) was used as a classifier. The results were validated by using the EBC from 17 PCD patients not included in the primary analysis. Different statistical models were built, which compared nCF/nPCD and HS, PCD and HS, all classes (nCF/nPCD-PCD-HS), and, finally, PCD and nCF/nPCD. In the PCD-nCF/nPCD model, four statistically significant metabolites were able to discriminate between the two groups, with only a minor reduction of the quality parameters. In particular, for nCF/nPCD, acetone/acetoin and methanol increased by 21% and 18%, respectively. In PCD patients, ethanol and lactate increased by 25% and 28%, respectively. They are all related to lung inflammation as methanol is found in the exhaled breath of lung cancer patients, acetone/acetoin produce toxic ROS that damage lung tissue in CF, and lactate is observed in acute inflammation. Interestingly, a high concentration of ethanol hampers cilia beating and can be associated with the genetic defect of PCD. Model validation with 17 PCD samples not included in the primary analysis correctly predicted all samples. Our results indicate that NMR of EBC discriminates nCF/nPCD and PCD bronchiectasis patients from HS, and patients with nCF/nPCD from those with PCD. The metabolites responsible for between-group separation identified specific metabotypes, which characterize bronchiectasis of a different etiology.

PMID: 33202684 [PubMed - in process]

Estimation of Proinflammatory Factors in the Saliva of Adult Patients with Cystic Fibrosis and Dental Caries.

Medicina (Kaunas). 2020 Nov 14;56(11):

Authors: Hildebrandt T, Zawilska A, Trzcionka A, Tanasiewicz M, Mazurek H, Świętochowska E

Abstract
Introduction: The available literature lacks data regarding the levels of resistin, lysozyme, lactoferrin, α-amylase activity, pH, and saliva buffer capacity, as well as oral health and hygiene in the group of adult patients with cystic fibrosis (CF). The aim of the research was to assess the selected saliva parameters in patients diagnosed with cystic fibrosis. Materials and methods: Examined group was composed of 40 patients diagnosed with CF, while the control group of 40 healthy individuals. Both groups underwent the same scheme of the assessment (DMT index, salivary pH, buffer capacity, analysis of total sialic acid, total protein estimation, lysozyme levels estimation, lactofferin levels measurement, α-amylase activity, estimation of the levels of resistin and TNF-α). Results: In the examined group, there were higher values of decayed teeth as well as values of sialic acid, total protein, lactoferrin, α-amylase, and TNF-α. However, mean lysozyme, and resistin levels, as well as pH and buffer capacity of the saliva, were lower. Conclusions: New diagnostic methods, including the evaluation of selected salivary biochemical parameters, may indicate the existence of factors predisposing to severe tooth decay in the study group. Appropriate preventive treatment to combat dental caries in adult patients with CF will significantly improve their comfort and life expectancy.

PMID: 33202617 [PubMed - in process]

Current Treatment Options for Cystic Fibrosis-Related Liver Disease.

Int J Mol Sci. 2020 Nov 14;21(22):

Authors: Staufer K

Abstract
Cystic Fibrosis-related liver disease (CFLD) has become a leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF), and affects children and adults. The understanding of the pathogenesis of CFLD is key in order to develop efficacious treatments. However, it remains complex, and has not been clarified to the last. The search for a drug might be additionally complicated due to the diverse clinical picture and lack of a unified definition of CFLD. Although ursodeoxycholic acid has been used for decades, its efficacy in CFLD is controversial, and the potential of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators and targeted gene therapy in CFLD needs to be defined in the near future. This review focuses on the current knowledge on treatment strategies for CFLD based on pathomechanistic viewpoints.

PMID: 33202578 [PubMed - in process]

Gastroesophageal Reflux Disease and Need for Antireflux Surgery in Children with Cystic Fibrosis: A Systematic Review on Incidence, Surgical Complications, and Postoperative Outcomes.

