ERJ Open Res. 2021 Nov 1;7(4):00353-2021. doi: 10.1183/23120541.00353-2021. eCollection 2021 Oct.

ABSTRACT

BACKGROUND: Diagnosis of primary ciliary dyskinesia (PCD) is challenging since there is no gold standard test. The European Respiratory (ERS) and American Thoracic (ATS) Societies developed evidence-based diagnostic guidelines with considerable differences.

OBJECTIVE: We aimed to compare the algorithms published by the ERS and the ATS with each other and with our own PCD-UNIBE algorithm in a clinical setting. Our algorithm is similar to the ERS algorithm with additional immunofluorescence staining. Agreement (Cohen's κ) and concordance between the three algorithms were assessed in patients with suspicion of PCD referred to our diagnostic centre.

RESULTS: In 46 out of 54 patients (85%) the final diagnosis was concordant between all three algorithms (30 PCD negative, 16 PCD positive). In eight patients (15%) PCD diagnosis differed between the algorithms. Five patients (9%) were diagnosed as PCD only by the ATS, one (2%) only by the ERS and PCD-UNIBE, one (2%) only by the ATS and PCD-UNIBE, and one (2%) only by the PCD-UNIBE algorithm. Agreement was substantial between the ERS and the ATS (κ=0.72, 95% CI 0.53-0.92) and the ATS and the PCD-UNIBE (κ=0.73, 95% CI 0.53-0.92) and almost perfect between the ERS and the PCD-UNIBE algorithms (κ=0.92, 95% CI 0.80-1.00).

CONCLUSION: The different diagnostic algorithms lead to a contradictory diagnosis in a considerable proportion of patients. Thus, an updated, internationally harmonised and standardised PCD diagnostic algorithm is needed to improve diagnostics for these discordant cases.

PMID:34729370 | PMC:PMC8558472 | DOI:10.1183/23120541.00353-2021

Ther Adv Chronic Dis. 2021 Oct 23;12:20406223211047003. doi: 10.1177/20406223211047003. eCollection 2021.

ABSTRACT

Allergic bronchopulmonary aspergillosis is an allergic pulmonary condition caused by hypersensitivity to antigens of Aspergillus sp. found most commonly in patients with underlying asthma or cystic fibrosis. Host factors which alter the innate and adaptive immune responses to this abundant airborne fungus contribute to the development of chronic airway inflammation, bronchiectasis, and fibrosis. Traditionally, treatment has focussed on reducing fungal burden and immune response to fungal antigens. However, a significant proportion of patients continue to suffer recurrent exacerbations with progressive lung damage, and the side effect burden of existing treatments is high. New treatments including novel antifungal agents, monoclonal antibodies against aspects of the adaptive immune response as well as targeted immunotherapies may be better tolerated and achieve improved outcomes but have not yet been studied in large-scale randomised control trials.

PMID:34729149 | PMC:PMC8543630 | DOI:10.1177/20406223211047003

Pediatrics. 2021 Nov 2:e2021053822. doi: 10.1542/peds.2021-053822. Online ahead of print.

NO ABSTRACT

PMID:34728548 | DOI:10.1542/peds.2021-053822

J Cyst Fibros. 2021 Oct 30:S1569-1993(21)02108-1. doi: 10.1016/j.jcf.2021.10.006. Online ahead of print.

ABSTRACT

BACKGROUND: In cystic fibrosis, adequate nutrition contributes to good long-term prognosis. A body mass index (BMI) at or above the 50th percentile for age and sex in all children has been recommended. As researchers have described a depletion of fat-free mass despite normal BMI, longitudinal studies using more sensitive nutritional parameters are warranted. We evaluated anthropometric measurements in an attempt to identify early indicators of deteriorating nutritional status in our paediatric cohort.

METHODS: We analysed datasets from children and adolescents between 2 and 17.9 years with at least two entries for triceps skinfold thickness and upper arm circumference in our patient database between January 1995 and December 2018. Arm muscle area (AMA) was calculated, and all values were expressed as z-scores from CDC growth charts.