Eur J Pediatr Surg. 2020 Nov 17;:

Authors: Ng J, Friedmacher F, Pao C, Charlesworth P

Abstract
INTRODUCTION:  Gastroesophageal reflux disease (GERD) is associated with accelerated decline in lung health in children with cystic fibrosis (CF). Thus, antireflux surgery (ARS) is offered to a selected CF cohort with refractory GERD, but outcomes remain poorly investigated. This study aimed to determine the incidence of GERD in children with CF and to evaluate complications and outcomes of ARS.
MATERIALS AND METHODS:  A systematic literature-based search was conducted using various online databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The number of GERD cases in pediatric CF cohorts who underwent diagnostic investigation(s) was recorded. Data on postoperative complications and outcomes (including symptoms, lung function, and nutritional status) following ARS were analyzed.
RESULTS:  Ten articles (n = 289 patients) met the defined inclusion criteria (51% male; age range, 0.5 month-36 years). The overall incidence of GERD was 46% (range, 19-81%), derived from seven studies (n = 212 patients). Four publications (n = 82 patients) reported on ARS due to uncontrolled GERD. All ARSs were Nissen fundoplication (majority with gastrostomy placement). Major postoperative complications occurred in 15 (18%) patients, two required redo-ARS. Median follow-up time was 2 years (range, 3 months-6 years); 59% showed symptom improvement, and pulmonary exacerbations and decline in lung function were reduced. Nutritional status mainly improved in milder CF cases. There were no deaths related to ARS.
CONCLUSION:  Approximately half of pediatric CF patients have GERD. Published data for children with CF are limited and heterogeneous in terms of GERD diagnosis and outcomes following ARS. However, ARS has shown to slow the deterioration of lung function in CF.

PMID: 33202431 [PubMed - as supplied by publisher]

Vitamin D Deficiency Is Associated with Increased Nontuberculous Mycobacteria Risk in Cystic Fibrosis.

Ann Am Thorac Soc. 2020 Nov 17;:

Authors: Richter WJ, Sun Y, Psoter KJ, Santos MN, Nguyen JA, Sidhaye A, Lechtzin N, Jennings MT, Cohen KA

PMID: 33202142 [PubMed - as supplied by publisher]

[Evidence-based treatment of cystic fibrosis].

Internist (Berl). 2020 Nov 17;:

Authors: Ringshausen FC, Hellmuth T, Dittrich AM

Abstract
Mucoviscidosis (cystic fibrosis [CF]) is the most common autosomal recessive inherited multisystem disease with fatal outcome. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to a dysfunctional chloride channel and a defective CFTR protein. As a consequence, retention of insufficiently hydrated mucus affects multiple essential organs, mainly the lungs and airways, pancreas, liver, biliary tract and intestines. This leads to inflammation and infection, fibrosis and progressive tissue destruction. Respiratory failure is the major cause of mortality; however, in the no more than 30 years since the molecular characterization of the basic CFTR defect causing CF, tremendous success has been made with respect to the long-term prognosis of people with CF. This improvement in the prognosis was achieved by the cooperative spirit and networking of the very active and international CF research community and by establishing a multidisciplinary clinical CF team that implements the existing evidence in various aspects of standardized care together with the CF patient. This narrative review article presents the evidence in selected aspects of CF treatment, with special consideration of the most recent development of highly effective CFTR modulator treatment. This treatment will soon become available for more than 90% of the global CF patients and transform the pathophysiology as well as the course of disease towards a treatable chronic condition in internal medicine.

PMID: 33201261 [PubMed - as supplied by publisher]

ADIPS 2020 guideline for pre-existing diabetes and pregnancy.

Aust N Z J Obstet Gynaecol. 2020 Nov 16;:

Authors: Rudland VL, Price SAL, Hughes R, Barrett HL, Lagstrom J, Porter C, Britten FL, Glastras S, Fulcher I, Wein P, Simmons D, McIntyre HD, Callaway L

Abstract
This is the full version of the Australasian Diabetes in Pregnancy Society (ADIPS) 2020 guideline for pre-existing diabetes and pregnancy. The guideline encompasses the management of women with pre-existing type 1 diabetes and type 2 diabetes in relation to pregnancy, including preconception, antepartum, intrapartum and postpartum care. The management of women with monogenic diabetes or cystic fibrosis-related diabetes in relation to pregnancy is also discussed.

PMID: 33200400 [PubMed - as supplied by publisher]