RESULTS: A total of 4,862 encounters from 161 paediatric patients (78 girls) were available, representing a median number of 28 visits during a median follow-up of 8.1 years per patient. Linear mixed effects models revealed relatively stable courses for weight, height, BMI and skinfold thickness up to adulthood. AMA was the only parameter which declined slightly (r = -0.036), particularly in boys. Kaplan-Meier-analyses showed that AMA was the earliest parameter to decrease below -1 z-score between 6 and 18 years.

CONCLUSIONS: The present data suggest that compared with weight or BMI, AMA could serve as an earlier indicator of a deteriorating nutritional status. The benefit of assessing skinfold thickness and arm circumference routinely and calculating AMA from these measurements should be evaluated in large, prospective, multi-centre studies.

PMID:34728152 | DOI:10.1016/j.jcf.2021.10.006

Cytokine Growth Factor Rev. 2021 Oct 17:S1359-6101(21)00076-9. doi: 10.1016/j.cytogfr.2021.10.004. Online ahead of print.

ABSTRACT

Coronavirus disease 2019 (COVID-19) has a broad range of clinical manifestations, highlighting the need for specific diagnostic tools to predict disease severity and improve patient prognosis. Recently, calprotectin (S100A8/A9) has been proposed as a potential biomarker for COVID-19, as elevated serum S100A8/A9 levels are associated with critical COVID-19 cases and can distinguish between mild and severe disease states. S100A8/A9 is an alarmin that mediates host proinflammatory responses during infection and it has been postulated that S100A8/A9 modulates the cytokine storm; the hallmark of fatal COVID-19 cases. However, it has yet to be determined if S100A8/A9 is a bona-fide biomarker for COVID-19. S100A8/A9 is widely implicated in a variety of inflammatory conditions, such as cystic fibrosis (CF) and chronic obstructive pulmonary disorder (COPD), as well as pulmonary infectious diseases, including tuberculosis and influenza. Therefore, understanding how S100A8/A9 levels correlate with immune responses during inflammatory diseases is necessary to evaluate its candidacy as a potential COVID-19 biomarker. This review will outline the protective and detrimental roles of S100A8/A9 during infection, summarize the recent findings detailing the contributions of S100A8/A9 to COVID-19 pathogenesis, and highlight its potential as diagnostic biomarker and a therapeutic target for pulmonary infectious diseases, including COVID-19.

PMID:34728150 | DOI:10.1016/j.cytogfr.2021.10.004

Auris Nasus Larynx. 2021 Oct 30:S0385-8146(21)00249-2. doi: 10.1016/j.anl.2021.10.006. Online ahead of print.

ABSTRACT

OBJECTIVE: Transglutaminase (TGM)2 and peroxisome proliferator-activated receptor (PPAR)γ are thought to participate in the pathogenesis of nasal polyp formation in cystic fibrosis (CF). We herein investigated expressions of cystic fibrosis transmembrane conductance regulator (CFTR), TGM2, PPARγ and isopeptide bonds, a reaction product of TGM, in non-CF nasal polyps.

METHODS: Nasal polyps and inferior turbinates were collected from chronic rhinosinusitis patients without CF during transnasal endoscopic sinonasal surgery. Expressions of CFTR, TGM2, isopeptide bonds and PPARγ were examined by fluorescence immunohistochemistry and quantitative RT-PCR. Expression of CFTR was also analyzed by Western blot.

RESULTS: Immunohistochemical fluorescence of the nasal polyp was significantly lower for CFTR and PPARγ, and significantly higher for TGM2 and isopeptide bonds than that of the turbinate mucosa. Lower expression of CFTR in the nasal polyp than in the turbinate mucosa was also observed in Western blot. Expression of PPARG mRNA was significantly lower in the nasal polyp than in the turbinate mucosa, whereas expressions of CFTR mRNA or TGM2 mRNA did not differ between the two tissues. Immunohistochemical fluorescence for CFTR showed significant negative correlation with that for TGM2 and isopeptide bonds, and significant positive correlation with that for PPARγ. The fluorescence for TGM2 was positively correlated with that for isopeptide bonds and negatively correlated with that for PPARγ. The fluorescence for isopeptide bonds tended to be negatively correlated with that for PPARγ.

CONCLUSIONS: These results suggest a possible role of the CFTR-TGM2-PPARγ cascade in the pathogenesis of nasal polyp formation in non-CF patients as in CF patients.

PMID:34728118 | DOI:10.1016/j.anl.2021.10.006

Cell Death Dis. 2021 Nov 1;12(11):1039. doi: 10.1038/s41419-021-04321-3.

ABSTRACT

Pro-apoptotic multi-domain proteins of the BCL2 family such as BAX and BAK are well known for their important role in the induction of mitochondrial outer membrane permeabilization (MOMP), which is the rate-limiting step of the intrinsic pathway of apoptosis. Human or mouse cells lacking both BAX and BAK (due to a double knockout, DKO) are notoriously resistant to MOMP and cell death induction. Here we report the surprising finding that BAX/BAK DKO cells proliferate less than control cells expressing both BAX and BAK (or either BAX or BAK) when they are driven into tetraploidy by transient exposure to the microtubule inhibitor nocodazole. Mechanistically, in contrast to their BAX/BAK-sufficient controls, tetraploid DKO cells activate a senescent program, as indicated by the overexpression of several cyclin-dependent kinase inhibitors and the activation of β-galactosidase. Moreover, DKO cells manifest alterations in ionomycin-mobilizable endoplasmic reticulum (ER) Ca2+ stores and store-operated Ca2+ entry that are affected by tetraploidization. DKO cells manifested reduced expression of endogenous sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (Serca2a) and transfection-enforced reintroduction of Serca2a, or reintroduction of an ER-targeted variant of BAK into DKO cells reestablished the same pattern of Ca2+ fluxes as observed in BAX/BAK-sufficient control cells. Serca2a reexpression and ER-targeted BAK also abolished the tetraploidy-induced senescence of DKO cells, placing ER Ca2+ fluxes downstream of the regulation of senescence by BAX/BAK. In conclusion, it appears that BAX/BAK prevent the induction of a tetraploidization-associated senescence program. Speculatively, this may contribute to the low incidence of cancers in BAX/BAK DKO mice and explain why human cancers rarely lose the expression of both BAX and BAK.

PMID:34725331 | PMC:PMC8560871 | DOI:10.1038/s41419-021-04321-3

Br J Hosp Med (Lond). 2021 Oct 2;82(10):1-3. doi: 10.12968/hmed.2020.0744. Epub 2021 Oct 14.

NO ABSTRACT

PMID:34726944 | DOI:10.12968/hmed.2020.0744

ACS Chem Biol. 2021 Nov 2. doi: 10.1021/acschembio.1c00168. Online ahead of print.

ABSTRACT

Channel-activating proteases (CAPs) play a fundamental role in the regulation of sodium transport across epithelial tissues mainly via cleavage-mediated fine-tuning of the activity of the epithelial sodium channel (ENaC). Hyperactivity of CAPs and subsequently increased ENaC activity have been associated with various diseases, including cystic fibrosis (CF). To date, there is only a limited number of tools available to investigate CAP activity. Here, we developed ratiometric, peptide-based Förster resonance energy transfer (FRET) reporters useful to visualize and quantify the activity of ectopic serine proteases including the CAPs prostasin and matriptase in human and murine samples in a temporally and spatially resolved manner. Lipidated varieties were inserted into the outer leaflet of the plasma membrane to detect enzyme activity on the surface of individual cells, that is, close to the protease substrates. The FRET reporters (termed CAPRee) selectively detected the activity of ectopic serine proteases such as CAPs in solution and on the surface of human and murine cells. We found increased CAP activity on the surface of cells with a genetic background of CF. The new reporters will contribute to a better understanding of ectopic serine protease activity and their regulation under physiological and pathophysiological conditions.

PMID:34726893 | DOI:10.1021/acschembio.1c00168

Acta Crystallogr D Struct Biol. 2021 Nov 1;77(Pt 11):1401-1410. doi: 10.1107/S2059798321009608. Epub 2021 Oct 20.

ABSTRACT

The capability to obtain essential nutrients in hostile environments is a critical skill for pathogens. Under zinc-deficient conditions, Pseudomonas aeruginosa expresses a pool of metal homeostasis control systems that is complex compared with other Gram-negative bacteria and has only been partially characterized. Here, the structure and zinc-binding properties of the protein PA4063, the first component of the PA4063-PA4066 operon, are described. PA4063 has no homologs in other organisms and is characterized by the presence of two histidine-rich sequences. ITC titration detected two zinc-binding sites with micromolar affinity. Crystallographic characterization, performed both with and without zinc, revealed an α/β-sandwich structure that can be classified as a noncanonical ferredoxin-like fold since it differs in size and topology. The histidine-rich stretches located at the N-terminus and between β3 and β4 are disordered in the apo structure, but a few residues become structured in the presence of zinc, contributing to coordination in one of the two sites. The ability to bind two zinc ions at relatively low affinity, the absence of catalytic cavities and the presence of two histidine-rich loops are properties and structural features which suggest that PA4063 might play a role as a periplasmic zinc chaperone or as a concentration sensor useful for optimizing the response of the pathogen to zinc deficiency.

PMID:34726168 | DOI:10.1107/S2059798321009608

Expert Rev Respir Med. 2021 Nov 2. doi: 10.1080/17476348.2021.2001333. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) is a genetically inherited disease, with mortality and morbidity associated with respiratory disease. The inflammatory response in CF is characterized by excessive neutrophil influx to the airways, mainly due to the increased local production and retention of interleukin-8 (IL-8), a potent neutrophil chemoattractant.

AREAS COVERED: : We discuss how the chemokine IL-8 more than any other dominates the inflammatory profile of the airways in CF lung disease. Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies are designed to correct the malfunctioning protein resulting from specific CFTR mutations. This review covers current evidence on the impact of CFTR impairment on levels of IL-8 and outlines the influence of effective CFTR modulation on inflammation in CF with a focus on cytokine production. Review of the literature was carried out using the PUBMED database, Google Scholar and The Cochrane Library databases, using several appropriate generic terms.

EXPERT OPINION: : Therapeutic interventions specifically targeting the defective CFTR protein have improved the outlook for CF. Accumulating studies on the effect of highly effective CFTR modulation on inflammation indicate an impact on IL-8 levels. Further studies are required to increase our knowledge of early onset innate inflammatory dysregulation and on anti-inflammatory mechanisms of CFTR modulators.

PMID:34726115 | DOI:10.1080/17476348.2021.2001333

Sci Rep. 2021 Nov 1;11(1):21419. doi: 10.1038/s41598-021-00421-4.

ABSTRACT

Infections by Burkholderia cenocepacia lead to life-threatening disease in immunocompromised individuals, including those living with cystic fibrosis (CF). While genetic variation in various B. cenocepacia strains has been reported, it remains unclear how the chemical environment of CF lung influences the production of small molecule virulence factors by these strains. Here we compare metabolomes of three clinical B. cenocepacia strains in synthetic CF sputum medium (SCFM2) and in a routine laboratory medium (LB), in the presence and absence of the antibiotic trimethoprim. Using a mass spectrometry-based untargeted metabolomics approach, we identify several compound classes which are differentially produced in SCFM2 compared to LB media, including siderophores, antimicrobials, quorum sensing signals, and various lipids. Furthermore, we describe that specific metabolites are induced in the presence of the antibiotic trimethoprim only in SCFM2 when compared to LB. Herein, C13-acyl-homoserine lactone, a quorum sensing signal previously not known to be produced by B. cenocepacia as well as pyochelin-type siderophores were exclusively detected during growth in SCFM2 in the presence of trimethoprim. The comparative metabolomics approach described in this study provides insight into environment-dependent production of secondary metabolites by B. cenocepacia strains and suggests future work which could identify personalized strain-specific regulatory mechanisms involved in production of secondary metabolites. Investigations into whether antibiotics with different mechanisms of action induce similar metabolic alterations will inform development of combination treatments aimed at effective clearance of Burkholderia spp. pathogens.

PMID:34725378 | DOI:10.1038/s41598-021-00421-4

Wiad Lek. 2021;74(9 cz 1):2094-2099.

ABSTRACT

OBJECTIVE: The aim: To determine the prevalence rate of Staphylococcus aureus infection among children with Cystic Fibrosis in the Dnieper region, to provide microbiological characteristics of the isolates and to elevate their susceptibility to antimicrobials.

PATIENTS AND METHODS: Materials and methods: Sputum, tracheobronchial lavage waters and/ or deep smear from the posterior pharyngeal wall were taken from children with genetically confirmed Cystic Fibrosis. Bacteriological method was the main. The first screening for small colony variants of Staphylococcus aureus was carried out after 48 hours of incubation. The antimicrobials susceptibility testing was determined by disk-diffusion method according to the EUCAST 2019. Microsoft Office Excel 2010 was used for statistical data processing.

RESULTS: Results: Twenty one children were enrolled in the survey. The culture of Staphylococcus spp. was obtained from all patients with 40.8% positive for Staphylococcus aureus. Small colony variants appeared with the prevalence rate 21.6% after 48 hours of incubation. The frequency of associations between Staphylococcus aureus with auxotroph phenotype with the presence of Pseudomonas aeruginosa was significantly higher than with wild-type group. The 3d-generation aminoglycosides, the 3d-generation fluoroquinolones, linezolid, rifampicin and tetracyclines showed the best antimicrobial activity, however, resistance to cefoxitin and gentamicin was significantly higher in auxotroph-modified group.

CONCLUSION: Conclusions: Infection Staphylococcus aureus is common among children. The appearance of auxotrophs registered after treatment with aminoglycosides and/ or co-trimoxazole and co-infection Pseudomonas aeruginosa. Isolates of Staphylococcus aureus showed good chemotherapeutic sensitivity, but tendency in increasing resistance registered for auxotroph-modified phenotype.

PMID:34725282

Medicina (B Aires). 2021;81 Suppl 2:1-32.

ABSTRACT

Last decades, a broad spectrum of inhaled devices (ID) had been developed to enhance efficacy and reduce adverse events. The correct use of IDs is a critical issue for controlling obstructive respiratory diseases. There is no recommendation on inhalation therapy in Argentina. This document aims to issue local recommendations about the prescription of IDs. Each device was reviewed regarding biophysical laws, indication, strength, limitations, correct technique of use, frequent mistakes, and device cleaning and maintenance. Nebulization should be restricted to drugs that are not available in other IDs (for example, for treatment of cystic fibrosis) or where other devices fail. Nebulization is not recommended during the SARS-CoV2 pandemic. A metered-dose inhaler must always be used with an aerochamber. Aerochambers reduce the incidence of adverse events and improve lung deposition. Metered-dose inhalers must be prescribed to patients who cannot generate a high inspiratory flow and dry powders to those who can generate an energetic inspiratory flow. We reviewed the use of different IDs in patients with cystic fibrosis and under mechanical ventilation. The individual choice of an ID will be based on several variables like clinical status, age, previous experience, patient preference, drug availability, and correct use of the device.

PMID:34724622

Eur J Gastroenterol Hepatol. 2021 Dec 1;33(12):1610. doi: 10.1097/MEG.0000000000002137.

NO ABSTRACT

PMID:34723874 | DOI:10.1097/MEG.0000000000002137

Transpl Infect Dis. 2021 Nov 1. doi: 10.1111/tid.13754. Online ahead of print.

ABSTRACT

RATIONAL: Pending the authorization of new anti-CMV drugs with fewer adverse effects, exploring the possibilities offered by CMV immunoglobulins (CMVIG) seems necessary. In France, access to CMVIG requires official authorization by the national Health authority and is restricted to second line rescue therapy for CMV infection/disease. The aim of this multicenter retrospective study is to describe the indications and clinical situations that justified its use in France.

METHODS: A multicenter retrospective study included twenty-two lung transplant patients over a 3-year period. Data on clinical indication, tolerance and efficacy were collected.

RESULTS: The main indication for CMVIG initiation, which was documented in 17 of them (82%) was complex clinical situations resulting from side effects to antiviral drug. CMVIG indication was documented as treatment for 15 patients (68%) and as a secondary prophylaxis for 7 patients (32%). Only one side effect (pruritus during infusion with no anaphylactic symptoms) attributable to CMVIG was reported. After CMVIG initiation, no recurrence of infection or disease was observed during a median follow-up of 174 [12-682] days after treatment initiation for respectively 68% and 66% of the patients.

CONCLUSION: This study describes an unusual indication of CMVIG use as a last resort treatment in complex situations, based on clinical needs. CMVIG could be useful to change the course of CMV infection with minimal adverse effects or comorbidity. This article is protected by copyright. All rights reserved.

PMID:34723405 | DOI:10.1111/tid.13754

J Clin Transl Endocrinol. 2021 Oct 25:100268. doi: 10.1016/j.jcte.2021.100268. Online ahead of print.

ABSTRACT

The novel SARS-CoV-2 coronavirus (COVID-19) has become a global health crisis since its initial outbreak in Wuhan, China in December 2019. On January 30, 2020, the WHO recognized the COVID-19 outbreak as a Public Health Emergency, and on March 11, 2020, it was declared a pandemic. Although all age groups have been affected, patients with cystic fibrosis (CF) and patients with diabetes have been categorized as highly vulnerable to SARS-CoV-2 infection. Thus far, studies have found that the incidence of SARS-CoV-2 in the CF population is lower than the general population. We review the underlying protective mechanisms which may reduce inflammation and lung damage in CF patients, thus decreasing their risk of severe COVID-19. While the effect of SARS-CoV-2 in those with diabetes related to CF is unknown, other forms of diabetes have been associated with more severe disease. To further understand the potential impact of SARS-CoV-2 in cystic fibrosis-related diabetes, we provide a comprehensive overview of the potential factors contributing to COVID-19 severity in other forms of diabetes, including direct viral effect on the pancreas and indirect effects related to hyperglycemia and immune dysregulation.

PMID:34722160 | PMC:PMC8545686 | DOI:10.1016/j.jcte.2021.100268

Front Immunol. 2021 Oct 15;12:733217. doi: 10.3389/fimmu.2021.733217. eCollection 2021.

ABSTRACT

The immune landscape of the paediatric respiratory system remains largely uncharacterised and as a result, the mechanisms of globally important childhood respiratory diseases remain poorly understood. In this work, we used high parameter flow cytometry and inflammatory cytokine profiling to map the local [bronchoalveolar lavage (BAL)] and systemic (whole blood) immune response in preschool aged children with cystic fibrosis (CF) and aged-matched healthy controls. We demonstrate that children with CF show pulmonary infiltration of CD66b+ granulocytes and increased levels of MIP-1α, MIG, MCP-1, IL-8, and IL-6 in BAL relative to healthy control children. Proportions of systemic neutrophils positively correlated with age in children with CF, whilst systemic CD4 T cells and B cells were inversely associated with age. Inflammatory cells in the BAL from both CF and healthy children expressed higher levels of activation and migration markers relative to their systemic counterparts. This work highlights the utility of multiplex immune profiling and advanced analytical pipelines to understand mechanisms of lung disease in childhood.

PMID:34721395 | PMC:PMC8554310 | DOI:10.3389/fimmu.2021.733217

Front Microbiol. 2021 Oct 15;12:750489. doi: 10.3389/fmicb.2021.750489. eCollection 2021.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease with lung abnormalities making patients particularly predisposed to pulmonary infections. Staphylococcus aureus is the most frequently identified pathogen, and multidrug-resistant strains (MRSA, methicillin-resistant S. aureus) have been associated with more severe lung dysfunction leading to eradication recommendations. Diverse bacterial traits and adaptive skills, including biofilm formation, may, however, make antimicrobial therapy challenging. In this context, we compared the ability of a collection of genotyped MRSA isolates from CF patients to form biofilm with and without antibiotics (ceftaroline, ceftobiprole, linezolid, trimethoprim, and rifampicin). Our study used standardized approaches not previously applied to CF MRSA, the BioFilm Ring test® (BRT®), the Antibiofilmogram®, and the BioFlux™ 200 system which were adapted for use with the artificial sputum medium (ASM) mimicking conditions more relevant to the CF lung. We included 63 strains of 10 multilocus sequence types (STs) isolated from 35 CF patients, 16 of whom had chronic colonization. The BRT® showed that 27% of the strains isolated in 37% of the patients were strong biofilm producers. The Antibiofilmogram® performed on these strains showed that broad-spectrum cephalosporins had the lowest minimum biofilm inhibitory concentrations (bMIC) on a majority of strains. A focus on four chronically colonized patients with inclusion of successively isolated strains showed that ceftaroline, ceftobiprole, and/or linezolid bMICs may remain below the resistance thresholds over time. Studying the dynamics of biofilm formation by strains isolated 3years apart in one of these patients using BioFlux™ 200 showed that inhibition of biofilm formation was observed for up to 36h of exposure to bMIC and ceftaroline and ceftobiprole had a significantly greater effect than linezolid. This study has brought new insights into the behavior of CF MRSA which has been little studied for its ability to form biofilm. Biofilm formation is a common characteristic of prevalent MRSA clones in CF. Early biofilm formation was strain-dependent, even within a sample, and not only observed during chronic colonization. Ceftaroline and ceftobiprole showed a remarkable activity with a long-lasting inhibitory effect on biofilm formation and a conserved activity on certain strains adapted to the CF lung environment after years of colonization.

PMID:34721354 | PMC:PMC8554194 | DOI:10.3389/fmicb.2021.750489

J Pediatr Psychol. 2021 Oct 26:jsab105. doi: 10.1093/jpepsy/jsab105. Online ahead of print.

ABSTRACT

OBJECTIVE: Cystic fibrosis (CF) is the most common indication for pediatric lung transplantation and the third most common for adults. The selection of candidates and timing of transplant is challenging and whether there is a survival benefit of this procedure for pediatric patients is controversial. Use of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a well-validated, disease-specific quality of life measure may improve pretransplant referral decision-making.

METHODS: This multicenter study evaluated whether specific domains on the CFQ-R (i.e., Physical Functioning, Respiratory Symptoms), assessed pretransplant, predicted survival 4-year post-transplant (n = 25). A two-step Cox regression, with physical predictors entered in step one (i.e., age, CF-related Diabetes, FEV1% predicted) and the Physical Functioning and Respiratory Symptoms CFQ-R scales entered in step two, was used to assess whether the CFQ-R explained additional and unique variance. Receiver Operating Characteristic (ROC) curves were used to assess the sensitivity and specificity of optimal cut-points of significant CFQ-R domains.

RESULTS: The Respiratory Symptoms scale predicted survival 4-year post-transplant (Exp(B) = 0.38, 95% CI = 0.14-1.01; area under the curve = 0.87) and once it was added to the model, no other individual predictors were significant. The incremental improvement beyond the physical parameters approached but did not reach statistical significance (χ2 Δ = 5.79, p = .06).

CONCLUSIONS: This study suggested that including patient-reported outcomes could aid pretransplant referral decision-making. The Respiratory Symptoms scale in particular may serve as a useful tool to help determine when to refer and evaluate an individual for transplant.

PMID:34718670 | DOI:10.1093/jpepsy/jsab105